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Mount Vernon Cancer Network Head & Neck NSSG Clinical Guidelines (11-1C-103i) Version number as approved and published Author Date Written Date Reviewed Review Date NSSG Ratified 0.12 Dr Kate Goodchild May 2011 February 2013 (Sarcoma pathway added) May 2014 1st September 2011 Agreed by: Position: Chair of the Network Board Name: Dr Jane Halpin Organisation: NHS Hertfordshire Date agreed: 1st Septmeber 2011 Position: Chair of the Head & Neck NSSG Name: Dr Kate Goodchild Organisation: East & North Herts NHS Trust Date agreed: 26th August 2011 1 Contents 1. 2. 3. 4. 5. 6. Referral Guidelines 1.1 Primary Care Referrals 1.2 Non 2WW Referrals 1.3 Inappropriate referrals to the Head, Neck & Thyroid Team 1.4 Referrals to the SMDT 1.5 Identification of patients for discussion at SMDT 1.6 Internal referral guidelines between teams 1.7 Radiotherapy/Oncology referrals 1.8 Pre-treatment Assessment & Management Cancer of the Oropharynx 2.1 Investigation and preparation 2.2 Management of primary tumour 2.3 Management of the neck 2.4 Surgery 2.5 Specific sites 2.6 Rehabilitation 2.7 Recurrent disease 2.8 Palliation 2.9 Follow-up Cancer of the Larynx 3.1 Assessment 3.2 Investigations 3.3 Management of primary tumour 3.4 Laryngeal sub-sites 3.5 Management of the neck 3.6 Voice rehabilitation 3.7 Recurrent disease 3.8 Palliative Care 3.9 Follow-up Cancer of the Hypopharynx 4.1 Assessment 4.2 Investigations 4.3 Management of the primary tumour 4.4 Hypopharyngeal sub-sites 4.5 Management of the neck 4.6 Rehabilitation 4.7 Recurrent disease 4.8 Palliative treatment 4.9 Follow-up Cancer of the Nasopharynx 5.1 Assessment 5.2 Investigations 5.3 Management of the primary tumour 5.4 Management of the neck 5.5 Recurrance 5.6 Palliative care 5.7 Follow-up Cancer of the Nose and Sinuses 6.1 Assessment 6.2 Investigations 6.3 Management of the primary tumour 6.4 Management of the neck 6.5 Recurrent disease Page 6 6 6 6 6 6 7 7 7 8 8 8 8 8 9 9 9 9 10 11 11 11 11 11 11 12 12 12 12 13 13 13 13 13 14 14 14 14 14 15 15 15 15 15 15 15 15 17 17 17 17 17 17 2 7. 8. 9. 10. 11. 12. 13. 14. 6.6 Palliative treatment 6.7 Follow-up Cancer of the Lip 7.1 Assessment 7.2 Investigations 7.3 Management of primary tumour 7.4 Recurrent disease 7.5 Palliation 7.6 Follow-up Cancer of the Oral Cavity- Tongue 8.1 Investigations 8.2 Management 8.3 Management of the neck 8.4 Chemotherapy 8.5 Rehabilitation 8.6 Recurrent disease 8.7 Palliation 8.8 Follow-up Cancer of the Oral Cavity- Floor of Mouth 9.1 Investigations 9.2 Management 9.3 Management of the neck 9.4 Chemotherapy 9.5 Recurrent disease 9.6 Palliation 9.7 Follow-up Cancer of the Oral Cavity- Retromolar Trigone 10.1 Assessment and investigations 10.2 Management 10.3 Management of the neck 10.4 Rehabilitation 10.5 Recurrent disease 10.6 Palliation 10.7 Follow-up Cancer of the Oral Cavity- Alveolar Ridge 11.1 Investigations 11.2 Management 11.3 Management of the neck 11.4 Chemotherapy 11.5 Rehabilitation 11.6 Recurrent disease 11.7 Palliation 11.8 Follow-up Malignant tumours of the salivary glands 12.1 Major salivary glands 12.2 Submandibular gland 12.3 Minor salivary glands Guidelines for the management of Thyroid Cancer 13.1 Screening 13.2 Diagnosis and referral 13.3 Investigations 13.4 TNM staging 13.5 Classification Differentiated Thyroid Cancer 14.1 Principles of treatment 14.2 Standard treatment 17 18 19 19 19 19 19 19 20 21 21 21 21 22 22 22 22 22 23 23 23 23 24 24 24 24 25 25 25 25 25 25 25 26 27 27 27 27 27 27 28 28 28 29 29 29 30 32 32 32 32 33 34 36 36 36 3 15. 16. 17. 18. 19. 20. 21. 22. 14.3 Procedure for 131 l ablative/therapy doses 14.4 Serum TSH measurements 14.5 Serum Thyroglobulin 14.6 Recombinant human TSH 14.7 Management of hypocalcaemia 14.8 Non standard / Low risk patients 14.9 External beam Radiotherapy 14.10 Recurrent disease 14.11 Palliative Chemotherapy 14.12 Diagnosis of thyroid cancer in pregnancy 14.13 Oxyphillic / Hurthle Cell Carcinoma Medullary Thyroid Carcinoma (Mtc) 15.1 Investigations 15.2 Treatment 15.3 Radiotherapy and Chemotherapy 15.4 Research studies in Thyroid cancer Thyroid Lymphoma 16.1 Investigations 16.2 Treatment Anaplastic Carcinoma 17.1 Treatment Lymph node resections on Thyroid cancer Follow-up guidelines for Head & Neck Cancer 19.1 General principles 19.2 L&D and Lister Hospital 19.3 Bedford Hospital 19.4 North West Hertfordshire Rarer Cancers 20.1 Treatments nor provided by Beds and Herts Centre 20.2 Childhood Head & Neck cancer 20.3 Management of soft tissue Sarcomas 20.4 Head & Neck Sarcomas 20.5 Rhabdomyosarcoma 20.6 Tumour involving the skull base Acute Oncology Services Rehabilitation APPENDICES Appendix 1: Primary Care Referral Guidelines for Head & Neck Cancer for the population of NHS Bedfordshire Appendix 2: Referral Proforma for patients outside the “Urgent Suspicion of Cancer” definition Appendix 3: Imaging Guidelines for patients with suspected Head & Neck Cancer (including Thyroid Cancer) Appendix 4: Head & Neck Cancer Team Clinical Follow-Up protocol Appendix 5: London and South East Sarcoma Network: Bone Sarcoma Presentation and Diagnostic Pathway Appendix 6: Head & Neck- Rehabilitation & Supportive care mapping template Appendix 7: Head & Neck Rehabilitation Plan 36 37 37 37 37 38 38 38 39 39 39 40 40 40 40 41 43 43 43 44 44 46 47 47 47 47 47 48 48 48 48 49 49 51 52 53 54 66 67 71 72 73 93 4 Appendix 8: Head & Neck Cancer Rehabilitation Protocol Appendix 9: Supportive Care Pathway for Head & Neck Cancer Specialist Surgery to support IOG recommendations Appendix 10: Mount Vernon Cancer Centre Head & Neck Radiotherapy & Chemotherapy Treatment Protocols Appendix 11: Pathology Guidelines: Tissue pathways for head and neck pathology-- Luton and Dunstable Hospital pathology department. Royal College of Pathology Datasets for Histopathology reports on Head & Neck carcinomas and salivary neoplasms (2nd edition) Royal College of Pathology Tissue pathways for Head & Neck Cancer Royal College of Pathology Dataset for Thyroid Cancer Histopathology Reports Royal College of Pathology Tissue Pathways for Endocine Pathology Appendix 12: Sarcoma Pathway 94 95 97 168 168 170 199 212 233 241 5 Guidelines for the Management of Head & Neck Cancer 1. Referral Guidelines 1.1 Primary Care Referrals (11-1A-206i) The Head, Neck & Thyroid NSSG agreed the MVCN Head, Neck & Thyroid 2 week wait (2WW) Urgent Cancer Referral proforma in December 2010. The agreed version is attached below. Agreed Head, Neck & Thyroid 2WW proforma.doc In addition the NSSG has agreed to adopt the primary care referral guidelines for the population of NHS Bedfordshire, and these can be found in appendix 1. 1.2 Non 2WW Referrals (11-1A-207i) For those patients that are outside of the 2WW “urgent suspicious of cancer” patients should be referred via the form in appendix 2 1.3 Inappropriate referrals to the Head, Neck & Thyroid Team Any referral received by the Head, Neck & Thyroid team that are deemed to be inappropriate, will be returned to the referring GP with an explanation letter dictated and signed by the consultant concerned within 24 hours of receipt by the consultant. The SMDT will report to the PCT’s, GP’s and GDP’s annually on appropriateness and timeliness on urgent suspect cancer referrals. 1.4 Referrals to the SMDT All confirmed thyroid cancers are referred to the Bedfordshire & Hertfordshire SMDT before definitive treatment is commenced but it is recognised that many are not confirmed until hemi-thyroidectomy has been performed in one or the diagnostic centres as cytological diagnosis is often not definitive. All thyroid lumps with Thy 4 or Thy 5 cytology are to be referred to the SMDT before surgery, surgery will be carried out in the surgical centre (ward 21). Cases requiring neck dissection(levels I-V &/or VII), mediastinal node dissection or extended thyroidectomy will undergo the surgery at the Luton & Dunstable Hospital Head, Neck & Thyroid Centre. Thy 3 lumps frequently turn out to be benign and are therefore removed by hemi-thyroidectomy at the diagnostic centre; if definitive histology confirms cancer then they are referred to the SMDT following staging investigations. Further surgery should be carried out at the surgical centre. The above pathways achieve compliance with NICE guidance as each SMDT serves a population exceeding one million. The number of surgeons carrying out definitive thyroid cancer surgery has reduced to three for the Beds & Herts network (2011). 1.5 Identification of patients for discussion at SMDT Clinicians wishing to refer a patient for discussion at SMDT should notify the pathway facilitator at the L&D by no later than by the end of the working day on Tuesdays. 6 1.6 Internal referral guidelines between teams (10-1A-208i, 10-1A-209i) Internal referral guidelines for non Head, Neck & Thyroid designated hospital clinicians; Patient with symptoms or signs suggestive of Head, Neck & Thyroid cancer; Cancer highly likely; urgent referral to Head, Neck & Thyroid MDT core consultant member without biopsy or further investigation. Cancer diagnosis uncertain and biopsy deemed necessary for initial diagnosis; urgent referral to core Head, Neck & Thyroid MDT consultant with the result of biopsy with or without imaging as per guidelines. These guidelines are distributed to designated consultant clinicians and non-designated head and neck consultant clinicians including ENT surgeons, endocrine surgeons, OMFS surgeons, oral medicine specialists, and endocrinologists through the cancer management teams. 1.7 Radiotherapy/Oncology Referrals Beds & Herts SMDT refers patients to Mount Vernon Cancer Centre. 1.8 Pre-treatment Assessment & Management Careful assessment of each patient’s clinical, nutritional and psychological state must be carried out to inform MDT decisions on treatment options. Co-morbidity, performance status, psychological state, nutritional status and alcohol dependence should be assessed. The Clinical Nurse Specialist should ensure that all patients and carers receive appropriate support and information, that their non medical needs are assessed and that there is effective liaison between hospital staff, primary care teams and other agencies as required. Patients who are dependant on smoking, drinking or other addictive substances that increase the risk of Head & Neck cancers should be offered interventions to help them stop. The full range of treatment options should be discussed with the patient with supporting written information if required. These discussions may be held over a number of meetings so that patients have adequate time to consider the MDT’s proposals. a) Dental Assessment Once a treatment plan has been agreed a dental assessment should be carried out on those patients where treatment will affect the mouth or jaws. Any necessary dental extractions should be carried out pre-treatment with sufficient time allowed for healing. The patients should be encouraged to have good oral hygiene and attend their general dental practitioner if appropriate. Referral to a specialist restorative dentistry consultant should be considered in appropriate patients. b) Speech and Language Therapist (SLT) and Nutritional Assessment If a patient is to have treatment that will affect eating or swallowing the team should discuss the method of feeding that will be used and inform the primary care team well in advance if tube feeding is required so that the patient can be supported at home. The dietitian and SLT should work together with the patient to explain swallowing and nutritional issues and make sure the patient is prepared, before treatment begins, for any short or long term interventions that may be required. Patients whose treatment is likely to affect the ability to communicate should be seen by the SLT before treatment begins to explain rehabilitation strategies and how the SLT will work with the patient to make the most of their potential for recovery of speech, voice and swallowing. c) Anaesthetic Assessment Patients who are to undergo surgery that will involve the airways should be assessed by the specialist anaesthetist who works with surgeons at the MDT. 7 2. Cancer of the Oropharynx Site includes tonsil, palate, the posterior one third of tongue & the posterior wall of the pharynx. Patients with biopsy-proven carcinoma of the oropharnyx will be fully investigated before being considered, with the results of investigations, at the multi-disciplinary team meeting attended by all members of the MDT. Treatment options will be discussed at the MDT and recommendations made to the patient in the following multi-disciplinary clinic. Advice and support from the clinical nurse specialists, speech and language therapists, dieticians and nutritional nurses and palliative care team will also be available in the clinic. 2.1 Investigation and preparation EUA and incisional biopsy MRI of the head and neck Ultrasound guided FNA of the neck Chest x-ray CT of the thorax for stages 2 and 3 Dental assessment Nutritional assessment – PEG if necessary SALT assessment Nutritional assessment and support as necessary. Patients with T1 and T2 lesions will usually require weekly nutritional assessment and support. The need for PEG insertion should be considered in patients with T3 and T4 lesions undergoing radical surgery and/or radiotherapy. Psychological assessment and assessment of social circumstances may indicate the need for psychological or social support. 2.2 Management of primary tumour T1 External beam irradiation has similar cure rates to radical surgery and produces less disability. T2 as for T1 T3 and T4 Radical surgery and postoperative radiotherapy+/_ chemotherapy offer the best chance of cure. However, the long-term disability following radical surgery may not intolerable so radiotherapy with or without chemotherapy should be considered. 2.3 Management of the neck N0 Neck irradiation or prophylactic dissection for all except localised soft palate & posterior wall tumours. N+ Radical neck dissection if primary treated surgically. Radical neck dissection if FNA positive after radiotherapy of neck. 2.4 Surgery Local resection for small tumours by a lateral pharyngotomy approach. More extensive tumours will require mandibulotomy and floor of mouth splitting approach. Preliminary tracheostomy will be necessary. Total or supraglottic laryngectomy may be necessary. Reconstruction will usually be by pectoralis major or free microvasular flap, crico-pharyngeal myotomy helps prevent postoperative dysphagia. Frozen section histology should be used to check margins. 8 2.5 Specific sites 2.5.1 Tongue T1 & 2 Surgery and radiotherapy having equivalent cure rates; elective neck dissection is essential. T3 & 4 Most will be treated by radiotherapy initially, with or without radical neck dissection (or neck irradiation and salvage neck dissection). For T4 tumours radical surgery offers best chance of cure but laryngectomy may be necessary. 2.5.2 Tonsil T1 & 2 Surgery & RT give similar results Elective neck dissection is essential T3 & 4 RT effective for exophytic T3 tumours Ulcerative T3 & T4 tumours better treated by surgery & RT with Segmental resection of mandible where necessary & neck dissection. 2.5.3 Posterior wall T1 & 2 Surgery with local flap repair with or without RT to neck T3 & 4 Surgery & RT & neck dissection; may require laryngopharyngectomy. 2.5.4 Soft palate T1 & RT RT effective & effective less likely to result in nasal regurgitation. T3 & 4 Surgery & RT with flap reconstruction of palate & neck dissection. 2.6 Rehabilitation Rehabilitation of speech & swallowing require support from SALT & specialist nurses. Dietician will need to advise post-operatively; many patients will need PEG feeding temporarily and some permanently. Management of the neck N0 Elective neck dissection or irradiation if T3 or 4 (selective lateral neck dissection). N1 – 3 Modified radical neck dissection + adjuvant RT. 2.7 Recurrent disease Histological confirmation and staging to be carried out. Treatment options to be discussed by MDT. Salvage laryngectomy often necessary and effective. 2.8 Palliation Symptom control and nutritional support will be provided by the MDT in conjunction with specialist pain and palliative care teams. Support from the community Macmillan nurses and from the hospital palliative care team will usually be available and, depending on patient’s and carer’s view, hospice care can be introduced. 9 2.9 Follow up 1st year 2nd year 3rd year 4th year 5th year Thereafter monthly 2 monthly 3 monthly 6 monthly 6 monthly discharge or annual review 10 3. Cancer of the Larynx 3.1 Assessment Patients with biopsy proven laryngeal squamous carcinoma will be fully investigated before being considered, with the results of investigations, at the multi-disciplinary team meeting attended by all members of the MDT. Treatment options will be discussed at the MDT and recommendations made to the patient in the following multi-disciplinary clinic. Advice and support from the clinical nurse specialists, speech and language therapists, dieticians and nutritional nurses and palliative care team will also be available in the clinic. 3.2 Investigations EUA & biopsy Chest X-ray MRI for T3 – 4 CT chest for T3 to 4 Dental assessment if RT proposed Nutritional assessment where necessary SALT assessment and advice prior to treatment and during & after where necessary Nutritional assessment and support as necessary. Patients with T1 and T2 lesions will usually require weekly nutritional assessment and support. The need for PEG insertion should be considered in patients with T3 and T4 lesions undergoing radical surgery and/or radiotherapy. Psychological assessment and assessment of social circumstances may indicate the need for psychological or social support. 3.3 Management of primary tumour T1 Usually radical radiotherapy but cordectomy for verrucous carcinoma and other appropriate lesion. T2 Usually radical radiotherapy; laser resection or vertical hemilaryngectomy may be appropriate in some cases. T3 Radical radiotherapy for favourable lesions. Stridor, cartilage invasion and difficulty in regular follow-up are indications for primary laryngectomy. T4 Laryngectomy usual treatment of choice; post-operative RT if margins close, multiple neck metastases or extra-capsular spread. 3.4 Laryngeal sub-sites Glottis; management as above. Supraglottis; Supraglottic laryngectomy & RND effective for T1 – T2 N+ if patient less than 60 years of age and good pulmonary function. Subglottis; T1 & 2 RT T3 & 4 Surgery & RT as appropriate. All sites; piecemeal laser resection may be appropriate for T1 – 3, followed by neck dissection depending on depth of invasion (Steiner W). 3.5 Management of the Neck 11 Glottic – T1 – T3 5% to 20% Primary echelons II, III, IV T4 25% to 40% T1 T2 no treatment to nodes T3 T4 irradiate or selective levels II, III, IV neck dissection All stages comprehensive neck dissection N0 neck N+ neck Supraglottic T1 5% to 25% Primary echelons II, III T2 30% to 70% T3 – T4 65% to 80% Occult metastases in 20% to 50% N0 neck N+ neck All stages irradiate nodes or selective neck dissection All stages comprehensive neck dissection Subglottic Cervical node involvement <20% Para-tracheal node involvement up to 45% treat para-tracheal nodes T1 T2 no treatment to neck nodes T3, T4 irradiate or selective neck dissection All stages comprehensive neck dissection All stages N0 neck N+ neck 3.6 Voice rehabilitation Immediate tracheo-oesophageal puncture at time of surgery in most cases with posterior midline myotomy. Rehabilitation to commence12 – 14 days post op under care of SALT and nurse specialist. Early use of HME recommended to reduce tracheal secretions especially in asthmatic patients. 3.7 Recurrent disease Will require appropriate histological confirmation and staging and assessment by the MDT. Salvage will usually require surgery. 3.8 Palliative care Palliation of symptoms including pain and nutritional support will be required. coordinate in conjunction with specialist pain control team and palliative care team. The MDT will Support from the community Macmillan nurses and from the hospital palliative care team will usually be available and, depending on patient’s and carer’s view, hospice care can be introduced. 3.9 Follow up 1st year 2nd year 3rd year 4th year 5th year Years 6- 10 1 monthly 3 monthly 4 monthly 6 monthly 6 monthly discharge or annual review 12 4. Cancer of the Hypopharynx 4.1 Assessment Patients with biopsy proven hypopharyngeal squamous cell carcinoma will be fully investigated before being considered, with the results of investigations, at the multi-disciplinary team meeting attended by all members of the MDT. Treatment options will be discussed at the MDT and recommendations made to the patient in the following multi-disciplinary clinic. Advice and support from the clinical nurse specialists, speech and language therapists, dieticians and nutritional nurses and palliative care team will also be available in the clinic. 4.2 Investigations EUA & biopsy Chest X-ray MRI for T2 – 4 CT chest for T3 – 4 Dental assessment if RT proposed Nutritional assessment where necessary SALT assessment and advice prior to treatment and during & after where necessary. Nutritional assessment and support as necessary. Patients with T1 and T2 lesions will usually require weekly nutritional assessment and support. The need for PEG insertion should be considered in patients with T3 and T4 lesions undergoing radical surgery and/or radiotherapy. Psychological assessment and assessment of social circumstances may indicate the need for psychological or social support. 4.3 Management of the primary tumour T1; Local resection (maybe endoscopic) or radical radiotherapy. T2; Radical radiotherapy or surgery which may be endoscopic or partial pharyngeal-laryngectomy. T3; Usually combined treatment with pharyngo-laryngectomy followed by radiotherapy. T4; Usually combined treatment with pharyngo-laryngectomy followed by radical radiotherapy. 4.4 Hypopharyngeal sub-sites Posterior pharyngeal wall: small well-circumscribed tumours may be locally resected endoscopically or via a lateral pharyngotomy. Small defects can be left to granulate but larger ones may be closed primarily or with a free radial forearm flap. Piriform fossa: T1 & T2 lesions may be irradiated and larger lesions will usually require total laryngectomy and partial or total pharyngectomy with reconstruction by pectoralis major or free jejunal flap. Post cricoid: Smaller tumours may be treated by radical radiotherapy with, if necessary, salvage surgery. Larger tumours may require total pharyngo-laryngectomy, at least 3cm of oesophagus below the lesion should be removed; the extent of this resection will determine whether reconstruction is by free jejunal flap or stomach pull up. Endoscopic laser resection may be suitable for certain posterior pharyngeal wall and piriform sinus tumours. 13 4.5 Management of the neck Approximately 2/3 of patients have no positive nodes at presentation and occult metastases are found in about 40% of neck dissections for N0 staged disease, usually Levels 2, 3 and 4. Midline tumours may spread to both sides. N0 neck First echelon nodes should be included in the radiotherapy field if primary treatment is by radiotherapy. If surgical treatment is used then select neck dissection of Levels 2, 3 and 4 are recommended. N1 – 3 neck Comprehensive neck dissection usually recommended. 4.6 Rehabilitation SALT input is usually required for rehabilitation for both speech and swallowing. 4.7 Recurrent disease Histological confirmation and staging to be carried out. Treatment options should be discussed by MDT. Salvage surgery will usually include total laryngectomy. Partial laryngectomy is not recommended as pattern of spread is unpredictable and healing may be impaired. 4.8 Palliative Treatment Symptom control and nutritional support will be provided by the MDT in conjunction with specialist pain and palliative care teams. Support from the community Macmillan nurses and from the hospital palliative care team will usually be available and, depending on patient’s and carer’s view, hospice care can be introduced. 4.9 Follow up 1st year 2nd year 3rd year 4th year 5th year Thereafter monthly 3 monthly 4 monthly 6 monthly 6 monthly discharge or annual review 14 5. Cancer of the Nasopharynx 5.1 Assessment Tumours will be fully investigated before being considered, with the results of investigations, at the multi-disciplinary team meeting attended by all members of the MDT. Treatment options will be discussed at the MDT and recommendations made to the patient in the following multi-disciplinary clinic. Advice and support from the clinical nurse specialists, speech and language therapists, dieticians and nutritional nurses and palliative care team will also be available in the clinic. 5.2 Investigations EUA & biopsy Chest X-ray EB virus - Serology (IgA anti-VCA, IgA anti-EA) High resolution CT or MR scan of middle cranial fossa, skull base, nasopharynx, sinuses, neck and thorax. OPG x-ray Bone scan if extensive nodal disease Liver ultrasound if extensive nodal disease Nutritional assessment and support as necessary. Patients with T1 and T2 lesions will usually require weekly nutritional assessment and support. The need for PEG insertion should be considered in patients with T3 and T4 lesions undergoing radical surgery and/or radiotherapy. Psychological assessment and assessment of social circumstances may indicate the need for psychological or social support. 5.3 Management of the primary tumour Radiotherapy for primary tumour and nodes of the neck whether N0 or N positive. chemotherapy is usually also employed. Adjunctive 5.4 Management of the neck Initial management of the neck is by radiotherapy, usually combined with chemotherapy. Surgery in the form of comprehensive neck dissection is undertaken for failed radiotherapy or recurrent disease. 5.5 Recurrence Recurrence should be biopsy-proven and staged. Treatment may be by local resection, by fenestration of the palate or LeFort 1 osteotomy. Brachytherapy may also be employed. 5.6 Palliative care The MDT will coordinate in conjunction with specialist pain control team and palliative care team. Support from the community Macmillan nurses and from the hospital palliative care team will usually be available and, depending on patient’s and carer’s view, hospice care can be introduced. 5.7 Follow up 1st year 2nd year 3rd year 4th year monthly 3 monthly 4 monthly 6 monthly 15 5th year Thereafter 6 monthly discharge or annual review 16 6. Cancer of the Nose and Sinuses 6.1 Assessment Patients with biopsy proven tumours of the nose and sinuses will be fully investigated before being considered, with the results of investigations, at the multi-disciplinary team meeting attended by all members of the MDT. Treatment options will be discussed at the MDT and recommendations made to the patient in the following multi-disciplinary clinic. Advice and support from the clinical nurse specialists, speech and language therapists, dieticians and nutritional nurses and palliative care team will also be available in the clinic. 6.2 Investigations EUA & biopsy, usually endoscopic CT of all primaries Chest X-ray CT or MRI neck for T3 - 4 CT of thorax T3 - 4 Dental assessment Nutritional assessment and support as necessary. Patients with T1 and T2 lesions will usually require weekly nutritional assessment and support. The need for PEG insertion should be considered in patients with T3 and T4 lesions undergoing radical surgery and/or radiotherapy. Psychological assessment and assessment of social circumstances may indicate the need for psychological or social support. 6.3 Management of the primary tumour Most tumours are managed by surgery alone or in combination with radiotherapy. approaches include: a) b) c) d) e) f) Surgical Lateral rhinotomy for septum and lateral wall tumours including melanomas. Mid-facial de-gloving to allow access to maxillary sinus, ethmoids, sphenoid and nasal cavity. Maxillectomy usually for squamous cell carcinoma, particularly when involving maxillary sinus or palate or with extension to pterygoid region. May be combined with orbital exenteration. Cranio facial resection. Commonly carried out for adeno carcinoma, olfactory neuroblastoma, condrosarcoma and sometimes squamous cell carcinoma. Neurosurgical expertise usually required. Orbital exenteration. Endoscopic surgery suitable for benign tumours such as inverted papilloma and some malignant melanomas. Chemotherapy used concomitantly with radiotherapy for some tumours. 6.4 Management of the neck N0 Expectant treatment. N1 – 3 Comprehensive neck dissection for squamous cell carcinomas. 6.5 Recurrent disease Recurrent disease should be biopsy-proven, staged and managed by the multi-disciplinary team. Salvage will usually require surgery unless radiotherapy has not previously been given/ 6.6 Palliative Treatment 17 The multi-disciplinary team will coordinate the management of symptoms with specialist pain control and palliative care team. Support from the community Macmillan nurses and from the hospital palliative care team will usually be available and, depending on patient’s and carer’s view, hospice care can be introduced. 6.7 Follow up 1st year 2nd year 3rd year 4th year 5th year Thereafter Monthly 3 monthly 4 monthly 6 monthly 6 monthly discharge or annual review 18 7. Cancer of the Lip 7.1 Assessment Patients with biopsy proven squamous cell carcinoma will be fully investigated before being considered, with the results of investigations, at the multi-disciplinary team meeting attended by all members of the MDT. Treatment options will be discussed at the MDT and recommendations made to the patient in the following multi-disciplinary clinic. Advice and support from the clinical nurse specialists, speech and language therapists, dieticians and nutritional nurses and palliative care team will also be available in the clinic. 7.2 Investigations Incisional biopsy. Dental assessment if RT is planned. Neck node present – FNAC, MRI H & N Nutritional assessment and support as necessary. Patients with T1 and T2 lesions will usually require weekly nutritional assessment and support. The need for PEG insertion should be considered in patients with T3 and T4 lesions undergoing radical surgery and/or radiotherapy. Psychological assessment and assessment of social circumstances may indicate the need for psychological or social support. 7.3 Management of primary tumour T1 Surgery or RT has similar cure rates. Surgery is preferable as treatment is likely to be one stage and primary closure gives good cosmetic and functional results. T2-4 Surgery and consider post-operative RT. Management of the neck: N0 Expectant policy. N+ Modified radical neck dissection ± adjuvant RT. If N1, RT to neck alone if the primary lesion is also treated with RT. Primary closure has good cosmetic and functional results when the post-resection defect is up to one third of the width of the lip. For larger defects, local flaps are adequate. Free tissue transfer is occasionally required after surgical ablation of locally advanced disease. Decision on reconstructive method is made jointly by the ablative surgeon and the reconstructive surgeon. 7.4 Recurrent disease Histological confirmation, clinical and radiological staging when necessary. Appropriate treatment options will be influenced by the extend of recurrent disease and the probability of cure, previous treatment modalities, co-morbidity, patient’s preference and the consensus opinion of members of the MDT. Treatments options with curative intend include surgery and /or RT. 7.5 Palliation Pain control and nutritional support will be co-ordinated and provided by members of the MDT. Palliative RT or chemotherapy to control symptoms will be considered by the clinical oncologist when appropriate. 19 Support from the community Macmillan nurses and from the hospital palliative care team will usually be available and, depending on patient’s and carer’s view, hospice care can be introduced. 7.6 Follow-up 1st year 2nd year 3rd year 4th and 5th year Thereafter 1 monthly 2 monthly 3 monthly 6 monthly discharge or annual review 20 8. Cancer of the Oral Cavity - Tongue All patients will be fully investigated before being considered, with the results of investigations, at the multi-disciplinary team meeting attended by all members of the MDT. Treatment options will be discussed at the MDT and recommendations made to the patient in the following multi-disciplinary clinic. Advice and support from the clinical nurse specialists, speech and language therapists, dieticians and nutritional nurses and palliative care team will also be available in the clinic. 8.1 Investigations Incisional biopsy and EUA when necessary. MRI H & N (except T1 with palpably normal neck). Chest X-ray. CT chest (Stage III & IV). Dental assessment. Pre-treatment assessment by SALT. Haematological investigations. Nutritional assessment and support as necessary. Patients with T1 and T2 lesions will usually require weekly nutritional assessment and support. The need for PEG insertion should be considered in patients with T3 and T4 lesions undergoing radical surgery and/or radiotherapy. Psychological assessment and assessment of social circumstances may indicate the need for psychological or social support. 8.2 Management The most appropriate options of treatment will be influenced by the size of the tumour, other coexisting medical conditions and personal preference of the patient, as well as the consensus opinion of members of the MDT. Primary tumour: T1 and ‘small’ T2(<3cm) Surgery or RT alone. Surgery with adjuvant RT. T2(>3cm), T3 and T4 Surgery and adjuvant RT. Reconstruction: Small defects may be closed primarily or left to heal spontaneously (± split skin graft). Larger defects will require pedicle flaps or preferably free tissue transfer. Decision on reconstructive method is made jointly by the ablative surgeon and the reconstructive surgeon. 8.3 Management of the neck This is influenced by the clinical and radiological staging of the neck, the T stage and the primary modality of treatment chosen for the primary tumour. N0 Watch and wait policy (T1 treated by surgery alone). Selective neck dissection (Levels I – IV) ± adjuvant RT. Elective irradiation. N+ Modified or classical radical neck dissections ± adjuvant RT. Bilateral neck dissections may be considered in large primary tumour crossing the midline. 21 8.4 Chemotherapy Concomitant chemo-radiation may be considered in some cases of advanced disease at the discretion of the clinical oncologist. 8.5 Rehabilitation Restoration of speech, swallowing and maintenance of nutrition are provided by SALT and dieticians. Expertise in prosthodontics including dental implantology is available in selected cases. 8.6 Recurrent disease Histological confirmation, clinical and radiological staging will be carried out. Appropriate treatment options will be influenced by extend of recurrent disease and the probability of cure, previous treatment modalities, co-morbidity, patient’s preference and the consensus opinion of members of the MDT. Treatments options with curative intend include surgery and /or RT (including chemo-radiation). 8.7 Palliation Pain control and nutritional support will be co-ordinated and provided by members of the MDT. Palliative RT or chemotherapy to control symptoms will be considered by the clinical oncologist when appropriate. Support from the community Macmillan nurses and from the hospital palliative care team will usually be available and, depending on patient’s and carer’s view, hospice care can be introduced. 8.8 Follow-up 1st year 2nd year 3rd year 4th and 5th year Thereafter 1 monthly 2 monthly 3 monthly 6 monthly discharge or annual review 22 9. Cancer of the Oral Cavity - Floor of mouth All patients will be fully investigated before being considered, with the results of investigations, at the multi-disciplinary team meeting attended by all members of the MDT. Treatment options will be discussed at the MDT and recommendations made to the patient in the following multi-disciplinary clinic. Advice and support from the clinical nurse specialists, speech and language therapists, dieticians and nutritional nurses and palliative care team will also be available in the clinic. 9.1 Investigations Incisional biopsy and EUA when necessary. MRI H & N (except T1 with palpably normal neck). Chest X-ray CT chest (Stage III & IV). Dental assessment. Pre-treatment assessment by SALT. Haematological investigations. Nutritional assessment and support as necessary. Patients with T1 and T2 lesions will usually require weekly nutritional assessment and support. The need for PEG insertion should be considered in patients with T3 and T4 lesions undergoing radical surgery and/or radiotherapy. Psychological assessment and assessment of social circumstances may indicate the need for psychological or social support. 9.2 Management The most appropriate options of treatment will be influenced by the size of the tumour, other coexisting medical conditions and personal preference of the patient, as well as the consensus opinion of members of the MDT. Primary tumour: T1 and ‘small’ T2(<3cm) Surgery alone. Surgery with post-operative RT. RT alone is undesirable if bone is close to or involved by tumour. T2(>3cm), T3 and T4 Surgery and post-operative RT. Reconstruction: Small defects may be closed primarily or left to heal spontaneously (± split skin graft). Local flaps may also be used in some cases. Larger defects will require free tissue transfer. When segmental mandululectomy is required, bony reconstruction will be necessary. Decision on reconstructive method is made jointly by the ablative surgeon and the reconstructive surgeon. 9.3 Management of the neck This is influenced by the clinical and radiological staging of the neck, the T stage and the primary modality of treatment chosen for the primary tumour. N0 Watch and wait policy (T1 treated by surgery alone). Selective neck dissection (Levels I – IV) ± adjuvant RT. Midline lesions may require bilateral selective neck dissections. 23 Elective irradiation. N+ Modified or classical radical neck dissections ± adjuvant RT. Bilateral neck dissections may be considered in primary tumour crossing the midline. 9.4 Chemotherapy Concomitant chemo-radiation may be considered in some cases of advanced disease at the discretion of the clinical oncologist. Rehabilitation: Restoration of speech, swallowing and maintenance of nutrition are provided by SALT and dietitians. Expertise in prosthodontics including dental implantology is available in selected cases. 9.5 Recurrent disease Histological confirmation, clinical and radiological staging will be carried out. Appropriate treatment options will be influenced by extend of recurrent disease and the probability of cure, previous treatment modalities, co-morbidity, patient’s preference and the consensus opinion of members of the MDT. Treatments options with curative intend include surgery and /or RT (including chemo-radiation). 9.6 Palliation Pain control and nutritional support will be co-ordinated and provided by members of the MDT. Palliative RT or chemotherapy to control symptoms will be considered by the clinical oncologist when appropriate. Support from community Macmillan nurses is available and depending on patient and carer’s view, hospice care can be introduced. Support from the community Macmillan nurses and from the hospital palliative care team will usually be available and, depending on patient’s and carer’s view, hospice care can be introduced. 9.7 Follow-up 1st year 2nd year 3rd year 4th and 5th year Thereafter 1 monthly 2 monthly 3 monthly 6 monthly discharge or annual review 24 10. Cancer of the Oral Cavity - Retromolar Trigone 10.1 Assessment and investigations Same as floor of mouth. 10.2 Management The most appropriate options of treatment will be influenced by the size of the tumour, other coexisting medical conditions and personal preference of the patient, as well as the consensus opinion of members of the MDT. Primary tumour: T1, T2 Surgery or RT equally effective T3, T4 Surgery and adjuvant RT Except in small T1 lesions, most cases require external approach with lip-splitting ± segmental or marginal mandibulectomy. Reconstruction: Small soft tissue defects may be closed primarily. Lateral mandibulectomy defects do no always require bony reconstruction. Larger soft tissue defects will need reconstruction with pedicled flap or free tissue transfer. Decision on reconstructive method is made jointly by the ablative surgeon and the reconstructive surgeon. 10.3 Management of the neck This is influenced by the clinical and radiological staging of the neck, the T stage and the primary modality of treatment chosen for the primary tumour. If an external approach via the neck is used to gain access to resect the primary tumour, it is logical to carry out elective neck dissection in N0 neck. N0 Expectant policy when small primary tumour was treated by surgery via intra-oral approach. Elective neck dissection – in continuity with resection of primary tumour. Elective irradiation when primary tumour is treated with RT. N+ Modified radical or classical neck dissection ± adjuvant RT. 10.4 Rehabilitation Restoration of speech, swallowing and maintenance of nutrition are provided by SALT and dieticians. Expertise in prosthodontics including dental implantology is available in selected cases. 10.5 Recurrent disease Histological confirmation, clinical and radiological staging will be carried out. Appropriate treatment options will be influenced by extend of recurrent disease and the probability of cure, previous treatment modalities, co-morbidity, patient’s preference and the consensus opinion of members of the MDT. Treatments options with curative intend include surgery and /or RT (including chemo-radiation). 10.6 Palliation 25 Pain control and nutritional support will be co-ordinated and provided by members of the MDT. Palliative RT or chemotherapy to control symptoms will be considered by the clinical oncologist when appropriate. Support from the community Macmillan nurses and from the hospital palliative care team will usually be available and, depending on patient’s and carer’s view, hospice care can be introduced. 10.7 Follow-up 1st year 2nd year 3rd year 4th and 5th year Thereafter 1 monthly 2 monthly 3 monthly 6 monthly discharge or annual review 26 11. Cancer of the Oral Cavity - Alveolar Ridge All patients will be fully investigated before being considered, with the results of investigations, at the multi-disciplinary team meeting attended by all members of the MDT. Treatment options will be discussed at the MDT and recommendations made to the patient in the following multi-disciplinary clinic. Advice and support from the clinical nurse specialists, speech and language therapists, dieticians and nutritional nurses and palliative care team will also be available in the clinic. 11.1 Investigations Incisional biopsy and EUA when necessary. MRI H & N. Chest X-ray CT chest (Large primary tumour). Dental assessment. Pre-treatment assessment by SALT. Haematological investigations. Nutritional assessment and support as necessary. Patients with T1 and T2 lesions will usually require weekly nutritional assessment and support. The need for PEG insertion should be considered in patients with T3 and T4 lesions undergoing radical surgery and/or radiotherapy. Psychological assessment and assessment of social circumstances may indicate the need for psychological or social support. 11.2 Management Primary tumour Most tumours have involved the bone and surgery is the mainstay of treatment. In the upper jaw, partial maxillectomy may be required. In the mandible, marginal or segmental mandibulectomy is required. Adjuvant radiotherapy may be required. Reconstruction: Small alveolar ridge defect without significant soft tissue involvement may be reconstructed with dental prosthesis including palatal obturator. Anterior segmental mandibular defect require bony reconstruction, preferably with composite free tissue transfer. Bony reconstruction of lateral mandibular defect should be individualized. Decision on reconstructive method is made jointly by the ablative surgeon and the reconstructive surgeon. 11.3 Management of the neck N0 Expectant policy if per-oral approach is used to resect tumour. Selective neck dissection (Levels I – IV) when the neck is used to gain access for resection or reconstruction. N+ Modified or classical radical neck dissection ± adjuvant RT. 11.4 Chemotherapy Concomitant chemo-radiation may be considered in some cases of advanced disease at the discretion of the clinical oncologist. 11.5 Rehabilitation 27 Restoration of speech, swallowing and maintenance of nutrition are provided by SALT and dietitians. Expertise in prosthodontics including dental implantology is available in selected cases. 11.6 Recurrent disease Histological confirmation, clinical and radiological staging will be carried out. Appropriate treatment options will be influenced by extend of recurrent disease and the probability of cure, previous treatment modalities, co-morbidity, patient’s preference and the consensus opinion of members of the MDT. Treatments options with curative intend include surgery and /or RT (including chemo-radiation). 11.7 Palliation Pain control and nutritional support will be co-ordinated and provided by members of the MDT. Palliative RT or chemotherapy to control symptoms will be considered by the clinical oncologist when appropriate.. Support from the community Macmillan nurses and from the hospital palliative care team will usually be available and, depending on patient’s and carer’s view, hospice care can be introduced. 11.8 Follow-up 1st year 2nd year 3rd year 4th and 5th year Thereafter 1 monthly 2 monthly 3 monthly 6 monthly discharge or annual review 28 12. Malignant tumours of the salivary glands All patients will be fully investigated before being considered, with the results of investigations, at the multi-disciplinary team meeting attended by all members of the MDT. Treatment options will be discussed at the MDT and recommendations made to the patient in the following multi-disciplinary clinic. Advice and support from the clinical nurse specialists, speech and language therapists, dieticians and nutritional nurses and palliative care team will also be available in the clinic. 12.1 Major salivary glands 12.1.1 Investigations FNAC. Trucut or rarely open biopsy when FNAC equivocal. MRI head & neck. Chest x-ray. Dental assessment. Haematological tests. Nutritional assessment and support as necessary. Patients with T1 and T2 lesions will usually require weekly nutritional assessment and support. The need for PEG insertion should be considered in patients with T3 and T4 lesions undergoing radical surgery and/or radiotherapy. Psychological assessment and assessment of social circumstances may indicate the need for psychological or social support. 12.1.2 Management Diagnosis occasionally made after surgical removal of the salivary gland containing a lump without clinical evidence of being malignant. The size and grade of the tumour are the most significant prognostic indicators. Parotid Parotidectomy with preservation of the facial nerve unless involved preoperatively. In locally advanced stage (T4), adjacent structures eg facial skin and mandible, will be included in the resection. Adjuvant RT is often necessary. Management of the neck N0 Expectant policy. Selective neck dissection in high grade and /or locally advanced disease. Adjuvant RT may be considered. N+ Modified or classical radical neck dissection. Adjuvant RT. 12.1.3 Reconstruction Pedicle flaps, free tissue transfer and /or nerve grafting may be required after resection of advancedstage tumour. Decision on reconstructive method is made jointly by the ablative surgeon and the reconstructive surgeon. 12.2 Submandibular gland 29 Wide submandibular clearance with selective neck dissection (Levels I – III) in N0 neck stage. Lingual and hypoglossal nerves may be sacrificed in locally advanced disease. N+ stage will need modified or classical neck dissection. Adjuvant RT is indicated in some situation, depending on histological results. 12.2.1 Reconstruction This may be necessary in some locally advanced cases. Decision on reconstructive method is made jointly by the ablative surgeon and the reconstructive surgeon. 12.3 Minor salivary glands 12.3.1 Investigations Incisional biopsy. MRI H & N. Chest x-ray. Dental assessment. Haematological tests. 12.3.2 Management Primary tumour: Similar to squamous cell carcinomas. Wide local excision ± adjuvant chemotherapy, depending on histological results. Management of the neck: N0 Expectant policy. N+ Modified or classical radical neck dissection. Adjuvant RT. Reconstruction will depend on the extend of surgical ablation. Decision on reconstructive method is made jointly by the ablative surgeon and the reconstructive surgeon. 12.3.3 Rehabilitation Restoration of speech, swallowing and maintenance of nutrition are provided by SALT and dietitians. Expertise in prosthodontics including dental implantology is available in selected cases. 12.3.4 Recurrent disease Histological confirmation, clinical and radiological staging will be carried out. Appropriate treatment options will be influenced by extend of recurrent disease and the probability of cure, previous treatment modalities, co-morbidity, patient’s preference and the consensus opinion of members of the MDT. Treatment options with curative intend include surgery and /or RT (including chemo-radiation). 12.3.5 Palliation Pain control and nutritional support will be co-ordinated and provided by members of the MDT. Palliative RT or chemotherapy to control symptoms will be considered by the clinical oncologist when appropriate. 30 Support from the community Macmillan nurses and from the hospital palliative care team will usually be available and, depending on patient’s and carer’s view, hospice care can be introduced. 12.3.6 Follow-up 1st year 2nd year 3rd year onwards 2 monthly 3 monthly 6 monthly Follow-up as long as possible. 31 13. Guidelines for Management of Thyroid Cancer Mount Vernon Thyroid Cancer Network manages patients according to the British Thyroid Association guidelines (published 2007) All patients with thyroid cancer will be managed by a Multi-disciplinary team specializing in the management of thyroid cancer. Management controversial Guidelines based on large retrospective series. Evidence available at levels II and III of AHCPR 1994. Recommendations are grades B and C. 13.1 Screening No screening programme for general population. Screening is possible for familial medullary thyroid carcinoma associated with specific genomic mutations. These cases should be referred to Royal Marsden Hospital. 13.2 Diagnosis and Referral Usual presentation is with a lump in the neck. Urgent referral (to see in 2 weeks) from GP if Thyroid lump increasing in size Unexplained hoarseness or voice change associated with goitre History of previous neck irradiation associated with a thyroid lump Extremes of age Cervical lymphadenopathy Presence of stridor should evoke emergency referral 13.3 Investigations Essential Clinical examination Routine haematology and biochemistry Thyroid function tests Thyroid antibody status Thyroid US FNA (with or without US guidance) Vocal cord examination (prior to surgery) Additional Investigations Respiratory function tests (flow-volume-loop) if symptoms of upper airway obstruction MRI neck or CT neck & chest(non-contrast enhanced) CXR Radionucleide imaging (99mTc or 123 I) Incisional biopsy: should never be carried out for differentiated thyroid cancer. However an open biopsy is necessary for suspected thyroid lymphoma Plasma calcitonin (if medullary carcinoma of thyroid suspected) 32 13.4 TNM STAGING T STAGE Tx PRIMARY CANNOT BE ASSESSED T0 No evidence of Primary tumour T1 T2 T3 T4a T4b T4a* T4b* Tumour≤ 2cm, limited to thyroid tumour >2cm ≤4cm,limited to thyroid Tumour>4cm, limtited to thyroid or any tumour with minimal extrathyroid extension (eg extension to sternothyroid muscle or perithyroid soft tissue) Tumour extends beyond the thyroid capsule and invades any of the following:subcutaneous soft tissues,larynx,trachea,oesophagus,recurrent laryngeal nerve Tumour invades prevertebral fascia,mediastinal vessels or encases carotid artery (anaplastic carcinoma only) Tumour (any size) limited to thyroid gland† (anaplastic carcinoma only) Tumour any size extends beyond thyroid capsule‡ Multifocal tumours of all histological types should be designated (m) (the largest determines the classification egT2(m) * All anaplastic/undifferentiated thyroid cancers are considered T4† Intrathyroidal anaplastic carcinoma-considered surgically resectable ‡ Extrathyroidal anaplastic carcinoma-considered surgically unresectable N STAGE NX N0 N1 Regional nodes cannot be assessed No regional LN metastasis Regional LN metastasis N1a metastasis in level VI (pretracheal and paratracheal,including pre-laryngeal and Delphian lymph nodes) N1b metastasis in other unilateral, bilateral, or contra-lateral cervical or upper/superior mediastinal lymph nodes M-Distant Metastasis MX M0 M1 Distant metastases cannot be assessed No distant metastases Distant metastases STAGE GROUPING Papillary or Follicular Under 45years Stage I Any T Any N M0 Stage II Any T Any N M1 Papillary or Follicular ≥ 45 years and Medullary Stage I T1 Stage II Stage III StageIVA Stage IVB N0 T2 T3 T1,T2,T3 T1,T2,T3 T4b M0 N0 N0 N1a N1b Any N M0 M0 M0 M0 M0 33 Stage IVC Any T Any N M1 Anaplastic?Undifferentiated (all cases are stage IV) Stage IVA Stage IVB Stage IVC T4a T4b Any N Any N Any N M0 M0 M1 13.5 CLASSIFICATION 1. Differentiated thyroid cancer - 2. 3. 4. Medullary thyroid cancer Anaplastic carcinoma Thyroid lymphoma Incidence 60% 17% papillary follicular mixed 4% 12% 5% 34 Differentiated Thyroid Cancer History and Clinical Examination Routine bloods, TFTs, Ca, CXR FNA, CT / MRI neck and mediastinum Total Thyroidectomy (Diagnosis certain) ¢ral compartment dissection (+selective LN dissection if LN +ve) Stop T3 for 14 days. Avoid fish, addded salt,(2 days) iodine containing medicines, X-ray contrast examinations (6-8weeks) Thyroid lobectomy (diagnosis uncertain) Completion Thyroidectomy & central compartment dissection (+ selective neck dissection if LN +ve) Ablation dose 3.7GBq 131I , 3 weeks post thyroidectomy . TSH prior Neck and body scan at 3 days. Start T3. OPD 6 weeks, TSH, Tg and T3. Consider starting T4 Abnormal scan at 3 days (suggestive of mets) Therapeutic dose 5.5GBq iodine 4-6 months after ablation OP 6 weeks, TSH Tg and T3, then diagnostic scan at 4 months Usual post ablation scan (uptake thyroid bed only) Re-ablation 3.7 or 5.5GBq Persistent uptake thyroid bed Whole body iodine scan, (4-6 months after ablation) Abnormal scan Normal scan, Known tumour, normal scan EBRT Abnormal scan, Tg >3g/l Annual Tg and TSH Repeat 5.5GBq therapy dose 35 14. Differentiated Thyroid Cancer 14.1 Principles of treatment Ablate remaining thyroid remnant after thyroidectomy to render the patient athyrotic. Suppression of TSH with thyroid replacement Surveillance with whole body radio-iodine scans (WBS) and thyroglobulin measurement Persistent or recurrent disease treated with therapy dose of radio-iodine 14.2 Standard Treatment (see flow chart) Diagnosis certain, do near-total thyroidectomy and central compartment LN dissection. If LN positive do selective neck dissection. 'Berry picking' no longer recommended. Diagnosis uncertain, do thyroid lobectomy first and follow up with completion thyroidectomy A pre-ablation scan is not routinely recommended since over 90% of patients post surgery will require an ablative dose. If a scan is done there is a risk that exposure of the thyroid to iodine may stun the thyroid tissue and decrease the efficiency of the ablative dose. If a scan is considered necessary then 123I is used, which is less likely to compromise the subsequent ablative dose of iodine. Ablation dose (3GBq) of 131I, 3 weeks after surgery (no thyroid replacement post-op) Whole body scan (150 - 170 MBq 131I ) 4 months later If normal WBS, change to T4 and follow with 6 monthly TSH and thyroglobulin. If abnormal scan, arrange therapy dose of 131I (5.5GBq). Repeat WBS 4 months later. If normal, change to T4 as above then follow with Tg and TSH 6 monthly. If still abnormal, repeat therapy dose of 131I until scans are normal. Intervals between therapy doses of radio-iodine should be at least 4 months. 14.3 Procedure for 131I ablative / therapy doses Written (information leaflet no ) and oral information given to patient Avoid fish, added salt, iodine containing medicines for 3 weeks prior to dose and no X-ray contrast examinations (CT) should have been done over 6-8 weeks prior to dose. Following a diagnostic whole body scan, 4 weeks should elapse before a therapy dose is delivered. For ablative dose the patient should not receive thyroid replacement post-operatively so that TSH can rise prior to ablative dose at 3 weeks. If the ablative dose is longer than 4 weeks post-op then the patient should be started on T3 and stopped 2 weeks prior to treatment. For therapy dose: - If patient of T3, stop 14 days prior to dose. - If patient on T4, change to T3 one month prior to 131I and then stop T3 at 14 days. Admit to room with appropriate protection and en-suite facilities (approved by radiation protection officer) Exclude pregnancy - if there is any doubt then pregnancy test should be done prior to dose. Pregnancy should be avoided for12months after radio-iodine administration. Breast feeding is contra-indicated for the same period. Pre-treatment sperm banking could be considered for patients who are likely to have repeated treatments. Patients who are incontinent or who have a urinary catheter/ileostomy/ colostomy should be discussed with medical physics before admission. Patient who are unable to swallow capsules should be discussed with Nuclear Medicine in advance as a liquid formulation may need to be administered. Patients receiving radio-iodine also need to be self-caring, due to time restrictions for nursing staff in the iodine room. Check TSH, thyroglobulin, FBC and U&E's on admission 36 Encourage fluid intake after radio-iodine administration. Sodium citrate lozenges or fruit(acid) sweets may help prevent sialadenitis and should be started on day 2. Scans of neck and whole body at 3 days (or as advised by Nuclear Medicine) Start thyroid replacement with T3 at 3 days. Patients should start back on replacement gradually and increase to dose of 20 microgrammes tds. Suggest 20 microgrammes od for 2 days, 20 microgrammes bd for 2 days then 20 microgrammes tds. Discharge after assessment by medical physics (when residual activity in thyroid bed < 800MBq) with advice on necessary precautions. Discharge will be at least 2 days after iodine administration. There is no maximum cumulative dose as long as individual doses do not exceed 2 Sv total body exposure and there is an interval of 4 - 6 months between doses. Patients receiving multiple doses will need a FBC prior to treatment as bone marrow suppression can occur. For patients with lung metastases pulmonary function tests are also useful. Patients who have received a therapy dose of iodine and are thought likely to require a further therapy dose, may be able to receive the therapy dose a week after the diagnostic scan in order to minimise the time off thyroid replacement. This will need to be done on an individual basis and discussed with medical physics. 14.4 Serum TSH measurements Whilst on thyroid replacement the TSH should be undetectable (<0.05g/l). T4 is more effective than T3 for TSH suppression The dose of T3 should be 20g tds (bd in elderly or frail) and T4 200mg od. The dose of T4 should be adjusted every 6 weeks by 25g until the target TSH concentration is reached 14.5 Serum Thyroglobulin Thyroglobulin is produced by normal and cancerous thyroid cells. Its measurement is only useful after thyroidectomy and remnant ablation when detectable thyroglobulin indicates residual or recurrent disease Diagnostic sensitivity is increased when TSH raised (e.g. at time of administration of 131I) It has a long serum half life and so should not be measured more often than 3 monthly The presence of auto-antibody can affect the measurement of thyroglobulin A raised serum thyroglobulin (i.e. above 3 - 5 g / l) post should be investigated initially with a whole body scan. If the whole body scan is normal but the Tg is persistently raised the options include further imaging with CT scan thorax, MRI / CT scan neck and PET scan. If investigations identify site of metastasis consider treatment options of surgery / radiotherapy. If investigations are negative consider therapeutic dose of radio-iodine in the absence of proven metastases (raised Tg only). 14.6 Recombinant human TSH Early trials of recombinant human TSH to avoid thyroid hormone withdrawal and hypothyroidism are promising but it is not yet generally available. For selected patients who are unable to tolerate severe hypothyroidism, Clinicians should apply to Dr Catherine Lemon, Lead Clinician for Thyroid Cancer For fundind for recTSH.Current studies have shown that Tg monitoring is more sensitive after rhTSH. 14.7 Management of hypocalcaemia Ionised calcium should be checked the day after surgery and daily until stable If hypocalcaemia develops (ionised calcium < 1mmol/l) or the patient becomes symptomatic at a higher calcium level, commence calcium supplements If it does not improve or worsens then - calcidol should be started at 3g per day and adjusted up or down according to response 37 Close monitoring is required to ensure that hypercalcaemia does not develop After total thyroidectomy 30% of patients will need calcium supplements +/- -calcidol, by 3 months only 2% will still require calcium supplements 14.8 Non Standard / Low Risk Patients Above protocol used for all patients with differentiated thyroid cancer except for - young women (less than 40 years) with tumours up to 1.5cm in diameter - any patient where the carcinoma is an incidental microscopic finding These patients are thought to have a better prognosis and surgery with thyroid lobectomy followed by TSH suppressive doses of thyroxine is thought to be adequate. (thyroglobulin measurements or whole body scans cannot be done in these patients) 14.9 External Beam Radiotherapy This is not routinely used. Indications include: Evidence at surgery of local invasion with a high suspicion of macro- or microscopic residual disease, especially in poorer prognosis patients (men or older women). Difficulty in these circumstances in ascertaining whether the tumour uptakes iodine. Therefore ablative iodine given prior to external beam radiotherapy (need to calculate dose to spinal cord from ablative iodine dose and work out cumulative cord tolerance from iodine and EBRT). Thyroid bed alone Technique is usually with anterior oblique wedged field (CT planned) to a total dose of 64Gy in 32 fractions over 6.5 weeks. Thyroid bed and nodal areas Phase I - 44 Gy using AP fields which can be extended to include the upper neck, mediastinum (to carina) and supra-clavicular areas. The fields are usually weighted 2:1 ant:post. Phase II - angled down lateral fields off cord for further 20Gy in 10 fractions (+/- matched posterior neck electron fields) For confirmed recurrent disease in the neck which is not amenable to further surgery or 131I treatment. This should be treated to a dose of 66Gy in 33 fractions over 6.5 weeks For palliation of metastatic disease in bone, cerebrum, spine and other areas. Consider high dose palliation if solitary metastasis (eg 45 Gy in 20 #) or standard palliative fractionation in advanced disease (eg 20Gy in 5 # or 8Gy single fraction) For locally advanced tumours which are inoperable for a variety of reasons it can be used for palliation along with TSH suppression. 14.10 Recurrent Disease Neck recurrences - surgery is the preferred option even if complete removal not possible. This is then combined with radio-iodine or EBRT where surgery is incomplete. Lung or other soft tissue areas not amenable to surgery are treated with 131I if the tumour takes up radio-iodine. Therapeutic doses of 131I are usually 5.5 MBq. Bone metastases should be treated with a combination of EBRT, Patients with a rising thyroglobulin in the absence of a positive radio-iodine scan can by managed in one of two ways: - Further imaging with MRI, CT or PET scan - Empirical treatment with 131I followed by post treatment scan 131 I or orthopaedic intervention 38 14.11 Palliative Chemotherapy No role in routine management Restricted to very select cases with end-stage disease uncontrolled by surgery, radio-iodine or EBRT for palliation.. Effective agents are doxorubicin and cisplatin (partial response rates 20-30%) 14.12 Diagnosis of thyroid cancer in pregnancy If diagnosed early in pregnancy consider thyroidectomy during second trimester and delay ablative dose of 131I until after delivery Patients diagnosed later in pregnancy can be managed after delivery Patients treated with 131I after delivery will not be able to breast feed. 14.13 Oxyphilic / Hurthle Cell Carcinoma This is a variant of follicular thyroid carcinoma. It does produce thyroglobulin but rarely uptakes iodine. Ablative iodine may be given in order to facilitate follow up with thyroglobulin. Prognosis is probably worse than follicular carcinoma. Long Term Follow up 3 monthly for the first two years, 6 monthly for 5 years, yearly thereafter. At each visit - Clinical examination - Assessment of TSH suppression - Measurement of thyroglobulin - Measurement of serum calcium if indicated 39 15. Medullary Thyroid Carcinoma (Mtc) Arises from C-cells (parafollicular cells) and produces calcitonin These tumours do not uptake radio-iodine 25% are familial as part of autosomal dominant cancer syndrome known as multiple endocrine neoplasia, type 2 (MEN - 2) - 10% give FH - 15% found to have familial involvement after investigation All cases should be referred to clincal geneticist Investigations include RET gene mutation analysis 9including exons 10,11,13,14,15,16) and genetic screening Even in the absence of a family history the patient may represent the herald case. Features which suggest a familial cause in the absence of a family history include - Early age at presentation (less than 40) - Multi-focal disease within the thyroid - The presence of C-cell hyperplasia on histology Guidelines for management of the family of an isolated case without family history - First degree relatives offered clinical and biochemical screening - Multi-focal disease or C-cell hyperplasia in index case should initiate prompt referral for germline RET analysis - Tumour analysed for RET gene mutation 15.1 Investigations Baseline calcitonin and CEA Exclude phaeochromocytoma (24 hour urinary catecholamines) and hyper-parathyroidism (serum calcium) Neck, thoracic and abdominal CT. Some MTCs are positive on MIBG scanning and this can be used therapeutically Pentavalent 99mTc DMSA has a place in detecting recurrent disease 15.2 Treatment Total thyroidectomy and central node (level VI) dissection. This can still be done for palliative reasons in the presence of disseminated disease Prophylactic surgery for disease free carriers of germline RET mutations, discovered during genetic screening. This is optimally performed as young as possible. 15.3 Radiotherapy and Chemotherapy RT may help control local disease in cases where there is residual disease or inoperable disease. Radiotherapy is given to a radical dose (66Gy in 33# over 6.5 weeks) using the same technique as for differentiated thyroid carcinoma. RT is more commonly used for MTC since potential residual disease will not uptake iodine. Chemotherapy is ineffective Therapeutic MIBG can be useful in selected cases Long term follow up recommended with clinical assessment and measurement of serum calcitonin. 40 15.4 Research Studies in Thyroid Cancer 1. HiLo Study Multicentre randomised trial of high dose versus low dose radioiodine, with or without recombinant human thyroid stimulating hormone, for remnant ablation following surgery for differentiated thyroid cancer 2. Phase II Studies Patients with metastatic differentiated (non-iodine avid) or medullary carcinoma of the thyroid should be referred to the thyroid service at the Royal Marsden Hospital for consideration of inclusion in phase II studies of sorafenib. 41 Medullary Thyroid Carcinoma Partial thyroidcetomy +/- lymph node biopsy History and Clinical Examination. Review histology. FBC, LFT, U&E, Ca, CXR, Calcitonin & CEA, CT scan neck thorax and abdomen Exclude phaeochromocytoma and hyper-parathyroidism. BP, 24hr catecholamines +/PTH Exclude familial MCT. Family history, blood for genetic markers. Referral to geneticist Completion thyroidectomy & central compartment resection +/- modified radical neck dissection. Neck and mediastinal RT if disease extensive Normal post op calitonin Elevated post-op calcitonin Determine site of tumour. CT scan neck, thorax, liver. Bone scan. DMSA whole body scan / mIBG / octreotide Annual clinical follow up. Calcitonin & CEA. Familial MCT, BP, 24hr catecholamines, Ca +/PTH annually Inoperable Operable Surgical excision + RT Diagnostic mIBG scan Negative Positive Therapeutic mIBG Repeat after 6 months Progressive & symptomatic Octreotide / interferon / chemotherapy +/- RT Normal calcitonin Asymptomatic Annual FU, calcitonin + CEA FU only 42 16. Thyroid Lymphoma 16.1 Investigations FNA suspicious for lymphoma - need open biopsy for precise diagnosis Usually high grade NHL but low grade NHL and Hodgkin's can occur Staging as for nodal lymphoma - FBC, ESR, LDH, U&E, LFT, Bone profile, Serum Igs, protein electrophoresis - CT thorax / abdomen / pelvis / neck - Bone marrow trephine and aspirate Consider GI investigations if symptoms since increased incidence of GI lymphoma 16.2 Treatment Localised disease CHOP - 3 cycles followed by RT to thyroid and involved nodal areas to dose of 35-40Gy in 20# over 4 weeks. If still residual disease can treat to further 20Gy in 10 #. Disseminated disease CHOP chemotherapy - CR plus 2 cycles (minimum 6 cycles) Cyclophosphamide Adriamycin Oncovin (Vincristine) Prednisolone 750mg /m2 IV infusion d1 50mg/m2 IV bolus d1 1.4mg/m2 IV bolus d1 100mg po daily d1-5 Repeat every 21d, up to 6-8 courses Prophylactic Allopurinol 300mg po daily week 1-4. Radiotherapy to sites of bulk disease 40 Gy / 20# /28d. 43 17. Anaplastic Carcinoma Very aggressive, early infiltration into surrounding tissues Does not produce thyroglobulin or uptake iodine Median survival 2-6 months Histology review 17.1 Treatment Surgical excision when possible (rare) Tracheostomy sometimes required for tracheal compression Radiotherapy to loco-regional tumour for local control Options: Radical CHARTWEL Phase I AP opposed fields (2:1 wt A:P) 37.5 Gy / 25# Phase II off cord 21Gy/14 # (matched post electrons where necessary) Total : 58.5Gy in 39 # over 2.5 weeks (3x/d) Palliative 39 Gy in 13 # over 2.5 weeks (Pb post cord shielding last #) Or 20 Gy in 5# over 1 week Systemic disease - chemotherapy Adriamycin single agent (60 mg/m2 q = 21d) 44 Anaplastic Carcinoma History and Clinical Examination Review histology. FBC, LFT, U&E, Ca, CXR, CT scan neck thorax and upper abdomen. Bone scan Predominantly metastatic disease Predominantly local disease Surgery Total resection if poss Tracheostomy if necessary Radiotherapy Localised Palliative RT Widespread progressive symptomatic Chemotherapy Symptomatic care 45 18. Lymph node resections on Thyroid Cancer (10-1C-109i) The following surgeons are authorised to perform lymph node resection on thyroid cancers; Mr P Kothari Mr G Mochloulis Ms J Panesar 46 19. Follow-up Guidelines for Head & Neck Cancer 19.1 General Principles Following completion of primary treatment and assessment that either full remission has been achieved or that further care will be palliative, without further anticancer therapy, then patients will be referred back to the original referring hospital for continuing follow-up and care by the local support team whenever possible. This decision will be taken by the treating MDT after the initial reactions to treatment have settled and review, with or without post-treatment imaging, suggests that no further anti-cancer treatment is required for this episode. 19.2 L & D and Lister Hospital Patients will be followed by the MDTs at these sites. Following surgical treatment at L & D patients referred by Lister Team will be followed up by them at Lister Hospital 19.3 Bedford Hospital Patients will be referred to the Bedford Hospital Head & Neck Combined clinic for follow-up by MDT members, Mr S Patel or Mr C H Chan as deemed appropriate by the MDT. 19.4 N W Hertfordshire Patients initially referred to the L & D team will continue to be followed up by the L & D MDT in the L & D Head & Neck clinic. Patients initially referred to the NWPH OMFS team will be followed up by them. 47 20. Rarer Cancers 20.1 Treatments not provided by Beds & Herts Centre Patients who are considered, following MDT discussion, to require treatments not provided at the Centre will be referred as appropriate. For photodynamic therapy patients will be referred to UCLH Head & Neck MDT or St Bartholomew’s Head & Neck MDT. For hyperbaric oxygen therapy patients will be referred to Whipp’s Cross Hospital Hyperbaric Oxygen treatment centre. 20.2 Childhood Head and Neck Cancer Children with head, neck & thyroid cancers (up to 16 years) are referred to a network agreed primary treatment centre to be cared for in an age appropriate environment, with specialist nurses, youth workers and social support, in line with the children and young persons improving outcomes guidance. Bedfordshire patients will be referred to Addenbrooks Hospital Paediatric Oncology service for and Hertfordshire patients to Great Ormond St Paediatric Oncology service. 20.2.1 Thyroid Tumours Specific Investigations: Neck ultrasound Thyroid function test including TSH and Thyroglobulin Thyroid antoantibodies Serum calcitonin Serum calcium, Vitamin D Treatment: CC:G guidelines. Tumour specific MDT Young persons with head, Neck & thyroid neoplasms (16-24) will be referred to the network agreed Young Persons MDT at UCLH for discussion. Place of treatment for this group will depend upon their age. 16/17/18 year olds will be treated at the PTC, but 19-24 year olds have the choice between being treated at the PTC or locally. This local treatment will follow the treatment plan agreed at the PTC MDT. 20.3 Management of Soft Tissue Sarcomas– please see appendix 12 for more detail of the pathway As defined in the NICE Improving Outcomes Guidance for the management of Sarcoma (2008) all sarcomas are to be discussed at a designated sarcoma centre. MVCN does not host a sarcoma centre, nor does it have a designated clinic operating in any of the 3 acute hospital trusts. All patients must be referred to the sarcoma (supranetwork) multidisciplinary team for discussion at the earliest suspicion of sarcoma, or when histology identifies an unexpected sarcoma. The MVCN designated centre is the London and South East Sarcoma Network, which is hosted by the Royal National Orthapedic Hospital, for bone sarcomas and UCLH for soft tissue sarcomas. The UCLH MDT is held on Fridays at 08:00, and is a joint MDT, videoconferenced with the RNOH Bone and soft tissue sarcoma MDT. 48 The contact details are: MDT Co-ordinator Maria Jose [email protected] Telephone - 0207 691 2303 ext 4821 Fax - 020 3447 9536 UCLH Sarcoma MDT Lead Clinician Dr Jeremy Whelan [email protected] 0207 380 9346 Please note: cut off for referrals is the Wednesday preceding the Friday meeting. The sarcoma MDT will review all cases of breast sarcoma. It is anticipated that surgery will be undertaken by local breast services after discussion with the sarcoma MDT. Management will be undertaken in accordance with guidelines agreed across the two sarcoma MDTs. Following discussion at the MDT: Patients with head & neck sarcomas will be referred to the Sarcoma SMDT at UCLH. Principle responsibility for ongoing treatment will be handed over to the receiving MDT, if appropriate, following their discussion, until & unless it is handed back. 20.4 Head & Neck sarcomas Head and neck sarcomas are likely to be diagnosed within the site-specific head and neck MDT. Patients will be managed by the sarcoma oncologist, in conjunction with the head and neck MDT for surgical management. Tumours may be of soft tissue (soft tissue sarcomas, rhabdomyosarcoma) or bone (Ewing’s sarcoma, osteosarcoma, chondrosarcoma) origin. 20.4.1 Diagnosis and staging Pathology review MRI head and neck CT thorax Other staging (e.g. bone scan, bone marrow aspirate and trephine) as indicated. 20.4.2 Treatment of localised disease For rhabdomyosarcoma and bone sarcomas, see tumour-specific sections above. For other soft tissue sarcomas management is likely to include a combination of chemotherapy, radiotherapy and surgery, which reflects the difficulty in achieving local tumour control in this disease location. The exact ordering of treatment modalities will be determined on an individual patient basis, following MDT discussion. 20.4.3 Treatment of metastatic disease See tumour-specific sections above. 20.5 Rhabdomyosarcoma Rhabdomyosarcoma (RMS) is typically a cancer of childhood, and is rare in adults. It may affect the extremities, genitourinary system, head and neck region, trunk, or other less frequent sites. Three main variants are recognised: Embryonal rhabdomyosarcoma (including botryoid variant) Alveolar rhabdomyosarcoma 49 Pleomorphic rhabdomyosarcoma (occurs in adults, is treated as a high grade soft tissue sarcoma) 20.5.1 Diagnosis and staging Biopsy, pathology review CT/MRI of primary site CT chest, abdomen and pelvis Whole body bone scan or PET-CT scan Bilateral Bone Marrow aspirate and trephine Assessment of cerebrospinal fluid for parameningeal tumours. Routine bloods including LDH and alkaline phoshatase. 20.5.2 Treatment of localized disease Patients are stratified according to the risk of their disease, based on a number of prognostic factors. The principles of treatment are: Low Risk → surgery + chemotherapy. Standard Risk → surgery + chemotherapy ± radiotherapy. High Risk → chemotherapy + surgery + radiotherapy. Very High Risk → chemotherapy +/- surgery + radiotherapy. Local therapy (surgery and/or radiotherapy) is carried out at around week 13. Vincristine, actinomycin D, and ifosfamide are the main chemotherapy agents. For the very high risk patients doxorubicin may be added to the standard regimens. Detailed guidelines for the management of all rhabdomyosarcomas including risk classification and available clinical trials are specified in the current Unit guidelines. 20.5.3 Treatment of metastatic disease There is no currently open clinical trial for patients with metastatic RMS. First-line treatment → chemotherapy: o IVADo Ifosfamide; Vincristine; Actinomycin D; Doxorubicin. Local treatment → radiotherapy preceded by surgery, if feasible (at week 18) 20.5.4 Treatment of relapsed disease Treatment will be given on an individualised basis. Regimens that can be considered include: Irinotecan and vincristine 20.5.5 Follow-up of rhabdomyosarcoma Clinical evaluation of the primary site MRI or CT scan of the primary site as clinically indicated Chest x-ray Recommended intervals for follow-up: Every 2 months in the first year. Every 3 months in years 2 - 3. Every 6 months in years 4 - 5. 50 Annually thereafter. For the most up-to-date schedule, see current individual unit guidelines. For the London and South East Sarcoma Network Presentation and Diagnostic Pathway for Bone Sarcomas please see appendix 5. 20.6 Tumour involving the skull base Patients with tumours involving the base of skull and requiring cranio-facial resection will be referred to the Head & Neck SMDT at Charing Cross Hospital. Principle responsibility for ongoing treatment will be handed over to the receiving MDT, if appropriate, following their discussion, until & unless it is handed back. 51 21. Acute Oncology Services National Chemotherapy Advisory Group, guided partly by reports from NCEPOD and NPSA and from previous cancer peer review results, has recommended that a more systematic approach should be taken to dealing with cancer-related emergencies. These recommendations have been embodied in the concept of the ‘Acute Oncology Service’. Work is now underway within the acute trusts within the Mount Vernon Cancer Network Locality to develop a strategic approach to managing acute oncological emergencies which reflects both local trust practice and a consistent network wide approach. In line with this a number of policies and protocols have been developed / revised to manage acute oncological emergencies as they present at A&E / AAU / MAU. These have been developed by the MVCC in collaboration with the trusts and have been agreed by the Network Acute Oncology Group. From referral into the system the patients will be triaged to appropriate oncological input earlier within the patient pathway. The AOS will ensure 24hr access for acute medical take and A&E doctors to oncological assessment. Oncological emergencies include the suspicion and diagnosis of spinal cord compression and in these cases referral in tot the service or presentation at A&E will result in MRI, and case discussion between MVCC and the designated spinal surgery centre to ensure earlier detection and management of this condition. 52 22. Rehabilitation Rehabilitation is a key component of the patient pathway. The rehabilitation specialist services consist of: o o o o o Dietetics Lymphoedema Occupational Therapy Physiotherapy Speech and Language Therapy The input from these professionals will vary depending on the patient’s diagnosis and treatment. The Mount Vernon Cancer Network Rehabilitation Services Directory is available through the MVCN website which identifies service availability across the network. See Appendix 8 for detailed pathway 53 Appendix 1 Primary Care Referral Guidelines for Head and Neck Cancer for the population of NHS Bedfordshire (11-1A-206i) Version: Draft v1.4 Date of approval: To be entered when approved Review date: To be entered – 2 years from approval date Authors: AngCN Head and Neck NSSG MVCN Head and Neck NSSG Ref No: AngCN-SSG-HN16 54 AngCN-SSG-HN16 Head and Neck Primary Care Referral Guidelines for the population of NHS Bedfordshire CONTENTS 1 INTRODUCTION ....................................................................................................................... 56 2 STRIDOR .................................................................................................................................. 56 3 NECK LUMP ............................................................................................................................. 56 3.1 NECK LUMP - CLINICALLY NON-THYROID ................................................................................ 56 3.2 NECK LUMP – CLINICALLY THYROID ....................................................................................... 57 4. FEATURES OF UAT MALIGNANCY +/- NECK LUMP ............................................................. 58 5. NO NECK LUMP AND NO URGENT FEATURES .................................................................... 59 6. APPENDICES ........................................................................................................................... 60 APPENDIX 1: DOCUMENT CONTROL .................................................................................................. 60 APPENDIX 2: REFERRAL SCHEMAS ................................................................................................... 62 APPENDIX 3: REFERRAL GUIDELINES FOR SUSPECTED CANCER ......................................................... 65 Approved mmyy (enter when approved) Insert filepath 55 AngCN-SSG-HN16 Head and Neck Primary Care Referral Guidelines for the population of NHS Bedfordshire 1. Introduction The Anglia Cancer Network (AngCN) and Mount Vernon Cancer Network (MVCN) Head and Neck Network Site Specific Groups (NSSG) have agreed the implementation of referral guidelines for patients where there is a suspicion of head and neck/thyroid cancer in line with the recommendations of the Manual for Cancer Measures and the Referral guidelines for suspected cancer from National Institute for Health and Clinical Excellence (Appendix 3). The primary care referring practitioner needs to decide on the basis of clinical examination and history: Does the patient have features suggestive of Head and Neck or Thyroid Cancer? Does the patient have a neck lump? Is the lump clinically a thyroid lump? Are there other features of urgency about the lump? Are there other urgent features which might suggest UAT or Haematological Malignancy? Does the patient have stridor? If there is no neck lump does the patient have features suggesting malignancy? The numbered paragraphs deal with the actions to be taken by the referring practitioner as outlined in the diagnostic schema in Appendix 2. 2. Stridor If the patient has stridor then it is essential to refer immediately (same day). Referral must be to the designated hospitals either to A&E or to the on call ENT team 3. Neck Lump 3.1 Neck Lump - Clinically Non-thyroid Features suspicious of cancer associated with the non-thyroid neck lump itself (reference: Department of Health Referral Guidelines for the Diagnosis of Cancer, reviewed 2005): Where the lump persists for more than three weeks despite antibiotics, infectious mononucleosis has been excluded and there are no non-lump features suggestive of malignancy. If the patient has the symptoms outlined above then a 2 week wait urgent referral should be made as shown on the following page: Approved mmyy (enter when approved) Insert filepath 56 AngCN-SSG-HN16 Head and Neck Primary Care Referral Guidelines for the population of NHS Bedfordshire Neck Lump Clinic Referral (Clinically non-Thyroid) Designated Hospital Designated Clinician Designated Contact Point (2ww office) Luton and Dunstable Mr. Pickles Miss Panesar Mr. Kothari Mr. Chan (OMFS) Mr. Camilleri (OMFS) Telephone Number: 01582 497247 2WW Fax Number: 01582 497910 or 497911 Bedford Mr Patel (ENT) Mr Chan (OMFS) Mr Simpson (OMFS) 01234 355122 Mr Patel ext 2894 or Mr Chan ext 2071 Or Mr Simpson ext 2070 01234 792133 (Fax) MDT Pathway Bedfordshire and Hertfordshire Head and Neck SMDT Hosted at Luton & Dunstable Hospital 3.2 Neck Lump – Clinically Thyroid The vast majority of thyroid nodules are benign and do not require urgent referral. Furthermore, thyroid cancer is uncommon in patients who are not euthyroid and assessment of biochemical thyroid status is useful in deciding on the referral pathway by the general practitioner. Immediate (same day) referrals Patients with stridor associated with a thyroid swelling should be referred immediately to secondary care (depending on locally provided facilities, this may be the accident and emergency department, head and neck or general surgical emergency services). Urgent referrals under the 2-week rule for suspected cancer The presence of the following symptoms or signs in association with a thyroid swelling may indicate more aggressive or advanced disease and should be referred urgently under the 2-week rule: unexplained hoarseness or voice change thyroid nodule/goitre in a child cervical lymphadenopathy associated with a thyroid lump (usually deep cervical or supraclavicular region) a rapidly enlarging painless thyroid mass over a period of weeks (a rare presentation of thyroid cancer and usually associated with anaplastic thyroid cancer or thyroid lymphoma). Patients in whom exclusion of thyroid cancer is required should be referred to a thyroid nodule clinic, or a surgeon, endocrinologist or nuclear medicine physician who has a special interest in thyroid cancer and is a member of the regional thyroid cancer MDT. Non-urgent referrals The following patients should be referred in the normal way: patients with nodules who have abnormal TFTs, who should be referred to an endocrinologist (thyroid cancer is very rare in this group) patients with a history of sudden onset of pain in a thyroid lump (likely to have bled into a benign thyroid cyst) patients with a thyroid lump that is newly presenting or has been increasing in size over months. The above guidelines are adopted from the British Thyroid Association (BTA), 2007, p.5-6, Guidelines for the management of thyroid cancer. Please see below for the referral pathway and contact points. Approved mmyy (enter when approved) Insert filepath 57 AngCN-SSG-HN16 Head and Neck Primary Care Referral Guidelines for the population of NHS Bedfordshire Neck Lump / Specialist Thyroid Clinic Referral Designated Hospital Designated Clinician/s Mr M Pittam Mr D Ravichandran Dr R Banerjee Luton & Dunstable Bedford Mr H Charfare (Thyroid) Mr T Hoare (ENT)/ Mr Patel (ENT) Designated Contact Point (2ww office) Telephone Number: 01582 497247 2WW Fax Number: 01582 497910 or 497911 MDT Pathway Bedfordshire and Hertfordshire Head and Neck SMDT Hosted at Luton & Dunstable Hospital 01234 355122 AngCN (West) Thyroid MDT Mr Charfare ext 2192 Mr Hoare ext 2850 Mr Patel ext 2894 Hosted at Addenbrookes 4. Features of UAT malignancy +/- neck lump Features suspicious of UAT cancer (reference: Department of Health Referral Guidelines for the Diagnosis of Cancer, revised 2005): Hoarseness for more than 6 weeks Oral mucosal ulcer persisting for more than 3 weeks Oral swelling persisting for more than 3 weeks Red or red and white patches of the oral mucosa Dysphagia, including odynophagia, for more than 3 weeks Unilateral nasal obstruction, especially with purulent discharge Unexplained tooth mobility, not associated with periodontal disease Cranial neuropathies Orbital masses Unilateral persistent sore throat Unilateral otalgaia with normal otoscopy If the patient has any of the symptoms outlined above then a 2 week wait urgent referral should be made as shown on the table on the following page: Approved mmyy (enter when approved) Insert filepath 58 AngCN-SSG-HN16 Head and Neck Primary Care Referral Guidelines for the population of NHS Bedfordshire UAT Malignancy +/- Neck Lump Clinic Referral Designated Hospital: Designated Clinicians: Designated Contact Point (2ww office): Mr J M Pickles Mrs J Panesar Mr P Kothari Telephone Number: 01582 497247 2WW Fax Number: 01582 497910 or 497911 Mr T Hoare (ENT/ thyroid) Mr Chan (OMFS) Mr Simpson (OMFS) Mr Patel (ENT) 01234 355122 Mr Hoare’s ext 2850 Mr Chan’s ext 2071 Mr Simpson’s ext 2070 Mr Patel’s ext 2894 Luton & Dunstable Bedford MDT Pathway: Head and Neck MDT Pathway Bedfordshire and Hertfordshire Head and Neck SMDT Hosted at Luton and Dunstable Hospital Thyroid MDT Pathway Bedfordshire and Hertfordshire Head and Neck SMDT Hosted at Luton and Dunstable Hospital AngCN (West) Thyroid MDT Hosted at Addenbrookes 5. No neck lump and no urgent features The patient should be referred as a routine appointment as follows: Hospital Booking Contact Point Luton & Dunstable Routine appointments requested by letter/or by choose and book Bedford Routine appointments requested by letter addressed to a specific consultant/or by choose and book ENT – 01234 355122 ext 2894 OMFS – 01234 355122 ext 2071 Approved mmyy (enter when approved) Insert filepath 59 AngCN-SSG-HN16 6. Head and Neck Primary Care Referral Guidelines for the population of NHS Bedfordshire Appendices Appendix 1: Document Control Document ratification and history: Approved by: Date placed on electronic library: XXX Review period: Authors: XXX 2 years (or earlier in the light of new evidence) Anglia Cancer Network and Mount Vernon Cancer Network Head and Neck NSSG Version number as approved and published: XXX Document Owner: Anglia Cancer Network Tel: 01638 608208 www.angliacancernetwork.nhs.u k Unique identifier no.: AngCN-SSG-HN1 Document distribution: Responsible for Distribution: To: Sent Via: Sent via: Date: Head and Neck NSSG Network Project Manager Anglia Cancer Network Email XXX Mount Vernon Cancer Network Email Anglia Cancer Network Email PCT Primary Care Leads XXX Mount Vernon Cancer Network Email PCT Primary Care Leads XXX Anglia Cancer Network Email Trust Lead Cancer Managers XXX Mount Vernon Cancer Network Email Trust Lead Cancer Managers XXX Designated consultant clinicians Primary Care medical practices, primary dental practices non designated head and neck consultant clinicians (ENT surgeons, endocrine surgeons, oral maxillofacial surgeons, oral medicine specialists, endocrinologists and restorative dentistry consultants) XXX XXX For comments / amendments to these guidelines, please contact: Name Richard Benson Tom Roques Hospital Addenbrookes NNUH Tel. No 01223 217019 01603 287671 Email [email protected] [email protected] Monitoring the effectiveness of the Process a) Process for Monitoring compliance and Effectiveness - Review of compliance as determined by audit. Any non compliance to be presented by QA Manager to the AngCN Business Meeting on an annual basis – the minutes of this meeting are retained for a minimum of five years. b) Standards/Key Performance Indicators – This process forms part of a quality system working to, but not accredited to, International Standard BS EN ISO 9001:2008. The effectiveness of the process will be monitored in accordance with the methods given in the quality manual, AngCN-QM Approved mmyy (enter when approved) Insert filepath 60 AngCN-SSG-HN16 Head and Neck Primary Care Referral Guidelines for the population of NHS Bedfordshire Equality and Diversity Statement This document complies with the Suffolk PCT Equality and Diversity statement – an EqIA assessment is available on request to Anglia Cancer Network QA Manager, Gibson Centre, Exning Road, Newmarket, CB8 7JG. Disclaimer It is your responsibility to check against the electronic library that this printed out copy is the most recent issue of this document. Please notify any changes required to the Anglia Cancer Network Quality Assurance Manager. Approved mmyy (enter when approved) Insert filepath 61 AngCN-SSG-HN16 Head and Neck Primary Care Referral Guidelines for the population of NHS Bedfordshire Appendix 2: Referral schemas Figure 1: SCHEMA – Features suspicious of cancer associated with a thyroid lump NECK LUMP? THYROID? FEATURES SUSPICIOUS OF MALIGNANCY? Stridor Clinically thyroid REFERRAL GUIDELINE STRIDOR? Features suspicious of thyroid cancer +/- stridor (see section 3.2) Neck Lump No features suspicious of thyroid cancer No Stridor Clinically nonthyroid Approved mmyy (enter when approved) Insert filepath Same day referral Designated clinicians or A&E Management then diagnosis See Figure 2 Fast-track referral Designated clinician for thyroid Thyroid / Neck Lump Clinic Routine appointment Designated clinicians for thyroid 62 AngCN-SSG-HN16 Primary Care Referral Guidelines for Head and Neck Cancers for the population of NHS Bedfordshire Figure 2: SCHEMA - Features suspicious of cancer associated with a non-thyroid neck lump NECK LUMP? FEATURES SUSPICIOUS OF MALIGNANCY? THYROID? See Figure 1 See Clinically thyroid Fast-track referral Designated clinician for UAT or Cons. HaemOnc. Neck lump clinic Lump persists after 3 weeks despite antibiotics Info. Mono. Excluded No associated (nonlump) features of malignancy (see section 3.1) Neck Lump No Stridor Clinically nonthyroid Lump has associated (non-lump) features of UAT malignancy +/- stridor (see section 4) Stridor Lump has associated (non-lump) features of haematological malignancy +/- stridor No Stridor Lump disappears within 3 weeks +/antibiotics or positive for Inf. Mono. No associated (nonlump) features of malignancy Approved mmyy (insert when approved) Insert filepath REFERRAL GUIDELINE STRIDOR? Fast-track referral Designated clinician for UAT Direct or at neck lump clinic Same-day referral Designated clinician or A&E Management then diagnosis Fast-track referral Designated clinician for UAT Direct or at neck lump clinic Not applicable 63 AngCN-SSG-HN16 Primary Care Referral Guidelines for Head and Neck Cancers for the population of NHS Bedfordshire Figure 3: SCHEMA - No neck lump NECK LUMP? THYROID? FEATURES SUSPICIOUS OF MALIGNANCY? Features suspicious of thyroid cancer +/- stridor No Stridor Stridor Patient has nonurgent UAT symptoms and no lump Insert filepath No Neck Lump Approved mmyy (insert when approved) REFERRAL GUIDELINE STRIDOR? Fast-track referral Designated clinician for UAT and Thyroid Direct Same-day referral Designated clinician or A&E Management then diagnosis Routine referral Central contact point of designated hospital referral proforma 64 Appendix 3: Head and Neck Referral Guidelines for suspected cancer National Institute for Health and Clinical Excellence (NICE), Referral for Suspected Cancer (CG27), 2011, p.19. Approved mmyy (insert when approved) Insert filepath 65 Appendix 2 Mount Vernon Head & Neck Cancer Network …………………..Hospital Suspected Head & Neck or Thyroid Neoplasm General Practitioner & General Dental Practitioner Urgent Referral Form Please see this patient with a suspected head and neck neoplasm in the urgent thyroid, neck lump, ENT clinic or Oral & maxillofacial surgery clinic as appropriate. The clinical features are as follows: (please circle) 1. Solitary thyroid lump refer to thyroid lump clinic 2. Non-thyroid neck lump refer to urgent neck lump clinic 3. Suspected neoplasm of throat or larynx nose, sinuses or ear refer to neck lump clinic or urgent ENT clinic 4. Suspected neoplasm of oral cavity, or jaws refer to OMFS clinic 5. Salivary Gland lump refer to neck lump ENT or OMFS clinic Clinical details Past medical history Medication Please fax via Urgent two-week-wait fax line Tel No. 01582 497910 66 Appendix 3 Mount Vernon Cancer Network Guidelines for imaging patients with suspected Head and Neck Cancer (11-1C-105i) Imaging should be arranged at the earliest possible opportunity following cytological or histological diagnoses, or on clinical diagnosis where suspicion is string, by designated clinicians of the diagnostic and treatment centres or members of the core team. See also the MVCN Head & Neck Clinical Guidelines for individual Cancer sites. Staging Investigations MRI scan Head & Neck All patients with biopsy proven Cancer of the Head and Neck (suprahyoid) should have an MRI scan of the Head and Neck with the following exceptions i) Patients with T1NO scc glottis ii) Patients of very poor performance status iii) Patients in whom MRI is contra-indicated eg. Claustrophobia, peacemaker, metal fragments in the Head and Neck (who should undergo a contrast enhanced CT scan of the Head and Neck) iv) Patients with very superficial tumours of anterior two-thirds of tongue CXR All patients should have an up-to-date CXR Contracts enhanced CT scanning of chest and upper abdomen (for those at high risk of distant metastases) i) Patients with N1-3 neck disease ii) Patients with T3-4 primaries iii) Patients in whom respiratory symptoms indicate pulmonary mets or a possible synchronous lung primary 1. Contrast enhanced CT scan of head & neck i) To assess presence/absence of bony invasion eg skull base, mandible, antrum, orbit 67 ii) To stage infrahyoid tumours and laryngeal carcinomas nut MRI is preferred for the assessment of cartilage invasion iii) Patients with contra-indications to MRI Head & Neck Ultrasound guided FNAC i) See unknown primary protocol ii) Patients with equivocal nodes on CT, MRI or PET-CT iii) Suspicious salivary gland enlargement PET-CT scans i) Mandatory for patients with unknown primaries (pre-EUA & Biopsy) and part of diagnostic work-up for nasopharyngeal carcinoma ii) Useful for imaging recurrence post-treatment iv) May be useful in other case scenarios but should in general be discussed in local MDM OPG i) To look for bony erosion in tumours of oral cavity ii) For pre-radiotherapy dental assessment Risk of distant metastases by primary tumour site (5019) Primary site Incidence of distant mets (%) Oral cavity 7.5 Faucial arch 6.7 Oropharynx 15.3 Nasopharynx 28.1 Paranasal sinuses, nasal cavity 9.1 Supraglottic larynx 15.0 Vocal cord 3.1 Hypopharynx 23.6 Total 10.9 Risk of distant metastases by stage Stage Risk (%) I 2.0 II 5.7 68 III 8.5 IV 19.5 T-stage 1 5.2 2 9.6 3 12.7 4 16.1 N-stage 0 4.9 1 11.8 2 21.8 3 27.1 Risk of synchronous primary Literature suggests of the order of 10-20%, commonest sites- bronchus, upper GI and head and neck (clinically it appears to be lower) 69 Thyroid imaging guidelines (11-1C-106i) Thyroid Cancer Diagnosis/Staging : • US + Fnac • MDCT (non contrast) NECK or MRI NECK : for locally extensive tumours with extra-capsular spread or equivocal extent evaluation on Ultrasound. • MDCT (non contrast) Chest : for locally extensive Tumours and/or Node positive Necks. • PET-CT- for patients with rising Thyroglobulin but poor Iodine uptake Thyroid Cancer Recurrence: US +/- Fnac and/or MDCT/ MRI (depending on local availability ) for localising and characterisation of abnormal uptake on Nuclear Medicine study. 70 Appendix 4 Head & Neck Cancer Team Clinical Follow up Protocol Luton & Dunstable Hospital Milton Keynes Hospital Bupa Responsible: Maxillofacial: L&D team Private Care West Herts Trust (Watford, Hemel Hempstead & St Albans) Responsible: ENT: L&D Team Maxillofacial: MVCC Lister Hospital Responsible: Mr. Camilleri QEII Hospital Responsible: As per Lister Hospital Bedford Hospital Responsible: Maxillofacial: Mr. Chan ENT: Mr. Patel Agreed and signed: Luton & Dunstable Hospital: Lister Hospital: Bedford Hospital: QEII Hospital: West Herts Hospitals Trust 71 Appendix 5 London and South East Sarcoma Network (www.lsesn.nhs.uk) Bone Sarcoma: Presentation and Diagnostic Pathway Referral and Presentation Secondary Care GP A&E Suspected Bone Sarcoma - clinical presentation/signs & symptoms - suspicious X-ray/imaging - post-operative diagnosis All plain films and MRI can be carried out at referring trusts but all biopsies to be carried out at RNOH Referral to The London Sarcoma Service (Royal National Orthopaedic Hospital and University College London Hospitals) 2WW form/Tertiary referral form faxed and imaging send to MDT Coordinator; Clare Brown, Sarcoma Unit, Muriel Sands House, RNOH, Brockley Hill, Stanmore, Middlesex HA7 4LP Telephone: 0208 954 2300 bleep 721 Fax: 0208 909 5709 Email: [email protected] via MDT Coordinator RNOH will request any further diagnostic tests required MDT triage referrals Patient presents to Primary/ Secondary Care with symptoms suggestive of recurrence Discuss at Pre-Diagnostic Meeting (RNOH) - MDT agree diagnostic plan Nurse-led Telephone Clinic - explain investigations required - send investigations leaflet Diagnostics via CNS All histology reviewed by Specialist Sarcoma Pathologist via consultant Diagnostic Investigations and additional primary tumour imaging If bone sarcoma suspected: MRI, CT Chest, Bone Scan (if not had), via CNS Biopsy +/- GA (only to be carried out at RNOH) Benign ‘Existing MDT’ (RNOH) - benign patients and metastatic bone tumours from other primaries discussed - treatment planning as appropriate Refer back to GP or local Trust as appropriate Malignant sarcoma/metastatic disease VTC Diagnostic MDT (RNOH & UCLH) - treatment planning Identification of treatment centre OPA - patient told results and given treatment plan - CNS present and counselling room available CNS send diagnosis fax to GP Palliative Care Contact points to refer back known patients with symptoms suspicious of recurrence: Patient: GP/CNS (key worker)/ MDT Coordinator (if previously discharged) Pre-Op Assessment Clinic Primary/Secondary Care: - same day as OPA if Consultant (via secretary) possible 72 Appendix 6 REHABILIATION - SUPPORTIVE CARE MAPPING TEMPLATE Head and Neck Milestones 1-3 1. Suspicion of Cancer 2. Diagnosis All oncology team Holistic assessment by key worker using PEPSI COLA aide memoir for referral to AHP services Diagnostic radiographer Provide general radiography service, available on demand for outpatient clinics and for GP referrals (if this is the practice at the hospital), including for example, chest X-ray, sinus Xray and orthopantomogram (OPG) _ Provide and arrange appointments for specialised imaging, for example, magnetic resonance imaging (MRI), computerised tomography (CT), barium investigations, sialogram, within an agreed timescale _ Ensure that appointment letter includes specific explanation relating to procedure/examination, when and where to attend, any preparation necessary and a contact telephone number _ Ensure that system is in place to contact specific persons, for instance, medical team, nurse specialists, counsellors, regarding patient queries _ Ensure privacy and space are available for patients to discuss 3. MDT Referral to AHP/AHP input at MDT where appropriate 73 1. Suspicion of Cancer 2. Diagnosis 3. MDT queries and concerns _ Ensure appropriate equipment is available during investigations, for example, for suctioning _ Ensure patient undergoes examination safely and with minimal stress, that a clear explanation of procedure is given and that patient knows when and where to get the results Dietitian Assess: – patient’s nutritional requirements and factors affecting nutritional status – potential impact of treatment on patient’s nutritional status – patient’s circumstances and ability to act on dietetic advice _ Advise and discuss importance of maintaining/achieving optimal nutritional status during treatment _ Provide practical dietary advice, including written information tailored to individual’s needs, prognosis and circumstances _ Request that GP prescribes sip feeds if nutritional status is compromised _ Draw up nutritional care plan to achieve optimal nutritional status – Liaise with other health professionals in the oncology team Occupational therapist Physiotherapist Speech and language therapist See referral for criteria See referral for criteria Speech and language therapist 74 1. Suspicion of Cancer 2. Diagnosis 3. MDT See Criteria for referral _ Make initial contact _ Give information regarding role and advice Therapeutic radiographer (At first appointment with clinical oncologist) _ Meet patient and relatives and explain role therapeutic radiographer will play in patient’s radiotherapy planning and treatment _ Provide specific information about mould room, radiotherapy planning and treatment _ Allow patient and relatives time for questions _ Discuss side effects of treatment _ Provide written information and contact number 4 Pre radiotherapy 5 Radiotherapy 6 Post radiotherapy All oncology team Holistic assessment by key worker using PEPSI COLA aide memoir for referral to AHP services Holistic assessment by key worker using PEPSI COLA aide memoir for referral to AHP services Holistic assessment by key worker using PEPSI COLA aide memoir for referral to AHP services Diagnostic radiographer See Milestone one _ Ensure that appointments Provide general Provide imaging services as in Milestones one and 75 4 Pre radiotherapy Physiotherapist 5 Radiotherapy for specialised imaging are arranged before patient is due to start treatment – including if patient has a CT/MRI scan to use as a baseline for post treatment comparison _ Ensure that relevant lymph nodes are included in CT/MRI scans so that assessment of secondary spread of disease can be made _ Liaise with mould room, dental department and treatment planning staff to minimise the number of journeys to hospital, especially if hospital transport is required _ (Depending on hospital practice) Arrange appointments for treatment planning scans/radiography _ Carry out any required radiological intervention procedures for managing nutritional problems, for example, gastrostomy, arranging appointments as necessary _ Be prepared to carry out appropriate interventions of the above type at any point in any treatment if patient is unable to swallow _ Discuss with referring clinician or radiologist changes to procedure due to individual patient needs, including in difficult cases, to ensure maximum results radiography services on demand for complications, for example, for siting of nasogastric tube _ Carry out radiological procedures that may be required if patient has nourishment problems, for example, gastrostomy (see Milestone one for procedure for arranging appointment) _ Liaise with staff involved in the patient’s care, for example, specialist nurse _ Co-ordinate examinations depending on treatment appointments _ Ensure previous imaging is available at time of current imaging _ See Milestone two _ Assess: Carry out referral for in/out-patient within one 6 Post radiotherapy two, with imaging comparable in technique to baseline scans _ Ensure that appointments to help monitor patient’s response to treatment are timed to allow for treatment effects to subside _ Provide specialised imaging within first three months only after discussion with the Radiology Department _ Ensure previous imaging is available at time of current imaging 76 4 Pre radiotherapy – patient’s respiratory status – patient’s general health, mobility and function of the neck and shoulders 5 Radiotherapy 6 Post radiotherapy week of commencing radiotherapy _ Give advice on respiratory exercises and care, clearance of secretions and explain risk of aspiration, if appropriate _ Explain possible side effects of treatment, for example, mucositis, sore mouth, difficulty with clearing thick, sticky secretions, tightening of skin over treated areas _ Teach tracheostomy care to patient and/or carer if appropriate or ensure that suitably qualified nurse undertakes to teach this _ Administer physiotherapy to maintain/improve range of movements and muscle strength over operation and radiotherapy sites, including donor areas _ Teach patient stretching exercises to help maintain the elasticity of irradiated tissues and provide written individual exercise sheets _ Teach pain relief techniques and provide help with relief of nausea/vomiting as required, for example, by transcutaneous electrical nerve stimulation (TENS), relaxation, acupuncture _ Continue above regime 77 4 Pre radiotherapy 5 Radiotherapy 6 Post radiotherapy as appropriate throughout the course of radiotherapy Occupational Therapist See also Criteria for referral _ Make initial contact to explain role of occupational therapist and to build rapport _ Make baseline assessment of mobility, in conjunction with physiotherapist, and personal and domestic activities of daily living _ Assess home situation, including liaison with relatives and carers, to ascertain their concerns, abilities and the level of support they can provide _ Assess where appropriate current role with regard to work and leisure _ Discuss patient’s and carers’ expectations, wishes and concerns regarding the short and long term outcomes of intervention and offer appropriate education and support _ Carry out initial assessment of psychological coping mechanisms, for example, altered body image and adjustments _ Liaise with other members of the multidisciplinary team as appropriate See also Criteria for referral _ Assess impact of treatment on patient’s coping adjustment and their quality of life _ Assist patient’s/carer’s psychological adjustment to disease and treatment, for example, altered body image, communication difficulties _ Assess functional implications of treatment on activities of daily living and intervene as necessary with aids/adaptations or compensatory techniques _ Assess patient’s social situation _ Teach appropriate adaptation techniques, for example: – relaxation – stress management – energy conservation to prevent fatigue – goal setting and problem solving _ Liaise with members of the multi-professional team and other internal/external agencies as required See Milestone eight _ Assess functional ability and equipment required to enable maximum functioning in home environment _ Provide treatment as indicated _ Liaise with multiprofessional team and internal/external agencies, for example, social services _ Carry out home visit if indicated and implement recommendations _ Ensure equipment required to enable independence in activities of daily living is delivered and fitted for discharge _ Discharge patient when recommendations implemented and goals achieved Speech and language therapist _ Prepare patient for impact of radiotherapy on speech and swallowing function Establish stage in treatment _ Evaluate Establish details of recent surgical/radiotherapy interventions 78 4 Pre radiotherapy Dietitian 5 Radiotherapy 6 Post radiotherapy _ Establish current extent of disease and proposed form of treatment _ Establish details of any previous medical/surgical and speech therapy interventions _ Evaluate oral/pharyngeal/laryngeal mechanism, noting presence of any surgical voice prosthesis _ Assess current communication skills and level of cognitive functioning _ Liaise with other team members oral/pharyngeal/laryngeal mechanism _ Assess communication and swallowing functions _ Ensure access to means of alternative communication where necessary _ Instigate further investigations, for example, nasoendoscopy, videofluoroscopy, where further information is required for effective management _ Instruct patient in therapeutic techniques, for example, maintaining range of motion in muscles of speech and mastication and compensatory strategies such as safe swallow _ Assist patient to maintain speech and swallowing functions as radiotherapy progresses _ Advise on good voice care and technique _ Maintain close liaison with relevant members of the team, referring to medical colleagues where further opinion is needed _ Evaluate oral/pharyngeal/laryngeal mechanism, noting presence of any surgical voice prosthesis _ Assess communication and swallowing functions _ Ensure access to means of alternative communication where necessary _ Instigate further investigations, for example, nasoendoscopy, videofluoroscopy, where further information is required for effective management _ Instruct in therapeutic techniques and compensatory strategies _ Liaise with other team members _ Refer to local speech and language therapy service, providing details of treatment and management during radiotherapy _ See Milestone two Also: _ Liaise with other health professionals in the oncology team regarding patient admission if patient is currently having out- Assess patient’s nutritional requirements and status _ Assess patient’s nutritional intake, including via following feeding methods/combinations: – nasogastric, gastrostomy, jejunostomy feeding 79 4 Pre radiotherapy 5 Radiotherapy patient radiotherapy and requires administration of nutritional support _ Draw up and review nutritional care plans to achieve optimal nutritional status _ Provide ongoing monitoring and support to patient, family and carers Therapeutic radiographer _ Ensure that clinical oncologist has completed treatment action sheet _ Instigate treatment preparation, either in simulator or mould room – if patient’s treatment is planned initially in the simulator (i.e. without a treatment mask), patient can proceed straight to first available appointment _ On arrival in mould room or simulator, explain fully all that going to happen, both at planning stage and treatment (mask making procedure may be performed by a mould room technician) _ Allow time for patient to ask questions and to discuss any worries or concerns they may have _ Ensure patient has had dental assessment before making the mask _ Make appropriate treatment mask according to the treatment technique to be used _ Ensure patient has details of simulator and/or CT planning appointments 6 Post radiotherapy – sip feeds – oral diet _ Liaise with GP, nutrition and home delivery companies and community based dietetic service regarding provision of nutritional support in the community if required _ Draw up nutritional care plan for provision of nutritional support in the community Escort patient into treatment room and explain treatment procedures, ensuring patient is as relaxed as possible before commencement of treatment _ Ensure patient has all relevant details regarding radiation treatment side effects for head and neck _ Check patient has signed the consent form _ Explain treatment procedure _ Ensure patient has been given written and verbal information concerning: – treatment reaction/side effects – review by doctor or other professional during course of treatment – number of treatments and overall duration of treatment course _ Refer to other healthcare professionals as and when necessary during treatment _ Assess patient carefully at each visit throughout 80 4 Pre radiotherapy _ Simulate patient’s treatments as instructed by the clinical oncologist using either simulator or CT simulator _ Arrange patient’s next appointment for verification of the treatment plan or treatment _ Produce, if necessary, a patient contour containing target volume and critical structures _ Produce, if necessary, the optimum computer isodose printout _ Check that each printout of dose distribution plans (which may be produced by medical physicists) is signed by therapeutic radiographers who computed it and by a planning superintendent radiographer, before being passed to clinical oncologist for prescription of patient’s treatments _ Check that treatment prescription is calculated in advance of patient’s attendance and that this is checked by another therapeutic radiographer – one of the staff involved should be a Senior II grade or above (see Appendix 5) _ Ensure that a superintendent therapeutic radiographer checks prescription as appropriate _ Check that patient has signed consent form for treatment _ Verify treatment plan in the simulator if requested by 5 Radiotherapy 6 Post radiotherapy course of radiotherapy to monitor: – any treatment reaction/side effects – patient’s well being – any changes to initial planning that may need to be taken into consideration/adjusted _ Ensure patient is seen by clinical oncologist, treatment review radiographer or specialist nurse in the weekly review clinic or more frequently, if required _ Organise any investigations/tests as directed by clinical oncologist, for example, blood tests _ Upon completion of treatment, inform patient about expected side effects and give advice about, for example, skin care 81 4 Pre radiotherapy 5 Radiotherapy 6 Post radiotherapy the clinical oncologist _ Ensure patient has relevant information of treatment appointment dates and time 7 Pre surgery/ Diagnostic radiographer Provide specialised imaging services (see Milestones one and two) to assess response _ (Post biopsy) Allow 2 weeks to elapse before carrying out specialised imaging _ Provide general on demand radiography service, if indicated, for example, preanaesthetic chest X-ray _ Liaise with ward staff if patient is in-patient (some patients may be treated as outpatients after surgery) _ Provide specialised imaging 8 Post surgery Provide general radiography service on demand for postoperative complications, for example, chest X-ray _ Ensure that appointments to help monitor patient’s response to treatment are timed to allow for treatment effects to subside _ Provide specialised imaging within first six weeks only after discussion with the 9 Chemotherapy Provide require specialised imaging, as indicated, to assess interval response _ Ensure previous imaging is available at time of current imaging 82 Dietitian Occupational therapist to assess feasibility of voicepreserving laryngeal surgery/ total laryngectomy (for laryngeal tumours) _ Ensure that scans to assess response to treatment are timed to allow for treatment effects to subside radiology department _ Ensure imaging is comparable in technique to baseline scans _ Ensure previous imaging is available at time of current imaging Assess: – patient’s nutritional requirements and status – factors affecting patient’s nutritional status – patient’s circumstances and ability to act on dietetic advice _ Discuss with patient and provide advice on effects that surgery may have upon eating, nutritional intake and nutritional status _ Discuss effects of altered body image on appetite and eating _ Discuss with patient and provide advice on methods of nutritional support to be implemented post-operatively _ Advise patient on importance of maintaining/achieving optimal nutritional status before and after surgery _ Liaise with other health professionals in the oncology team with regard to the provision of nutritional support _ Provide support to patient, family and carers Liaise with other health professionals in the oncology team with regard to the provision of nutritional support _ Implement nutritional support, which may involve the following modalities: – total parenteral nutrition – if gut is not functional or accessible – percutaneous endoscopic gastrostomy (PEG) – if long term feeding is anticipated (more than 21 days) or if patient is to have post-operative radiotherapy, and where it is anticipated there will be severe side effects – nasogastric feeding – for short term enteral feeding (less than 21 days) – dietary supplementation – e.g. modified food textures, high calorie diets, nutritional supplement drinks – where patient is otherwise unable to maintain nutritional status _ Discuss feeding modalities with patient _ Draw up nutritional care plan for the provision of postsurgical nutritional support _ Educate patient regarding nutritional support regime _ See Milestone three Assess effects of surgery on baseline assessment of mobility Assess: – patient’s nutritional requirements and status – factors affecting patient’s nutritional status – patient’s circumstances and ability to act on dietetic advice Discuss and provide advice on effects that chemotherapy may have upon eating, nutritional intake and nutritional status _ Discuss and provide advice on methods of nutritional support to be implemented _ Advise upon importance of maintaining/achieving optimal nutritional status _ Implement nutritional support indicated _ Liaise with other health professionals in the oncology team with regard to the provision of nutritional support _ Provide support to patient, family and carers See Criteria for referral _ See Milestone three 83 Physiotherapist Ensure that patient is referred on admission to ward and activities of daily living _ Discuss with patient their ongoing concerns and expectations following the outcome of surgery and ascertain their level of insight into their condition and possible prognosis _ Liaise with relatives regarding their concerns, abilities and level of short and longer term support available _ In collaboration with the patient/carers, formulate graded treatment plan outlining goals that will optimise safety, physical and psychological function, independence, dignity and self worth _ Assist the patient to come to terms with both physical and psychological loss through relearning of old skills and/or the acquisition of new skills _ Support patient in psychological adjustment post operatively and during period before any further interventions _ Contribute to formulating an appropriate discharge plan including carrying out of a pre-discharge home visit where indicated _ Liaise with other members of the multidisciplinary team and other internal/external agencies as required _ Where appropriate assess for the provision of adaptive equipment and/or mobility aids (in conjunction with physiotherapist) Also: _ Assess patient’s functional ability and equipment required to enable maximum functioning in home environment _ Provide treatment as indicated _ Carry out home visit if indicated and implement recommendations _ Ensure equipment required to enable independence in activities of daily living is delivered and fitted for discharge _ Discharge patient when recommendations implemented and goals achieved _ Provide post-operative care, starting first day See patient as referred by doctor 84 Speech and language therapist _ Assess patient’s: – respiratory status – general mobility and function – circulation – social circumstances – head, neck, facial and shoulder movements _ Assess for range of movement all joints involved in donor graft areas _ Assess muscle power and function of operative and donor sites _ Teach patient appropriate exercises for initial postoperative period, including breathing, circulatory, and mobility exercises for operative and donor graft sites _ Provide any respiratory treatment indicated _ Explain post-operative treatment regime to patient and relatives and providing advice (including written) about: – tracheostomy – post operative care on Intensive Care Unit (if indicated) – progression of treatment after surgery _ Assess patient’s respiratory function and plan treatment regime indicated _ Begin circulatory exercises on first postoperative day _ Assess operative and donor graft sites daily and begin appropriate exercises when indicated, for example, mobility, postural and strengthening exercises _ Explain care of any plaster used for the donor graft site _ Ensure necessary support network in place following surgery, for problems associated with altered body image _ Commence facial stimulation if indicated and teach facial exercises and massage if appropriate _ If patient is expected to have a permanent tracheostomy, teach patient and carers tracheostomy care _ Contribute to multiprofession assessment of appropriate time for tracheostomy decannulation _ Continue to re-assess and modify and progress treatment programme _ Commence mobilisation when indicated and supply suitable walking aids if needed _ If surgery is likely to produce problems with balance, assess static and dynamic balance _ If balance is impaired, begin vestibular rehabilitation exercises _ Provide treatment and support as indicated, for example, for respiratory problems, functional or mobility problems, nausea, vomiting and pain Establish nature and extent of surgery planned _ Establish patient’s social history, occupational status and support mechanisms Continue to consolidate contact with patient and carers and be available for consultation _ Ensure means of non- _ See Milestone four Also: _ Provide psychological/emotional support 85 _ Evaluate orofacial/pharyngeal/laryngeal mechanism _ Where appropriate, assess suitability for surgical voice restoration _ Assess current communication skills and level of cognitive functioning _ Explain likely post-operative changes in communication and swallowing and establish an effective communication method, particularly for those unable to read or write _ Where appropriate, introduce to the patient a visitor who has had similar surgery, for example, laryngectomy _ Provide additional written/audio-visual material _ Liaise with other team members oral communication is established, and where necessary provide a communication aid _ Confirm nature of surgery and, where appropriate, form of reconstruction _ Provide ongoing assessment and review of orofacial, pharyngeal and laryngeal function for speech and swallowing _ Instigate further investigations, for example, nasoendoscopy, videofluoroscopy, where further information is required for effective management _ Instruct in compensatory strategies and therapy techniques _ Liaise with other team members, for example, with physiotherapist if facial stimulation indicated _ Continue to develop therapeutic relationship with client _ Provide ongoing information to carers and team members _ Plan for outpatient speech and language therapy or joint clinic reviews with medical team and liaise with local speech therapy service as appropriate 86 10 Post treatment follow up 11 Metastatic disease All oncology team Holistic assessment by key worker using PEPSI COLA aide memoir for referral to AHP services Holistic assessment by key worker using PEPSI COLA aide memoir for referral to AHP services Dietitian See Milestone four Also: _ Review nutritional care plan for the provision of nutritional support in the community according to: – severity of radiotherapy side-effects – reconstructive surgery conducted – nutritional status – nutritional intake Occupational therapist Conduct follow up home visit to assess ongoing functional ability and any difficulties within the home _ Formulate a graded treatment plan, outlining goals to be achieved that will optimise safety, physical and psychological function, independence, dignity and self worth, focused on the patient’s role within their home environment _ Where relevant, and through use of graded activity, assist in development of new skills or reacquisition of previous skills associated with engaging in activities necessary for successful return to work and/or leisure _ Offer ongoing education, support and advice, as necessary, for patient undergoing further 12 Quality assurance 87 10 Post treatment follow up 11 Metastatic disease 12 Quality assurance surgical/therapeutic intervention _ Liaise with statutory and voluntary community based agencies as required Physiotherapist At discharge planning _ Arrange for the loan of any walking aids required _ Liaise with district nurses for provision of any respiratory equipment required for home use, for example, portable suction machine _ Arrange any follow-up out-patient treatment at patient’s local hospital, for example, for follow-up of use of facial stimulator, ongoing vestibular rehabilitation _ Give written and verbal advice about exercises and activity at home _ Give written and verbal advice on tracheostomy care at home, if indicated _ Give name and contact number of physiotherapist, to be used if the patient develops problems or questions after discharge _ Give verbal and written information of support groups and their contact numbers, if appropriate Out-patient follow-up clinic _ See patient at 4-6 weeks after discharge in outpatient clinic _ Assess range of movement of affected joints and power of affected muscle groups _ Assess functional abilities _ If patient is continuing to use walking aids assess 88 10 Post treatment follow up 11 Metastatic disease 12 Quality assurance whether they are still indicated and alter aids accordingly _ Ensure ongoing assessment of any facial stimulator _ Assess respiratory status and tracheostomy care _ Arrange any further physiotherapy treatment if indicated _ Refer to and liaise with local physiotherapist if ongoing physiotherapy treatment is required Arrange for supply of any equipment required, for example, walking aids, nebulisers _ Give verbal and written advice for skin care, chest care and general joint mobility and physical activity, as required by patient _ Give written contact name and telephone number after discharge _ If patient is receiving chemotherapy refer to local physiotherapist if appropriate Speech and language therapist Provide assessment of speech and swallowing functions to identify if patient requires ongoing therapeutic intervention _ Instigate further investigations, for example, nasoendoscopy, videofluoroscopy, where further information is required prior to goal setting _ Start therapeutic programme _ Set goals of intervention 89 10 Post treatment follow up 11 Metastatic disease 12 Quality assurance aiming to facilitate neuromuscular recovery and compensatory strategies _ Introduce and teach to patient other means of communication, for example, oesophageal speech, surgical voice _ Instruct in management of swallowing difficulties _ Monitor any changes in function that could be indicative of structural changes or recurrent disease, and refer back to medical team Diagnostic radiographer Provide general radiography service on demand for patient attending outpatient clinic _ Provide specialised imaging services as in Milestone one _ Ensure that imaging is comparable in technique to baseline scans _ Ensure previous imaging is available at time of current imaging Therapy radiographer Criteria for referral to occupational therapist Occupational therapy for head and neck cancer patients can be provided on four levels: Basic Grade – able to provide generalised occupational therapy input requiring indirect supervision 90 Senior II – has wider occupational therapy experience and some experience of oncology and is able to provide more wide ranging assessment and intervention Senior I – has experience of oncology and palliative care issues and is able to work independently, providing a specialist focused service, and is also able to act as a resource for Senior II and Basic Grade Therapists Head III – has wider experience of occupational therapy, oncology and palliative care issues and is able to work independently, providing a specialist, focused service. Can adopt a strategic role in the planning and development of oncology services. There is a special interest group, HOPE (Occupational Therapy in HIV/AIDS, Oncology, Palliative Care and Education) available for support and information. Criteria for referral Patient is having difficulty with personal care that has the potential to affect their functional ability to cope at home Patient has difficulty with mobility and transfers which may affect their safety and ability to cope at home Patient is main carer at home and due to their reduced functional ability is experiencing increasing difficulty in fulfilling this role Patient needs to acquire new skills or learn how to carry out new tasks in order to adapt to changes in their daily living as a result of their current level of dysfunction Patient requires education and support to adapt emotionally, physically and psychologically to any change in their role both at home and/or work Patient is experiencing problems as a result of reduced exercise tolerance associated with fatigue and may require assistance/support within the home Levels of care and criterion for referral to a speech and language therapist Head and neck cancer patients should have access to a specialist speech and language therapist who has received post-graduate dysphagia training and has experience and specialist training giving competence in: videofluoroscopy use of instrumentation, for example, fibreoptic laryngoscopy interpretation post-laryngectomy voice restoration and techniques post-surgical speech rehabilitation voice therapy techniques Criterion for referral Patient is experiencing difficulties with communication and/or swallowing arising from disease of the head and neck and its associated treatmen Criteria for referral to a physiotherapist On admission to hospital Patient is attending for radiotherapy Patient is admitted for surgery Patient develops respiratory problems Patient develops mobility problems Patient has pre-existing mobility problems which are exacerbated by surgery Patient is attending for chemotherapy On discharge Patient has continued loss of function, which is expected to improve with further physiotherapy treatment 91 Patient has a chronic problem which needs to be monitored, for example, long term tracheostomy, facial palsy, requiring regular re-assessment if the patient is using the trophic stimulator After discharge Patient develops further respiratory problems Patient develops mobility problems due to loss of function of the operation or donor sites Dental services To a dental surgeon Patient requires dental assessment and removal of any decayed teeth within the area to be treated by radiotherapy (failure to remove decayed teeth may result in osteoradionecrosis). There should be a delay of 10-14 days after extractions before starting radiotherapy. Dentist should encourage long term dental care and refer to dental hygienist if necessary. To a dental hygienist All patients receiving head and neck cancer treatments should preferably be seen by a dental hygienist prior to treatment, especially those whose dentition, jaw or salivary glands are to be in the path of radiation: 1. Patients with healthy teeth require a comprehensive oral care programme to inform them in preventative dental disease methods 2. Patients with poor dental and oral health require dental treatment prior to commencing radiotherapy/chemotherapy At a minimum patients should have access to appropriate information, outlining: side-effects of radiotherapy/chemotherapy on oral health – notably on reduction in salivary function which frequently causes dental disease and tooth loss importance of frequent mechanical cleansing for oral health care, to maintain a moist, clean, infection-free mouth The dental hygienist is available to: assess, treat and advise on dental and oral health and hygiene refer to dentist as appropriate educate patient and staff in preventive measures to minimise possible side-effects of cancer treatments assess and advise patient who has other medical conditions which necessitate dietary habits that conflict with good oral health – for example, diabetes which may require the eating of small amounts of high carbohydrate diet at regular intervals arrange routine follow-up after cancer treatment to monitor oral care and assess and maximise dental prevention outcomes Criterion for referral Patient must be referred by their consultant, GP or dental surgeon Early referral is advisable for optimum outcome. 92 Appendix 7 Head & Neck Rehabilitation Plan Name of Keyworker………………………….. Keyworker informed: yes / no Additional named contact:………………….. Rehabilitation Need Required ? Please tick Relevant to: Referral made to: Team Member (instigating referral) Name & Date: Wound care/ trachy care/ Psychological Speech/communication Swallowing District Nurses Speech & Language Therapy Speech & Language Therapy Name & Date: Name & Date: Name & Date: Nutrician PEG support Dietician Nutrition Nurse Name & Date: Palliation e.g. symptom control Macmillan Name & Date: Specialist Psychological support Clinical Psychologist Name & Date: Reduced mobility Poor upper limb movement Physiotherapy Personal care and financial advice Social services Welfare rights Name & Date: Name & Date: Oral/dental care Ongoing Support Group Altered body image Restorative Dentist/Hygienist H&N CNS H&N Group Buddy system Red X camouflage Service Name & Date: Name & Date: Name & Date: Smoking addiction Stop Smoking Name & Date: Alcohol addiction Local AA services Name & Date: Drug addiction Local services Lymphodeama Macmillan unit Activities of Daily Living Occupational Therapy Name & Date: Name & Date: 93 Appendix 8 Head & Neck Cancer Rehabilitation Protocol Diagnoses Palliative – nil treatment Radical/Palliative Radiotherapy PDT Brachytherapy Chemotherapy Other Surgery Rehabilitation Plan completed by ward/MDT Local support teams unable to manage specific problems, refer patient back to MDT Signed discharge letter sent to CNS Appropriate referrals made to local support teams Copy in patient’s notes and copy to key worker Dietetics Written and verbal handovers are given to local support teams for all PEG patients, in all areas, even if care is continued at L&D. 94 Appendix 9 SUPPORTIVE CARE PATHWAY FOR HEAD & NECK CANCER SPECIALIST SURGERY TO SUPPORT IOG RECOMMENDATIONS Lister Hospital DIAGNOSIS 1. Clinic Patient informed of diagnosis. CNS to be present GP Fax Proforma completed and sent Discuss probable treatment plans and time frame if appropriate Patient given CNS contact details / MVCN patient information file Key worker identified Holistic assessment and refer to other agencies as appropriate Explanation of MDT process SMDT 2. Patient discussed at SMDT with CNS input. Acts as patient advocate Core member of MDT participates in decision making 3. Patient attends Joint Oncology Clinic/Pre Treatment - CNS present Appropriate written information given Provide patient and family with the opportunity to ask questions about treatment options Provide level 2 psychological support Ensure informed consent Holistic assessment and referral to other agencies as appropriate Complexities of treatment and adjustment to potential change, dysfunction and altered body image introduced Patient consents to receive a copy of GP letter Discuss preparation for planned treatment, pre and post operative care Introduce patient / family to another patient (befriending) Information given on patient support groups available Refer to Luton & Dunstable Hospital CNS / complete transfer sheet and send copy of completed holistic assessment Luton andLuton Dunstable Hospital NHS Foundation Trust Patient given and Dunstable Hospital CNS contact details 95 Pre Operative Assessment (POA) 4. Luton and Dunstable Hospital CNS to meet patient and family at preop assessment appointment Provide further information / written and verbal if needed Liaise with appropriate MDT members Liaise with Pathway Facilitator (PF) as appropriate Liaise with POA staff and surgeons if necessary. Supportive Care during Admission at Luton and Dunstable Hospital 5. Luton and Dunstable Hospital CNS Holistic supportive care services. Welfare / emotional / psychological Verbal / written information given to patient Co-ordination and monitoring of patients during surgical interventions Communication with outside agencies Direct referral for palliative care if appropriate Ensure that patient has a follow-up appointment at referring hospital Discharge from Luton and Dunstable Hospital 6. Luton and Dunstable Hospital CNS to: Discuss further treatment planning options, if appropriate Provide psychological support Level 2 To be present when histology results given (if it is available) Liaise with ward staff to ensure safe and supported discharge, refer to integrated discharge team Ensure that referral to local DN and Community Macmillan Nurse, as appropriate, including copy of holistic assessment Transfer of key worker / contact Follow up / Rehabilitation 7. Lister Hospital CNS to: Be present when histology results are given Prepare for treatment planned, and give appropriate information Provide psychological support level 2 Offer telephone advice Provide symptom / psychological management Signpost to support groups and rehabilitation programmes Provide key worker review Ensure pathway for patient access back into services Provide information on signs of recurrence and what to do 96 Appendix 10 Mount Vernon Cancer Centre Head and Neck Radiotherapy and Chemotherapy Treatment Protocols Consultant Lead: Dr Catherine Lemon Consultant Dr Kate Goodchild Consultant Dr Russell Moule Version 1 Valid From June 2010 Review Date June 2011 Signature Date Signature Date Signature Date 97 Contents General Principles 1.1 1.2 1.3 1.4 1.5 1.6.1 1.6.2 1.7 1.8 Incidence and Epidemiology TNM Staging Patient Assessment Patient Position Planning Guidelines for nodal treatment CT Planning Post-operative radiotherapy Palliative radiotherapy Radiotherapy Treatment Protocols 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 2.10 Larynx Oropharyngeal carcinoma Hypopharynx Nasopharynx Oral Cavity Parotid gland Neck Orbit Ear and temporal bone Nose and sinuses 3. IMRT 4. Chemotherapy Treatment Protocols 5. Management of patients during treatment 6. Management of patient with recurrent disease / palliative patients 7. Research Protocols Appendix 1Appendix 2 – Appendix 3 – Appendix 4 – Appendix 5 Appendix 6 - References Compensation of gaps in radical radiotherapy Anti emetic protocol Neutropenic sepsis policy Physics RT Protocol Flow Charts PL-FLO-03 & 04 98 1. GENERAL PRINCIPLES 1.1 Incidence and Epidemiology Cancer of the head and neck is a relatively rare cancer accounting for 6% of all cancer deaths. The incidence in men is 17.2 per 100,000 and women, 5.6 per 100,000. If one takes an average of about 12 per 100,000, this means that there are about 4,700 cases in the United Kingdom. The main aetiological factors are excessive alcohol intake and smoking. 1.2 TNM Staging (UICC 2002 sixth edition) All patients with head and neck cancer discussed in the MDM will be staged according to the UICC TNM classification 2002 –sixth edition Nodal staging for all head and neck sites identical except nasopharynx (+thyroid) Midline nodes are considered ipsilateral nodes except in thyroid N0 N1 N2 a N2b N2c N3 No neck nodes Ipsilateral single node< 3cm Ipsilateral single node >3-6cm Ipsilateral multiple nodes <6cm Bilateral,contralateral nodes <6cm >6cm The definitions of the M categories for all head and neck sites are the same MX Distant metastases cannot be assessed M0 No distant metastases M1 Distant metastases The categories M1 and pM1 may be further specified according to the following notation Pulmonary PUL Osseous OSS Hepatic HEP Brain BRA Lymph nodesLYM Bone marrowMAR Pleura PLE Peritoneum PER Adrenals ADR Skin SKI Other OTH Lip, Oral Cavity TX T Tis Primary Tumour cannot be assessed No evidence of primary tumour Carcinoma in situ T1 T2 Tumour≤2 cm Tumour > 2 to 4 cm 99 T3 Tumour > 4 cm T4a Lip: Tumour invades adjacent structures eg through cortical bone,inferior alveolar nerve, floor of mouth, skin (chin or nose) T4a Oral cavity: Tumour invades adjacent structures eg through cortical bone, into deep/ extrinsic muscle of tongue (genioglossus,hyoglossus,palatoglossus, and styloglossus), maxillary sinus, skin of face T4b(lip and oral cavity) Tumour invades masticator space, pterygoid plates, or skull base, or encases internal carotid artery (superficial erosion of bone/tooth socket by gingival primary is not sufficient to classify as T4 tumour) Stage Grouping Stage 0 Stage I Stage II Stage III Stage IVA Stage IVB Stage IVC Tis T1 T2 T1,T2 T3 T1,T2,T3 T4a Any T T4b Any T N0 N0 N0 N1 N0,N1 N2 N0,N1,N2 N3 Any N Any N M0 M0 M0 M0 M0 M0 M0 M0 M1 Pharynx Oropharynx TX T Tis T1 T2 T3 T4a Primary Tumour cannot be assessed No evidence of primary tumour Carcinoma in situ Tumour ≤ 2 cm Tumour > 2 to 4 cm Tumour > 4 cm Tumour Invades any of the following larynx, deep/extrinsic muscles of tongue (genioglossus,hyoglossus,palatoglossus, and styloglossus),medial pterygoid, mandible,hard palate, T4b Tumour Invades any of the following: lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, skull base or encases carotid artery 100 Nasopharynx T1 Nasopharynx only N1 Unilateral metastasis in lymph node(s) </= 6cm, above supraclavicular fossa T2 Soft tissue of oropharynx and/or nasal fossa T2a No parapharyngeal N3 extension Parapharyngeal extension Invades bony structures and/or paranasal sinuses Intracranial extension, involvement of cranial nerves, infratemporal fossa, hypopharynx, orbit or masticator space T2b T3 T4 N2 Bilateral metastasis in lymph node(s)</ = 6cm, above supraclavicular fossa [a] > 6cm [b] extension to supraclavicular fossa (parapharyngeal extension denotes postero-lateral infiltration of tumour beyond pharyngo-basilar fascia) Hypopharynx TX T Tis T1 T2 T3 T4a T4b Primary Tumour cannot be assessed No evidence of primary tumour Carcinoma in situ Tumour≤ 2 cm and limited to one subsite Tumour > 2 to 4 cm or involving more than one subsite or an adjacent site without fixation of hemilarynx Tumour > 4 cm or with larynx fixation Tumour invades any of the following:eg thyroid/cricoid cartilage, ,hyoid bone, thyroid gland, oesophagus, central compartment soft tissue of neck(prelaryngeal strap muscles &subcutaneous fat), Tumour invades prevertebal fascia,encases carotid artery, or invades mediastinal structures Stage Grouping (Oro and Hypopharynx) Stage 0 Stage I Stage II Stage III Stage IVA Stage IVB Stage IVC Tis T1 T2 T1,T2 T3 T1,T2,T3 T4a Any T T4b Any T N0 N0 N0 N1 N0,N1 N2 N0,N1,N2 N3 Any N Any N M0 M0 M0 M0 M0 M0 M0 M0 M1 101 Stage Grouping Nasopharynx Stage 0 Stage I Stage IIA Stage IIB Stage III Stage IVA Stage IVB Stage IVC Tis T1 T2a T1 T2a T2b T1 T2a,T2b T3 T4 Any T Any T N0 N0 N0 N1 N1 N0,N1 N2 N2 N0,N1,N2 N0,N1,N2 N3 Any N M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M1 Larynx TX T0 Tis Primary Tumour cannot be assessed No evidence of primary tumour Carcinoma in situ Supraglottis T1 Tumour limited to one subsite, normal mobility T2 Tumour Involving mucosa of more than one adjacent subsite of supraglottis or glottis or region outside the supraglottis eg mucosa of BOT,vallecula,medial wall of pyriform sinus), without fixation of larynx T3 Tumour limited to larynx with vocal cord fixation and/ or invades any of the following: post cricoid area,pre-epiglottic tissues,paraglottic space, and/or with minor thyroid cartilage erosion eg inner cortex T4a Tumour invades through thyroid cartilage, and/or extends into soft tissues of the neck including trachea, deep/extrinsic muscles of tongue (genioglossus, hyoglossus, palatoglossus, and styloglossus), strap muscles,thyroid, oesophagus T4b Tumour invades prevertebral space, mediastinal structures, or encases carotid artery Glottis T1 Tumour limited to vocal cord (s) (may involve anterior or posterior commissure) with normal mobility T1a tumour limited to one vocal cord T1b tumour involved both vocal cords T2 Tumour extends to supraglottis and/or subglottis, and/or with impaired cord mobility T3 Tumour limited to larynx with vocal cord fixation and/or invades paraglottic space, and/or with minor thyroid cartilage erosion eg inner cortex T4a Tumour invades through thyroid cartilage, and/or extends into soft tissues of the neck including trachea, deep/extrinsic muscles of tongue (genioglossus, hyoglossus, palatoglossus, and styloglossus), strap muscles,thyroid, oesophagus 102 T4b Tumour invades prevertebral space, mediastinal structures, or encacarotid artery Subglottis T1 Tumour limited to subglottis T2 Tumour extends to vocal cord(s) with normal/impaired mobility T3 Tumour limited to larynx with cord fixatiion T4a Tumour invades through thyroid cartilage, and/or extends into soft tissues of the neck including trachea, deep/extrinsic muscles of tongue (genioglossus, hyoglossus, palatoglossus, and styloglossus), strap muscles,thyroid, oesophagus T4b Tumour invades prevertebral space, mediastinal structures, or encacarotid artery Stage Grouping Larynx Stage 0 Stage I Stage II Stage III Stage IVA Stage IVB Stage IVC Tis T1 T2 T1,T2 T3 T1,T2,T3 T4a Any T T4b Any T N0 N0 N0 N1 N0,N1 N2 N0,N1,N2 N3 Any N Any N M0 M0 M0 M0 M0 M0 M0 M0 M1 (parapharyngeal extension denotes postero-lateral infiltration of tumour beyond pharyngo-basilar fascia) Paranasal Sinuses TX T0 Tis Primary Tumour cannot be assessed No evidence of primary tumour Carcinoma in situ Maxillary Sinus T1 Tumour limited to antral mucosa with no erosion or destruction of bone T2 Tumour causes bone erosion/destruction, except for posterior antral Wall and pterygoid plates, including extension into hard palate or middle nasal meatus T3 Tumour Invades any of the following:bone of posterior wall of maxillary sinus, subcutaneous tissues, , floor/medial wall of orbit, pterygoid fossa, ethmoid sinus, T4a Tumour Invades any of the following: anterior orbital contents,skin of cheek, pterygoid plates, infratemporal fossa, cribriform plate, sphenoid or frontal sinuses 103 T4b Tumour Invades any of the following:orbitl apex, dura, brain, middle cranial fossa, cranial nerves other than maxillary division of trigeminal nerve V2, nasopharynx, clivus Nasal Cavity and Ethmoid Sinus T1 Tumour restricted to one subsite of nasal cavity or ethmoid sinus, with or without bony invasion T2 Tumour involves two subsites in a single site or extends to involve an adjacent site within the nasoethmoidal complex, with or without bony invasion T3 Tumour invades medial wall or floor of orbit, maxillary sinus, palate or cribriform plate T4a Tumour Invades any of the following: anterior orbital contents, skin of nose or cheek, minimal extension to anterior cranial fossa, pterygoid plates, sphenoid or frontal sinuses T4b Tumour Invades any of the following:orbital apex, dura, brain, middle cranial fossa, cranial nerves other than V2, nasopharynx, clivus Stage Grouping Stage 0 Stage I Stage II Stage III Stage IVA Stage IVB Stage IVC Tis T1 T2 T1,T2 T3 T1,T2,T3 T4a Any T T4b Any T N0 N0 N0 N1 N0,N1 N2 N0,N1,N2 N3 Any N Any N M0 M0 M0 M0 M0 M0 M0 M0 M1 Salivary Glands TX T0 Tis Primary Tumour cannot be assessed No evidence of primary tumour Carcinoma in situ T1 T2 T3 T4a T4b Tumour ≤ 2 cm, without extraparenchymal extension Tumour > 2 to 4 cm, without extraparenchymal extension Tumour having Extraparenchymal extension , and/or > 4 to 6 cm Tumour invades skin,mandible, ear canal, seventh nerve, Tumour invades base of skull, ptergoid plates or encases carotid artery Extraparenchymal extension is clinical or macroscopic evidence of invasion of soft tissues or nerves except those listed under T4a or T4b. Microscopic evidence alone does not constitute extraparenchymal extension for classification purposes. Stage Grouping Stage 0 Tis N0 M0 104 Stage I Stage II Stage III Stage IVA Stage IVB Stage IVC T1 T2 T1,T2 T3 T1,T2,T3 T4a Any T T4b Any T N0 N0 N1 N0, N1 N2 N0,N1,N2 N3 Any N Any N 1.3 M0 M0 M0 M0 M0 M0 M0 M1 Patient Assessment All patients seen within the Head and Neck Unit will have : Been discussed in the multi-disciplinary team meeting and seen in the combined clinic. At this time, a decision will be made as to whether the treatment will be palliative or radical and the modality of treatment(s) to be used. (See management guidelines) Patents who are planned for combined modality treatment ie surgery followed by (chemo)radiotherapy are booked for their post-operative radiotherapy prior to surgery so that the radiotherapy can start within 6 weeks of surgery whenever possible. This would usually mean that planning should start approximately 3 weeks after surgery is completed to allow any swelling to settle and healing to start. All patients with head and neck cancer will be treated by the head and neck team comprising Dr Lemon , Dr Goodchild and Dr Moule. All patients requiring radiotherapy will be discussed in the multi-disciplinary RT planning meeting which takes place weekly on a Tuesday morning. All consultants will be responsible for a handover of their patients to the covering consultant whilst they are on annual leave Any patients treated off protocol will have been discussed in the Rt planning meeting and the reason for treating off protocol will be documented in the patient’s notes Adequate documentation including histology, MRI, CT and PET-CTscan reports, EUA and operation notes should be available in the patient’s notes. Discs containing diagnostic scans from referring hospitals should be available in the notes for RT planning purposes. Head and neck cancer patients should receive RT fractions according to their prescription, gaps should be avoided wherever possible and radical patients should be treated over bank holidays. Management of gaps should be according to Compenstaion of gaps in Radiotherapy (see appendix 2) 105 All suitable patients should be considered for IMRT (see section 3) Pre Radiotherapy Treatment Assessment 1. 2. 3. 4. 5. 6. 7. Full blood count, urea and electrolytes, LFT’s Dental assessment – patients will have an OPG and assessment by the appropriate OMFS team. Speech and Language Therapy assessment where appropriate Nutritional assessment / PEG/RIG insertion. (see PEG/RIG policy) -All patients who have chemoradiation will require enteral nutrition. Other patients will be assessed on a case by case basis. Consent. With appropriate information leaflets (see appendix) Advise patients to: Stop smoking Reduce alcohol intake (stop spirits) Assessment by Clinical Nurse Specialist 1.4 Patient Position All patients should be treated in an immobilisation shell made of either Perspex or orfit. All palliative patients and most radical patients will have orfit shells. Patients who will need posterior neck electrons, treatment close to orbit, post laryngectomy patients and all nasopharynx patients should be considered for Perspex shells. At the time of booking the appropriate pathway for planning will be specified (see flowchart). Also in planning meeting prior to simulator appointment the patients’ position and any other relevant information will be discussed: Patient supine Neck Position Extent of shell If mouthbite required If angled down or CT coronal planning. Patients are positioned with an appropriate head rest, the head is in the neutral position and the spinal cord straight. The exceptions are:a) b) c) d) Nasopharynx where the head is extended but spinal cord straight Parotid – the head is extended so that the fields come beneath the eyes Subglottic carcinoma – if this field is to extend into the mediastinum, then the lower cervical spine needs to be straight. Postcricoid – for planning this tumour the cervical and thoracic spine need to be straight and the head will probably be flexed. An inclined head rest may be necessary. 106 Mouth gag A mouth gag is used in patients with carcinoma of the oral cavity, nasal septum/columella and maxillary sinuses where it may be possible to exclude either the upper half of the mouth or the lower half of the mouth from the field. 1.5 Planning Most patients with advanced head and neck cancer having primary radiotherapy are treated in two phases:Phase 1 The clinical target volume (CTV44) should include the primary tumour, any involved lymph nodes and areas of likely microscopic lymphatic spread . Phase 2 The clinical target volume should (CTV66) encompass the primary tumour and involved nodes Guidelines for nodal treatment (as defined by CHART protocol) The recommendations for specific node groups to be included in the field of treatment are meant as a guide. The responsible clinical oncologist must make the final decision on the individual features of the case. In some cases eg. T1-2 N0 glottic carcinoma, the two volumes may be the same. The following are guidelines for inclusion of lymph node areas in the phase 1 volume. Lymph node levels are defined as follows:Level I a Level Ib Level II Level III Level IV Level V Level VI Level VII - Submental Submandibular Upper deep cervical Mid- deep cervical Lower deep cervical Posterior triangle Anterior neck nodes Paratracheal nodes Nasopharynx Squamous carcinoma T1 N0 Squamous carcinoma T2-4 N0 All undifferentiated carcinoma and squamous carcinoma with node involvement - no neck irradiation Level Ib, II, III, IV, V, bilaterally Level Ib, II, III, IV, V, bilaterally 107 Paranasal sinuses Squamous carcinoma N0 Squamous carcinoma N+ - Lateral pharyngeal nodes only Levels Ib to V bilaterally Oral Cavity T1 / 2 N0 with well lateralised primary T2 N1 with well-lateralised primary T2 N0 with primary approaching midline All others Levels I to IV on same side Levels I and V to same side Levels I, II and IV (bilaterally) Levels I to V (unilaterally if well lateralised or bilaterally if primary approaching midline or significant nodal disease) Oropharynx T1 N0 tonsil (well-lateralised) T2 N0 tonsil (well-lateralised) - - Levels Ib to II on same side Levels Ib to III on same side T1/T2 N1 tonsil T2 N0 midline tonsil primary + other sites - Levels Ib to V on same side - Levels Ib, II and III bilaterally All others - Levels Ib to V bilaterally Larynx T1/T2 N0 glottic T3-4 N0 glottic T1/T2 N0 supraglottic All others - No nodal irradiation Levels Ib, II, III and IV bilaterally Levels Ib, II and III bilaterally Levels Ib to V bilaterally Hypopharynx All 1.6.1 - Levels Ib to V bilaterally Conventional Planning (R1on PL-FLO-03, P1,2,3 on PL-FLO-04) Early larynx patients (T1/2) will be planned conventionally in simulator and then CT scanned and a plan produced. These patients who have high shoulders and where lateral fields are difficult should be CT planned (with anterior oblique fields or coronal technique- see R3). Palliative patients who are treated with parallel opposed fields will usually be planned conventionally. Palliative patients who are treated with oblique fields will be CT planned-(see P4) 1.6.2 CT Planning(PL-FLO-03, R2 & R3 & PL-FLO-04, P4) Most head and neck patients are planned with the help of a contrast enhanced CT scan. The planning scan is performed with contrast. Three millimetre slices are acquired throughout the volume from vertex to carina.(see planning protocol for use of contrast). 108 Well lateralised tumours which are treated with lateral wedged pair fields will be CT planned from the outset (PL-FLO-03, R3). Other patients who require bilateral neck fields will be planned conventionally/virtually simulated for Phase I and by CT planning for Phase II (PLFLO-03, R2). It is advised that planning target volumes be done prior to starting treatment to confirm the phase I fields and help with definition of areas requiring shielding (brainstem and oral cavity). Any changes to standard protocol will be discussed in the head and neck planning meeting. Outlining of target volumes will be performed in the Planning department in following the guidance in the Radiotherapy Treatment Planning Protocol (Physics) using standard nomenclature GTV,CTV, PTV and OAR (see ICRU 50). Once the volumes and Oar doseshave been approved by a Consultant, an RT plan will be created. For patients who have had radical surgery the post operative field is outlined as CTV. In standard risk patients this volume will be treated to the equivalent dose of 60Gy in 30 fractions over 6 weeks, High risk areas (with extra-capsular spread and positive (or <1mm) margins will be treated with a boost of a further 4Gy in 2 fractions Nodal levels are outlined according to the Gregoire defined levels (EORTC) and can be referred to on the physics computer (physics intranet). Outline organs at risk (OAR’s) Specify acceptable doses to OAR Organ Brain stem Hypothalamus Normal tissue tolerance (2Gy/#) 10Gy max no limit 40Gy max 50Gy (max point dose 55Gy if other eye intact) 50Gy 48 Gy (46Gy Chemoradiation) 50 Gy 50Gy Parotid Optic chiasm 24-27Gy (when possible) 50Gy (max point dose 55Gy) Lens Cornea Retina Optic nerve Spinal cord These doses should not be exceeded. If the extent of tumour risks these tolerance doses being exceeded this should be discussed in the planning meeting and documented in the notes and on the consent form signed by the patient and 109 consultant ( this dose not include lens and parotid doses where the dose may be exceeded). 1.7 Post operative Radiotherapy Fifteen factors have been identified as important -predictors of recurrence. The first two are absolute indications for post op chemoradiation in fit patients under the age of 70 years (see ref 1, 2). i) ii) positive resection margins extra-capsular lymph node spread Standard dose is 60 Gy in 30 fractions with a 4 Gy boost to any areas where one of the two high risk factors are present. Two of the remainder suggest post-op RT should be recommended. Concurrent chemotherapy may be considered. iii) iv) v) vi) vii) viii) ix) x) xi) xii) xiii) xiv) xv) close margins <5 mm invasion of soft tissues Two or more LN +ve more than 1 +ve nodal group involved node more than 3 cm in diameter multicentre primary peri-neural invasion vascular invasion poor differentiation stage T3/4 oral cancer CIS, dysplasia at edge of resection margin uncertainties concerning surgical/pathological findings High risk of recurrence associated with either (i) or (ii) alone or presence of two or more of factors iii-ix. Intermediate risk is associated with the presence of any one of the factors iiiix. Factors x to xiv may be of some importance in predicting recurrence and should be borne in mind. Treatment volume should encompass the area of surgical resection and will include all areas considered at risk of recurrence. A margin of 10mm around the maximal extent of surgery should be included. Where nodal involvement has been proven, the field should be extended to include the lymphatic drainage down to the clavicle with a boost to the small area which includes sites at greatest risk with 10mm margin. 110 1.8 Dose Fractionation Summary For squamous cell carcinomas,most patients are treated with a daily dose of 2Gy per fraction daily Monday to Friday Primary Radical Radiotherapy Macroscopic disease should receive 66 Gy – 68 Gy/33-34 #. Microscopic disease should receive 44 – 50 Gy/22-25#. For small volume disease eg T1/2 N0 larynx and occasionally post op parotid patients a 4 week fractionation schedule is used. 4 week regimen T1 larynx T2 larynx Post op parotid Cord dose 54Gy/20# (equivalent to 64Gy/32#) 55Gy/20# (equivalent to 66Gy / 33#) 50Gy/20# (equivalent to 60Gy/30#) 54Gy/20# (equivalent to 64Gy/32#) 40Gy The cosmetic results and late toxicity of XRT given over four weeks may be poorer than those obtained from a six week schedule. In the past, it has been generally accepted that 50 Gy is required to sterilise microscopic disease, but evidence from randomised controlled trial, including the CHART trials, where a dose of 44 Gy was given to microscopic disease has indicated that around 44 Gy may well be adequate. This is also supported by the work of Peter Levendarg; in their group of 61 patients, 46 Gy was prescribed to the neck and in 34 N0 patients, that is 65 necks, there were only 4 recurrences. In addition, when attempting conformal therapy and IMRT, to avoid vital structures like the parotid, it becomes more and more difficult to give 50 Gy to microscopic disease and somewhere between 44 and 46 is becoming more acceptable. Some patients will be treated in a single phase. For more complex treatments a two phase technique is used:Phase I 44 Gy intersection dose in 22#, 2 Gy per fraction over 30-34 days(including cord if necessary) Phase II. 22– 24 Gy intersection dose, 11-12# over 12-16 days External Beam Therapy Plus Implant 111 Implants are rarely used. If indicated the patient should be discussed with Professor Hoskin. The dose used is:Conventional radiotherapy, 44 – 50Gy, 22 – 25 fractions once daily plus 20 – 25Gy at 0.5 cm (dose rate 35-45Gy per hour) with implant. Gaps Patients should not miss treatments during a course of radiotherapy. Arrangements are made for patients to be treated on a different treatment machine if their usual treatment machine is being serviced. If patients are too unwell to travel for radiotherapy as an outpatient then they should be admitted to the ward. If any patient miss any treatments these missed treatments are compensated for using the flow chart (see appendix 2) Altered Fractionated Schedules CHART schedule - Continuous Hyperfractionated Accelerated Radiotherapy has recently been evaluated in a UK wide study. This intensive regime is costly to deliver. It shows a local control benefit for larynx patients but has yet to show overall survival advantage in head and neck cancer. Accelerated regimes show improvement in local control rates similar to the improvement seen by adding chemotherapy to conventional radiotherapy. Adding chemotherapy to accelerated regimes is only used in a trial setting. This schedule is also used omitting the weekends for convenience and is known as CHARTWEL (Continuous Hyperfractionated Accelerated Radiotherapy Weekend Less). CHART / CHARTWEL schedules are currently being used for treatment of rapidly growing tumours such as columella and anaplastic thyroid patients. These schedules are also used for selected patients who may require radiotherapy as an inpatient to reduce the overall treatment time. DAHANCA schedule - There is evidence from the meta-analysis that a modest acceleration of radiotherapy maintaining the dose at 66Gy is advantageous Post op Radiotherapy Post op should receive 60Gy/30# Post op high risk areas (ECS and/ or positive margins) should receive 64Gy/32# PALLIATIVE RADIOTHERAPY] Dose schedules for palliation include:27 Gy in 6#, followed by a boost (off spinal cord) of 4.5 Gy 2#/week 27 Gy in 6 #(if spinal cord within irradiated volume) weeks 37-39 Gy in 13# (2.84-3 Gy/#) treating daily Monday to Friday } } over 3 112 OTHER TUMOUR TYPES LYMPHOMAS These patients should receive a total dose of 40Gy in 20 fractions (high grade) and 30Gy in 15 fractions (low grade). These patients are treated by the lymphoma team. Plasmacytomas These patients should receive a total dose of 50Gy in 25 fractions. 113 2. RADIOTHERAPY TREATMENT PROTOCOLS 2.1 LARYNX GLOTTIC TUMOURS Position Supine Cervical spine straight T1 Centred on vocal cord (1cm below thyroid promontory) CTV to include the whole larynx. Extends from the hyoid superiorly encompassing the cricoid inferiorly and covering the width of the thyroid cartilage. Anterior bolus 5mm thick and 2cm wide will be used over the shell if there is anterior commissure involvement. No prophylatic nodal radiotherapy T2 CTV should include the whole larynx andwill be expanded based on the supraglottic and/or subglottic extension. Usually no prophylactic nodal irradiation but if large tumour immediate lymph nodes (field anterior to cord) may be irradiated. The para-oesophageal and paratracheal lymph nodes are included for extensive subglottic extension T3 CTV to include include the whole larynx and pre-epiglottic space. Extends from above the hyoid to 1cm below the cricoid (lower if subglottic spread). If there is a trachostomy then this must be also included. Nodal fields: level 1, 2, 3 and 4 bilateral T4 Primary surgery with or without neck dissection combined with postoperative radiotherapy is the treatment of choice. Synchronous chemotherapy and radiation offer an alternative in those patients who are medically unfit. Technique Parallel opposed pair Wedged fields (under wedge if anterior commissure involved) Anterior oblique fields if short neck Dose < 42cm2 or 6cm or less in length 55Gy/20 (5#/week) > 42cm2 64-66 Gy/32-33# (5#/week) SUPRAGLOTTIC TUMOURS 114 T1/2/3 N0 These tumours are associated with a high incidence of occult positive nodes Position Supine Cervical spine neutral Phase I CTV includes the whole larynx and extends upwards to include the preepiglottic space. T2/3 treat nodes level 1, 2, 3, bilateral. Phase II To encompass the primary tumour only. Technique Parallel opposed wedged fields. N+ Supraglottic Tumours Position Supine Cervical spine neutral Technique Parallel opposed wedged fields Anterior neck split Phase I CTV Includes the whole larynx , level 1 – 5 nodes bilaterally Lower anterior neck split field to treat the lower cervical nodes and supraclavicular nodes Parallel opposed photon beams Phase II Ctv includes the whole larynx and involved regional nodes Anterior neck Parallel opposed photon beams Posterior neck Electron fields SUBGLOTTIC TUMOURS T1/T2/T3/T4 Position Supine Cervical spine neutral Technique CTV Includes the whole larynx with expansion to cover subglottic extension Anterior oblique field arrangements usually used. The inferior extent may necessitate a coronal technique. 115 POST-OPERATIVE RADIOTHERAPY N0 disease Can be treated with one phase as the fields do not extend over the spinal cord N+ Phase 1 Parallel opposed with anterior neck split Phase 2 Tumour only –photons for ant neck Electrons for post neck 2.2 OROPHARYNGEAL CARCINOMA TONSILLAR TUMOURS T1/T2/N0 Position Supine Cervical spine straight Clinical Target Volume Tonsillar fossa, Ipsilateral level 1 to III nodes Technique Anterior and posterior wedged pair (+/- matched low ipsilateral neck) T1/T2/N+ Position Supine Cervical spine straight Technique. Phase I bilaterally. CTV to include Tonsillar fossa, level 1-5 nodes Parallel opposed fields Anterior split neck field, shield centrally 116 Phase II nodes CTV to include tonsillar fossa and involved neck Anterior Upper neck – parallel opposed photon fields Posterior upper neck – electron fields Matched ipsilateral neck Or Oblique parallel pair upper neck and matched low ipsilateral neck T3/T4 NO or N+ Position Technique Phase I Phase II Supine Cervical spine straight tonsillar fossa and level I-5 nodes bilaterally Parallel opposed fields Anterior neck split CTV to include tonsillar fossa and involved neck nodes anterior upper neck - Parallel opposed photon fields Posterior upper neck - Electron fields Matched low neck as appropriate POSTERIOR THIRD OF TONGUE T1-4 N0-1 Position Supine Cervical spine straight TECHNIQUE Phase I bilaterally CTV to include Base of tongue, level 1-5 nodes Parallel opposed fields Ant neck split 117 Phase II nodes CTV to include primary tuour and involved regional Upper anterior neck – parallel opposed photon fields Posterior upper neck (if required) – electron fields N+ (>2cm, N2, N3) Technique as for N+ tonsil SOFT PALATE N0 DISEASE Position Supine Cervical spine straight Technique Phase I CTv to include Soft Palate primary, level 1 2 3 nodes bilaterally Parallel opposed fields Phase II Ctv to include primary only Upper anterior neck – parallel opposed photon fields N+ Disease As for N+ tonsil HYPOPHARYNX PYRIFORM FOSSA N0- (any T) Position Supine Cervical spine straight 118 Phase I CTv to include Primary site, level 1-5 nodes bilaterally Include skull base and mastoid Phase II Ctv to include Primary site only Technique Phase 1 parallel opposed & ant neck split Phase II anterior neck parallel opposed N+ (any T) Technique as for N+ tonsil POSTERIOR PHARYNGEAL WALL N0 (any T) Position Supine Cervical spine straight Phase I CTV to include whole hypopharynx, level 1-5 nodes bilaterally Phase II CTV to include primary site only Technique Lateral parallel opposed fields, angled down if necessary. N+ (any T) Technique as for N+ tonsil POST CRICOID CARCINOMA N0 (any T) Position Supine Cervico-thoracic spine straight Technique CTV to include Primary tumour including the hypopharynx and if possible 3-4cm of cervical oesophagus below the known tumour extent. If there is nodal involvement, radiotherapy may have to be palliative as the full dose cannot be given to all the tumour without compromising the cord dose. Consider IMRT in this situation. . 3 field arrangement, 2 anterior oblique fields and an anterior field with a sup-inf. wedge 2.4 NASOPHARYNX Lymph node positive disease Position: Supine 119 Neck extended Chin up as far as possible Patients will be CT planned for Phase II and III and may be CT planned for Phase I. Phase I Large parallel opposed fields extending from the skull base to the low neck then match lower anterior neck avoiding junction over nodes Clinical target volume includes: Base of skull (middle temporal fossa) Posterior half of the orbit Posterior half of the nasal fossa Para-pharyngeal space Lateral pharyngeal, posterior and upper deep cervical nodes Dose 30Gy/15# Phase II The volume is split into two parts: Primary area: Parallel opposed pair to the nasopharynx, parapharyngeal space, base of sphenoid and posterior orbit – ensuring that there is sufficient cover of disease extension The neck is treated by a matched ant post neck with central shielding to spinal cord. Dose 20Gy/10# Phase III Primary The volume is reduced further to avoid the retina, optic nerve and optic chiasm using a 2 or 3 field plan Undifferentiated NPC Dose 16 -18Gy/8 - 9# Differentiated NPC Dose 16 -18Gy/8 - 9# Involved nodes are treated to a further dose of 16 – 18 Gy using shortened AP fields or electrons. LYMPH NODE NEGATIVE (Well–differentiated NPC) Phase I Dose As the phase II technique described above or as Phase I but with higher junction 50Gy/25# Phase II Two or Three field technique as described above. Dose 16 -18Gy/8 -9# 120 2.5 ORAL CAVITY ANTERIOR 2/3 TONGUE T1/smaller T2 Lesions These patients are usually treated with surgery. Brachytherapy can be considered but is rarely used the majority of these patients will be treated with external beam irradiation only. Small T1 tumours Brachytherapy only dose 65Gy, T2 Phase 1 - 44 – 50Gy external beam in 22 – 25 fractions once daily plus 20 – 25Gy at 0.5 cm (dose rate 35-45Gy per hour) with implant. External Beam (Ipsilateral treatment only – T1,2 well lateralised, N0 or 1) Radiotherapy Position Supine Cervical spine straight Mouth bite Technique CTv to include primary site and regional lymph nodes (as previously defined) Lateral Wedged field arrangement Pterygoid fossa is included in RMT tumours External Beam (Bilateral treatment – T1,2 midline, all T3,4 all N2, 3) Radiotherapy Position Supine Cervical spine straight Mouth bite 121 Technique. Phase I CTV to include oral cavity tumour, level 1-5 nodes bilaterally. Parallel opposed fields Anterior split neck field, shield centrally Phase II fields Anterior Upper neck – parallel opposed photon Posterior upper neck – electron fields Matched ipsilateral neck Or Oblique parallel pair upper neck and matched low ipsilateral neck FOM / Buccal Mucosa As above with FOM counted as a midline tumour. Buccal mucosa tumours are generally well lateralised and so treatment may be limited to ipsilateral treatment as described for ant 2/3 tongue. 2.6 PAROTID GLAND INDICATIONS FOR POSTOPERATIVE RADIOTHERAPY Pleomorphic adenoma Incomplete removal Recurrence post-surgical excision combined with surgery to remove bulk disease Large adenoma of the deep lobe (consider) Recurrence rate reduced from 30% to 5% Risk of 2nd malignancy 0.7% Low Grade Malignancy If there is any doubt about resection margins anatomically or histologically, consider radiotherapy to the parotid bed 122 High Grade Malignancy Post-operative radiotherapy for mucoepidermoid, adenocarcinoma, adenoid cystic and squamous cell carcinoma Consider elective neck irradiation in squamous, adenocarcinoma, high grade mucoepidermoid and anaplastic. Position Supine Head extended Mandible perpendicular to couch top CT Plan Entire parotid bed must be included Include the parotid duct, parapharyngeal space and scar (if at high risk) Adenoid cystic carcinomas spread along nerves and therefore this should be considered in planning Outline contralateral parotid and lens Technique Anterior and posterior wedged fields Dose Pleomorphic adenoma Post – op high grade 50Gy/25# 60-64Gy/30-32# 2.7 NECK NECK ONLY – POST-OPERATIVE OR UNKNOWN PRIMARY Position Supine Cervical spine straight Chin up as high as possible CTV To include levels 1-5 nodes (see Gregoire paper) Technique Anterior/posterior parallel opposed fields Asymmetric diaphragm for midline Separation at vocal cords < 14cm – 10MV anterior only Separation at vocal cords >14cm – Parallel opposed 6MV Patients who present with neck nodes and an unknown primary site will be investigated according to the unknown primary pathway (see network management guidelines)). 123 If following investigation there is no likely primary site then patients can be treated either with radiotherapy to the neck only( ipsilateral irradiation only) as above or to include possible mucosal primary sites (bilateral irradiation). Concurrent chemotherapy may also be given to certain individuals following MDM discussion If it seems highly likely that the primary tumour lay in oro-pharynx, hypo-pharynx, or nasopharynx then radiotherapy is given as for these sites. These possible primary sites will usually be treated to a dose of 50Gy in 25 fractions unless the PET scan suggests macroscopic disease where a full radical dose will be used to these areas (total 66Gy in 33 fractions). 2.8 ORBIT All orbital tumours treated with radical radiotherapy will be CT planned. Sarcomas and lymphomas will be referred to the appropriate teams. EXTRACONAL TUMOURS – EYE INTACT Includes lacrimal gland tumours Position Supine Neck straight Technique Direct anterior and angled or asymmetric lateral field Weighted anteriorly Pencil lead to shield the lens, eyeball and intraconal space* (*must be certain that no tumour lies within the shielded area) If the tumour extends superiorly or inferiorly the anterior field can be angled superiorly or inferiorly to ensure that the corneal shadow falls outside the PTV INTRACONAL TUMOURS/GROSS PROPTOSIS/LATERAL GLOBE DISPLACEMENT The technique for extraconal tumours is unsuitable if there is intraconal disease, proptosis or tumour both inside and outside the muscle cone. Position Supine Neck straight Technique Superior and inferior anterior fields Eye open during treatment to spare cornea 124 POSTERIOR ORBIT Position Supine Neck straight Technique thyroid eye disease Single lateral field where low doses are used Anterior margin 0.25cm in front of the lateral bony margin of the orbit Asymmetric technique or gantry angle of 85 to avoid the opposite lens 20-40Gy depending upon whether intent is palliative or radical. Thyroid eye disease dose 20Gy/10# POST-OPERATIVE Position Supine Neck straight CT Plan Outline CTV Outline contralateral eye, lens, pituitary fossa and brainstem Technique Anterior and antero-lateral wedged pair 60-64Gy in 30-32# 2.9 EAR AND TEMPORAL BONE Tumours included • All cutaneous tumours of the pinna and ear canal • All tumours of the middle ear • Tumours of the parotid invading the facial nerve and temporal bone PINNA Modality: Technique: electrons or photons For electrons: GTV outlined. PTV = CTV + 1cm margin, a wax backed Pb shield is placed behind the area to be treated, wax / wet tissue build up is applied to ensure that the surface dose is 100%, a Pb cut out may be required 125 Dose: 55Gy in 20# 66-68Gy in 33-34# EXTERNAL AUDITORY MEATUS (not penetrating the middle ear) Position: Technique: Supine, neck extended so that exit beam avoids lens. Anterior and posterior wedged fields MIDDLE EAR Position Supine Neck extended (to avoid exit of posterior field through the eyes). CT Planning The CTV includes the GTV plus the pre and post-auricular lymph nodes. Outline brainstem and both eyes Technique Anterior and posterior wedged fields 2.10 NOSE AND SINUSES MAXILLARY ANTRUM Position Supine Cervical spine straight Mouthbite CT Plan Clinical target volume will include the maxilla, pterygoid fossa, ethmoid sinus, nasal fossa and lateral pharyngeal node Care should be taken to shield the brain stem, optic pathways, eyeball, lacrimal gland and orbit wherever possible. Field Arrangement Anterior and one or 2 lateral fields (angled behind the eyes or using asymmetric jaw centred behind the outer canthus to avoid exit through contralateral eye), fields weighted anteriorly. ETHMOID SINUS 126 Position Supine Cervical spine straight Mouthbite CT Plan Clinical target volume will include the medial half of the maxilla on the involved side, pterygoid fossa, both ethmoid sinuses and nasal fossa. Care should be taken to shield the brain stem, optic pathways, eyeball, lacrimal gland and orbit wherever possible. Field Arrangement Field arrangements will depend on the dose to OAR within the PTV eg: optic chiasm and eye. Anterior and one or 2 lateral fields (angled behind the eyes or using asymmetric jaw centred behind the outer canthus to avoid exit through contralateral eye), fields weighted anteriorly. NASAL VESTIBULE, COLUMELLA AND SEPTUM Position Supine Cervical spine straight CT Plan CT assessment is needed as the posterior margins of columella lesions may be difficult to assess. Field Arrangement Anterior wedged pair of photon fields or an anterior electron field can be used in conjunction with a wax block. In many cases, the whole of the nasal cavity has to be included. Anterior wedge fields are then employed with lead to shield the lenses and optic chiasm. 127 3. INTENSITY MODULATED RADIATION THERAPY IMRT was introduced at MVCC in June 2009. This treatment technique allows the treatment of complex target volumes. The planning target volume and organs at risk are defined on a CT planning scan. Varying the intensity of dose across the beam and using multiple beams with multi-leaf collimation allows the radiation beam to be shaped to fit the PTV as closely as possible. This allows normal tissues to be spared and dose escalation to the PTV to be facilitated. The PARSPORT study has shown that the incidence of xerostomia can be significantly reduced in patients undergoing IMRT for orophayngeal and hypopharyngeal cancer without loss of local tumour control and survival (see appendix). Therefore all eligible patients with oropharyngeal and hypopharyngeal cancers will be considered for IMRT. Eligible patients with T1-4,N0-3,M0 will be identified in the head and neck MDMs. All patients with parotid cancers who require post-operative radiotherapy will be considered for the COSTAR study. Any patient with nasopharyngeal carcinoma can be considered for IMRT. All patients with differentiated thyroid cancer who require post – operative radiotherapy by virtue of heavy node involvement (with extranodal spread or incomplete resection) or who are iodine-resistant can be considered for post-operative IMRT. All treatment will be CT planned, with scans taken at intervals through the primary tumour site (2) and cervical lymph nodes (2mm). Clinical target volumes for macroscopic disease and areas at risk of harbouring microscopic disease will be outlined on each CT slice, as will critical structures. MRI scans, clinical information and EUA findings may be used to assist the definition of target volumes. The parotid glands, submandibular glands, spinal cord, brain stem, mandible and oral cavity will be outlined. Elective nodal irradiation volumes will be outlined as in the guidelines of Nowak et al 1999, Wijers et al 1999 and Gregoire et al 2000. CTV 1 includes the primary tumour and involved nodes. The CTV around the primary tumour will be the gross tumour volume plus first station nodes (i.e. ipsilateral II) with a 1cm margin to account for microscopic tumour spread. The margins can be reduced at the borders of an uninvolved anatomic space. CTV 2 includes the lymph node groups at risk of harbouring metastatic disease. This volume will vary depending on the site and stage of the 128 primary tumour. For oropharyngeal tumours it should include ipsilateral Ib, bilateral levels II-V, and retropharyngeal nodes in all cases. For tumours that cross the midline, contra-lateral level Ib is target. Level Ia is only target for tumours that involve the floor of mouth or if level Ib is involved. For tonsil tumours the upper deep jugular (above the digastric muscle) may be omitted on the contra-lateral side to allow contralateral parotid gland sparing. A margin not less than 3mm in all directions will be added to the CTV to produce the PTV. IMRT planning A 5-9 field technique will be used. Goals for treatment planning will be to deliver 65Gy in 30 fractions to the PTV. The method of treatment planning will be inverse planning using the Eclipse planning system with dynamic MLCs. Dose distributions should be calculated corrected for in-homogeneities and deliverable beams. Dose and fractionation Primary radiotherapy: A total dose of 65 Gy in 30 daily fractions over 6 weeks (radiobiologically equivalent to 70Gy, 2Gy/ fraction; five times per week) will be delivered to macroscopic primary tumour and involved/high risk lymph nodes (PTV1). Clinically uninvolved lymph node areas (PTV2) in patients will be treated to the radiobiologically equivalent dose of 54Gy in 30 fractions. Dose prescription Prescription of IMRT plans. For IMRT plans, the prescription will be to the median dose point on the DVH such that the prescription dose (65Gy) is received by 50% of the PTV1. The minimum and maximum doses to the PTV should be within 90 –110% of the prescription dose (see table below). Less than 5% of the volume outside the PTV should receive >110% of the prescription dose. Acceptable under- and over-dose for the PTV % PTV 2% 5% 7% 2% % Dose <90% <95% >107% >110% Dose limits for Organs at Risk (OARs) The dose limits for radiosensitive organs are given below and should be assessed from dose-volume histograms of 3D volumes: Contra-lateral parotid gland Mean dose <24Gy 129 Spinal cord with chemotherapy) Brain stem Maximum dose 48Gy (46Gy Maximum dose 60Gy Verification of dose delivery This will be done by measurement of the delivered dose using ion chambers. Quality assurance QA of the delivered dose will be co-ordinated by Physics. 130 4. CHEMOTHERAPY PROTOCOLS FOR HEAD AND NECK CANCER Patients <70 years, of good performance status, with node postive head and neck cancer or T3/T4 primary tumours shoud be considered for concurrent chemoradiation using cisplatin. Pre treatment assessment 1. Baseline FBC 2. Baseline biochemical profile inc. U+E, LFT’s, bone profile 3. Assessment of GFR with EDTA (preferable) or Cockcroft – Gault calculation: Women: Creatinine clearance in ml/min = 0.85 x (140-age (yr) x body wt (kg) 72 x serum creatinine (mol/l) Men: Creatinine clearance in ml/min = 1 x (140-age (yr) x body wt (kg) 72 x serum creatinine (mol/l) Chemotherapy should not be administered if the GFR is <40ml/min. If the GFR is <60ml/min then carboplatin should be used AUC =5. 4. Informed consent 5. When receiving cisplatin chemotherapy, all patients should receive pre and post hydration and anti-emetics (usually 5HT antagonist and dexamethasone as highly emetogenic) according to protocol. 6. All patients should be considered for an audiogram 7. Men should be offered sperm banking and women with child bearing potential should be counselled about the risks of infertility. Patients can be referred to UCLH for further assessment. Concomitant chemotherapy Cisplatin 80 - 100mg/m2 IV or carboplatin (AUC 4 or 5) day 1, 22 and 43 of radiotherapy Weekly FBC and U&E will be monitored carefully during treatment. Scheduling of Concurrent Chemotherapy and Radiotherapy 131 Radiotherapy should be delivered after the chemotherapy. This requires the chemotherapy to be commenced early in the morning to allow RT to be given before 5pm. Standard timings are for patient to be admitted to the ward at 2pm on the day before chemotherapy is due. If blood tests can be done a day or two prior to this admission it is easier. Otherwise a blood test is done urgently on admission. The chemotherapy is taken off hold by 4pm that afternoon. Pre-hydration starts at 12 midnight so that the cisplatin chemotherapy can run from 6 – 10 am. Radiotherapy is administered between 10am and 2pm and the post hydration schedule will generally finish by around 4pm allowing the patient to be discharged. Patients on hospital transport will usually stay in two nights in total. Standard anti-emetic protocol used (see appendix 3). Neutropenic sepsis is treated according to Mount Vernon Hospital neutropenic sepsis policy (see appendix 4). Neo-adjuvant chemotherapy Cisplatin 80-100mg/m2 IV day 1 5FU 1g/m2 infused IV days 1 to 4 repeat day 22, 43 etc. This is used rarely for symptom relief while patients are being planned for their radiotherapy. Induction with a taxane based regimen (TPF) can be considered for patients with advanced disease who have a WHO performance status of 0/1. Taxotere 75mg/m2 d1 Cisplatin 75 mg/m2 d1 5-fluoro-uracil 750 mg/m2 d1-5 Schedule repeated every 21 days for 2 – 3 cycles Concurrent cetuximab with radiotherapy A Phase III study has demonstrated a local control, disease-free and overall survival benefit for patients with locally advanced head and neck cancer who receive cetuximab and radiacal radiotherapy versus radiotherapy alone(ref 3, see appendix 1) No benefit was seen for patients with a Karnofsky Performance Status 80 who were 65 years of age or older. In June 2008 NICE approved the use of concurrent cetuximab with radical radiotherapy for patients with locally advanced head and neck cancer receiving radical radiotherapy who had a Karnofsky performance status > 90% and in whom cisplatin based chemotherapy was contra-indicated. A cetuximab radiotherapy initiation form is completed and sent with the C form to pharmacy. 132 . Cetuximab is administered once a week concomitantly with radiation therapy. A loading dose of 400mg/m2 over 120 minutes should be administered intravenously one week before radiotherapy begins and should be continued weekly at a dose of 250 mg/m2 over 60 minutes iv until the end of the radiation period. Prior to each infusion, the patient should be pre-medicated with an antihistamine eg chlorpheniramine 10 mg iv. Patients should be monitored for an allergic reaction for at least 60 minutes after administration. Weekly monitoring of FBC, U&Es, LFTs is not required but these tests should be performed prior to the commencement of treatment (and should be normal before preceeding with treatment) and on at least one occasion during treatment. Patients may experience an infusion related reaction which is rare and dyspnoea. Skin reactions are common which should be treated with appropriate antibiotics eg tetracyclines. Severe skin reactions ( grade 3: NCICTC) require cessation of cetuximab therapy until skin reaction has resolved to grade 2. (see appendix ) 133 5. MANAGEMENT OF PATIENTS ON TREATMENT Patients are reviewed weekly whilst on treatment by the team. The patient will have the radiotherapy head and neck radiotherapy nurse specialist as their key worker during treatment. Patients will have her contact details if there are any problems during treatment. Any problems during the week between the hours of 9am and 5pm are dealt with initially by the head and neck nurse and then the team are involved as appropriate. After 5pm and at weekends patients will contact either the ward or the senior nurse on call at Mount Vernon Hospital. The patients’ regular medication is assessed by the team and converted to soluble / liquid preparations when appropriate. Patients are instructed to shave using an electric razor if they shave during treatment. Aqueous cream is supplied and patients are instructed to apply regularly (at least twice a day) to the irradiated area. This should not be applied immediately prior to their radiotherapy treatment. Telodont mouthwash tablets are used to ensure oral hygiene during treatment and small soft toothbrushes are also available. Patients undergoing chemoradiation will have a weekly FBC and U&Es, creatinine Nutritional assessment Weekly weight measurement and assessment by the dietitiion if using PEG/RIG tube or diet compromised in any way. Analgesia assessment / Mucositis management Analgesia used according to a typical analgesic ladder. Initial – mild mucositis Aspirin mouthwash 300-600mg tds Paracetamol (soluble)1g qds Moderate mucositis Cocodamol (disp) 30/500 two qds Voltarol (disp) 50mg tds (if no history of peptic ulceration / indigestion) Severe mucositis Oramorph (10mg/5ml) 5 ml prn initially If required on a regular basis, stop cocodamol and start fentanyl 25mcg patches (changed every 3 days) with oramorph for breakthough pain. Voltarol can be continued. 134 A regular laxative such as 1-2 movicol sachets daily should be started when opiate analgesia commenced. Patients intolerant to opioids will be treated with oxycodone (5mg/5ml) 5 mg 4 hourly The palliative care team will be involved for difficult pain control issues. Management of excessive mucus production Saline nebulisers are available for patients to borrow to help with excessive mucus. Management of Skin Reaction Erythema and dry desquamation is managed with regular application of aqueous cream. Moist desquamation is best managed by application of paraffin gauze dressings up to 3 times a day. The head and neck radiotherapy nurse will supervise this and instruct patient / carers appropriately. Speech and Language therapy Assessment Patient with speech or swallowing difficulties will be assessed weekly when appropriate in the clinic. Follow up On completion of treatment patients will continue to be seen weekly / fortnightly in the ‘on treatment clinic’ until the radiotherapy reactions are settled. Patients will usually return to the joint head and neck clinic 6-8 weeks after completing treatment. Patients who have had treatment with primary (chemo)radiotherapy will be scanned at 6-8 weeks prior to returning for discussion at the MDM and the patient attending the joint clinic. Persistent mucositis may delay this assessment but should be performed by 16 weeks after the end of radiotherapy. Patients who have received radiotherapy post operatively may have a baseline assessment scan at this time especially if it is felt that the normal anatomy is significantly changed by the treatment. Further follow up schedule as Network Protocol. 135 6. MANAGEMENT OF RECURRENT DISEASE AND PALLIATIVE PATIENTS Management of recurrence. Patients who are suspected of having recurrence should be assessed clinically. Recurrence should be histologically proven where possible. Patients should be re-staged with an MRI of the head and neck, CT chest/upper abdomen. Other investigations eg bone scan or PET-CT may be required. Patients with recurrence should be discussed in the head and neck MDM where a management plan can be formulated. Treatment options will depend on previous treatment received, current symptoms, co-morbidities, performance status and patient choice. Patients should be referred to their local palliative care team with their consent. Close links should be maintained between the hospital based team and the community team. Management of Palliative Head and Neck Patients The decision to recommend palliative treatment will have been discussed in the MDM and thn communicated to the patient and their family or carer. This decision is based on the TMN stage, performance status, co-morbidities and social circumstances of the individual. The pros and cons of palliative chemotherapy and/ or radiotherapy in the management of the patient should be discussed with the patient and the family/carer. Written information leaflets will be provided as listed in section. Radiotherapy schedules (see PL-FLO-04, P1-4) Palliative treatment requires high doses, and short fractionation regimes are associated with marked acute toxicity. Regimens that can be considered on an individual basis include: 27Gy in 6# , 4.5 Gy/# treating twice a week for 3 weeks 37Gy in 13# ,2.85 Gy/#, treating daily (if spinal cord in field) 39Gy in 13#, 3Gy/# (if spinal cord NOT in field) Patients treated with palliative intent do not usually require a dental assessment. Palliative chemotherapy schedules Cisplatin 5FU 75mg/m2 IV day 1 or carboplatin (AUC4 or 5) 1g/m2 infused IV days 1 to 4 repeat (q=21d) Patients will be assessed for response after 2-3 cycles (clinically or with MRI/CT) and will receive 4-6 cycles if there is evidence of clinical response Patients should be considered for entry into appropriate clinical trials. 136 Patients who are treated with palliative intent, should, with their consent be referred to the Community Palliative Care Team and close liaison between the hospital based team and community team should be maintained at all times. Cetuximab may be combined with first line platinum and 5FU (4-6 cycles) through individual application to the Cancer Drugs Fund. Cetuximab is continued weekly until progression. The criteria for cetuximab need to be satisfied for approval: histological or cytoloigcall proven SCC of the Head and Neck, stage III/IV metastatic or recurrent disease, not previoulsly treated with chemotherapy except in multi-modality treatment completed > 6 months previously, and Karnofsky performance status of >70%. Once approved the Cancer Drugs Fund requires a record of treatment and outcome monitoring every 3 months or until progression. Second line chemotherapy schedules All patients who progress on first line chemotherapy and remain fit should be considered for the DORA study (contact Prof Chris Boshoff at UCLH) Taxotere 75 mg/m2 (q=21 days) iv Patients require a pre-medication with anti-histamines and steroids (see protocol, appendix ). Patients will be assessed for response after 2-3 cycles (clinically or with MRI/CT) and will receive 4-6 cycles if there is evidence of clinical response 137 7. HEAD AND NECK CANCER RESEARCH PROTOCOLS All patients discussed in the network MDM will be considered for inclusion in trial protocols. The following studies are open for patients with locally advanced disease 1. COSTAR – Phase III randomized study of post operative IMRT vs conventional radiotherapy in patients receiving surgery for parotid carcinoma NCRN adopted 2. ARIX- A phase III randomized study assessing whether acupuncture can alleviate xerostomia in patients who have received radical radiotherapy for head and neck cancer. NCRN adopted 3. EGF 105998 – Phase III study of lapatanib with chemoradioation in post op setting. A randomized, double blind, placebo controlled multi-centre phase III study of post-operative adjuvant lapatinib or placebo and concurrent chemoradiotherapy followed by maintenance lapitinib or placebo monotherapy in high risk subjects with rescted squamous cell carcinoma of the head and neck (EGF 105998) sponsored by GSK and NCRN adopted PET NECK trial A PET-CT guided watch and wait policy versus planned neck dissection for locally advanced (N2/N3) nodal metastases in stage III and IV patients with head and neck squamous cell carcinoma treated with radical chemoradiation sponsored by the NCRN. Has MVCC R&D approval. The following study closed in 2009 A Phase III randomized trial or chemotherapy with or without panitumumab in patients with metastatic and/or recurrent squamous cell carcinoma of the head and neck (AMG 954, panitumumab 20050251) sponsored by AMGEN and NCRN adopted The following study closed in 2008 EGF 105884 – Phase II Lapatanib study with primary chemoradiation A randomized, double blind, placebo-controlled,multicentre, phase II study of lapatinib in combination with concurrent radiotherapy and cisplatin versus radiotherapy and cisplatin alone, in subjects with stage III and IVA,B 138 squamous cell carcinoma of the head and neck (EGF 105884) sponsored by GSK and NCRN adopted A Phase 1b study of cetuximab and combretastatin (C4A-P) in combination with radical radiotherapy in patients with locally advanced head and neck cancer The following studies closed in 2007 Phase 1 pilot study of serial PET scans during RT This study evaluating serial FDG –PET-CT images acquired during conventionally fractionated radiotherapy or chemoradiotherapy for squamous cell carcinoma of the head and neck Target accrual 20 patients Accrual completed Palifermin Study A Phase III, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of weekly doses of palifermin (recombinant Human Keratinocyte Growth Factor, rHuKGF) for the reduction of oral mucositis in subjects with advanced head and neck cancer receiving adjuvant radiotherapy and chemotherapy (RT/CT) Target accrual 5 patients Actual accrual 3 patients 139 Appendix 1 References 1. Cooper J, Pajak TF, Forastiere A, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. New England Journal of Medicine 2004;350:1937–1944. 2. Bernier J, Domenge C, Ozsahin M, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. New England Journal of Medicine 2004;350:1945–1952. 3. Bonner J,Harari P, Giralt J, Azarnia N, Shin D, Cohen R, Jones C, Sur R, Raben D, Jassem J, Ove R, Kies M, Baselga J, Hagop Y, Amellal N, Rowinsky E and Ang K. Radiotherapy plus Cetuximab for Squamous-Cell Carcinoma of the Head and Neck. New England Journal of Medicine 2004; 354:567-578 4. First results of a phase III multicenter randomized controlled trial of intensity modulated (IMRT) versus conventional radiotherapy (RT) in head and neck cancer. Nutting et al. Proc ASCO JCO 2009;27(2):799s 140 APPENDIX 2-Compensation for Gaps in Radiotherapy Treatment 141 Are there enough days before the planned treatment end date to accelerate the remaining fractions by treating twice daily or using weekends? Yes Accelerate the remainder of the treatment using weekends or twice daily treatments, keeping dose per fraction, total dose and fraction number the same, completing treatment on the same end date. Must allow 6 hour gap between treatments Weekend treatments are preferable to BD treatments Increased fractional dose If there has been a single missed day in a 2 Gy per fraction treatment with no critical normal tissue in the field (eg skin cancer) Deliver a 3.22 Gy dose on the day after the gap and then proceed with the original dose and fractionation. This should not be performed more than 3 times in a treatment course. No A radiobiological calculation is required Should only be used if there is insufficient time to allow acceleration. Equivalent dose calculation This can only be used if a treatment gap is predicted before the start of the treatment course. Or for an early gap where acceleration is not possible 1) Calculate the BED for the proposed treatment (for both tumour and late-reacting normal tissue) using the formula: BED = nd[1 + d/(α/β)] 2) Then calculate the dose per fraction for the reduced number of fractions (E.g. For a standard 30# treatment, if 2 days are to be lost, re-calculate for 28 fractions, i.e. 30 x 2 Gy ~ 28 x 2.1 Gy) Increased Total Dose 1) Calculate the tumour and normal tissue BED using the formula: BED = nd [1+d(α/β)]-K(T-Tdelay) Where n = number of fractions, d = dose per fraction, T = overall treatment time, K = biological dose per day required to compensate for repopulation (~ 0.9 for tumour, = 0 for late-responding normal tissue) T delay = delay time (from beginning of treatment) before the onset of accelerated repopulation ≈ 28 days. 2) Determine overall time until start of the unscheduled gap and the respective BEDs prior to the gap 3) Determine a treatment option which will give the minimum extension of treatment time 4) Calculate dose per fraction to achieve this and now re-calculate tumour and normal tissue BEDs 5) May need to ‘fine-tune’ the compensation to maximise tumour BED whilst minimising normal tissue BED 142 Are there enough days before the planned treatment end date to accelerate the remaining fractions by treating twice daily or using weekends? Yes Accelerate the remainder of the treatment using weekends or twice daily treatments, keeping dose per fraction, total dose and fraction number the same, completing treatment on the same end date. Must allow 6 hour gap between treatments Weekend treatments are preferable to BD treatments Increased fractional dose If there has been a single missed day in a 2 Gy per fraction treatment with no critical normal tissue in the field (eg skin cancer) Deliver a 3.22 Gy dose on the day after the gap and then proceed with the original dose and fractionation. This should not be performed more than 3 times in a treatment course. No A radiobiological calculation is required Should only be used if there is insufficient time to allow acceleration. Equivalent dose calculation This can only be used if a treatment gap is predicted before the start of the treatment course. Or for an early gap where acceleration is not possible 1) Calculate the BED for the proposed treatment (for both tumour and late-reacting normal tissue) using the formula: BED = nd[1 + d/(α/β)] 2) Then calculate the dose per fraction for the reduced number of fractions (E.g. For a standard 30# treatment, if 2 days are to be lost, re-calculate for 28 fractions, i.e. 30 x 2 Gy ~ 28 x 2.1 Gy) Increased Total Dose 1) Calculate the tumour and normal tissue BED using the formula: BED = nd [1+d(α/β)]-K(T-Tdelay) Where n = number of fractions, d = dose per fraction, T = overall treatment time, K = biological dose per day required to compensate for repopulation (~ 0.9 for tumour, = 0 for late-responding normal tissue) T delay = delay time (from beginning of treatment) before the onset of accelerated repopulation ≈ 28 days. 2) Determine overall time until start of the unscheduled gap and the respective BEDs prior to the gap 3) Determine a treatment option which will give the minimum extension of treatment time 4) Calculate dose per fraction to achieve this and now re-calculate tumour and normal tissue BEDs 5) May need to ‘fine-tune’ the compensation to maximise tumour BED whilst minimising normal tissue BED 143 APPENDIX 3 – Anti-emetic protocol GUIDELINES FOR THE MANAGEMENT OF NAUSEA AND VOMITING IN ADULT PATIENTS RECEIVING CHEMOTHERAPY AND/OR RADIOTHERAPY SCOPE The following guidelines have been designed for use within Mount Vernon Cancer Network for adult oncology and haemato-oncology patients receiving chemotherapy and/or radiotherapy. AIM To ensure appropriate prescription and administration of antiemetics for patients receiving chemotherapy and/or radiotherapy. To reduce the risk of emesis and minimise the side effects and complications of antiemetic drugs. RISK FACTORS Certain risk factors exist which predict those patients likely to be more susceptible to the emetogenic effects of chemotherapy or radiotherapy: Female gender Young (<30 years old) History of nausea and vomiting (e.g. sickness in pregnancy, motion sickness) Poor control of emesis with prior chemotherapy or radiotherapy Anxiety There should be a low threshold for increasing the level of antiemetic cover for patients with more than two of any of these risk factors. CHEMOTHERAPY Section 1: Notes on Use of Guidelines 1.1 Choice of antiemetics Consult section 2 for the antiemetic category of the relevant individual cytotoxic drugs or specific oncology/haemato-oncology chemotherapy regimen being prescribed. The categories represent minimal (category A), low (category B), moderate (category C) or high (category D) levels of emetogenicity. Choose and prescribe the appropriate pre and post chemotherapy antiemetic regimen from the relevant category listed in section 3. For combination chemotherapy regimens not specifically listed in section 2, choose the appropriate antiemetic regimen for the most emetogenic drug in the regimen. For multiple day chemotherapy regimens, prescribe the appropriate pre chemotherapy antiemetics for each day of the highest emetogenic drug and prescribe post chemotherapy antiemetics from the day after the final dose of the highest emetogenic drug. Many chemotherapy regimens for haemato-oncology patients incorporate corticosteroid treatment (commonly with prednisolone or dexamethasone). These patients should NOT receive dexamethasone as part of their antiemetic regimen even if the chemotherapy regimen falls into Category B, C or D in section 2. Generally no patient with acute leukaemia should receive dexamethasone as an antiemetic even if the drug/regimen falls into category B, C or D (although some of these regimen may include a corticosteroid as part of the anti-cancer treatment). Note: A chemotherapy regimen named in section 2 does not imply approval to prescribe, if that regimen contains a non-NICE approved high cost drug. 582727853 October 2008 144 1.2 Antiemetic failure If prolonged/distressing nausea occurs or 2 or more episodes of vomiting in 24 hours occurs after a course of chemotherapy, move onto suggested antiemetic regimens for the next category level of emetogenicity. Ensure patient has taken post chemotherapy antiemetic drugs regularly as prescribed. 1.3 Anticipatory nausea and vomiting Prescribe lorazepam 1-2mg orally/sublingually at least 1 hour prior to chemotherapy, in addition to standard antiemetics. If severe, consider 1mg night before chemotherapy and 1mg on the morning of chemotherapy. 582727853 October 2008 145 Section 2: Categorisation of Individual Chemotherapy Drugs and Specific Chemotherapy Regimens Notes: (a) This list is in alphabetical order based on the name of the drug or regimen. (b) Check comments column for any special instructions related to the antiemetic or chemotherapy regimen. (c) In the “tumour site” column, “various” denotes that the drug or regimen is used in more than two tumour sites. Drug / Regimen ABCM Tumour Site Antiemetic Category (refer to section 3) Haemato-onc Comments or special instructions AB week only C ABCM ABVD AC ACE ADE (AML 15) Haemato-onc Haemato-onc Breast Germ cell Haemato-onc A D C D C Alemtuzumab Amsacrine Asparaginase BCG intravesical BEP Bevacizumab Bleomycin Haemato-onc Haemato-onc Haemato-onc Urology Germ cell Lower GI Various A A A A D A A Bortezomib Capecitabine Carboplatin Haemato-onc Lower GI Germ cell / gynaecology Lung Head & neck Haemato-onc / CNS Lung Haemato-onc Lower GI Haemato-onc Haemato-onc Haemato-onc B A C Carboplatin / Etoposide Carboplatin / 5-FU Carmustine CAV CDT Cetuximab Chlorambucil ChlVPP CHOP C A B A A C Various Gynaecology Gynaecology D D D Various Haemato-onc Haemato-onc D A B CMF C-VAMP Breast Haemato-onc B C CVP Haemato-onc C Various Various A C Drug / Regimen 582727853 Tumour Site October 2008 No dexamethasone as antiemetic Dexamethasone 8mg PO premedication to prevent reactions C C C Cisplatin Cisplatin / Doxorubicin Cisplatin weekly/oral etoposide (Van Der Burg regimen) Cisplatin / 5-FU Cladribine CMD Cyclophosphamide Cyclophosphamide CM week only Antiemetic No Dexamethasone as antiemetic. All regimens 2-CDA No Dexamethasone as antiemetic. No Dexamethasone as antiemetic. No Dexamethasone as antiemetic. Oral only IV doses <1500mg/m2 Comments or special 146 Category (refer to section 3) Cyclophosphamide Cytarabine Haemato-onc Haemato-onc D B Cytarabine Haemato-onc C C-Z-DEX Haemato-onc C DA (AML 15/16) Haemato-onc C Dacarbazine Daunorubicin / Clofarabine (AML 16) Daunorubicin De Gramont (standard/modified) Deoxycoformycin Docetaxel Melanoma Haemato-onc D C Haemato-onc Lower GI C A Haemato-onc Breast A B Urology (prostate) B Docetaxel / Capecitabine Breast B Docetaxel / Carboplatin Lung / gynaecology C Lung D Various Breast Upper GI Upper GI C C D D Docetaxel Docetaxel / Cisplatin Doxorubicin EC ECF ECX 582727853 October 2008 instructions IV doses >1500mg/m2 IV doses <1000mg/m2 (No dexamethasone as antiemetic if AML) IV doses >1000mg/m2 (No dexamethasone as antiemetic if AML) No Dexamethasone as antiemetic. No dexamethasone as antiemetic No dexamethasone as antiemetic Pentostatin Dexamethasone 8mg PO BD for 3 days starting day before docetaxel + post chemo metoclopramide as per section 3. Given the concurrent use of prednisolone, the recommended premedication regimen is oral dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before the docetaxel + metoclopramide as per section 3 Dexamethasone 8mg PO BD for 3 days starting day before docetaxel + metoclopramide as per section 3 Dexamethasone 8mg PO BD for 3 days starting day before docetaxel + ondansetron / metoclopramide as per section 3 Dexamethasone 8mg PO BD for 3 days starting day before docetaxel + ondansetron / metoclopramide as per section 3 147 EP Epi-CMF Epi-CMF Epirubicin Erlotinib ESHAP Germ cell / lung Breast Breast Breast Lung Haemato-onc D C B C A D Etoposide Etoposide Various Various A B Drug / Regimen Etoposide Tumour Site Antiemetic Category (refer to section 3) Germ cell C EV FAD Lung Haemato-onc B C FC (Fludarabine / Cyclophosphamide) FEC FLAG-Ida (AML 15) Haemato-onc C Breast Haemato-onc C C Fludarabine 5-Fluorouracil Haemato-onc Various A A FMD Haemato-onc B GCP Germ cell C Gefitinib Gemcitabine Gemcitabine / Carboplatin Gemcitabine / Cisplatin Gem-TIP Lung Various Lung Lung / Urology Germ cell A A C D D Gemtuzumab Ozogamicin Hydroxycarbamide Hyper-CVAD + Rituxumab Haemato-onc Haemato-onc Haemato-onc A A C Idarubicin Haemato-onc C Ifosfamide Ifosfamide / Doxorubicin Imatinib Various Sarcoma GIST / Haemato-onc Renal Lower GI Lower GI C C A Upper GI Haemato-onc Gynaecology CNS Haemato-onc C C B A B Interferon alfa Irinotecan Irinotecan / De Gramont (FOLFIRI) Irinotecan / Mitomycin C IVE Liposomal Doxorubicin Lomustine MACE (AML 15) 582727853 October 2008 Epirubicin only CMF only No Dexamethasone as antiemetic. Oral only IV only (except high dose etoposide for germ cell) Comments or special instructions High dose 1.6gm/m2 etoposide for germ cell No Dexamethasone as antiemetic. All epirubicin doses No dexamethasone as antiemetic Oral and IV Includes continuous infusional 5-FU and 5-FU + RT regimens. No Dexamethasone as antiemetic. Dexamethasone 20mg IV pre 3 weekly paclitaxel (instead of 8mg) plus other antiemetics as per section 3. Dexamethasone 20mg IV pre 3 weekly paclitaxel (instead of 8mg) plus other antiemetics as per section 3. Hydroxyurea No Dexamethasone as antiemetic. No dexamethasone as antiemetic if AML A C C No dexamethasone as antiemetic 148 Melphalan Haemato-onc A Mercaptopurine Haemato-onc A Various A Methotrexate Drug / Regimen Tumour Site Antiemetic Category (refer to section 3) Methotrexate Haemato-onc C MidAC (AML 15) Haemato-onc C MiniBEAM MiniBEAM Mitomycin C Mitomycin C / Capecitabine Mitomycin C / 5-FU Haemato-onc Haemato-onc Urology Lower GI Lower GI C B A B B Mitoxantrone MM MMM MVC MVP OMB Oral C-weekly Oxaliplatin Oxaliplatin / Capecitabine (XELOX) Oxaliplatin / De Gramont (FOLFOX) Paclitaxel Various Breast Breast Urology Mesothelioma Germ cell Haemato-onc Lower GI Lower GI B B B D D C A C C Lower GI C Various B Paclitaxel / Carboplatin Gynaecology / lung C PCV Pemetrexed CNS Lung / mesothelioma A B PMB PMitCEBO Gynaecology Haemato-onc D C PMitCEBO POMB Procarbazine Raltitrexed R-CHOP Haemato-onc Germ cell Haemato-onc Lower GI Haemato-onc A D A B C 582727853 October 2008 Including PO melphalan + prednisolone; IV melphalan + dexamethasone. No dexamethasone as antiemetic if ALL Oral and IV doses <300mg/m2 only. Comments or special instructions IV doses > 300mg/m2 (No dexamethasone as antiemetic if ALL) No dexamethasone as antiemetic Day 1 & 6 only Day 2 – 5 only Intravesical only For Mitomycin C weeks only All regimens. For Mitomycin C weeks only Dexamethasone 20mg IV pre three weekly paclitaxel or 8mg IV pre weekly paclitaxel plus other antiemetics as per section 3. Dexamethasone 20mg IV pre three weekly paclitaxel or 8mg IV pre weekly paclitaxel plus other antiemetics as per section 3. Dexamethasone 4mg PO BD for 3 days starting day before pemetrexed + other antiemetics as per section 3. MitCE week only. No Dexamethasone as antiemetic. BO week only. No Dexamethasone as antiemetic. 149 R-CVP Haemato-onc C R-ESHAP Haemato-onc D R-FC Rituximab R-IVE R-MiniBEAM R-MiniBEAM Haemato-onc Haemato-onc Haemato-onc Haemato-onc Haemato-onc C A C C B Drug / Regimen Tumour Site Antiemetic Category (refer to section 3) R-PMitCEBO Haemato-onc C R-PMitCEBO Sorafenib Stanford V Haemato-onc Renal Haemato-onc A A C Stanford V Haemato-onc A Sunitinib Temozolamide Thalidomide Tioguanine TIP Renal CNS Haemato-onc Haemato-onc Germ cell A A A A D Topotecan Trastuzumab Trastuzumab / Docetaxel Gynaecology Breast Breast B A B Trastuzumab / Paclitaxel Breast B Trastuzumab / Vinorelbine UK ALL XI Induction Phase 1 UK ALL XI Induction Phase 2 Day 1, 15, 29 UK ALL XI Induction Phase 2 Day 8, 22 UK ALL XI Intensification – high dose MTX UK ALL XI Consolidation Cycle 1, 2, 4 UK ALL XI Consolidation Cycle 3 Day 1, 8, 15, 22, 29 VAD Breast Haemato-onc A C Haemato-onc C Haemato-onc B Haemato-onc C Haemato-onc B Haemato-onc C Haemato-onc C VAMP Haemato-onc C VAPEC-B Haemato-onc C VAPEC-B Vinblastine Haemato-onc Various A A 582727853 October 2008 No Dexamethasone as antiemetic. No Dexamethasone as antiemetic. Day 1 & 6 only Day 2 – 5 only Comments or special instructions MitCE week only. No Dexamethasone as antiemetic. BO week only. Week 1, 3, 5, 7, 9, 11 only. No Dexamethasone as antiemetic. Week 2, 4, 6, 8, 10, 12 only. Thioguanine Dexamethasone 20mg IV pre 3 weekly paclitaxel (instead of 8mg) plus other antiemetics as per section 3. Dexamethasone 8mg PO BD for 3 days starting day before docetaxel + metoclopramide as per section 3. Dexamethasone 20mg IV pre 3 weekly paclitaxel (instead of 8mg) plus other antiemetics as per section 3. No dexamethasone as antiemetic No dexamethasone as antiemetic No dexamethasone as antiemetic No dexamethasone as antiemetic No dexamethasone as antiemetic No dexamethasone as antiemetic No dexamethasone as antiemetic No dexamethasone as antiemetic Week 1 & 3 only. No Dexamethasone as antiemetic. Week 2 & 4 only 150 Vincristine Vinorelbine Vinorelbine / Carboplatin Vinorelbine / Cisplatin VIP Z-DEX Various Breast / lung Lung Lung Germ cell Haemato-onc A A C D D C No dexamethasone as antiemetic Section 3: Antiemetic Regimen Categories (grouped according to emetogenic potential) Category A: MINIMAL EMETOGENIC POTENTIAL PRE CHEMOTHERAPY POST CHEMOTHERAPY No routine antiemetic indicated DOMPERIDONE 20mg PO TDS prn Category B: LOW EMETOGENIC POTENTIAL PRE CHEMOTHERAPY POST CHEMOTHERAPY DEXAMETHASONE 8mg PO (IV only if nausea / vomiting / dysphagia) and DOMPERIDONE 20mg PO (Metoclopramide 20mg IV only if nausea / vomiting / dysphagia) DEXAMETHASONE 4mg PO BD regularly x 3 days and DOMPERIDONE 20mg PO TDS x 3 days, then prn ANTIEMETIC FAILURE (see definition – section 1) Recommend Domperidone postchemotherapy to be taken regularly. Commence on first line antiemetics for breakthrough nausea and vomiting (Section 4). Treat on subsequent courses of chemotherapy as for low emetogenic (Category B). ANTIEMETIC FAILURE (see definition – section 1) Ensure took antiemetics regularly post chemotherapy (as prescribed). Commence on first line antiemetics for breakthrough nausea and vomiting (Section 4) or subsequent line if had before with no benefit. Treat on subsequent courses of chemotherapy as for moderate emetogenic (Category C). Category C: MODERATE EMETOGENIC CHEMOTHERAPY PRE CHEMOTHERAPY POST CHEMOTHERAPY ONDANSETRON 8mg PO (8mg IV if nausea/vomiting/dysphagia) DEXAMETHASONE 4mg PO BD regularly x 3 days and and DEXAMETHASONE 8mg PO (IV only if nausea / vomiting / dysphagia) DOMPERIDONE 20mg PO TDS x 3 days, then prn ANTIEMETIC FAILURE (see definition – section 1) Ensure took antiemetics regularly post chemotherapy (as prescribed). Commence on first line antiemetics for breakthrough nausea and vomiting (Section 4) or subsequent line if had before with no benefit. Treat on subsequent courses of chemotherapy as for high emetogenic (Category D). Category D: HIGH EMETOGENIC CHEMOTHERAPY PRE CHEMOTHERAPY 582727853 POST CHEMOTHERAPY October 2008 ANTIEMETIC FAILURE (see definition – section 1) 151 ONDANSETRON 8mg PO (8mg IV if nausea/vomiting/dysphagia) and DEXAMETHASONE 8mg PO (IV only if nausea / vomiting / dysphagia) ONDANSETRON 8mg PO BD x 1 day and DEXAMETHASONE 4mg PO BD x 3 days and DOMPERIDONE 20mg PO TDS x 3 days, then prn Cisplatin >70mg / m2 Cisplatin >70mg / m2 As above but also: As above but also: APREPITANT 125mg PO (Fosaprepitant 115mg IV only if nausea / vomiting / dysphagia) APREPITANT 80mg PO OD on days 2&3 post chemo Ensure took antiemetics regularly post chemotherapy (as prescribed) and used suppositories if vomiting. Commence on first line antiemetics for breakthrough nausea and vomiting (Section 4) or subsequent line if had before with no benefit. Consider treating on subsequent courses with: Ondansetron 8mg PO BD for up to 5 days maximum and/or Regular antiemetic from Section 4 in addition to the post chemotherapy antiemetic regimen. Consider aprepitant for patients with grade 3 / 4 N&V if they are not already receiving it Note: TTA’s – For category D drugs/regimens, prescribe DOMPERIDONE suppositories 30mg PR QDS prn if vomiting) Section 4: Breakthrough nausea and vomiting DRUG AND SCHEDULE 1st Line Cyclizine 50mg PO TDS 2nd Line COMMENTS Prescribe regularly in addition to recommended post chemotherapy antiemetics Prochlorperazine – replaces Metoclopramide as post chemotherapy antiemetic Metoclopramide – replaces Domperidone as post chemotherapy antiemetic Prescribe regularly in addition to recommended post chemotherapy antiemetics. Consider adding first line if anxiety component/anticipatory nausea Prochlorperazine 5-10mg PO TDS or 25mg PR TDS or Metoclopramide 10-20mg PO QDS or 30mg PR QDS 3rd Line Lorazepam 1mg PO/SL upto TDS (2mg in patients > 100kg) 4th Line Methotrimeprazine 12.5mg PO nocte – BD 582727853 October 2008 Methotrimeprazine – replaces Metoclopramide as post chemotherapy antiemetic 152 or Consider instituting S/C infusion of Cyclizine 1st or 2nd line if severe vomiting occurs in inpatients. Only in patients who have failed the category D antiemetic regimen and have CTC grade 3 / 4 Nausea and Vomiting. Cyclizine 100-150mg continuous subcutaneous infusion over 24 hours or Nabilone 1mg PO TDS 5th Line Aprepitant 125mg PO prior to chemotherapy, followed by 80mg od for 2 days after chemotherapy Radiotherapy guidelines for PATIENTS AT mount vernon cancer centre Notes on Use of Guidelines Major determinants of emetic risk include treatment field, dose of radiotherapy administered per fraction, pattern of fractionation and previous chemotherapy. RISK Low Moderate AREA RECEIVING RT ANTIEMETIC REGIMEN Breast Head and Neck Extremities Pelvis Thorax No routine antiemetics – treat symptomatically with Upper abdominal Abdominal – pelvic Mantle Cranium Craniospinal Before each fraction: Dexamethasone 4-8mg PO and either: Metoclopramide 20mg PO or Ondansetron 4-8mg PO (or 4-8mg IV) Metoclopramide 10mg PO QDS prn (and Metoclopramide 10mg PO QDS prn after radiotherapy) High 582727853 Hemibody Irradiation TBI October 2008 Before each fraction Dexamethasone 8mg PO/IV and 153 Ondansetron 8mg PO (or 8mg IV) (and 8mg PO BD for one day after) Antiemetic failure: If patients suffer breakthrough nausea and vomiting while receiving the above recommended antiemetics, additional therapy should be commenced in accordance with the guidelines for breakthrough nausea and vomiting for adult chemotherapy patients in Section 4. Chemoradiation: Treat according to the highest emetogenic risk based on radiotherapy treatment field or cytotoxic drug(s)/regime. 582727853 October 2008 154 APPENDIX 4 - Neutropenic sepsis protocol GUIDELINES FOR THE USE OF GRANULOCYTECOLONY STIMULATING FACTOR (G-CSF) IN ADULT ONCOLOGY AND HAEMATOLOGY PATIENTS Signature Produced by: Michael Powell, Network Lead Pharmacist Ratified by: MVCN Chemotherapy Steering Group Kay Bell, Chair Date: Date for review: 582727853 July 2007 July 2009 October 2008 155 Mount Vernon Cancer Network GUIDELINES FOR THE USE OF GRANULOCYTE-COLONY STIMULATING FACTOR (GCSF) IN ADULT ONCOLOGY AND HAEMATOLOGY PATIENTS Section 1: Background Chemotherapy-induced febrile neutropenia is a serious side effect of cancer treatment and is not only a major risk factor for infection-related morbidity and mortality, but is also a significant dose-limiting toxicity. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or delays to their chemotherapy schedule. This may impact on the success of treatment, particularly when treatment intent is either curative or to prolong survival (1). One method of reducing the incidence of severe or FN is through the prophylactic use of G-CSF – those commercially available at the current time are filgrastim, lenograstim and pegfilgrastim. G-CSF may also be used to increase neutrophils in those patients experiencing severe prolonged neutropenic episodes after chemotherapy treatment or in those patients requiring mobilisation of peripheral blood stem cells for harvesting. The aim of this guideline is to provide evidence-based guidance to clinicians and other health professionals on the rational prescribing and safe administration of G-CSF and to promote harmonisation of prescribing practice across Mount Vernon Cancer Network. (Please note: these guidelines do not apply to acute leukaemia patients – follow guidelines stated within the relevant trial protocol). Section 2: Indications G-CSF may be prescribed for the following indications, according to the criteria for G-CSF prescribing outlined in section 4: a. Chemotherapy support for regimens with curative/radical intent (primary/secondary prophylaxis). b. Supportive therapy for severe neutropenic sepsis. c. Peripheral blood stem cell mobilisation. d. Clinical trials where appropriate and stated within the trial protocol. Note: Patients receiving palliative chemotherapy should not generally receive prophylactic GCSF for chemotherapy support – manipulations to minimise neutropenic episodes and sepsis must initially include dose delay and/or dose reduction (refer to individual chemotherapy protocols for guidance) as there is no evidence that dose maintenance or escalation improves clinically important outcomes. The use of G-CSF in this setting must be approved on an individual patient basis by the appropriate directorate manager or lead clinician. Section 3: Approval to Prescribe For all indications except in peripheral blood stem cell mobilisation: A consultant oncologist/haematologist or specialist registrar must initiate G-CSF treatment for these indications (except in exceptional cases within the network where patients are admitted under a general physician for management of neutropenic complications, in which case a general medical physician may prescribe but must do so according to these guidelines). Senior house officers, pre-registration house officers or staff grade doctors may only initiate treatment for these indications under instruction from a consultant oncologist/haematologist or specialist registrar and this instruction must be documented in the patient’s medical notes. 582727853 October 2008 156 Peripheral blood stem cell mobilisation: Any member of the oncology or haematology medical team may prescribe G-CSF according to the appropriate protocol for the particular patient. Section 4: Criteria for G-CSF Prescribing (1)(2)(3) The following criteria must be adhered to prior to prescribing G-CSF: Criteria 1a: Chemotherapy support for regimens with curative/radical intent: Primary Prophylaxis (first and subsequent cycle use) Recommendation: Chemotherapy patients should not routinely be prescribed prophylactic G-CSF after their first cycle of chemotherapy. Primary prophylaxis may only be considered for patients with a high overall risk (> 20%) of febrile neutropenia as defined below: Patients receiving myelotoxic chemotherapy with curative or radical intent (including adjuvant/neoadjuvant chemotherapy) and which has a documented incidence rate of FN of > 20% (refer to Appendix 1 for list of relevant network chemotherapy regimens) Or Patients receiving myelotoxic chemotherapy with curative/radical intent (including adjuvant/neoadjuvant chemotherapy) and which has a documented incidence rate of FN of 10 – 20% (refer to Appendix 2 for list of relevant network chemotherapy regimens) And any one or more of the following pre-disposing patient risk factors: Pre-existing neutropenia due to disease infiltration of bone marrow or other aetiology Age > 65 years Advanced disease stage Poor performance status Previous episodes of febrile neutropenia whilst receiving earlier chemotherapy of a similar or less dose intensity Extensive prior chemotherapy Previous irradiation to large volume of bone marrow Poor nutritional status Active infections or increased risk of infections (e.g. presence of open wounds) Serious co-morbidities Refer to section 5 for GCSF dosage and administration guidelines in the prophylactic setting. Criteria 1b: Chemotherapy support for regimens with curative/radical intent: Secondary Prophylaxis (prophylactic use for subsequent cycles after initial episode(s) of severe and/or febrile neutropenia) Recommendation: Secondary prophylaxis should only be considered in patients: Receiving myelotoxic chemotherapy with curative or radical intent And in any one of the following circumstances: Where two or more dose reductions have occurred due to neutropenia or febrile neutropenia after a chemotherapy cycle Where chemotherapy treatment is delayed on two or more occasions due to neutropenia or febrile neutropenia Note: Dose modifications will be a reasonable alternative in many clinical situations. Secondary prophylaxis may only be considered after one delay in chemotherapy treatment or one dose reduction due to an episode of neutropenia or febrile neutropenia for the following patient groups: 582727853 October 2008 157 Lymphoma patients (non-hodgkins lymphoma or hodgkins disease) Germ cell tumours (non-seminomatous germ cell tumours, seminomas or other germ cell derived tumour) Patients receiving the sequential FEC100-Docetaxel regimen for adjuvant treatment of early breast cancer Radical chemoradiation (where delay or omission of chemotherapy treatment during concurrent therapy may have a negative impact on disease control) Refer to section 5 for GCSF dosage and administration guidelines in the prophylactic setting. Criteria 2: Supportive therapy for severe neutropenic sepsis Recommendation: G-CSF must not be routinely prescribed for the treatment of patients with uncomplicated febrile neutropenia or afebrile neutropenia. G-CSF may only be prescribed for the supportive treatment of patients with severe febrile neutropenia in scenarios as defined below: Profound febrile neutropenia: defined as absolute neutrophil count (ANC) < 0.1 x 109/L and patient febrile And any one of the following prognostic factors that are predictive of poor clinical outcome: Clinically unwell with signs such as hypotension, organ dysfunction etc indicating potential risk of septic shock Expected prolonged duration of neutropenia (> 10 days) Persistent pyrexia despite appropriate antibiotics/antifungals Uncontrolled primary disease Pneumonia Proven or suspected invasive fungal infection Patients who have already received pegfilgrastim as primary or secondary prophylaxis should not receive further daily G-CSF as supportive therapy for severe neutropenic sepsis unless more than 14 days since pegfilgrastim administration. Refer to section 5 for GCSF dosage and administration guidelines in the neutropenic sepsis setting. Criteria 3: Peripheral blood stem cell mobilisation Recommendation: G-CSF should be prescribed to all patients undergoing harvesting of peripheral blood stem cells in conjunction with priming cytotoxic chemotherapy. Refer to section 5 for GCSF dosage and administration guidelines in the stem cell harvesting setting. Criteria 4: Clinical trials where appropriate and stated within the trial protocol Recommendation: G-CSF may be prescribed to patients receiving chemotherapy with radical or curative intent who are being treated within a clinical trial and where G-CSF is recommended or allocated as part of the trial protocol. Refer to section 5 for GCSF dosage and administration guidelines in the clinical trial setting. Section 5: Choice of G-CSF and Dosage and Administration Guidelines The following G-CSF products may be used in the relevant criteria settings: Criteria 1a/1b: Chemotherapy support for regimens with curative/radical intent Table 1: G-CSF Dosage and Administration Guidelines for patients fulfilling criteria 1a/1b Days to prescribe (see note 1) 582727853 October 2008 158 Drug Patient weight Dosage Route Frequency Pegfilgrastim (see note 2 below) Filgrastim All 6mg S/C Once only < 85 kg 300mcg S/C daily Filgrastim > 85 kg 480mcg S/C daily Lenograstim All 263mcg S/C daily Weekly chemo cycle 2 weekly chemo cycle 3 weekly chemo cycle 4 weekly chemo cycle At least 24 hours after completion of chemotherapy Day 3 - 7 Day 5 – 11 Day 3 - 7 Day 5 – 11 Day 3 - 7 Day 5 – 11 Day 5 – 11 Day 5 – 11 Day 5 – 11 Day 5 – 11 Day 5 – 11 Day 5 – 11 Note 1: The optimal timing and duration of G-CSF administration in the prophylactic setting has not been defined however the recommendations above should be considered as a guide. Note 2: Pegfilgrastim may only be used in those hospitals in the network that are receiving a discount from the pharmaceutical company, otherwise conventional G-CSF should be prescribed. Note 3: G-CSF should not normally be prescribed for prophylactic use after the final chemotherapy cycle unless the patient is at high risk of severe febrile neutropenia and hospital admission. Criteria 2: Supportive therapy for severe neutropenic sepsis Table 2: G-CSF Dosage and Administration Guidelines for patients fulfilling criteria 2 Drug Dosage Route Frequency Filgrastim Patient Weight or BSA < 85 kg 300mcg S/C daily Filgrastim > 85 kg 480mcg S/C daily Lenograstim < 2m2 263mcg S/C daily Lenograstim > 2m2 526mcg S/C daily Criteria for stopping treatment Stop G-CSF once ANC > 0.5 x 109/L for at least two consecutive days Note: Pegfilgrastim is not approved for use in this setting. Criteria 3: Peripheral blood stem cell mobilisation (4) Commence G-CSF at day + 1 after priming chemotherapy and generally continue until stem cell harvesting complete. GCSF - 5mcg/kg/day (plus priming chemotherapy) Patient weight < 85kg >85kg 582727853 Drug/dose/route Lenograstim 263mcg S/C daily Lenograstim 526mcg S/C daily October 2008 159 <48kg 48-60kg 61-96kg >96kg Filgrastim 5mcg/kg S/C daily Filgrastim 300mcg S/C daily Filgrastim 480mcg S/C daily Filgrastim 780mcg S/C daily GCSF alone or with chemotherapy Filgrastim 10mcg/kg/day for 5-7 days Weight <30 30-39 40-49 50-60 61-78 79-90 >90 Dose/route 300mcg S/C 300mcg S/C 480mcg S/C 600mcg S/C 780mcg S/C 900mcg S/C 960mcg S/C Vials used 1 x 300 mcg 1 x 300 mcg 1 x 480 mcg 2 x 300 mcg 1 x 300 mcg + 1 x 480 mcg 3 x 300 mcg 2 x 480 mcg Lenograstim 10mcg/kg/day for 5-7 days Weight <30 30-39 40-54 55-64 65-79 80-84 >85 Dose/route 263 mcg S/C 368 mcg S/C 526 mcg S/C 631 mcg S/C 789 mcg S/C 894 mcg S/C 1052 mcg S/C Vials used 1 x 263 mcg 1 x 263 mcg + 1 x 105 mcg 2 x 263 mcg 2 x 263 mcg + 1 x 105 mcg 3 x 263 mcg 3 x 263 mcg + 1 x 105 mcg 4 x 263 mcg Note: Pegfilgrastim is not approved for use in this setting. Criteria 4: Clinical trials where appropriate and stated within the trial protocol The G-CSF brand, dosage and administration schedule used within a clinical trial should be that recommended within the trial protocol. Section 6: G-CSF Side Effects and Management For those patients who suffer from musculo-skeletal side effects due to G-CSF administration (e.g bone pain/aches, other musculo-skeletal pains): Treat with simple analgesics (e.g. paracetamol) If severe or intolerable, consider reducing frequency of administration of non-pegylated G-CSF products to alternate days. If patient receiving pegfilgrastim, consider changing to alternate daily non-pegylated G-CSF. For full information about each G-CSF product including other side effects, refer to the individual G-CSF Summaries of Product Characteristics. References: (1) Aapro et al. Position paper: EORTC Guidelines for the Use of Granulocyte-Colony Stimulating Factor to reduce the Incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphomas and solid tumours. Eur J Cancer 42 (2006): 2433 – 2453. 582727853 October 2008 160 (2) Smith et al. 2006 Update of Recommendations for the Use of White Blood Cell Growth Factors: An Evidence-Based Clinical Practice Guideline. J Clin Oncol July 1 2006; 24 (19): 3187 – 3205. (3) National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (2007). Myeloid Growth Factors. (4) North London Cancer Network (2004): D Blake and N.Saini. Guidelines for the use of Haematopoietic Colony-Stimulating Factors in Adult Oncology and Haematology Patients. 582727853 October 2008 161 APPENDIX 5- Cetuximab protocol MOUNT VERNON CANCER CENTRE PROTOCOL GUIDELINES NAME OF PROTOCOL Single Agent Cetuximab + Radiotherapy INDICATION Locally advanced squamous cell cancer of the head and neck (patients with Karnofsky PS > 90% and where platinum based chemo/radiotherapy is contraindicated)(1) DOSAGE(2) Cetuximab 400mg/m2 (loading dose) IV infusion over 2 hours Week 1 then 250mg/m2 IV infusion over 1 hour every week thereafter for total of 7-8 weeks (i.e. until last week of radiotherapy). Start cetuximab one week prior to radiotherapy treatment. FREQUENCY OF REGIMEN(2) Weekly DURATION OF REGIMEN 7 – 8 weeks total (depending on duration of radiotherapy) SUPPORTIVE TREATMENTS Pre-medication: Antihistamine should be administered prior to each weekly dose of cetuximab – Chlorphenamine 10mg IV bolus. ANTIEMETICS Refer to Cancer Network Antiemetic Guidelines(3). No routine antiemetics should be necessary. PRE-TREATMENT INVESTIGATIONS FBC, U&E’s including creatinine, serum magnesium and LFT’s must be performed prior to commencement of treatment and at 4 and 8 weeks during therapy. Normal hepatic, renal and haematological function should be confirmed prior to treatment commencement in week 1. The results of these investigations are not required prior to drug administration in week 4 and 8. DOSE MODIFICATIONS 1. Haematological toxicity Not applicable 2. Hepatic impairment(2) Cetuximab has not been investigated in patients with hepatic impairment. Only patients with adequate hepatic function have been investigated to date (transaminases < 5 times and bilirubin < 1.5 times the upper limit of normal). 582727853 October 2008 162 3. Renal impairment(2) Cetuximab has not been investigated in patients with renal impairment. Only patients with adequate renal function have been investigated to date (serum creatinine < 1.5 times the upper limit of normal). POTENTIAL TOXICITIES AND MANAGEMENT 1. Pulmonary toxicity(2) Dyspnoea has been reported in up to 25% of patients. In elderly patients and in patients with reduced performance status or pre-existing cardiac or pulmonary disorders, an increased incidence of dyspnoea, sometimes severe, was observed. It may occur in close temporal relationship to the cetuximab infusion as part of an infusion-related reaction, but has also been reported after several weeks of therapy, possibly related to an underlying disorder. If patients develop dyspnoea during the course of cetuximab treatment, it is recommended to investigate them for signs of progressive pulmonary disorders as appropriate. Individual cases of interstitial lung disorders of unknown causal relationship to cetuximab have been reported. If interstitial lung disease is diagnosed, cetuximab must be discontinued and the patient be treated appropriately. 2. Cardiotoxicity(2) No significant incidence of cardiotoxicity has been reported. However, a rare manifestation of the cetuximab-induced infusion related reaction (see section 5) may include angina pectoris, myocardial infarction or cardiac arrest. 3. Gastro-intestinal toxicity(2) (a) Nausea and Vomiting The incidence of nausea and vomiting is low with cetuximab and radiotherapy. Patients should be managed with standard antiemetics as required. (b) Mucositis In combination with local radiotherapy, additional undesirable effects observed were those typical of radiation therapy to the head and neck area including mucositis and dysphagia. Symptomatic management should include the use of appropriate topical mouthwashes and analgesics as required. (c) Diarrhoea Not applicable 4. Neurologic toxicity Not applicable 5. Hypersensitivity reactions(2) Mild or moderate infusion-related reactions comprising symptoms such as fever, chills, nausea, vomiting, headache, dizziness, or dyspnoea often occur in a close temporal relationship mainly to the first cetuximab infusion. Severe infusion-related reactions may occur, in rare cases with fatal outcome. They usually develop during or within 1 hour of the initial cetuximab infusion (but may occur after several hours or with subsequent infusions) and may include symptoms such as rapid onset of airway obstruction (bronchospasm, stridor, hoarseness, difficulty in speaking), urticaria, hypotension, or loss of consciousness; in rare cases, angina pectoris, myocardial infarction or cardiac arrest have been observed. It is recommended to warn patients of the possibility of such a late onset of symptoms and to instruct them to contact the hospital if symptoms of an infusion-related reaction occur. Although the underlying mechanism has not been identified, some of these reactions may be anaphylactoid / anaphylactic in nature. If the patient experiences a mild or moderate infusion-related reaction, the infusion rate may be decreased. It is recommended to maintain this lower infusion rate in all subsequent infusions. 582727853 October 2008 163 Occurrence of a severe infusion-related reaction requires immediate and permanent discontinuation of cetuximab therapy and may necessitate emergency treatment. 6. Other toxicities(2) Dermatological toxicity - In the Bonner study(4), the incidence of severe acute radiation dermatitis was slightly higher in patients receiving radiation therapy in combination with cetuximab than in those receiving radiation therapy alone. Cetuximab-induced skin reactions may develop in more than 80% of patients and mainly present as acne-like rash and/or, less frequently, as pruritus, dry skin, desquamation, hypertrichosis, or nail disorders (e.g. paronychia). Approximately 15% of the skin reactions are severe, including single cases of skin necrosis. The majority of skin reactions develop within the first three weeks of therapy. They generally resolve, without sequelae, over time following cessation of treatment if the recommended adjustments in dose regimen are followed (see below). According to NCICTC, grade 2 skin reactions are characterised by rash up to 50% of body surface area, while grade 3 reactions affect equal or more than 50% of body surface area. If a patient experiences a severe skin reaction ( grade 3; US National Cancer Institute - Common Toxicity Criteria, NCI-CTC), cetuximab therapy must be interrupted. Treatment may only be resumed, if the reaction has resolved to grade 2. If the severe skin reaction occurred for the first time, treatment may be resumed without any change in dose level. With the second and third occurrences of severe skin reactions, cetuximab therapy must again be interrupted. Treatment may only be resumed at a lower dose level (200 mg/m² body surface area after the second occurrence and 150 mg/m² after the third occurrence), if the reaction has resolved to grade 2. If severe skin reactions occur a fourth time or do not resolve to grade 2 during interruption of treatment, cetuximab treatment should be permanently discontinued. For > grade 1 acne-like rash, treatment with systemic antibiotics should also be considered (e.g. Doxycycline 100mg PO daily). Skin lesions induced by cetuximab may predispose patients to superinfections (e.g. with S. aureus), which may lead to subsequent complications, e.g. cellulitis, erysipelas, or, potentially with fatal outcome, staphylococcal scalded skin syndrome or sepsis. Electrolyte disturbances – Progressively decreasing serum magnesium levels have been observed leading to severe hypomagnesaemia in some patients. Hypomagnesaemia is reversible following discontinuation of cetuximab. Depending on severity, other electrolyte disturbances, mainly hypocalcaemia or hypokalaemia, have also been observed. Determination of serum electrolyte levels is recommended prior to and periodically during cetuximab treatment. Electrolyte repletion is recommended, as appropriate. Ocular disorders – Conjunctivitis may be expected in approximately 5% of patients. Hepatotoxicity - Mild to moderate increase in liver enzyme levels (AST, ALT, ALP) have been reported commonly. PRECAUTIONS(2) Hypersensitivity – due to the risk of cetuximab-induced infusion related reactions, all patients should be pre-medicated with anti-histamine IV prior to each week’s treatment (see “Supportive Treatments”). Close monitoring of the patient is also required during the infusion and for at least 1 hour after the end of the infusion, with each dose of drug. COMMON DRUG INTERACTIONS(2) There are no known significant drug interactions with cetuximab. No formal interaction studies with cetuximab have been performed in humans. REFERENCES (1) National Institute for Health and Clinical Excellence. Cetuximab for the treatment of locally advanced squamous cell cancer of the head and neck. Technology Appraisal Guidance 145 (June 2008). Available at www.nice.org.uk. (2) Summary of Product Characteristics – Cetuximab (Merck Serono). Accessed from the eMC 20/8/08. 582727853 October 2008 164 (3) Mount Vernon Cancer Network – Guidelines for the Management of Nausea and Vomiting in Adult Patients receiving Chemotherapy and/or Radiotherapy. November 2006. (4) Bonner et al. Radiotherapy plus Cetuximab for Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med 2006; 354:567-78. Protocol written by: Signature: Michael Powell, Senior Oncology Pharmacist Protocol approved by: Dr Kate Goodchild, Consultant Oncologist Date produced: October 2008 October 2010 Signature: Review date: Mount Vernon Cancer Centre CHEMOTHERAPY PROTOCOL SUMMARY Consultant: (place in Patient Notes) Ht (cm): Wt (kg): BSA (m2): Intent: Radical Patient label Protocol: Cetuximab with Radiotherapy Diagnosis: Locally advanced head and neck cancer REGIMEN: Cetuximab 400mg/m2 (loading dose) IV infusion over 2 hours Week 1 then 250mg/m2 IV infusion over 1 hour every week thereafter for total of 7-8 weeks (i.e. until last week of radiotherapy). Start cetuximab one week prior to radiotherapy treatment. Supportive medication: Pre-medication: antihistamine should be administered prior to each weekly dose of cetuximab – Chlorphenamine 10mg IV bolus. Total No. of cycles intended: 7 – 8 weeks DATE Week No. 1 Haemoglobin (g/dL) WBC (x109/L) Neutrophils (x109/L) Platelets (x109/L) Intravenous Dose Cytotoxic 582727853 2 Dose Review every _______ weeks 3 Dose October 2008 4 Dose 5 Dose 6 Dose 7 Dose 8 Dose 165 Cetuximab IV infusion (over 2 hours week 1, over 1 hour subsequent weeks) Pre-medication Dose Dose Dose Dose Dose Dose Dose 10mg IV 10mg IV 10mg IV 10mg IV 10mg IV 10mg IV 10mg IV Dose Chlorphenamine 10mg IV Ordered by: Prescribed by: Given by: PRESCRIPTION SHEET DOCTORS NOTES DOSE MODIFICATIONS: 582727853 October 2008 166 Mount Vernon Cancer Centre INPATIENT CHEMOTHERAPY PRESCRIPTION SHEET Regimen: Cetuximab with Radiotherapy Patient label Cycle No.: Date BSA: DRUG DOSE Chlorphenamine Cetuximab ROUTE DILUENT VOLUME INFUSION DURATION 10mg IV - - Bolus ____mg IV Sodium Chloride 0.9% 250ml JOB/BATCH NO. ____hours* NURSES SIGNATURE TIME STARTED PHARMACY 1 2 1 2 * Infuse cetuximab over 2 hours Week 1 and over 1 hour in subsequent weeks. Signature of doctor authorising chemotherapy administration: __________________________ Full Blood Count results (only if applicable) Hb WBC Neutrophils Platelets 167 Appendix 11 MVCN Pathology Guidelines Reporting of pathology specimens for Head & Neck UAT and thyroid cancer specimens will follow the appropriate Royal College of Pathologists guidelines (see below). Additional local guidelines for major specimens are as follows. Tissue pathways for head and neck pathology-- Luton and Dunstable Hospital pathology department. Staffing and workload. All of pathologist in this unit are competent in the reporting of specimen from the head and neck. However two pathologists take the lead and deputy lead role. Lead pathologists in future will participate in a specialist head and neck EQA scheme. All are newly diagnosed malignancies are doubled reported. All cases discussed at the MDT are reviewed by the MDT pathologist prior to the meeting. The department uses the guidelines for staffing and workload in cellular pathology generated by the Royal College. Time for MDT work is allocated in accordance with the college recommendation. Laboratory facilities A full range of routine laboratory facilities are available including access to immunocytochemistry, frozen section facility . A dedicated FNA service is available. Protocols for decalcification, immunocytochemistry and specimen dissection and reporting are provided , thus maintaining Uniformity. Specimen submission and dissection. All specimens are those seen in the laboratory in formalin. Complex specimens are received with orientation and the macroscopical the features are usually discussed with the surgeon before blocks are taken. Photograph facilities are available. Mucosal biopsies Specimens where appropriate are inked for marginal assessment. The sections are taken according to the individual sample and mostly are sampled across the short axis for closest excision margin assessment. Major salivary glands Blocks are taken to sufficiently sample adequacy of surgical margins, adjacent mucosa and normal salivary glands, one block per centimetre diameter of tumour, proximal and distal aspect of nerves if identifiable and any intra glandular or adjacent lymph nodes. Immunocytochemistry and special mucin stains are regularly used for assessment. 168 Larynx , pharynx and tonsil The specimens are orientated usually with the help of the surgeon. Relevant margins are inked. Measurement is usually three-dimensional. Weight is noted where relevant. Complex specimens are dealt according to college guidelines. Associated lymph nodes , thyroid , salivary gland, blood vessels, nerves adipose tissue art examined and relevant blocks taken. In addition to free text Royal College protocol is used for reporting. The report content records the type of tumour, tumour interface, relationship the major vessels and nerves and nearest surgical margin. References. Tissue Pathways for Head & Neck Pathology. September 2008. Royal College of Pathologists (Appendix 1) Standards and datasets for reporting cancers Dataset for thyroid cancer histopathology reports April 2010 Royal College of Pathologists (Appendix 2) 169 The Royal College of Pathologists Pathology: the science behind the cure Standards and Datasets for Reporting Cancers Datasets for histopathology reports on head and neck carcinomas and salivary neoplasms (2nd edition) June 2005 This dataset was commissioned by The Royal College of Pathologists' Working Group on Cancer Services. It replaces the first edition published in 1998. According to the College’s pre-publication policy, this document was placed on the College website for consultation from 16 November to 12 December 2004. Five pieces of feedback were received, which were forwarded to the lead author and considered in this final version. Professor John A Lee Director of Publications Acknowledgement The Royal College of Pathologists’ Working Group on Cancer Services acknowledges the use of the Appraisal Instrument for Clinical Guidelines (Cluzeau F, Littlejohns P, Grimshaw J, Feder G. London: St George’s Hospital Medical School, May 1997) in the preparation of this publication. The Royal College of Pathologists 2 Carlton House Terrace London SW1Y 5AF Website: www.rcpath.org Registered Charity No. 261035 © 2005 Royal College of Pathologists 170 CONTENTS General introduction to the Standards and Datasets for Reporting Cancers Recommendations Feedback The Royal College of Pathologists’ Working Group on Cancer Services References 1 1 1 1 1 Dataset for histopathology reports on head and neck carcinomas and salivary neoplasms General overview 2 Section A Mucosal malignancies of the head and neck region Specimen request form Preparation of the specimen before dissection Notes on site-specific considerations and block selection Core data items to be included in the histopathology report 1. Clinical data (provided by the surgeon or oncologist) 2. Pathological data 3. Diagnostic coding of primary carcinomas 4. Reporting criteria for small biopsy specimens 5. Use of frozen section diagnosis 3 3 3 4 4 4 4 7 7 7 Section B Salivary gland neoplasms Specimen handling and block selection 1. Pathological data 2. Diagnostic coding 3. Grading of salivary malignancies 8 8 8 9 9 Section C Neck dissection specimens Specimen request form Preparation of the specimen before dissection Notes on dissection and block selection Core data items to be included in the histopathology report 1. Clinical data (provided by the surgeon) 2. Pathological data 3. Diagnostic coding of metastases 4. Sentinel node biopsy 11 11 12 12 13 13 13 14 14 References 15 Appendix A TNM classification of malignant tumours General principles Site-specific ‘T’ codes 18 18 19 Appendix B SNOMED ‘T’ codes 21 Appendix C SNOMED ‘M’ codes 23 Appendix D Request forms for primary mucosal carcinomas and node dissections 24 Appendix E Reporting proformas Head and neck carcinoma dataset Salivary carcinoma dataset 26 26 27 171 General introduction to the Standards and Datasets for Reporting Cancers All these documents are evidence-based and define the minimum standards for reporting each group of tumours. They conform to a standard format and include a proforma that is intended to function as an aide memoire when reporting specific tumours. Although the data in the proforma may be presented as or supplemented by free text, the use of proformas in histopathological reporting is recommended; published audits have shown that they are very effective in ensuring that all necessary data are provided.1,2 Copies of the reporting forms are available at the end of this booklet and can also be downloaded from the College website (www.rcpath.org/publications). Recommendations The Royal College of Pathologists’ Working Group on Cancer Services recommends that: • • • • • • the datasets for reporting tumours are used in the system of standard setting, data collection, audit and feedback for those involved in caring for these patients histopathology laboratories nominate a lead pathologist for each of the main cancers with responsibility for liaising with relevant local committees and clinicians and ensuring that the relevant cancers are examined, sampled and reported appropriately and in a consistent fashion histopathologists should be members of multidisciplinary teams dedicated to the diagnosis and management of patients with specific cancers (and be involved in auditing the service) the SNOMED coding system is used to achieve as much uniformity as possible from centre to centre and to facilitate reliable cancer registration. Either the 1979 or 1993 version of SNOMED can be used, as currently there is no clear consensus for using one or the other histopathologists reporting cancers should participate in appropriate external quality assessment (EQA) schemes Cancer Centres and Units should be supported only by laboratories accredited with CPA (UK) Ltd and staffed in accordance with the recommendations of The Royal College of Pathologists and the Association of Clinical Pathologists. Feedback Anyone wishing to make specific or general comments on any of the documents should contact Dr Timothy Helliwell, Department of Pathology, University of Liverpool, Duncan Building, Daulby Street, Liverpool, L69 3GA. Email: [email protected] This document will be reviewed if new evidence emerges. Members of The Royal College of Pathologists’ Working Group on Cancer Services Dr Tim Helliwell (Chair) Dr Derek Allen Dr Ian Ansell Dr Mark Ashton Dr Clair du Boulay Dr Gill Lawrence Dr Nicholas Mapstone References 1. Cross SS, Angel CA. Five audit cycles of the informational content of histopathological reports of bladder carcinoma. J Pathol 1997;181:7A. 2. Cross SS, Feeley KM, Angel CA. The effect of four interventions on the informational content of histopathology reports of resected colorectal carcinomas. J Clin Pathol 1998; 51:481–482. 172 Datasets for histopathology reports on head and neck carcinomas and salivary neoplasms (2nd edition) Coordinators: Dr TR Helliwell and Dr JA Woolgar, University of Liverpool GENERAL OVERVIEW These guidelines present the core data that should be provided in histopathology reports of specimens of squamous carcinomas originating in the mouth, nose, pharynx and larynx, malignant neoplasms arising in the major salivary glands, and neck dissection specimens for metastatic disease. The datasets for squamous carcinoma and neck dissections are unchanged since the first edition of this publication, but the guidelines have be n revised in the light of a national audit in 2001 and more recent evidence supporting the inclusion of specific data items. The appendices list current systems of classification and staging for these malignancies, as well as illustrative histopathology request forms and proforma reports. The guidelines should be implemented for the following reasons. 1. Certain features of invasive mucosal carcinomas (type, size and grade of the primary carcinoma, the pattern of invasion and proximity of carcinoma to resection margins, lymph node status and the presence of extranodal spread) have been shown to be related to clinical outcome.1–8 Similar principles apply to salivary malignancies.9–11 These features may therefore be important in: a) deciding on the most appropriate treatment for particular patients, including the extent of surgery and the use and choice of adjuvant radiotherapy or chemotherapy b) monitoring changing patterns of disease, particularly by cancer registries. 2. These features provide sufficiently accurate pathological information that can be used, clinical data, for the patient to be given a prognosis. together with 3. To allow the accurate and equitable comparison of surgeons in different surgical units, to identify good surgical practice and the comparison of patients in clinical trials. The criteria have been widely discussed by pathologists and surgeons, and formal approval was sought from the British Society of Oral and Maxillofacial Pathology, the British Association of Head and Neck Oncologists, the British Association of Oral and Maxillofacial Surgeons, the British Association of Otolaryngology – Head and Neck Surgeons, the UK Association of Cancer Registries. Comments from specialist and general histopathologists on the draft version of this document, which was published for consultation on the College website in 2004, have been considered as part of this dataset. On the request forms, we are grateful to Professor DG McDonald, University of Glasgow, for permission to use the diagrams of the oral cavity and jaws, and to the International Union Against Cancer (UICC) and SpringerVerlag to use the diagrams of the larynx and neck that are adapted from the TNM Atlas (3rd edition), 1989 173 Section A Mucosal malignancies of the head and neck region This section applies to the reporting of squamous carcinomas of the upper aerodigestive tract, i.e. those arising in the nose and paranasal sinuses, mouth (including the tongue), pharynx (including nasopharynx, hypopharynx, oropharynx and tonsillar area) and larynx. Squamous carcinoma accounts for 95% of malignant neoplasms arising at these sites, but similar principles may be applied to the reporting of other mucosal malignancies arising in this anatomical area including adenocarcinomas, undifferentiated nasopharyngeal carcinomas, malignant melanoma, and to neuroendocrine epithelial neoplasms including carcinoid tumour, small cell carcinoma and olfactory neuroblastoma, that are important considerations in the differential diagnosis but are not described in detail. Optimal reporting of specimens from the head and neck area requires a partnership between the pathologist and surgeon/oncologist. The surgeon can help the pathologist to provide the information necessary for patient management by the appropriate handling and labelling of the specimen in the operating theatre. Regular discussion of cases at clinicopathological meetings and correlation with pre-operative imaging studies are important in maintaining and developing this partnership. 12 The guidelines are presented as a proforma that lists the core data items that may be applied across the head and neck region. The proforma may be used as the main reporting format or may be combined with free text as required. Individual centres may wish to expand the detail in some sections, e.g. for sites and subsites, to facilitate the recording of data for particular tumour types. A detailed dissection protocol is beyond the scope of these guidelines, but a brief summary of dissection methods and block selection is included to facilitate recording of the core data items. SPECIMEN REQUEST FORM The request form should include patient demographic data, the duration of symptoms, whether surgery is palliative or curative, details of previous histology or pathology reports and the core clinical data items (see below). Clinical TNM stage is useful as the final pathological T coding at some sites, e.g. the larynx, will be determined by clinical features such as vocal cord mobility.13 A history of previous radiotherapy or chemotherapy should be included, as this may influence the interpretation of the histological changes and should prompt a comment on the extent of any response to treatment. The request form should provide the opportunity for surgeons to provide annotated diagrams of specimens either as free-hand drawings or on standard diagrams (see Appendix D). Copies of reports that are sent to the Cancer Registries should include the patient’s address if possible. PREPARATION OF THE SPECIMEN BEFORE DISSECTION Resection specimens should be orientated by the surgeon and pinned or sutured to cork or polystyrene blocks. The surgeon should indicate surgically critical margins using metal tags or sutures. Fixation is in a formaldehyde-based solution for 24–48 hours in a container of adequate size (the volume of fixative should be ten times that of the tissue). Photography and radiography of the specimen may be used to record the nature of the disease and the sites from which tissue blocks are selected. Surgical margins should be painted with Indian ink or an appropriate dye to facilitate the later recording of the proximity of carcinoma to the margin. 174 NOTES ON SITE-SPECIFIC CONSIDERATIONS AND BLOCK SELECTION Oral cavity and oropharynx In general, these specimens may be assessed by cutting the specimen with a large knife into 5 mm slices to demonstrate both the relationship of the tumour to mucosal resection margins and the maximum depth of invasion by the tumour. Specimens from the central and lateral parts of the mouth should be cut in the coronal plane, while specimens from the anterior mouth should be sliced in the sagittal plane. If the tumour is close to bone, the specimen should be decalcified with soft tissue in situ. Larynx and hypopharynx 5 mm thick horizontal slices provide optimal demonstration of the relationship between the tumour and the laryngeal cartilages. For supraglottic carcinomas, blocks should include the relationship between the carcinoma and the anterior (submucosal) resection margin at the base of the tongue; blocks taken in the sagittal plane are more appropriate to demonstrate this feature. The description should include the subsite of origin of carcinoma, and the extent of involvement of laryngeal cartilages and extra-laryngeal tissues.14 Paranasal sinuses and maxillectomy specimens These are complex specimens that require careful orientation and labelling by the surgeon if the pathologist is to provide accurate information. When appropriate, the surgeon should assist the pathologist in the dissection of the intact specimen to ensure that critical margins are oriented and submitted for histological examination. For partly disrupted specimens, it may sometimes be necessary for surgically critical margins to be sent as separate specimens to the laboratory. Selection of blocks for histology • • • • • • • Tumour – at least one block per 10 mm diameter of tumour, including one selected to demonstrate the maximum depth of invasion; whole tumour if less than 10 mm. Blocks of defined mucosal and soft tissue margins. Non-neoplastic mucosa. Bone surgical margins (if applicable). Bone or cartilage (larynx, nose), if grossly involved by tumour. Thyroid if present in laryngectomy. Tracheostomy site. CORE DATA ITEMS TO BE INCLUDED IN THE HISTOPATHOLOGY REPORT 1 Clinical data (provided by the surgeon or oncologist) 1.1 Site(s) and side(s) of the carcinoma(s). For carcinomas that involve more than one site, the principal site of involvement should be recorded and coded; this may not be the site of origin. If required, the involvement of associated sites can be noted to help in later data analysis. Sites and subsites should be recorded according to the International Union Against Cancer (UICC) nomenclature (see Appendix A). 1.2 Type of resection specimen, e.g. total or partial glossectomy, laryngectomy. 2 Pathological data 2.1 Maximum diameter of tumour (in millimetres). The macroscopic diameter should be used (Figure 1) unless the histological extent is greater than macroscopically apparent, in which case the microscopic dimension is used. As for other tissues, e.g. breast, measurements are madepragmatically, acknowledging distortion of tissues by fixation and processing 2.2 Maximum depth of invasion (millimetres) below the luminal aspect of surface; if the tumour has ulcerated then the reconstructed surface should be used (Figure 1). The aim should be to provide a best estimate of tumour depth; for large carcinomas this may be an approximation. A more detailed comment on the nature of the tissues invaded (mucosa, muscle, etc.) should occur in the ‘Comments’ sections. Tumour thickness is significantly related to nodal metastasis, although the optimal cut-off point for prognostic purposes is uncertain, with 3 mm and 5 mm being suggested by different studies of lingual carcinomas.15, 16 175 Figure 1 Descriptors of the size of the primary carcinoma. (A) for a nodular carcinoma and (B) for an ulcerated carcinoma. Note that depth of invasion refers to the depth of greatest spread in presumed continuity below the top of the adjacent mucosa. For both nodular and ulcerated tumours, the line of the original mucosal surface is reconstructed to determine the true thickness. 2.3 Histological type of carcinoma. These guidelines specifically apply to conventional squamous carcinomas. Subtypes of squamous carcinoma, such as papillary, verrucous, basaloid, adenosquamous and spindle cell carcinomas, should be recognised 17 and listed in the core dataset and potential prognostic implications noted in the ‘Comments’ sections. 2.4 Degree of differentiation. Grading is based on the degree of resemblance of the carcinoma to the normal epithelium and follows the descriptions in the World Health Organization (WHO) classification.17 The most aggressive area (medium magnification field) is graded as well differentiated, moderately differentiated or poorly differentiated. This system is widely used and prognostically useful, even though it suffers from inter-observer variability and sampling problems.5,18 While most squamous carcinomas will be moderately differentiated, it is important for prognostication to separate well differentiated and poorly differentiated tumours. 2.5 Invasive front of the carcinoma. The pattern of invasion by the carcinoma at its deep margin is of proven prognostic value for oral carcinomas.4,19,20 The few published studies of tumours at other sites suggest that a similar approach may be of value.3 Scoring systems for histopathological features of squamous carcinomas include features relatedto differentiation and to the tumour/stromal interaction. 1–3 While these have the potential to improve the consistency of reporting, they are not in widespread use and for these guidelines it is suggested that the recording of differentiation and invasive pattern is made separately. It should be recognised that the pattern of tissue invasion by carcinoma is a continuous spectrum of changes. For prognostic purposes, two groups can be recognised: carcinomas composed of broad cohesive sheets of cells or strands of cells (more than 15 cells across), and carcinomas composed of narrow strands, non-cohesive small groups or single cells (see Figure 2).4 176 Figure 2 Patterns of invasion by squamous carcinoma. a, b, c are examples of cohesive patterns. d, e, f are examples of non-cohesive or infiltrating patterns. 2.6 Distance from invasive carcinoma to surgical margins (in millimetres). Measure the distance histologically for both mucosal and deep margins. From a surgical point of view, >5 mm is ‘clear’,1–5 mm is ‘close’ and <1 mm is ‘involved’. Incomplete resection or the presence of dysplasia at themargin is associated with a significantly increased risk of local recurrence.21 In the ‘Comments’section, it may be noted that if the tumour has an infiltrating pattern of invasive front (or vascular or perineural spread ahead of the invasive front) and a close margin, this may be associated with a high risk of local recurrence. Note that comment on the deep resection margin of a laryngectomy specimen may be inappropriate unless the tumour extends close to the base of tongue or into the soft tissues of the neck. 2.7 Vascular invasion. The presence or absence of vascular invasion should be mentioned if it is an obvious feature on medium magnification examination of the tumour. The presence of carcinoma cells within an endothelial-lined space is the essential criterion. It is not necessary to distinguish between small lymphatics and venous channels. 2.8 Nerve invasion. The presence or absence of invasion of the perineural space ahead of the invasive front of the carcinoma should be recorded. This is especially important for carcinomas of the lip where this feature predicts local recurrence. Intra-tumoural perineural invasion is of doubtful prognostic significance. 2.9 one invasion or cartilage invasion. The involvement of bone may be by non-invasive erosion of the cortex, or diffuse infiltration of medullary intertrabecular and perineural tissues. 13 These should be distinguished in the ‘Comments’ section. If bone margins can be identified, the resence or absence of carcinoma at the margins should be described in the ‘Comments’ section. 2.10 Severe dysplasia/in situ carcinoma. Epithelial dysplasia forms a continuous spectrum of appearances from mild to severe dysplasia/carcinoma in situ. Detailed discussion of the criteria and reproducibility of grading systems is not part of these guidelines and consensus has not been reached on the most clinically appropriate and reproducible grading system. The options include the standard WHO system,17 the system based on grades of squamous intraepithelial neoplasia22 and the Ljubliana classification for laryngeal lesions.23 Severe dysplasia and carcinoma in situ are generally regarded as synonymous and are associated with a high risk of progression to carcinoma. The presence of severe dysplasia/carcinoma in situ adjacent to the primary carcinoma and at the resection margins (where it may predict local recurrence) should be recorded. 24,25 177 Other features form part of a complete description, but are not core data items These features should be included as part of a comprehensive description of a carcinoma and the surrounding tissues. Some are preferences of individual centres, but are considered to be of uncertain prognostic significance at most sites in the head and neck region and therefore are not part of the dataset at present. • • • • Type and intensity of inflammatory infiltrate and desmoplastic stromal response. Involvement of a tracheostomy (if present). Response to previous therapy (if applicable). Results of other investigations, e.g. flow cytometry, molecular and immunohistochemical studies. Molecular markers including measures of cell proliferation and nuclear DNA content, the expression of involucrin, blood group antigens, cell adhesion molecules and oncogenes, and the intensity of neoangiogenesis have been investigated as potential prognostic factors. These features generally correlate with cellular differentiation but do not provide any consistent independent prognostic information. 6,26,27 While molecular markers predictive of tumour behaviour or response to therapy may be required pathological data in the future, current surgical practice does not demand their inclusion in the dataset .8,21 Immunocytochemical studies may help to resolve differential diagnostic problems. Most antibodies lack a precise tissue or neoplastic specificity, so that a combination of appropriate results is required to make a diagnosis. These results should always be consistent with the haematoxylin and eosin appearances. 3 Diagnostic coding of primary carcinomas 3.1 pT status should be recorded according to the UICC guidelines (see Appendix A).13 3.2 SNOMED ‘T’ code(s) should be recorded for primary site(s). A list of ‘T’ codes against site and subsite is provided in Appendix B. 4 Reporting criteria for small biopsy specimens 4.1 The data that can be obtained from small biopsy specimens will be determined, in part, by their size. The type of carcinoma and its grade are the minimum data required to determine treatment. It is recognised that, in large tumours, the grade in superficial biopsy material may not be representative of the most aggressive part of the invasive front. If severe dysplasia/in situ carcinoma is present, this should be recorded as it may influence the position of excision margins. For larger diagnostic biopsies, as may be obtained from oral neoplasms, the pattern of invasion can be determined. It is not realistic to assess reliably the tumour thickness or presence of vascular invasion in small biopsies. 5 Use of frozen section diagnosis 5.1 The initial diagnosis of carcinoma will usually be made before definitive surgery is performed. On occasions, intra-operative frozen section diagnosis of the nature of a neoplasm will be required. While it will usually be possible to identify the presence of neoplastic tissue, the nature of a poorly differentiated neoplasm may be impossible to determine on frozen sections. 5.2 The assessment of the presence or absence of carcinoma at surgical resection margins is the most common indication for intra-operative frozen section diagnosis. The surgeon should select the tissue for frozen section diagnosis with care, bearing in mind that it is not usually possible to section material more than 10 mm in diameter. 5.3 The report on the frozen section specimen should form part of the final diagnostic report on the case. 178 Section B Salivary gland neoplasms Malignant tumours of the salivary glands are usually removed by partial excision of the gland including the tumour mass, or by total excision of the gland. Parotid tumours may require an extended radical procedure with resection of the subcutis and skin of the pre/infra-auricular region and upper neck. Resection margins around salivary tumours will be either salivary tissue and/or soft tissue. The most important prognostic features are the histological tumour type, the clinical/pathological stage and the adequacy of the excision. 11,28 The dataset does not cover benign salivary neoplasms, although pathology reports on these neoplasms would be expected to include an overall description of the specimen and the tumour, the histological type (WHO classification) and the proximity of the neoplasm to the resection margins. The parotid gland is richly supplied with two networks of lymphatic vessels, paraglandular and intraglandular, which may or may not intercommunicate. Each gland contains 20–30 lymph nodes that may be the site of metastases from salivary tumours and other malignancies, particularly those arising in the head and neck region. The efferent lymphatics from the parotid drain primarily to the superior deep cervical nodes (level II). The submandibular gland does not contain intraglandular lymph nodes and the parenchyma drains to the 2–5 submandibular nodes that lie close to the gland, and then to nodes at level II. The sublingual gland drains to the submandibular, submental and level II nodes.29 SPECIMEN HANDLING AND BLOCK SELECTION The exposed margin of the excised tissue should be marked with Indian ink or a suitable pigment before the tissue is serially sliced. If a major nerve has been resected, the proximal and distal margins should be indicated by the surgeon, thus facilitating accurate assessment of any peri- or intra-neural invasion. Blocks to be taken • • • Representative blocks of tumour (at least one per 10 mm of tissue diameter) to include tissue and the relationship between tumour and the nearest resection margin. Lymph nodes within the gland or in peri-glandular soft tissue. Blocks from designated resection margins of nerves. normal Neck dissection specimens associated with salivary neoplasms are handled as described in Section C. 1 PATHOLOGICAL DATA 1.1 Macroscopic features Core data items for a salivary tumour are: • • • • • • • the maximum diameter of the tumour (in millimetres) the distance from the tumour to the nearest resection margin (the macroscopic measurements should be confirmed histologically and, if there is a discrepancy, then the histological distance should be stated in the dataset) macroscopic extraglandular extension to involve adjacent structures the histological type of neoplasm (according to the WHO classification) the grade of malignancy (see below) the presence or absence of perineural or vascular invasion the presence or absence of lymph node involvement. 179 1.2 Other macroscopic features form part of a complete description, but are not core data items: • • • • • • • • the type of specimen (superficial or total parotidectomy, extent of any neck dissection the overall size of the specimen with regard to anatomical features the length of the excretory duct, if obvious the size of the tumour in three dimensions a note of the presence and size of lymph nodes around or within the gland the nature of the tumour: solitary or multifocal; solid or cystic, etc. the nature of the edge of the tumour: discrete (well defined) or poorly defined the appearance and texture of the cut surface: translucent or cartilaginous, brown or haemorrhagic, cystic, necrotic, etc. 1.3 Other microscopic features form part of a complete description, but are not core data items: • • • • • mitotic index microscopic encapsulation or invasion of normal tissues changes in the macroscopically normal salivary tissue immunocytochemical labelling may help to characterise some types of neoplasm that contain myoepithelial cells (e.g. caldesmon, calponin, p63, S-100 protein), luminal cell cytokeratins (CK 8, 18, 19) or mitochondria, but diagnosis should be based primarily on morphological criteria molecular markers such as MIB-1, bcl-2, p53, HER-2 may have prognostic value,11, 30 but are not routinely performed. 2 DIAGNOSTIC CODING 2.1 pTNM stage according to standard criteria (see Appendix A). The TNM staging according to the UICC classification applies to tumours of the major salivary glands.13 Salivary-type neoplasms of minor glands should be staged according to the criteria for mucosal squamous carcinomas. 2.2 SNOMED ‘T’ and ‘N’ codes (see Appendix B). 3 GRADING OF SALIVARY MALIGNANCIES 3.1 Mucoepidermoid carcinoma Grading of mucoepidermoid carcinomas is related to metastatic potential and survival, whichever system is used.9,31–33 In general, low-grade (cytologically benign) tumours with abundant mucous cells and mucin production are less aggressive and rarely metastasise. Tumours that are predominantly solid and have a preponderance of epidermoid cells have the greatest metastatic potential. There has been considerable debate around grading criteria and the relative merits of 2 and 3 grade systems. A modification of the American Forces Institute of Pathology (AFIP) grading system31 has the merit of simplicity and appears to allow good discrimination between tumours with good and poor prognosis. This system scores a range of histological features but, in essence the presence of two or more poor prognostic features indicates a high grade tumour (see Table 1). 180 Table 1 Prognostic features for mucoepidermoid carcinoma 31 Grade 1 Predominant goblet cell component. Lack of aggressive features. Grade 2 Predominant intermediate cell component. Aggressive invasion pattern but lacks other features of grade 3. Grade 3 Predominant squamous cell component. Aggressive invasion pattern plus one or more of the following features: • necrosis • >4 mitoses per 10 high power fields • high-grade nuclear pleomorphism • perineural invasion • vascular invasion •bony invasion 3.2 Acinic cell carcinoma Acinic cell carcinomas are usually circumscribed but incompletely encapsulated. Cytologically lowgrade tumours show several configurations (solid, papillary, follicular, clear-cell) but neither the configuration nor the cytological grade are generally accepted as useful indicators of behaviour ,10,34 and hence do not form part of a core dataset. 3.3 Adenoid cystic carcinoma The histological type of adenoid cystic carcinoma is related to metastatic potential, with 0–4% of cribriform, hyaline and tubular carcinomas, and 33% of solid (basaloid) carcinomas metastasising to local lymph nodes .9,35 Distant metastasis is more common in solid tumours.10,30 3.4 Carcinoma in pleomorphic adenoma Carcinomas arising in pleomorphic adenomas may be of any histological type, but are thought to be particularly aggressive and the prognosis of the carcinomatous component is poorer than that of comparable carcinomas developing de novo.9,10,36 Evidence for a pre-existing adenoma (remnants of myxochondroid stroma, focal scarring, hyalinised nodular ‘ghost’) should be sought in all carcinomas, particularly those showing multiple histological types and a varied histological appearance. The extent of invasion should be measured for these tumours as it is prognostically useful, although precise criteria are not defined. Invasion more than 5–6 mm from the capsule of the residual adenoma is associated with a high risk of local recurrence and distant metastasis. 37,38 181 Section C Neck dissection specimens SPECIMEN REQUEST FORM The type of neck dissection and node levels present should be specified by the surgeon using standard terminology.39 It may be appropriate to use a request form that encourages the annotation of a schematic diagram to indicate the extent of the dissection. As the terminology applied to modified operations is potentially confusing, dissections should be described by specifying which node groups and non-lymphatic structures the surgeon has dissected and the relevant non-lymphatic structures that have been preserved or removed. Three main types of neck dissection may be received: • comprehensive neck dissection, which includes both radical and modified radical (functional) dissections. A radical neck dissection includes removal of cervical lymph nodes (levelsI–V), sternomastoid muscle, internal jugular vein, spinal accessory nerve and the submandibular salivary gland, while in a functional dissection, the sternomastoid muscle, internal jugular vein, or the spinal accessory nerve may not be removed • selective neck dissection involves removal of the nodal group(s) considered to be the most likely site for metastasis, preserving one or more nodal groups that are routinely removed in a radical dissection • extended neck dissection when additional lymph node groups or non-lymphatic structures are removed. Terminology of node groups Six major anatomical groups (levels) of lymph nodes are described (see Figure 3). • Level I: nodes of the submandibular and submental triangles. • Levels II, III and IV: nodes of the upper, middle, and lower jugular chain. These nodes lie deep to the upper, middle and lower thirds of the sternocleidomastoid muscle respectively. The point at which the omohyoid muscle crosses deep to the sternocleidomastoid muscle is a useful landmark separating levels III and IV. Level IV extends from the omohyoid muscle to the clavicle. • Level V: nodes of the posterior triangle, behind the posterior border of the sternocleidomastoid muscle. • Level VI: nodes of the anterior compartment, around the midline visceral structures of the neck from the hyoid bone to the suprasternal notch. Imaging studies may subclassify node levels II and V.40 It is not suggested that this should be part of routine pathological practice but if separate groups are submitted, e.g. IAA and IIB, this should be noted in the pathology report. Figure 3 Diagrammatic representation of lymph node levels in the neck 182 PREPARATION OF THE SPECIMEN BEFORE DISSECTION • • • • • • Resection specimens should be orientated by the surgeon and pinned or sutured to cork or polystyrene blocks. The surgeon should indicate surgically critical margins and identify the general territories of node groups by placing markers such as metal tags or sutures at the centre of each anatomical group. A practical alternative for selective dissections is for the surgeon to separate the node groups, mark the superior margin of each group with a suture, and place each group in a separately l abelled container. Nodes in addition to the main groups, e.g. parapharyngeal nodes, should be sent as separate specimens. Fixation is in a formaldehyde-based solution for 24–48 hours in a container of adequate size (the volume of fixative should be ten times that of the tissue). Photography of the specimen may be used to record the nature of the disease and the sites from which tissue blocks are selected. Surgically important margins may be marked with Indian ink or an appropriate dye. NOTES ON DISSECTION AND BLOCK SELECTION 1. Identify the component structures. From the outer aspect: the submandibular salivary gland; the sternocleidomastoid muscle; the omohyoid muscle; the external jugular vein; the spinal accessory nerve; the tail of the parotid gland. Some dissections may include skin or other structures such as the stylohyoid and digastric muscles. From the deep aspect, identify the internal jugular vein. 2. Lymph nodes are identified by inspection and palpation around the vein, and around the submandibular gland and adipose tissue of the anterior and posterior triangles, and assigned to the appropriate anatomical level (this should be indicated by surgical markers). Each discrete node is dissected out with attached pericapsular adipose tissue. Larger nodes should be bisected or sliced. If there is obvious metastatic tumour, the half/slice with the more extensive tumour should be processed, together with the perinodal tissues to show the extent of extracapsular spread. If the node appears negative, all slices should be processed. Small or flat nodes should be processed whole, and several nodes (from the same anatomical level) can be processed in the same cassette. One H&E stained section from each block is usually sufficient for routine assessment. 3. An alternative method, that may be particularly useful for selective dissections is to serially slice the fixed specimen and to embed all of the tissue.41 Care should be taken not to double-count larger nodes that are present in more than one block. Note that large nodes containing obvious metastatic carcinoma only need to be sampled to identify any extracapsular spread. 4. A radical neck dissection may yield an average of 20 nodes (range 10–30), in the absence of previous chemotherapy or irradiation, although on occasions 50–100 nodes may be identified. This examination would be expected to include, as a minimum, all palpable nodes greater than 3 mm in diameter. 5. Other blocks for histology: submandibular gland, jugular vein and sternomastoid if involved tumour. by 183 CORE DATA ITEMS TO BE INCLUDED IN THE HISTOPATHOLOGY REPORT 1 Clinical data (provided by the surgeon) 1.1 Nature of neck dissection (comprehensive or selective). 1.2 Node levels present. 2 Pathological data 2.1 At each anatomical level, record the total number of nodes identified and number of nodes involved by carcinoma. For practical purposes, the critical factor is involvement of levels IV or V. Including level III provides some leeway when describing spread so one is not forced into only saying upper or lower nodes are involved. 2.2 Size of largest metastatic deposit. Note that this is not the same as the size of the largest node. The size of the largest metastasis is a determinant in the TNM staging.13 2.3 Presence or absence of extra-capsular rupture and the node level(s) showing this feature. Extracapsular spread should be recorded as present or not identified. Any spread through the full thickness of the node capsule is recorded, and the previous separation into macroscopic and microscopic spread is now considered not to be necessary.42 Involvement of adjacent anatomical structures should be recorded separately in the ‘comments’ section. If histological evidence of extracapsular spread is uncertain, it should be recorded as ‘present’. This should prompt the use of adjuvant radiotherapy. Extracapsular spread is a manifestation of the aggressiveness of a carcinoma and is associated with a poor prognosis.6,42–45 2.4 The prognostic significance of micrometastases (<2 mm diameter) is not certain,46,47 their presence should be included in the number of involved nodes and TNM coded as pN1(mi) or pN2(mi). 2.5 The 6th edition of the TNM classification13 has introduced a category of pN0(i+) for nodes that contain clumps of isolated tumour cells (<0.2 mm) that are usually only detected by immunocytochemistry but may be seen on H&E stained sections. The prognostic significance of isolated tumour cells is not known for head and neck cancer, but studies of sentinel nodes may provide such data. At present, it is suggested that dissection and sectioning protocols are not modified, and that nodes containing isolated clumps of tumour cells are classified as pN0(i+) with the comment that “previously such cases would have been classified as pN+”. 2.6 Involvement of lymphatic channels in neck is a poor prognostic factor, and may be mentioned the text of the report. 2.7 If there is obvious metastatic disease with fusion (matting) of lymph nodes, record: a) the level(s) of nodes involved by the mass b) the maximum dimension c) an estimate of the number of nodes that might be involved in the mass. 2.8 Isolated nodules of tumour in the connective tissue may represent discontinuous extensions of the primary tumour, soft tissue metastases or nodal metastases that have destroyed the node. Absolute distinction between these possibilities is not always possible and, while the 6th edition of the TNM classification13 recommends regarding all deposits that do not have the contour of a node as discontinuous tumour extension, there does not appear to be any evidence for this approach in the head and neck. A practical approach is to regard any tumour nodule in the region of the lymphatic drainage as a nodal metastasis, and to only diagnose discontinuous extension of a carcinoma within 10 mm of the primary carcinoma and where there is no evidence of residual lymphoid tissue. 14 in 184 Other features form part of a complete description, but are not core data items These features should be included as part of a comprehensive description of a neck dissection specimen but are of uncertain prognostic significance: • presence of other pathology in cervical nodes • presence of evidence of response of tumour, e.g. keratin debris, to previous therapy. 2 Diagnostic coding of metastases pN status should be recorded according to the UICC guidelines13 (see Appendix A), apart from the designation of isolated nodules of tumour cell (see Section 2.8). 3 Sentinel node biopsy Sentinel lymph node biopsy has been suggested as a method to reduce the morbidity associated with cervical node dissections. 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Oral Oncol 2003;39:343–349. a 188 Appendix A TNM classification of malignant tumours 13 GENERAL PRINCIPLES PT Primary tumour pTX Primary tumour cannot be assessed. pT0 No evidence of primary tumour. pTis Carcinoma in situ. pT1, pT2, pT3, pT4: increasing size and/or local extent of the primary tumour (see specific sites). pN Regional lymph nodes (for all primary sites, except nasopharynx) pNX Nodes cannot be assessed. pN0 No nodal metastasis. pN0(i+) Isolated tumour cells only (<0.2 mm). pN1(mi) Micrometastasis (2mm or less) only, in single node pN1 Metastasis in single ipsilateral node 30 mm or less in diameter pN2(mi) Micrometastasis (2 mm or less) only, in multiple or bilateral nodes pN2a Metastasis in single ipsilateral node 31–60 mm diameter pN2b Metastasis in multiple ipsilateral nodes <61 mm diameter pN2c Metastasis in bilateral or contralateral lymph nodes, none more than 60 mm in greatest pN3 Metastasis in lymph node more than 60 mm diameter. dimension. Notes (i) For nasopharyngeal primary carcinomas: pN1 – unilateral metastasis <61 mm above supraclavicular fossa pN2 – bilateral metastases <61 mm above supraclavicular fossa pN3 – metastasis in nodes >60 mm or in supraclavicular fossa. (ii) Direct extension of a primary into a node is classified as nodal metastasis. (iii) A tumour nodule >3 mm in the connective tissue without residual node is classified as a nodal metastasis. A nodule <3 mm is classified in pT as discontinuous extension. (iv) When size is a criterion for pN classification, measure the size of the metastasis, and not that the entire node. (v) Midline nodes are considered ipsilateral. M Distant metastasis MX Distant metastasis cannot be assessed. M0 No distant metastasis. M1 Distant metastasis (may be subgrouped by site of metastasis). of 189 SITE-SPECIFIC ‘T’ CODES Lip, oral cavity and oropharynx T1 Tumour 20 mm or less in greatest dimension. T2 Tumour 21–40 mm in greatest dimension. T3 Tumour >40 mm in greatest dimension. T4 Tumour invades adjacent structures. Nasopharynx T1 Tumour confined to nasopharynx. T2 Tumour extends to soft tissue of oropharynx and/or nasal fossa. T3 Tumour invades bone and/or paranasal sinuses. T4 Tumour with intracranial extension and/or involvement of cranial nerves, infratemporal fossa, hypopharynx or orbit. Hypopharynx T1 Tumour limited to one subsite and 20 mm or less in greatest dimension. T2 Tumour involves more than one subsite or measures 21–40 mm in size. T3 Tumour >40 mm in size or with fixation of hemilarynx. T4 Tumour invades adjacent structures. Larynx, supraglottis T1 Tumour limited to one subsite with normal vocal cord mobility. T2 Tumour invades more than one adjacent subsite without fixation of larynx. T3 Tumour limited to larynx with vocal cord fixation, and/or invades postcricoid area, pre- epiglottic tissues or deep base of tongue. T4 Tumour invades through thyroid or cricoid cartilage and/or invades tissues beyond the larynx, soft tissues of neck, thyroid or into oesophagus. e.g. Larynx, glottis T1 Tumour limited to vocal cords with normal mobility. T2 Tumour extends to supraglottis and/or subglottis, and/or with impaired vocal cord mobility. T3 Tumour limited to larynx with vocal cord fixation and/or invades the paraglottic space and/or invasion of inner cortex of thyroid cartilage. with T4 Tumour invades through thyroid or cricoid cartilage and/or invades tissues beyond the larynx, soft tissues of neck, thyroid or into oesophagus. e.g. 190 Larynx, subglottis T1 Tumour limited to subglottis. T2 Tumour extends to vocal cords with normal or impaired mobility. T3 Tumour limited to larynx with vocal cord fixation. T4 Tumour invades through thyroid or cricoid cartilage and/or invades tissues beyond the larynx, soft tissues of neck, thyroid or into oesophagus. e.g. Maxillary sinus T1 Tumour limited to antral mucosa with no bone involvement. T2 Tumour causing bone erosion or destruction, except for posterior wall. T3 Tumour invades posterior wall of sinus, subcutaneous tissues, floor or medial wall of orbit, infratemporal fossa, pterygoid plate, ethmoid sinuses. T4 Tumour invades skin of cheek, orbital contents beyond floor and medial wall, base of skull, nasopharynx, sphenoid sinus or frontal sinus. Nasal cavity and ethmoid sinus T1 Tumour restricted to one subsite in the nasal cavity or ethmoid sinus, with or without bone erosion. T2 Tumour involves two subsites** within one site or extends to involve an adjacent site within the nasoethmoidal complex, with or without bone erosion. T3 Tumour extends to involve the medial wall or floor of the orbit, maxillary sinus, palate or cribriform plate. T4 Tumour with intracranial extension, anterior orbital extension, or involves sphenoid or frontal sinuses and/or skin of nose. ** Sites for classification are the individual maxillary and ethmoidal sinuses and the nasal cavity. The nasal cavity is divided in the following subsites: septum, floor, lateral floor and vestibule. Major salivary glands Tx Primary tumour cannot be assessed. T0 No evidence of primary tumour. T1 Tumour 20 mm or less in greatest dimension without extraparenchymal extension. T2 Tumour more than 20 mm but not more than 40 mm in greatest dimension without extraparenchymal extension. T3 Tumour more than 40 mm and/or tumour with extraparenchymal extension. T4a Tumour invades skin, mandible, ear canal or facial nerve. T4b Tumour invades base of skull, pterygoid plates or encases carotid artery. Note: Extraparenchymal extension is clinical or macroscopic evidence of invasion of soft tissues or nerve except those listed under T4a or b. Microscopic evidence alone does not constitute extraparenchymal extension for classification purposes. 191 Appendix B SNOMED ‘T’ codes SNOMED ‘T’ code Sites and subsites T-52000 T-52230 T-52240 T-52003 Lip External upper lip (vermilion border) External lower lip (vermilion border) Commisures T-51000 T-51300 T-52250 T-51030 T-51600 T-51010 T-54920 T-54930 T-51110 T-53000 T-53120 T-53123 T-51200 Oral cavity Buccal mucosa Mucosa of upper and lower lips Cheek mucosa Retromolar areas Bucco-alveolar sulci Upper alveolus and gingiva (upper gum) Lower alveolus and gingiva (lower gum) Hard palate Tongue Dorsum and lateral borders of anterior 2/3 Inferior (ventral) surface Floor of mouth T-60200 T-53122 T-53130 T-60230 T-60220 T-61100 T-61240 T-61150 T-60210 T-51120 T-51130 Oropharynx Anterior wall (glosso-epiglottic area) Base of tongue Vallecula Lateral wall Tonsil Tonsillar fossa and pillars Tonsillar pillars Posterior wall Superior wall Inferior surface of soft palate Uvula T-23000 T-23001 T-23002 T-51122 Nasopharynx Postero-superior wall Lateral wall (includes fossa of Rosenmuller) Inferior wall (superior surface of soft palate) 192 SNOMED ‘T’ code Sites and subsites T-60300 T-24080 T-60320 T-60350 Hypopharynx Pharyngo-oesophageal junction (post-cricoid area) Piriform sinus Posterior pharyngeal wall T-24100 T-24010 T-24310 T-24320 T-24440 T-24400 T-24470 T-24450 Larynx Epiglottis Aryepiglottic fold, laryngeal aspect Ventricular bands (false cords) Glottis Vocal cords Commissures Subglottis T-21000 T-21030 T-21320 T-21340 T-21360 Nose T-22000 T-22100 T-22200 T-22300 T-22400 Paranasal sinuses Maxillary sinus Frontal sinus Ethmoid sinus Sphenoid sinus T-55000 T-55100 T-55200 T-55300 T-55400 Salivary glands Parotid gland Submandibular gland Sublingual gland Minor salivary gland Olfactory region of nose Nasal vestibule Nasal septum Nasal turbinate 193 Appendix C SNOMED ‘M’ codes Note: This is not a comprehensive list of all malignancies and other codes should be used as necessary. Squamous carcinoma and variants M-80702 Squamous carcinoma in situ M-80703 Squamous carcinoma M-80705 Microinvasive squamous carcinoma M-80713 Keratinising squamous carcinoma M-80723 Non-keratinising squamous carcinoma M-80743 Spindle cell squamous carcinoma M-80753 Adenoid squamous carcinoma M-85603 Adenosquamous carcinoma Salivary malignancies M-85503 Acinic cell carcinoma M-84303 Mucoepidermoid carcinoma M-82003 Adenoid cystic carcinoma M-82003 Polymorphous low grade adenocarcinoma (terminal duct adenocarcinoma) M-85623 Epithelial-myoepithelial carcinoma M-81473 Basal cell adenocarcinoma M-84103 Sebaceous carcinoma M-84503 Papillary cystadenocarcinoma M-84803 Mucinous adenocarcinoma M-82903 Oncocytic carcinoma M-85003 Salivary duct carcinoma M-81403 Adenocarcinoma M-89823 Malignant myoepithelioma (myoepithelial carcinoma) M-89413 Carcinoma in pleomorphic adenoma (malignant mixed tumour) M-80703 Squamous cell carcinoma M-80413 Small cell carcinoma M-80203 Undifferentiated carcinoma 194 Appendix D Draft request forms for primary mucosal carcinomas and node dissections Surname: Consultant: Forename: Location: Date of Birth: Sex: Hospital Number: NHS No: Relevant medical or dental history: Clinical diagnosis: Site of lesion Previous reports (laboratory number if known) Duration of symptoms: Predisposing factors: Other information: Date of operation: Signature: Right Left Left Right 195 Right Left Left Right Right Left 196 Appendix E Reporting proformas HEAD AND NECK CARCINOMA DATASET Surname ……………………….…..Forenames ……………..….. Date of birth …...… … Sex …...... Hospital …………………………… Hospital no ………………... NHS no …....……..………….……. Date of receipt …………….……… Date of report …………..…. Report no ……..…….…….….….... Pathologist ……………………………..……….. Surgeon ………...….…...…………..……………..… Clinical TNM stage ……………………… Previous radiotherapy Yes � No � Unknown � T…… N…… M…… No � Unknown � Previous chemotherapy Yes � Primary tumour Site ………………………………………. Maximum diameter ………………. (mm) Subsite(s) …………………………….….. Maximum depth of invasion …….. (mm) Right � Left � Midline � Distance from invasive tumour to Type of resection ……………………….. mucosal margin ……….………. (mm) Histological type: Squamous carcinoma � deep margin …………...…….… (mm) Other/subtype…………….. Vascular invasion Yes � No � Differentiation Well � Nerve invasion Yes � No � Moderate � Bone/cartilage invasion Yes � No � Poor � Severe dysplasia present Yes � No � Invasive front Cohesive � Non-cohesive � Severe dysplasia at margin Yes � No � Right neck dissection : Yes � No � Left neck dissection: Yes � No � Comprehensive � Selective � Comprehensive � Selective � Node levels present: I II III IV V VI Other � Node levels present: I II III IV V VI Other � Total number of nodes……………… Total number of nodes……………… Number positive nodes……………... Number positive nodes……………... Levels with metastases: I II III IV V VI Other � Levels with metastases: I II III IV V VI Other � Largest metastasis …..……….. (mm) Largest metastasis …..……….. (mm) Extracapsular spread Yes � No � Extracapsular spread Yes � No � Levels with ECS……………………… Levels with ECS……………………… Summary of pathological data: Tumour site………………………….……… pTNM stage pT.….. pN……. pM…..… SNOMED codes New primary � Recurrence � Not known � T……………… M………………. Tumour type……………………………… T……………… M………………. Resection of pri Signed: Date: 197 SALIVARY CARCINOMA DATASET Surname ……………………….….. Forenames ……………..….. Date of birth ……...…... Sex …...... Hospital …………………………… Hospital no ………………... NHS no …....……..………….……. Date of receipt …………….……… Date of report …………..…. Report no ……..…….…….….….... Pathologist ……………………………..……….. Surgeon ………...….…...…………..……………..… Primary tumour Site: Parotid � Submandibular � Sublingual � Left / Right Other � Please specify ………………………………………………..…… Histological type ……………………………………….. Histological grade (if appropriate) …………………… Maximum dimension …………………………… (mm) Macroscopic extraglandular extension: Yes / No Minimum excision margin …………………...… (mm) Right neck dissection : Yes � No � Left neck dissection: Yes � No � Comprehensive � Selective � Comprehensive � Selective � Node levels present: I II III IV V VI Other � Node levels present: I II III IV V VI Other � Total number of nodes……………… Total number of nodes…………… Number positive nodes……………... Number positive nodes……………... Levels with metastases: I II III IV V VI Other � Levels with metastases: I II III IV V VI Other � Largest metastasis …..……….. (mm) Largest metastasis …..……….. (mm) Levels with metastases: I II III IV V VI Other � Levels with metastases: I II III IV V VI Other � Largest metastasis…….(mm) Largest metastasis…….(mm) Extracapsular spread Yes � No � Extracapsular spread Yes � No � Levels with ECS……………………… Levels with ECS…………………. Comments/additional information: Summary of pathological data: pTNM stage pT.….. pN……. pM…..… Tumour site………………………….……… SNOMED codes New primary � Recurrence � Not known � T……………… M………………. Tumour type……………………………… T……………… M………………. Resection of primary tumour clear � close � involved � Signed: date: 198 The Royal College of Pathologists Pathology: the science behind the cure TISSUE PATHWAYS FOR HEAD AND NECK PATHOLOGY September 2008 Unique document number G077 Document name Tissue pathways for head and neck pathology Version number 1 Produced by Professor Paul Speight, University of Sheffield (Writing Group Lead), Dr Adam Jones, University of Sheffield, Dr Séamus Napier, Royal Group of Hospitals, Belfast Dr Tim Helliwell, University of Liverpool on behalf of the College’s Cancer Services Working Group Date active April 2008 Date for review April 2011 Comments In accordance with the College’s pre-publications policy, this document was put on The Royal College of Pathologists’ website for consultation from 1 April – 2 May 2008. Fifteen pieces of feedback were received, and the authors considered them and amended the document accordingly. Please email [email protected] if you wish to see the responses and comments. Professor Carrock Sewell Communications The Royal College of Pathologists Director of 2 Carlton House Terrace London, SW1Y 5AF Tel: 020 7451 6700 Fax: 020 7451 6701 Web: www.rcpath.org Registered charity in England and Wales, no. 261035 © 2008, The Royal College of Pathologists 199 CONTENTS General introduction Section A Mucosal biopsies Section B Teeth Section C Cysts: odontogenic and non-odontogenic Section D Minor salivary glands Section E Major salivary glands Section F Jaw lesions Section G Nasal cavity and paranasal sinuses Section H Larynx, pharynx and tonsil Section I Neck lesions Section J References GENERAL INTRODUCTION 1. Staffing and workload Preferably at least two or more pathologists in a unit should be competent in the reporting of specimens from the head and neck. If one of these is not an Oral and Maxillofacial Pathologist with expertise in oral mucosal biopsies and of the special tooth-related and odontogenic pathology of the jaws, then access to this expertise should be ensured. Pathologists reporting head and neck specimens should participate in an appropriate EQA scheme. Lead pathologists should participate in a specialist Head and Neck EQA scheme. There are no clear maximum workloads for a full time head and neck pathologist. The Royal College of Pathologists Guidelines for Staffing and Workload in Histopathology and Cytopathology Departments1 are a guide. Workload may vary considerably according to the nature of the specimens received. Pathologists undertaking a significant amount of oncology work will be able to report fewer requests per year than a pathologist dealing primarily with non-neoplastic specimens. 2. Laboratory facilities The full range of routine laboratory facilities is needed, including access to immunocy to chemistry and electron microscopy, which may be off site. Facilities for sectioning of hard tissue are required, including an appropriate saw (band saw or diamond- coated saw) for dissection of bone resections of the jaws, expertise in decalcification and preparation of specimens of bones and teeth. Fixation in formalin for 24-48 hours after slicing bone, and before decalcification, may improve morphology. Facilities and expertise for the preparation of ground sections of teeth are also sometimes necessary (or should be available off site). Detailed protocols for decalcification are beyond the scope of this document (see Bancroft and Gamble5) and an appropriate balance needs to be reached between slower decalcification for optimal morphology and more rapid decalcification to facilitate patient management. Some decalcifying protocols may interfere with immunocytochemistry and excessive 200 decalcification affects the morphology. In general, strong acids e.g. nitric acid, are best avoided as decalcification is rapid and difficult to control. For most purposes, 5% formic acid is an appropriate decalcifying agent, with the end point confirmed by palpation and/or ammonium hydroxide5. Unless the tissue is likely to fragment or otherwise be distorted, it is recommended that bone is trimmed to block size (approximately) before decalcification. This should allow decalcification to be completed in 1-10 days, although very dense bone may take longer. 3. Specimen submission and dissection Most specimens are received in the laboratory in formalin as routine diagnostic or therapeutic specimens according to standard procedures. For most specimens no special facilities are required for specimen dissection and preparation apart from bone and teeth as mentioned above. It is good practice to photograph large specimens so that a permanent record of the macroscopic appearance and location of blocks can be recorded and filed in the patient records. Specimen dimensions are measured in mm. Fresh tissue specimens are occasionally required primarily for the diagnosis of vesiculobullous lesions using direct immunofluorescence. In these cases a mucosal biopsy is submitted fresh to the laboratory, either immediately wrapped in damp gauze, or in a suitable transport medium. The guidelines for the handling of head and neck specimens may vary according to the type of specimen2. SECTION A. TISSUE PATHWAY: MUCOSAL BIOPSIES 1. Specimen dissection Most of these specimens are small. The specimen is measured in three dimensions. Identify and describe the colour and texture of the mucosa as well as any identifiable lesion e.g. polyp, ulceration. Incisional biopsies of sufficient size are bisected through the long axis, and may be inked to indicate orientation for embedding purposes. For excision specimens the closest excision margins are often best sampled by sectioning across the short axis (transversely). 2. Sectioning Routinely a single section is usually sufficient for diagnostic purposes.Lesions where dysplasia is suspected or needs to be excluded, or from high risk sites (e.g. floor of mouth, non-homogeneous leukoplakia) should have three levels cut at 100µm intervals. 3. Staining Haematoxylin and eosin (H&E) stained sections are required for all cases. White lesions and dysplastic lesions, which are often infected with Candida species, may be stained using PAS with prior diastase digestion. 4. Further investigations These are occasionally needed to confirm a diagnosis and are requested as necessary. Examples include stains for amyloid, immunocytochemistry for suspect lymphomas or melanomas. Immunofluorescence Fresh samples submitted for vesiculobullous disorders are stained for IgG, IgA, IgM and C3. 201 5. Report content The report specifically refers to the overlying epithelium, lamina propria and other identified tissues including an indication of the depth of the biopsy (e.g. by reference to muscle on the deep aspect). Any infective agents or dysplastic features (graded according to the WHO guidelines) are highlighted within the report. For excision specimens of oral leukoplakia, the presence and degree of dysplasia at surgical margins is noted (this is not relevant for small, diagnostic mucosal biopsies). SECTION B. TISSUE PATHWAY: TEETH 1. Specimen dissection Teeth are received in formalin usually with odontogenic cysts or as part of a resection specimen and may require histological examination to determine the vitality of the pulp. This can inform the pathogenesis of a periapical lesion. Occasionally a clinical diagnosis of a tooth disorder requires histological confirmation for example for idiopathic resorption, or developmental disorders. Tooth notation, site, morphology, presence of caries, and filling material are recorded. Assess enamel and dentine structure including colour, transparency, banding, erosion, abrasion and relative hardness. Root number, morphology and presence of resorption are identified. Teeth are usually decalcified before dissection and sectioning. However for diagnosis of enamel defects a ground section is required. In this case the tooth is bisected in a band saw and a ground section taken from one half and the other half submitted to decalcification. 2. Sectioning Incisors, canines and premolar teeth are sectioned in the bucco-lingual plane. Molar teeth are sectioned mesio-distally. 3. Staining Ground sections are viewed using Canada Balsalm as an embedding agent as this has a similar refractive index to normal enamel. Decalcified sections are stained using H&E. 4. Further investigations Accurate clinical information including family history, extent of teeth affected, presence of metabolic bone disorders and examination of radiographs is required for accurate diagnosis of developmental disorders. Disorders of tooth structure require the availability of polarised light microscopy. 5. Report content The report refers to the enamel including thickness, structure, presence of enamel matrix and appearance of amelodentinal junction, and to the dentine including the appearance and presence of mantle zone, pre-dentine, primary, secondary, tertiary and inter-globular dentine. Specifically the appearance and presence of dentine tubules including relative width and orientation as well as the location of dysplastic dentine. Pulp examination includes assessment of the root apex, vitality, inflammation, relative size and location. 202 SECTION C. TISSUE ODONTOGENIC PATHWAY: CYSTS–ODONTOGENIC AND NON 1. Specimen dissection Most of these specimens are small, soft and fragmentary in nature. Record the number of pieces and dimensions of the largest piece. Small hard tissue fragments are common and decalcification overnight is often sufficient. Large fragments of bone and identifiable teeth or tooth fragments are described, decalcified and blocked separately. The relationship to the tooth such as attachment to the cement-enamel junction or root apex is recorded. Tooth notation, caries status and the presence of restorations are documented. Large cysts require a description of the wall and the presence of mural thickening or nodules. Examination of the cyst lumen and its contents may reveal the presence of keratin squames, cholesterol or intraluminal nodules. Small fragmented lesions are embedded in their entirety. Small intact cysts can be bisected. For large cysts, representative transverse slices are best. Care is taken to sample any nodules or mural thickenings. 2. Sectioning A single section is usually sufficient for diagnostic purposes. 3. Staining H&E stains are required for all cases. 4. Further investigations Clinical information and preferably examination of radiographs is required for accurate diagnosis since it is often important to know the relationship to the teeth. Unusual findings require three levels at 100μm as well as further representative samples. Stains for PAS, alcian blue or mucicarmine may be useful in the diagnosis of glandular odontogenic cysts. 5. Report content The report specifically describes the cyst lining and the type and nature of the epithelium e.g. the presence of keratinisation or basal palisading, mucous metaplasia, hyaline (Rushton) bodies, or atypical features. The capsule is described, particularly the presence or absence of inflammation and features such as daughter cysts, calcifications, odontogenic rests or foreign material. SECTION D. TISSUE PATHWAY: MINOR SALIVARY GLANDS 1. Specimen dissection Most of these specimens are relatively small and less than 15mm. Mucoceles are usually fluctuant and may be covered by mucosa. The presence of minor salivary gland tissue is identified. The specimen is measured in three dimensions and may be bisected in the longitudinal plane. For excision specimens, dissection is in planes appropriate to sample the closest excision margins. If multiple lobules of minor salivary gland tissue are received then the collective area is measured. Certain sites such as the upper lip are at an increased risk of tumour development even though these may clinically and macroscopically appear to be mucoceles. Resection specimens are orientated as indicated by the surgeon on the request form. Deep 203 and peripheral excision margins are inked. Care is taken to examine the capsule and record any areas where it is incomplete or ruptured. Where a tumour is suspected, describe its location, consistency (i.e. solid, cystic, gelatinous), capsule and circumscription. Blocks required include: • One block per 10mm diameter of tumour for larger specimens; most specimens will be blocked in their entirety. • Sufficient sampling to determine adequacy of surgical margins • Adjacent mucosa and normal salivary glands. 2. Sectioning A single section from each block is usually sufficient for diagnostic purposes in cystic and inflammatory conditions. 3. Staining H&E stains are required for all cases. 4. Further investigations Stains for PAS, alcian blue or mucicarmine are useful for identifying subtle extravasation of mucin and in the diagnosis of benign salivary gland tumours. Immunohistochemistry is occasionally useful for the diagnosis of salivary gland tumours. 5. Report content Cysts • Nature of cyst and lining i.e. epithelium or connective tissue • Type of inflammatory infiltrate. Presence of atrophy, mucous extravasation, ductal ectasia and minor salivary gland tissue. Benign tumours • Type of tumour as based on WHO guidelines3 • Distance of tumour from the nearest peripheral margin • Distance of tumour from the deep margin • Presence of a capsule and any breach. Any unsuspected malignancy is reported according to the RCPath Head and Neck Cancer Dataset4. SECTION E. TISSUE PATHWAY: MAJOR SALIVARY GLANDS 1. Specimen dissection Submandibular and sublingual glands are usually removed entirely as a result of sialolithiasis. Radiographs may be used to identify a sialolith. Parotid gland specimens most often comprise a superficial parotidectomy of the lower pole of the superficial lobe. Total parotidectomies are rare for benign disease but may be performed 204 for deep lobe tumours. The superficial and deep lobes may be provided separately. Specimens should be orientated by the surgeon and in cases of doubt the surgeon must be consulted. Superficial parotidectomy specimens resemble a triangle, with the smooth surface representing the superficial surface and the shortest profile the superior margin. Deep lobes of the parotid and sublingual glands are difficult to orientate and are best done surgically by the operating clinician. The submandibular gland can be orientated by the indentation produced by mylohyoid on the deep margin and by the duct at the anterior aspect. Required measurements include: • Dimensions and weight (g) of the specimen • Dimension and number of cysts • Dimensions of any identifiable tumour • Distance to the nearest margins • Presence of a capsule and whether or not this is intact. Describe the location of any tumour, its consistency (i.e. solid, cystic, gelatinous), capsule and circumscription. Blocks required include: • One block per cm diameter of tumour • Sufficient sampling to determine the adequacy of surgical margins • Adjacent mucosa and normal salivary glands • Proximal and distal aspect of nerves if identifiable • Any intra-glandular or adjacent lymph nodes. 2. Sectioning Routinely a single section of each block is sufficient for diagnostic purposes in cystic, infective and inflammatory conditions. 3. Staining H&E stains are required for all cases. 4. Further investigations Mucin stains, e.g. PAS, alcian blue or mucicarmine are helpful in the diagnosis of benign salivary gland tumours. Immunohistochemistry is occasionally useful for the diagnosis of salivary gland tumours and for the differential diagnosis of benign lymphoepithelial lesions from extranodal marginal zone (MALT) lymphoma. This can be supplemented by molecular analysis for light and heavy chain restriction. 5. Report content Cysts • Nature of cyst and lining i.e. epithelium or connective tissue 205 • Type of inflammatory infiltrate • Presence of atrophy, mucous extravasation and ductal ectasia • Presence of salivary gland tissue. Benign tumours • Type of tumour as based on WHO guidelines3 • Distance of tumour from the nearest peripheral margin • Distance of tumour from the deep margin • Presence of a capsule and any breach. Any malignancy is reported accordingly4. SECTION F. TISSUE PATHWAY: JAW LESIONS 1. Specimen dissection This category includes a number of benign lesions which necessitate major resective surgery. This includes ameloblastomas and fibro-osseous lesions among other conditions. The presentation of jaw specimens is variable and includes enucleated specimens composed of fragmented pieces of soft tissue or bone as well as bone resections. If multiple fragments are included the number of pieces, total dimensions and dimensions of the largest piece are recorded. It is important to determine the relationship between resection specimens and separate fragments, especially with regard to excision margins. This is particularly relevant to maxillectomy specimens which may become fragmented during removal. If small, all samples are processed, otherwise representative sections are usually sufficient. Some odontogenic tumours and hamartomas are cystic in nature. If associated with teeth, the relationship is documented. In addition, examination of the cyst lumen can reveal the presence of mural or luminal nodules in unicystic ameloblastomas. For larger specimens identification of operation type and orientation is required. Photographs are used and carefully labelled to indicate orientation and the origin of blocks. Radiographs are useful in assessing the extent of the lesion, tooth resorption and the presence of calcification. Required measurements include: • Antero-posterior diameter along the alveolar ridge • Maximum bone height i.e. ramus • Dimensions of tumour • Distance and location of the nearest margin. Surgical margins e.g. mucosal, deep, superior limit of ramus etc. may be inked. Small specimens can be decalcified in their entirety before sampling or blocking out. For large resections, especially of the mandible, it is often helpful to takes slices of 5-8mm on a band saw. It may also be possible to slice maxillary specimens. Sometimes these are very fragile and decalcification of the entire specimen helps sampling and to preserve orientation. As most lesions are intraosseous, dissection of soft tissue from bone is usually not necessary. However, evidence of cortical perforation requires close soft tissue examination and handling as for those resections in malignant disease4. 2. Sectioning 206 A single section of each block is usually sufficient for diagnostic purposes. 3. Staining H&E stains are required for all cases. 4. Further investigations Accurate clinical information is required for accurate diagnosis. In general, hard tissue lesions are not reported without examination of radiographs and/or CT images. Congo red, alizarin red or thioflavine T are useful for the detection of amyloid proteins in adenomatoid and calcifying epithelial odontogenic tumours. Van Gieson stains are useful in identifying dentinoid material e.g. in calcifying cystic odontogenic tumours. Immunohistochemistry is rarely required. 5. Report content An accurate description of any epithelium, including any reference to the formation of duct– like structures as well as the presence of atypical features such as mitotic figures. Atypical features such as pleomorphism are common in some odontogenic tumours including the calcifying epithelial odontogenic tumour. If no odontogenic epithelium is identified this is stated. The appearance of the stroma is described including the presence of enamel, dentine, bone or other calcified material. The presence of amyloid is confirmed with special stains. Comment is made upon the relationship to normal structures, e.g. teeth, bone. The presence of a capsule and nature of the surgical margins are recorded. Any malignant tumour is reported accordingly4. SECTION G. TISSUE PATHWAY: NASAL CAVITY AND PARANASAL SINUSES 1. Specimen dissection Most of these specimens are small and fragmentary in nature. Specimens should be measured in three dimensions. Identify and describe the colour and texture of the mucosa as well as any identifiable lesion e.g. polyp, ulceration. Small specimens are measured and usually embedded whole. Specimens of sufficient size are best bisected through the long axis. Larger samples and sinonasal polyps should have representative samples taken. Unilateral nasal polyps are usually blocked in their entirety because unilateral lesions have a slightly higher risk of being neoplastic than bilateral lesions. Small hard tissue fragments are common and decalcification overnight is often sufficient. Large fragments of bone should be described, decalcified and blocked separately 2. Sectioning A single section of each block is usually sufficient for diagnostic purposes. Three levels at 100µm intervals may be indicated for more detailed examination of papillomas where dysplasia or invasive malignancy is suspected. 3. Staining H&E stains are required for all cases. 207 4. Further investigations PAS, Grocott’s and Gram stains are useful for detecting fungal and bacterial infections. Mycobacterial stains are required in granulomatous conditions. If Wegener’s granulomatosis is suspected, an elastic van Gieson stain may be helpful in identifying damaged vessels and further clinical information on the presence of positive c-ANCA tests and ESR is useful. Immunohistochemistry is usually not necessary in the diagnosis of benign nasal lesions. However, rare soft tissue tumours such as extrapleural solitary fibrous tumour, pituitary gland neoplasm and meningioma may occur. Minor salivary gland tumours and fibro-osseous lesions are reported as indicated in the relevant sections. 5. Report content The report may refer to the overlying epithelium, lamina propria and other identified tissues. Note the type of inflammatory infiltrate. Any infective agents or dysplastic features (graded according to the WHO guidelines) are highlighted. The presence and degree of dysplasia at surgical margins is noted for excision specimens, but this is usually not possible in fragmented samples.. Specific diagnoses are provided for any polypoid lesion i.e. allergic / inflammatory type, inverted papilloma, in view of the potential risk of malignant transformation in the latter. SECTION H. TISSUE PATHWAY: LARYNX, PHARYNX AND TONSIL 1. Specimen dissection Most of these specimens are small or fragmentary in nature. Identify and describe the colour and texture of the mucosa as well as any identifiable lesion, e.g. polyp, ulcer. Measure in three dimensions. Specimens of sufficient size are bisected through the long axis or sliced serially. Piecemeal resection specimens of the pharynx are embedded in their entirety. Resection specimens are orientated as indicated by the surgeon on the request form. Deep and peripheral excision margins are inked. Care is taken to examine the capsule and record any areas where it is incomplete or ruptured. Describe the location of the tumour, consistency (i.e. solid, cystic, gelatinous), capsule and circumscription. Dissection should be in planes appropriate to sample the closest excision margins Laryngectomy specimens and major resections for benign disease are treated as for laryngeal malignancy4. Tonsillectomy specimens : • Are orientated (if possible) and the deep margins inked • Are measured in three dimensions and may be weighed. • Are examined grossly and cut into 4-5mm transverse slices • Should have any abnormality measured and described • Should have representative blocks taken. If there is no macroscopic abnormality, then 2 blocks are sufficient. Note: the ipsilateral tonsil is often the source of metastatic squamous cell carcinoma in the neck, particularly cystic metastases that can mimic branchial cysts. The primary lesion may be microscopic. In cases of tonsillectomy for patients who have proven or suspected metastasis in neck nodes and where tumour is not clearly identified within the tonsil at macroscopic examination, the tonsillectomy specimen is blocked serially and submitted in 208 total to exclude a microscopic primary in the tonsil itself. 2. Sectioning A single section from each block is usually sufficient for diagnostic purposes. Lesions from high risk sites i.e. non-homogeneous leukoplakia from the vocal cords have three levels at 100µm intervals. Retention of unstained sections is preferable, if resources permit. 3. Staining H&E stains are required for all cases. Lesions suspicious of Candida infection are stained with PAS and diastase pre-treatment . 4. Further investigations Immunohistochemistry is usually not required, although this may be beneficial for some rare diagnoses. 5. Report content The report specifically refers to the overlying epithelium, lamina propria and other identified tissues. Any infective agents or dysplastic features (graded according to the WHO guidelines) are highlighted within the report. The presence and degree of dysplasia at surgical margins is noted. Salivary and other benign tumours are reported as discussed in the relevant sections. SECTION I. TISSUE PATHWAY: NECK LESIONS 1. Specimen dissection Swellings of the neck can be associated with any closely related structures such as lymph nodes, thyroid, salivary glands, blood vessels, nerves or fat. A wide variety of disease may present but most relate to cervical lymph node enlargement. For benign disease, most neck specimens are small excisional biopsies. Neck dissection is handled as for malignant disease4. Lymph nodes – small nodes (up to 4 mm in maximum dimension) are embedded whole. Nodes up to 10 mm around the equator (around the girth) are bisected longitudinally through the hilum (or “bivalved”) and embedded in total. Nodes larger than 10 mm in the equatorial plane are sliced serially at approximately 4mm intervals and have 2 or 3 representative slices embedded. Cysts - measure in three dimensions. Thyroglossal cysts usually present as a strip of fibrous tissue surrounded by fat and muscle. Branchial cysts are typically submitted intact. Sufficient sampling of branchial cysts is required to rule out the possibility of a cystic metastatic carcinoma. Examine the cyst lumen for nodules and record the nature of contents and thickness of the cyst wall. Small specimens are bisected or embedded intact, while larger specimens are serially sliced and representative blocks (2-4) taken. Soft tissue tumours and carotid body paragangliomas - these are not usually orientated and may be fragmented. Ink the external surfaces and measure: 209 • Dimensions of the specimen • Dimensions of the tumour (if different from those of the specimen) • Distance from tumour to the nearest surgical margin or to marked vessels and nerves. Describe the tumour including the colour, whether encapsulated or infiltrative, and the presence of haemorrhage and necrosis. Serially slice the tumours into 4-5mm sections. Representative blocks include one block per cm of tumour. Record the presence of necrotic and haemorrhagic areas. 2. Sectioning A single section per block is usually sufficient for diagnostic purposes. Lymph nodes – usually one section per block (see also lymph node Tissue Pathway).. 3. Staining H&E stains are required for all cases. 4. Further investigations Immunohistochemistry may be useful for a range of neck lesions including for micrometastases, to exclude lymphomas, and in the diagnosis of soft tissue tumours. 5. Report content For cysts the report should record: • Cyst lining i.e. keratinisation, presence of atypical features and mitotic figures • nature of the capsule such as fibrous, fibro-myxoid and the degree of inflammation • Presence of foreign body reaction to ruptured cysts. For tumours the report should record: • Type • Tumour – tissue interface i.e. infiltrative or encapsulated • Relationship to major vessels and nerves • Nearest surgical margin. REFERENCES 1. Guidelines on Staffing and Workload for Histopathology and Cytopathology Departments. 2 edition. RCPath. June. 2005. http://www.rcpath.org/resources/pdf/GuideHistoCytoWorkload0605.pdf nd 2. Allen DC, Cameron RI. Histopathology Specimens: Clinical, Pathological and Laboratory Aspects. Springer-Verlag. London. 2004. 3. Barnes L, Eveson JW, Reichart P, Sidransky D. World Health Organization Classification of Tumours: Pathology and Genetics of Head and Neck Tumours. IARC Press. Lyon. 2005. 4. Helliwell TR, Woolgar JA. Standards and Datasets for Reporting Cancers: Datasets for histopathology reports on head and neck carcinomas and salivary neoplasms. 2nd edition. Royal College of Pathologists. 2005. 210 http://www.rcpath.org/resources/pdf/HeadNeckDatasetJun05.pdf 5. Bancroft JD, Gamble M. Theory and practice of histological techniques. Fifth edition. Churchill Livingstone, London, 2002, pages 274-279. 211 Standards and datasets for reporting cancers Dataset for thyroid cancer histopathology reports April 2010 Coordinators: Professor Timothy J Stephenson, Sheffield Teaching Hospitals NHS Foundation Trust Dr Sarah J Johnson, Royal Victoria Infirmary, Newcastle upon Tyne Unique document number Document name Version number Produced by Date active Date for review Comments G098 Dataset for thyroid cancer histopathology reports 2 Professor Timothy J Stephenson, Sheffield Teaching Hospitals NHS Foundation Trust Dr Sarah J Johnson, Royal Victoria Infirmary, Newcastle upon Tyne April 2010 April 2012 In accordance with the College’s pre-publications policy, this document was on The Royal College of Pathologists’ website for consultation from 22 February to 22 March 2010. 40 items of feedback were received and the authors considered them and amended the document if deemed appropriate. Please email [email protected] if you wish to see the responses and comments. Dr Peter Cowling Director of Communications The Royal College of Pathologists 2 Carlton House Terrace, London, SW 1Y 5AF Tel: 020 7451 6700 Fax: 020 7451 6701 Web: www.rcpath.org Registered charity in England and W ales, no. 261035 © 2010, The Royal College of Pathologists PUB 190410 1 V1 Final 212 Contents Foreword ............................................................................................................................3 1. Introduction ...................................................................................................................3 2. Clinical information required on the specimen request form .........................................4 3. Specimen handling, description and block selection.....................................................5 4. Microscopic report.........................................................................................................6 5. Core data items.............................................................................................................7 6. Non-core data items....................................................................................................10 7. Recommendation: TNM pathological staging (seventh edition, UICC)........................10 8. SNOMED coding.........................................................................................................11 9. Audit criteria ................................................................................................................11 10. References ................................................................................................................12 Appendix A TNM staging (seventh edition, UICC).............................................................16 Appendix B SNOMED codes ............................................................................................18 Appendix C Dataset for thyroid cancer histopathology ......................................................19 Appendix D Thyroid carcinoma dataset monitoring sheet (AGREE standards) .................21 213 Foreword The Cancer Datasets published by the Royal College of Pathologists are guidelines that should assist pathologists in providing a high standard of care for patients. Guidelines are systematically developed statements to assist the decisions of practitioners and patients about appropriate health care for specific clinical circumstances and are based on the best available evidence at the time the dataset was prepared. It may be necessary or even desirable to depart from the guidelines in the interests of specific patients and special circumstances. Just as adherence to the guidelines may not constitute defence against a claim of negligence, so deviation from them should not necessarily be deemed negligent. The dataset has been reviewed by the Cancer Services Working Group and was placed on the College website for consultation with the membership from 22 February to 22 March 2010. All comments received from the Working Group and membership have been addressed by the authors to the satisfaction of the Chair of the Working Group and the Director of the Professional Standards Unit. No major organisational changes have been identified that would hinder the implementation of the dataset. Each year, the College will ask the authors of the dataset, in conjunction with the relevant sub-specialty adviser to the College, to consider whether or not the dataset needs to be revised. This dataset was developed without external funding to the writing group. The College requires the authors of datasets to provide a list of potential conflicts of interest; there are none. 1. Introduction 1.1. Endocrine cancer datasets The management of endocrine tumours is the responsibility of an appropriately experienced multidisciplinary team (MDT). Since these tumours bridge various anatomical divides, they are dealt with by a number of specialist teams. Because several mimics of thyroid carcinomas exist,1,2 the pathologist reporting them should ideally have a special interest in endocrine pathology. Alternatively, he/she should have an interest in endocrine tumours in his/her area of systematic pathology or, if a general pathologist, should participate in a network with the opportunity for specialist pathology review since observer variation is well documented in thyroid tumours3,4 and the range of prognostic features5 can require experience in their recognition. The reporting pathologist should either be a core member of the Thyroid Cancer MDT or have access to a pathologist who is a core member, for review purposes. Each group of tumours is dealt with in a separate section. Although the guidelines of The Royal College of Pathologists (RCPath) are primarily aimed at collecting core data in the reporting of cancers, we suggest that the endocrine guidelines also provide a useful template for the reporting of benign endocrine tumours and for hyperplastic conditions. We have therefore included some of these options in the dataset proforma (see Appendix C, section on adjacent thyroid). 1.2. Thyroid cancer dataset 214 The proper handling and reporting of the thyroid tumour specimen is important as gross and histological features contribute to the staging of the tumour, and this has implications for prognosis and therapy. There are several systems for staging thyroid tumours. The Royal College of Physicians (RCP) and the British Thyroid Association’s recent guidelines6 recommended the use of the TNM system of staging, using both its pathological component and the suggested conversion to clinical staging. Our recommendation is to adopt the seventh edition,7 as it reinstates a therapeutically important feature of the fifth edition which was deleted in the sixth edition. We have restricted our recommended data to the pathological component of TNM; the seventh edition7 may be consulted for detail of how to map this to the recommended clinical stage if desired locally. These proposals for the reporting of thyroid cancers should be implemented for the following reasons: 1. Pathological staging is important in deciding the correct clinical management of these tumours. 2. Outcome has been shown to be related to particular features (e.g. variants of papillary carcinoma; minimal or wide invasion in follicular carcinoma, and since publication of the previous thyroid cancer dataset, number of foci of capsular and/or vascular invasion in encapsulated follicular variant papillary carcinoma, number of foci of vascular invasion in both minimally invasive and widely invasive follicular carcinoma8,9 and the proper definition of poorly differentiated thyroid cancer).10,11 These features should therefore be included in histopathology reports to: a) provide prognostic information to the surgeon/physician treating the patient; b) provide accurate data for cancer registration and national datasets. This document has been devised to include the data required for a careful assessment of a thyroid cancer specimen. Where possible, it is evidence based. It has been widely discussed and approved by the UK Endocrine Pathology Society (www.ukeps.net), the British Thyroid Association (www.british-thyroid-association.org), the British Association of Endocrine and Thyroid Surgeons (www.baes.info) and the British Association of Head and Neck Oncologists (www.bahno.org.uk). Panels of specialist and general histopathologists acting on behalf of the College have also reviewed it. The following text outlines the approach to be taken in handling specimens. Aspects of best practice in handling thyroid specimens have been reviewed12 and there are descriptions of the clinically-oriented pathology of the thyroid.13 A synoptic reporting proforma has been provided as an aide memoire for the core data on these neoplasms. This may be supplemented by a more detailed written report. It is beyond the scope of this document to discuss the details of fine needle aspiration (FNA) cytology of thyroid, but most lesions should have had FNA before surgery, so a differential diagnosis may be available. The cytopathologist should be a member of the MDT or have access to a pathologist who is. The descriptive cytology report will inform the clinical d e c i s i o n s o n management. We r e c o m m e n d a d d i t i o n a l u s e o f t h e n u m e r i c a l categories Thy1−5 as proposed in the guidelines of the RCP/British Thyroid Association,6 recently updated by the RCPath in consultation with the British Society for Clinical Cytology and other interested parties.14 Intraoperative frozen section is occasionally used to confirm the diagnosis of papillary carcinoma, medullary or anaplastic carcinoma, or to identify lymph node involvement. It should not be used to differentiate follicular carcinoma from adenoma. This is because follicular carcinoma is an architectural diagnosis, based on the finding of capsular or vascular invasion which can be very focal. Incision of an unfixed specimen can, 215 additionally, disrupt the capsule rendering subsequent assessment of the fixed tissue difficult. Even with papillary carcinoma, which can be diagnosed on frozen sections, extra care needs to be taken as the characteristic nuclei with their clearing are an artefact of formalin fixation/paraffin processing and they may not be fully developed in frozen sections15,16 2. Clinical information required on the specimen request form This should include full patient details, clinical presentation, results of previous cytology and biopsies, and of imaging investigations. The patient’s thyroid hormonal status should be given where relevant, together with details of any hormonal or drug therapy and any familial cancer or endocrine tumour syndromes. If the operation has resulted in multiple specimens or parts thereof, then these should be catalogued explicitly. Any specimens which may bedifficult to orientate should have orientation markers attached and these should be described on the specimen request form, with diagrams where words alone will not suffice. 3. Specimen handling, description and block selection 3.1. Gross examination The specimen will usually be described as total (or near-total) thyroidectomy; right or left hemithyroidectomy (+/- isthmus) or isthmusectomy. It should be noted whether the thyroid capsule appears intact on receipt (excluding the intrathyroidal margin on lobectomy specimens). The specimen should be weighed, measured and described grossly, particularly if there are any unusual features. In thyroidectomy specimens, measurements of each lobe and isthmus (plus pyramidal lobe if present) should be noted where possible. The surface should be inked. The specimen should then be sliced (usually transversely) at intervals no thicker than a tissue block, and the cut surfaces of all the slices should be inspected. The appearance and location(s) of the lesion(s) should be noted. The inclusion of a diagram or photograph in the records with annotation of block selection is best practice. It is important to record the greatest dimension of the lesion (or of the largest lesion, if multiple) as this defines the pT status. If this is < 20 mm, the macroscopic size should be confirmed or adjusted by the microscopic measurement of size. The presence of macroscopically- apparent direct extension beyond the thyroid, which is prognostic,17 should be recorded, including which anatomical structures are invaded, to inform the pT3/4 staging. Clearances from the thyroid capsule and relevant resection margins should be measured and noted. The site of any possible parathyroid glands should be noted and they should be sampled if present. The number and site of lymph nodes submitted or identified in the main specimen should be recorded, and all the nodes should be sampled. Sampling of formal neck dissections should follow protocols published with the guidelines for tumours of the head and neck (http://www.rcpath.org/index.asp?PageID=1158). Central/level VI lymph nodes are often submitted with known papillary carcinoma specimens. 3.2. Block selection The number of blocks taken will vary according to the tumour type. Tumour type may be known or suspected from any preoperative cytology, enabling appropriate block taking when the specimen is initially dissected. Alternatively, the specimen may require extra blocks to be taken after the initial histological diagnosis has been made. The use of mega 216 blocks may be considered to show resection margin relationships to large lesions and they may show the entire circumference of capsule of such lesions in one section. 3.2.1. Papillary carcinoma (PTC) For papillary carcinoma, there are few published studies regarding sampling. Some recommend that the whole gland is processed.18 However, a more practical approach is to block the whole tumour if the lesion is ≤ 20 mm in diameter; if larger, it should be sampled widely enough (as a compromise we suggest at least two blocks per cm diameter of tumour) to permit diagnosis and to assess whether the tumour is of uniform type. Blocks of the tumour edge and of the thyroid margin closest to the tumour should be taken to assess completeness of excision. Any surgical excision margin within the thyroid (e.g. isthmic margin in a lobectomy specimen) should be processed. Any apparent extrathyroidal extension should be sampled. Apparently normal tissue from the ipsilateral lobe and the contralateral lobe (where present) should be examined carefully for evidence of tumour. Any suspicious areas, such as nodules or pale scarred-looking areas, should be sampled. Even when no other lesions are identified by naked-eye examination, two blocks of normallooking tissue should be taken from each lobe. This is to assess whether the lesion is single or multifocal, as multifocal lesions have a poorer outcome,19 and to look for other background conditions. The presence of multifocal disease is reflected in the staging; therefore, if one papillary microcarcinoma (equivalent to stage pT1a)7 is found, the rest of the specimen should be examined carefully for multifocality. 3.2.2. Follicular neoplasms Follicular lesions that are not grossly invasive should be widely sampled at the interface between the tumour capsule and normal gland,15 to detect capsular and/or vascular invasion. Some suggest that the total interface is examined histologically in all cases.20 A more practical approach is to process small lesions (≤ 30 mm in diameter) in their entirety and to take at least 10 blocks from larger lesions.21,22 Where there are multiple nodules, the largest should be processed as described. Any others showing obvious encapsulation should also be sampled, as should those with unusual features, such as solid areas or a pale colour. Follicular lesions that are grossly invasive should be sampled widely enough to allow identification of any poorly differentiated carcinoma,10 documentation of foci of vascular invasion,8,9 measurement of distance to resection margins, and recognition of spread beyond the thyroid capsule with documentation of the tissues found to be invaded. 3.2.3. Medullary carcinoma In cases of intrathyroidal medullary carcinoma, the specimen should be blocked adequately to confirm the diagnosis, recognise the relationship to the thyroid capsule and detect any extrathyroidal extension with definition of which tissues are invaded.18 The non-involved gland may be examined for evidence of C-cell hyperplasia in an attempt to identify familial cases. C cells are usually found in the central parts of the middle and upper thirds of the lobes so these areas must be sampled. See section 5.3 regarding genetic testing for familial mutations which should be discussed at the MDTM and is tending to replace detailed histology for indentification of C cell hyperplasia. 4. Microscopic report There are a number of features that should be documented in all tumours, and specific features relating to the individual tumour types. Differentiated tumours may contain a minority component of more poorly differentiated tumour. Reports should specifically state whether or not any foci of poorly differentiated carcinoma have been found, as they may confer a worse prognosis.10,23 Such poorly differentiated components may be recognised by tumour necrosis and elevated mitotic count,11 as well as by growth pattern. Only when poorly differentiated carcinoma constitutes the majority (> 50%) of the tumour should the 217 overall classification change. However, where there is any focus of anaplastic change, the tumour should be classified overall as undifferentiated/anaplastic (further, all anaplastic carcinomas are defined as stage pT4).7 4.1. Core data items for all malignant thyroid tumours • Type of malignancy. • Whether a carcinoma is a single lesion or multifocal. • Maximum dimension of carcinoma (largest if multifocal). • Closest distance to surgical resection margin. • Extension into extrathyroidal tissues, which should be identified, and whether the extension is macroscopic or microscopic. • Number of foci of any lymphatic/vascular invasion. • Site and number of lymph nodes sampled and number of those involved. • SNOMED codes, in a version approved by the local cancer registry. 4.2. Non-core data items • • Detailed tumour subtypes, beyond the core data, may be recorded. Incidental microscopic conditions in the background thyroid should be recorded: 1. to account for macroscopically described lesions that have prompted block taking; 2. when they may have affected the clinical impression of tumour extent (e.g. benign, background nodules); and 3. when they may have clinical implications for the aftercare of the patient (e.g. hyroiditis). 5. Core data items 5.1. Papillary carcinoma There are a number of variants which have to be defined as they are prognostically important. Papillary microcarcinoma A single classical papillary microcarcinoma (≤ 10 mm in diameter) discovered incidentally in the examination of a hemithyroidectomy/thyroidectomy performed for another disease is not thought to have a significant risk of recurrence or metastasis. These should be defined separately.2,6,24 When such a microcarcinoma is identified, any residual thyroid tissue should be examined carefully for multifocal disease. The report must state clearly whether there is unifocal or multifocal carcinoma as the recommended treatment differs.5,25−28 Clinical papillary carcinoma These tumours present clinically as thyroid masses or with lymph node metastases. A number of variants of papillary carcinoma have been defined including the follicular variant, the encapsulated variant and the solid variant, all of which are thought to have a similar prognosis to the typical papillary carcinoma. It is important to differentiate the tall cell and columnar variants, as there is some evidence that these may show more aggressive behaviour.29,30 The outcome of the diffuse sclerosing variant is a matter of debate.31,32 As with follicular tumours, an oncocytic variant is also recognised but this should only be diagnosed when the characteristic nuclear features of papillary carcinoma are present. Papillary architecture in a follicular oncocytic tumour should not be misinterpreted.33,34 Follicular variant of papillary carcinoma (FVPTC) Evidence is emerging that FVPTC should be divided into two entities: a non-encapsulated 218 invasive type which has a metastatic potential like classical papillary carcinoma, and encapsulated type which has behaviour that is partially similar to follicular carcinoma.11,35 In particular, encapsulated FVPTC has very low metastatic potential if no capsular or vascular invasion is found, leading some authors to recommend use of the term (which we have not adopted): “well differentiated tumors of uncertain malignant potential (WDT-UMP)”.36 This metastatic potential increases significantly if four or more foci of capsular or vascular invasion are found in total, and even more if ten or more invasive foci are identified.11 Some thyroid nodules have small, non-contiguous foci individually qualifying as FVPTC within them, posing a dilemma as to whether to regard these as multifocal microcarcinomas or as unifocal and equivalent to the maximum diameter of the whole nodule. The latter approach is recommended on the basis of molecular biological evidence that the entire extent of these lesions tends to have features of FVPTC.37 The FVPTC may also show oncocytic change. As with the usual PTC, these are differentiated from oncocytic follicular tumours on the basis of nuclear features. FVPTC is subject to observer variability in its diagnosis,3,4 which relies upon identification of the defining nuclear features for papillary carcinoma: optically clear, enlarged, oval nuclei which have frequent nuclear grooves, some intranuclear cytoplasmic inclusions and may overlap each other.3,4 The threshold for referring lesions thought to be FVPTC to an expert thyroid pathologist should be low. In the hands of such pathologists, and in laboratories regularly performing immunohistochemistry on such tumours, the expression of recognised markers of papillary carcinoma, including its variants, can be useful in the identification of FVPC. The markers found to be useful include cytokeratin 19, high molecular weight cytokeratins and HBME1. 38,3 9 The adverse histological subtypes of the rare tall cell and the even rarer columnar cell PTC variants, defined by their cell height to width ratio and their detailed nuclear features, should be specifically mentioned if present in other than occasional small foci.20 To prevent overdiagnosis of the variant, we suggest a stringent approach to diagnosis of the tall cell variant, whereby a height to width ratio of 3x is required in the majority (> 50%) of the tumour. At present, grading of such tumour has not been included in the reporting proforma, although there is emerging evidence that grade, especially presence of the poorly differentiated grade (however defined), is important in prognosis.11, 40, 41 5.2. Follicular neoplasms A follicular neoplasm is defined as carcinoma on the basis of capsular and/or vascular invasion. Capsular invasion is characterised by complete penetration of the capsule, often with capsular blunt-ended breaks. Care should be taken in assessing this, as the invading tongue of tumour may stimulate the formation of a neocapsule.1,4 Entrapment of groups of cells or follicles in the capsule is not defined as invasion. Distinction between this entrapment and true invasion may need levels to be cut and/or the taking of further blocks. Pseudoinvasive changes may be seen following FNA.42, 43 These are usually accompanied by inflammation, haemosiderin deposition and/or new fibrosis.43 Vascular invasion is defined as invasion of large calibre vessels within or beyond the tumour capsule. The tumour cells should normally project into the vessel lumen, attach to the luminal aspect of the vessel wall and be covered by endothelium.21 Minimally invasive tumours show only focal microscopic vascular and/or capsular invasion. It is important to indicate whether there is only capsular invasion or whether the tumour is angioinvasive, and to define the frequency of vascular invasion. Tumours showing only capsular invasion have a minimal risk of metastasis. However, those with vascular invasion have a higher risk, and this increases with the frequency of vascular involvement, being demonstrably worse if four or more foci of vascular invasion are documented.9,11 219 The tumour is defined as widely invasive when it shows obvious gross invasion or extensive microscopic infiltration of thyroid parenchyma, capsular or extratumoural vessels, or extrathyroidal tissues. In most cases, these are not difficult to recognise. However, where the diagnosis is made on the basis of histology, there are no absolute published criteria for defining the threshold. Some would put otherwise minimally invasive tumours with high incidences (e.g. 10 or more) of demonstrable vascular invasion into this category, although we recommend leaving these in the minimally invasive category and communicating the adverse prognosis through recording in the dataset the number of foci of vascular invasion found. Widely invasive tumours have a worse prognosis than the minimally invasive lesions11 and the prognosis worsens still further in proportion to the number of foci of vascular invasion found.9 For diagnostic purposes, oncocytic (Hürthle cell) follicular tumours are regarded as a variant of follicular tumours and the criteria for the assessment of malignancy are the same. This category should be restricted to tumours comprising at least 75% oncocytic cells.18,33,34 More focal oncocytic change can be found in ordinary follicular lesions. The distinction from oncocytic follicular variant of papillary carcinoma is made on the nuclear features, as outlined above. Other variants of follicular carcinoma including clear cell and signet ring cell tumours are described, but there is no evidence that their behaviour is significantly different.18 For thyroid carcinoma, including the follicular category, there is emerging evidence there may be higher grade variants of tumour that confer a worse prognosis. In particular, the finding of a trabecular or solid growth pattern and/or a mitotic count of 1−4 per 10 hpf is thought to be associated with an adverse prognosis,7 although we have not extended the dataset specifically to include this in the current revision. 5.3. Medullary carcinoma In best practice, the diagnosis should be confirmed by calcitonin immunoreactivity. In the written histology report, it is usual to describe the cellular pattern, but this has no prognostic significance,45 so is omitted from the dataset. The presence of amyloid, confirmed by appropriate histochemical stains, is thought to confer a better prognosis, but does not influence treatment, so again this is omitted from the dataset. Tumour desmoplasia is thought to be an adverse prognostic indicator,46 but has been omitted from the dataset until there is further confirmation. In less well-differentiated tumours, where calcitonin immunoreactivity is lost, positivity for carcinoembryonic antigen (CEA) may serve as a surrogate marker.47 Loss of calcitonin immunoreactivity is now considered not to be of adverse prognostic significance.44 In the syndromes of multiple endocrine neoplasia (MEN) Type 2 and familial medullary thyroid carcinoma (FMTC), medullary carcinoma is often multifocal and preceded/accompanied by C-cell hyperplasia.48 However, the histological evaluation of Ccell hyperplasia can be difficult, as the normal range is not properly defined.49 In addition, extension of the tumour within the gland may produce nodules in the near vicinity. Finally, the presence of C-cell hyperplasia may not necessarily correlate with familial disease as there are data to suggest that mild degrees can be found around other tumours and in a variety of other pathological conditions.45 We suggest, therefore, that this diagnosis is only made when nodules of C cells, confirmed by calcitonin immunoreactivity, are found in blocks that do not contain the main tumour. Diagnosing C-cell hyperplasia histologically is optional as clinical guidelines recommend that all newly diagnosed patients with medullary carcinoma have genetic testing for RET mutations to detect familial syndromes.50 5.4. Poorly differentiated carcinoma 220 This group includes follicular cell-derived tumours with necrosis and/or with mitotic counts of 5 or more per 10 hpf.11 Their growth patterns may be insular (the cells arranged in welldefined nests resembling pancreatic endocrine tumours),10 trabecular or solid.51 Before the tumour is placed in this category, the ‘majority (> 50%)’7 or ‘predominant’11 component should have this appearance. We have, however, included mention of minority components of poorly differentiated carcinoma in the dataset as there is a report that even the presence of a minor component of poorly differentiated carcinoma significantly worsens the prognosis.52 It is also important to note that if the nuclei have the characteristic features of papillary carcinoma and the tumour has a solid growth pattern, then it should not be diagnosed as poorly differentiated carcinoma but as the solid variant of papillary cancer, which has a rather better prognosis than poorly differentiated carcinoma.51 It is important to recognise poorly differentiated carcinomas as they have a worse prognosis than differentiated carcinoma, although in the few instances where the poorly differentiated carcinoma only shows minimal invasion or is encapsulated, the prognosis is worsened to the same degree.11 Poorly differentiated carcinoma usually expresses thyroglobulin, may or may not respond to radio-iodine treatment and is generally thought to represent part of the spectrum between differentiated and anaplastic tumours.53 Where there is concern that a poorly differentiated appearing tumour may be C-cell derived (i.e. medullary carcinoma), the immunohistochemistry should include CEA and calcitonin antibodies as the term poorly differentiated carcinoma is reserved for follicular cell-derived tumours. Medullary carcinoma is classified as such irrespective of the growth pattern. 5.5. Undifferentiated/anaplastic carcinoma Where a follicular or papillary carcinoma shows even a minor undifferentiated (anaplastic) component, the diagnosis is that of undifferentiated/anaplastic carcinoma.7 Most undifferentiated tumours will not have a surgical resection, but will be diagnosed by FNA or occasionally by open biopsy. Where a resection is performed, multiple blocks should be taken and immunostaining for thyroglobulin, TTF1 and calcitonin may be performed to attempt to identify a differentiated component. These stains are almost always negative in the anaplastic areas. Immunocytochemistry for cytokeratins (testing for a wide range is recommended) may confirm the epithelial nature.34,39 Often, however, the diagnosis is one of exclusion, and the most important differential diagnosis to exclude is lymphoma,54, 55 as this has a radically different prognosis and treatment. 5.6 Mixed/combination tumours When one or multiple foci recognisable as papillary carcinoma are present within what would otherwise be an encapsulated follicular adenoma, it is accepted convention to stage the tumour as a unifocal follicular variant papillary carcinoma equivalent to the full size of the encapsulated lesion.37 Other rare tumours include mixed follicular/medullary and mixed papillary/medullary carcinomas.56 These may show immunohistochemical features of both components. 6. Non-core data items Tumourgrade We do not advocate use of tumour grading systems beyond the grades and types in the core data since only the latter have consistently proven to be of clinical significance. Histological subtypes beyond the core data These may be included to facilitate teaching and research, and to demonstrate to any 221 reviewing pathologist that they have been recognised, but their clinical significance has been proven to be low, compared with the core data. Parathyrois Where possible parathyroid glands should be identified macroscopically, and processed to confirm their nature and the presence or absence of any pathology. The presence of any parathyroid tissue or glands should be stated in the report, to provide correlation with any clinical concerns over calcium status. Adjacent thyroid It is recommended that pathological evidence of autoimmune thyroid disease (AITD) is recorded in the dataset. This may help elucidate the relationship between AITD and the pathogenesis of thyroid tumours and is good practice in correlating with clinical status. Incidental neoplasia may be found, such as incidental papillary microcarcinoma, prompting a search for multifocal disease or rendering an already-diagnosed papillary carcinoma multifocal. 7. TNM pathological staging (seventh edition, UICC) The recommendation to use the seventh edition7 (see Appendix A) is based on the fact that the pT1a cut-off is ≤ 10 mm, allowing the identification of papillary microcarcinomas as a separate group. This is important as they generally have a benign biological behaviour and may be treated by lobectomy and thyroid stimulating hormone suppression rather than total thyroidectomy and radioactive iodine therapy.2,6 In the sixth edition, these were grouped together with tumours up to 2 cm. The latter have a different prognosis and treatment, which led many groups at that time to recommend continued use of the fifth edition. Resection (R) stage is deemed R0 when there is no microscopic evidence of true resection margin (RM) involvement. (No definition exists of a tumour distance from the RM that indicates RM involvement.) Microscopic RM involvement defines the stage as R1 while macroscopic RM involvement defines it as R2. For R2, the surgeon will typically infer that resection has been incomplete. 8. SNOMED coding See Appendix B. 9. Audit criteria The following standards are suggested as some of criteria that might be used in periodic reviews of the thyroid pathology service. • • • • Completeness of histopathology reports expressed as average proportion of the core data items recorded, or as proportion of the reports that successfully include 100% of the items – the standard is that all contain 100% of the items; Size distribution of tumour maximum diameters as a graph – the standard is that the distribution should be smooth and continuous with no obvious rounding of measurements, e.g. to nearest 0 or 5 figure; Number of lymph nodes found in specific specimen types; Inter- and intra-observer studies in classification of tumours. 222 10. References 1. Al-Sam S, Lakhani SR, Davies JD. A Practical Atlas of Pseudomalignancy. London: Hodder Arnold, 1998. 2. Lloyd RV, Douglas BR, Young WF. Endocrine Diseases: AFIP Atlas of Nontumor Pathology. Washington: American Registry of Pathology and Armed Forces Institute of Pathology, 2002. 3. Hirokawa M, Carney JA, Goellner JR, DeLellis RA, Heffess CS, Katoh R, et al. Observer variation of encapsulated follicular lesions of the thyroid gland. Am J Surg Pathol 2002;26:1508−1514. 4. Elsheikh TM, Asa SL, Chan JK, DeLellis RA, Heffess CS, LiVolsi VA, et al. Interobserver and intraobserver variation among experts in the diagnosis of thyroid follicular lesions with borderline nuclear features of papillary carcinoma. Am J Clin Pathol 2008; 130: 736−744. 5. 6. Stephenson TJ. Prognostic and predictive factors in endocrine neoplasia. Histopathology2006;48:629−643. Guidelines for the Management of Thyroid Cancer (2nd edition). Royal College of Physicians and British Thyroid Association, 2007. http://www.british-thyroid-association.org/news/Docs/Thyroid_cancer_guidelines_2007.pdf 7. Sobin LH, Gospodarowicz MK, Wittekind C. TNM Classification of Malignant Tumours (7thedition). Oxford: Wiley-Blackwell, 2009. 8. Ghossein RA, Hiltzik DH, Carlson DL, Patel S, Shaha A, Shah JP, et al. Prognostic factors of recurrence in encapsulated Hurthle cell carcinoma of the thyroid gland: a clinicopathologic study of 50 cases. Cancer 2006;106:1669−1676. 9. Collini P, Sampietro G, Pilotti S. Extensive vascular invasion is a marker of risk of relapse in encapsulated non-Hürthle cell follicular carcinoma of the thyroid gland: a clinicopathological study of 18 consecutive cases from a single institution with a 11year median follow-up. Histopathology 2004;44:35−39. 10. Decaussin M, Bernard MH, Adeleine P, Treilleux I, Peix JL, Pugeat M et al. Thyroid carcinomas with distant metastases: a review of 111 cases with emphasis on the prognostic significance of an insular component. Am J Surg Pathol 2002;26:1007−1015. 11. Ghossein RA. Problems and controversies in the histopathology of thyroid carcinomas of follicular cell origin. Arch Pathol Lab Med 2009;133:683−691. 12. Anderson CE, McLaren KM. Best practice in thyroid pathology. J Clin Pathol 2003;56:401–405. 13. 14. Arora A, Tolley N, Tuttle RM. Practical Manual of Thyroid and Parathyroid Disease. Oxford: Wiley-Blackwell, 2009. Royal College of Pathologists. Guidance on the reporting of thyroid cytology specimens. London, The Royal College of Pathologists, 2009. 223 http://www.rcpath.org/resources/pdf/g089guidanceonthereportingofthyroidcytologyfinal.pdf 15. Thompson LDR. Endocrine Pathology. Philadelphia: Elsevier, 2006. 16. Osamura RY, Hunt JL. Current practices in performing frozen sections for thyroid and parathyroid pathology. Virchows Arch 2008;453:433-440. 17. Arora N, Turbendian HK, Scognamiglio T, Wagner PL, Goldsmith SJ, Zarnegar R et al. Extrathyroidal extension is not all equal: Implications of macroscopic versus microscopic extent in papillary thyroid carcinoma. Surgery 2008;144:942-948. 18. Rosai J, Carcangiu ML, DeLellis RA. Atlas of Tumor Pathology: Tumors of the Thyroid Gland (3rd series). Washington: Armed Forces Institute of Pathology, 1992. 19. Loh KC, Greenspan FS, Gee L, Miller TR, Yeo PP. Pathological tumor-node metastasis (pTNM) staging for papillary and follicular thyroid carcinomas: a retrospective analysis of 700 patients. J Clin Endocrinol Metab 1997;82:3553–3562. 20. LiVolsi VA, Asa SL. Endocrine Pathology. Edinburgh: Churchill Livingstone, 2002. 21. Lester SC. Manual of Surgical Pathology (2nd edition). Philadelphia: Churchill Livingstone,2006. 22. Westra WH, Hruban RH, Phelps TH, Isacson C. Surgical Pathology Dissection: An Illustrated Guide (2nd edition). London: Springer Verlag, 2003. 23. Sasaki A, Daa T, Kashima K, Yokoyama S, Nakayama I, Noguchi S. Insular component as a risk factor of thyroid carcinoma. Pathol Int 1996;46:939–946. 24. Noguchi S, Yamashita H, Uchino S, Watanabe S. Papillary microcarcinoma. World J Surg 2008;32:747−753. 25. Baudin E, Travagli JP, Ropers J, Mancusi F, Bruno-Bossio G, Caillou B et al. Microcarcinoma of the thyroid gland: the Gustave-Roussy Institute experience. Cancer 1998;83:553−559. 26. Hay ID, Grant CS, van Heerden JA, Goellner JR, Ebersold JR, Bergstralh EJ. Papillary thyroid microcarcinoma: a study of 535 cases observed in a 50-year period. Surgery 1992;112:1139−1147. 27. Lin JD, Kuo SF, Chao TC, Hsueh C. Incidental and nonincidental papillary thyroid microcarcinoma. Ann Surg Oncol 2008;15:2287−2292. 28. Chow SM, Law SC, Chan JK, Au SK, Yau S, Lau WH. Papillary microcarcinoma of the thyroid – prognostic significance of lymph node metastasis and multifocality. Cancer 2003;98:31−40. 29. Prendiville S, Burman KD, Ringel MD, Shmookler BM, Deeb ZE, Wolfe K, et al. Tall cell variant: an aggressive form of papillary thyroid carcinoma. Otolaryngol Head Neck Surg 2000;122:352–357. 224 30. Ghossein R, LiVolsi VA. Papillary thyroid carcinoma tall cell variant. Thyroid 2008;18:1179−1181. 31. Albareda M, Puig-Domingo M, Wengrowicz S, Soldevila J, Matias-Guiu X, Caballero A, et al. Clinical forms of presentation and evolution of diffuse sclerosing variant of papillary carcinoma and insular variant of follicular carcinoma of the thyroid. Thyroid 1998;8:385–391. 32. Soares J, Limbert E, Sobrinho-Simões M. Diffuse sclerosing variant of papillary thyroid carcinoma. A clinicopathologic study of 10 cases. Pathol Res Pract 1989;185:200–206. 33. Asa SL. My approach to oncocytic tumours of the thyroid. J Clin Pathol 2004;57:225232. 34. Montone KT, Baloch ZW, LiVolsi VA. The thyroid Hürthle (oncocytic) cell and its associated pathologic conditions: a surgical pathology and cytopathology review. Arch Pathol Lab Med 2008;132:1241−1250. 35. Rivera M, Tuttle RM, Patel S, Shaha A, Shah JP, Ghossein RA. Encapsulated papillary thyroid carcinoma: a clinico-pathologic study of 106 cases with emphasis on its morphologic subtypes (histologic growth pattern).Thyroid 2009;19:119−127. 36. Rosai J. The encapsulated follicular variant papillary thyroid carcinoma: back to the drawing board. Endocr Pathol 2010; 21; 7-11. 37. Baloch ZW, LiVolsi VA. Our approach to follicular-patterned lesions of the thyroid. J Clin Pathol 2007;60:244−250. 38. Prasad ML, Pellegata NS, Huang Y, Nagaraja HN, de la Chapelle A, Kloos RT. Galectin-3, fibronectin-1, CITED-1, HBME1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors. Mod Pathol 2005;18:48−57. 39. Lam KY, Lui MC, Lo CY. Cytokeratin expression profiles in thyroid carcinomas. Eur J Sur Oncol 2001;27:631–635. 40. Akslen LA, LiVolsi VA. Poorly differentiated thyroid carcinoma – it is important. Am J Surg Pathol 2000;24:310–313. 41. 42. Akslen LA, LiVolsi VA. Prognostic significance of histologic grading compared with subclassification of papillary thyroid carcinoma. Cancer 2000;88:1902–1908. Baloch ZW, LiVolsi VA. Post fine-needle aspiration histologic alterations of thyroid revisited. 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LiVolsi VA. C cell hyperplasia/neoplasia. J Clin EndSocrinol Metab 1997;82:39–41. 49. 50. Mete O, Asa SL. Composite medullary and papillary thyroid carcinoma in a patient with MSN 2B. Case report and review of C-cell lesions of the thyroid. Pathol Case Rev 2009; 14: 208-213. Bugalho MJ, Domingues R, Sobrinho L. Molecular diagnosis of multiple endocrine neoplasia Type 2. Expert Rev Mol Diagn 2003;3:769–779. 51. Volante M, Collini P, Nikiforov YE, Sakamoto A, Kakudo K, Katoh R, et al. Poorly differentiated thyroid carcinoma: the Turin proposal for the use of uniform diagnostic criteria and an algorithmic diagnostic approach. Am J Surg Pathol 2007;31:1256−1264. 52. Nishida T, Katayama S, Tsujimoto M, Nakamura J, Matsuda H. Clinicopathological significance of poorly differentiated thyroid carcinoma. Am J Surg Pathol 1999;23:205−211. 53. Lam KY, Lo CY, Chan KW, Wan KY. 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Intern Med 1998;37:909–910. 226 Appendix A Pathological TNM staging (UICC edition 7)7 pTX pT0 pT1a pT1b pT2 pT3 Primary tumour cannot be assessed No evidence of primary tumour ≤ 10 mm, limited to thyroid ≤ 20 mm but > 10 mm, limited to thyroid > 20 mm, ≤ 40 mm, limited to thyroid > 40 mm, limited to thyroid or any tumour with minimal extrathyroidal extension, e.g. extension to sternothyroid muscles or perithyroid soft tissues pT4a Tumour invades beyond thyroid capsule and invades any of: subcutaneous soft tissues, larynx, trachea, oesophagus, recurrent laryngeal nerve pT4b Tumour invades prevertebral fascia, mediastinal vessels, or encases carotid artery All anaplastic carcinomas are considered pT4 tumours pT4a Anaplastic carcinoma limited to thyroid pT4b Anaplastic carcinoma extends beyond thyroid capsule Multifocal tumours (≥ 2 foci) of all histological types should be designated (m), the largest focus determining the classification, e.g. pT2(m) pNX Cannot assess regional lymph nodes pN0 No regional nodes involved pN1a Metastasis in level VI (pretracheal, paratracheal and prelaryngeal/Delphian) lymph nodes pN1b Metastasis in other unilateral, bilateral or contralateral cervical (levels I, II, III, IV or V) or retropharyngeal or superior mediastinal lymph nodes M1 RX R0 R1 R2 Distant metastases proven histologically (MX is not used in TNM v7 which considers that proof of M0 cannot be arrived at by surgical pathology alone) Cannot assess presence of residual primary tumour No residual primary tumour Microscopic residual primary tumour Macroscopic residual primary tumour 227 Clinical staging This is mentioned for ease of reference as it may be mentioned in MDT discussion and in relation to clinical trials, but we recommend that pathology reports include only the pathological TNM staging. The translation of the pathological data into staging differs with the tumour type.6 In papillary and follicular carcinoma, there is evidence that prognosis is poorer in older patients and therefore different criteria are applied to patients under 45 years from those to patients aged 45 years and older. In medullary carcinoma, no age stratification applies. All undifferentiated/anaplastic tumours are regarded as categories within stage IV. Papillary or follicular under 45 years Stage I Stage II Any T Any T Any N Any N M0 M1 N0 N0 N0 N1a N1b N0, N1 Any N Any N M0 M0 M0 M0 M0 M0 M0 M1 Papillary or follicular 45 years or over Stage I Stage II Stage III Stage IVA Stage IVB Stage IVC T1a, T1b T2 T3 T1, T2, T3 T1, T2, T3 T4a T4b Any T Medullary carcinoma Stage I Stage II Stage III Stage IVA T1a, T1b T2, T3 T1, T2, T3 T1, T2, T3 T4a T4b Any T N0 N0 N1a N1b Any Stage IVB N Stage IVC Any Any N N Anaplastic/undifferentiated carcinoma M0 M0 M0 M0 M0 M0 M1 All are considered stage IV Stage IVA Stage IVB Stage IVC T4a T4b Any T Any N Any N Any N M0 M0 M1 228 Appendix B SNOMED codes The codes for the more common types are: Thyroid used TB6000 or T96000, depending on SNOMED edition Papillary carcinoma* Follicular carcinoma* Poorly differentiated carcinoma Anaplastic carcinoma Medullary carcinoma C-cell hyperplasia M80503 M83303 M80213 M80203 M85103 T96050 + M72000 *When Hürthle (oncocytic) differentiation present, add M82903 229 Appendix C Dataset for thyroid cancer histopathology Surname……………………… Forenames………………….… Date of birth………… Hospital………….…………… Hospital no……………….…... NHS no…………….... Date of receipt………….……. Date of reporting………..…..... Report no……………. Pathologist……….…………... Surgeon………………….…… Sex…. Specimen type Tick the least number of boxes that fully accounts for everything received Thyroidectomy Total Near total Not stated Hemithyroidectomy Right Left Not stated Total Near total Isthmus Biopsy of thyroid Biopsy/resection of metastasis (define site)………………………………… Gross description of thyroid specimen Location of carcinoma(s) Right lobe Left lobe Isthmus Unknown Microscopic report Papillary carcinoma Single incidental microcarcinoma Multiple incidental microcarcinoma Variant: Encapsulated FVPTC Non-encapsulated FVPTC Classical PTC Other type (specify) ……………… For encapsulated FVPTC, no. of foci of capsular invasion ........ and number of foci of vascular invasion …..... Follicular carcinoma Not Hürthle cell type or Hürthle cell (oncocytic) follicular carcinoma Minimally invasive (capsule only) Minimally invasive (angioinvasion) Select both types of invasion if both are seen Widely invasive Number of foci of angioinvasion found for the follicular carcinoma Medullary carcinoma Definite background C-cell hyperplasia For all above types Minority poorly differentiated (not anaplastic) component Poorly differentiated carcinoma …………….. Absent Present (Majority (> 50%) of tumour is poorly differentiated) Undifferentiated/anaplastic carcinoma Differentiated component identified (specify)…………………………. Mixed follicular/papillary and medullary carcinoma 230 Surname……………………… Forenames………………….… Date of birth………… Hospital no……………….…... For all tumour types Confined to thyroid Unifocal Multifocal Size ………………………………… mm Minimal extension beyond thyroid capsule into sternothyroid or perithyroidal soft tissues only, pT3 Microscopic extension beyond thyroid capsule into subcutaneous soft tissues, larynx, trachea, oesophagus or recurrent laryngeal nerve, pT4a Microscopic extension beyond thyroid capsule into prevertebral fascia, mediastinal vessels or encasement of carotid artery, pT4b Any macroscopic extension beyond thyroid capsule, pT4b Lymphatic/vascular invasion Yes Total number of lymph nodes ……… Number of foci found …….. Uncertain No Number of lymph nodes positive …………….. Site of lymph nodes involved …………………………………………………………… Unilateral Level VI Excision margins Any other group Unable to assess Free of tumour Minimum distance ……mm Tumour present on microscopy Tumour present macroscopically Adjacent thyroid Normal Mild thyroiditis Severe thyroiditis C-cell hyperplasia (medullary carcinoma only) Yes Other (define)……………….. Nodular goitre No Uncertain Comments…………………………………………………………………………………….. Parathyroids identified Stage pT ………. Number …….. pN ………. M1? Site(s) …… Pathology …………..…………………….. R ………. Signature …………………… Date……………… SNOMED code TB6 M……………. 231 Appendix D Thyroid carcinoma dataset monitoring sheet The Cancer Datasets of the Royal College of Pathologists comply with the AGREE standards for good quality clinical guidelines (www.agreecollaboration.org). The sections of this dataset that indicate compliance with each of the AGREE standards are indicated in the table. AGREE Standard SCOPE AND PURPOSE 1. The overall objective(s) of the guideline is (are) specifically described 2. The clinical question(s) covered by the guidelines is (are) specifically described 3. The patients to whom the guideline is meant to apply are specifically described STAKEHOLDER INVOLVEMENT 4. The guideline development group includes individuals from all the relevant professional groups 5. The patients’ views and preferences have been sought 6. The target users of the guideline are clearly defined 7. The guideline has been piloted among target users RIGOR OF DEVELOPMENT 8. Systematic methods were used to search for evidence 9. The criteria for selecting the evidence are clearly described 10. The methods used for formulating the recommendations are clearly described 11. The health benefits, side effects and risks have been considered in formulating the recommendations 12. There is an explicit link between the recommendations and the supporting evidence 13. The guideline has been externally reviewed by experts prior to its publication 14. A procedure for updating the guideline is provided CLARITY OF PRESENTATION 15. The recommendations are specific and unambiguous 16. The different options for management of the condition are clearly presented 17. Key recommendations are easily identifiable 18. The guideline is supported with tools for application APPLICABILITY 19. The potential organisational barriers in applying the recommendations have been discussed 20. The potential cost implications of applying the recommendations have been considered 21. The guideline presents key review criteria for monitoring and/or audit purposes EDITORIAL INDEPENDENCE 22. The guideline is editorially independent from the funding body 23. Conflicts of interest of guideline development members have been recorded Section of dataset 1 1 1 1 N/A 1 Feedback follows use of a previous edition 1 1 1 1 3-5, 10 1 Foreword 3-5 3-5 3-5 Appendix C 1,3 N/A 3-7 1 1 232 Tissue pathways for endocrine pathology July 2008 Unique document number G078 Document name Tissue pathways for endocrine pathology Version number 1 Produced by Dr Anne Marie McNicol (Writing Group Lead), Dr Tim Stephenson, Dr Sarah Johnson, Dr David Poller, Dr Debra Milne and Dr Catriona Anderson, on behalf of the College’s Specialty Advisory Committee on Histopathology and the Cancer Services Working Date active July 2008 Group July 2010 Date for review Comments In accordance with the College’s pre-publications policy, this document was put on The Royal College of Pathologists’ website for consultation from 21 May – 20 June 2008. Four pieces of feedback were received, none of which suggested any changes. Professor Carrock Sewell Director of Publications The Royal College of Pathologists 2 Carlton House Terrace London, SW1Y 5AF Tel: 020 7451 6700 Fax: 020 7451 6701 Web: www.rcpath.org Registered charity in England and Wales, no. 261035 © 2008, The Royal College of Pathologists 233 Contents A Adrenalectomy specimens ................................................................................. 2 References .................................................................................................................... 3 B Parathyroidectomy specimens............................................................................5 References .......................................................................................................................6 C Thyroidectomy and thyroid lobectomy specimens ...........................................7 References .......................................................................................................................8 234 A Adrenalectomy specimens 1 Indications Bilateral adrenalectomy as treatment for Cushing’s disease, where pituitary surgery is not possible or has failed. Bilateral adrenalectomy as treatment for ectopic adrenocorticotrophic hormone (ACTH) syndrome, where the source of ACTH has not been identified or surgical removal of the tumour secreting ACTH is not possible or is incomplete. Bilateral adrenalectomy as treatment for Cushing’s syndrome in primary pigmented nodular dysplasia (PPND, part of Carney’s complex).1 Bilateral adrenalectomy in Cushing’s syndrome associated with nodular hyperplasia and suppressed ACTH. Occasionally, unilateral adrenalectomy in Cushing’s syndrome or Conn’s syndrome with unilateral nodular hyperplasia. Bilateral adrenalectomy at the stage of medullary hyperplasia in multiple endocrine neoplasia type 2 (MEN2). Adrenalectomy for other indication (e.g. adrenal mass on imaging, diagnosis unclear). 2 Staffing and workload Ideally, there should be two consultant pathologists with a special interest or experience in endocrine pathology. It is recognised that this may be difficult in small departments. If there is only one, there should be a network for referral/review. There is currently no EQA scheme. 3 Specimen submission Usually received in formalin, which should be of adequate volume. If received fresh, formalin is added. 4 Specimen dissection Where there is an apparently single nodule, the specimen is dealt with according to The Royal College of Pathologists’ guidelines for reporting of adrenal cortical carcinoma and malignant phaeochromocytoma.2 The specimen will usually comprise the adrenal gland and surrounding fat. The total weight and dimensions are noted. Specimens removed by laparoscopic procedure may be disrupted; if present, this is noted in the description. Where possible, the fat is stripped and the dimensions and weight of the gland noted. The head, body and tail of the gland are identified. The gland is sliced from head to tail. The appearance of the cortex is described, including the presence or absence of nodules (including maximum dimension of large nodules). The distribution of the medulla is recorded as extension into the tail indicates hyperplasia.3 In most cases, one block is taken from each of the head, the body and the tail. However, additional blocks are taken if there are focal abnormalities. In some cases it can be useful to have photographs of the gross and dissected specimen for orientation and discussion. 235 5 Sectioning and staining A single haematoxylin and eosin (H&E) stained section per bloc is adequate for examination, provided the sections cover the full face of the blocks. If there is tangential sectioning, deeper levels may be necessary. 6 Further investigations None is usually required. 7 Report content4 i. Cushing’s syndrome The pattern of zonation of the cortex is described and the presence of nodules where appropriate. If nodular, the appearance of the intervening cortex is noted. In pituitarydependent Cushing’s syndrome, the whole cortex is hyperplastic. Nodular hyperplasia is not common in ectopic ACTH syndrome. In the rare cases of primary pigmented nodular dysplasia, the intervening cortex is usually atrophic. The distribution of the medulla is described. ii. Adrenal medullary hyperplasia The distribution of medullary tissue is described and note made as to whether the hyperplasia is nodular or diffuse. An arbitrary limit of 10 mm is the cut-off between nodular hyperplasia and phaeochromocytoma. The pattern of zonation of the cortex is described and the presence of nodules noted. 8 References 1. Shenoy BV, Carpenter PC, Carney JA. Bilateral primary pigmented nodular adrenocortical disease. Rare cause of the Cushing syndrome. Am J Surg Pathol 1984;8:335–344. 2. The Royal College of Pathologists. Dataset for histopathology reporting in adrenal cortical carcinoma and malignant phaeochromocytoma/paraganglioma. The Royal College of Pathologists, 2006. www.rcpath.org/publications 3. DeLellis RA, Wolfe HJ, Gagel RF, Feldman ZT, Miller HH, Gang DL et al. Adrenal medullary hyperplasia. A morphometric analysis in patients with familial medullary thyroid carcinoma. Am J Pathol 1976;83:177–196. 4. Lloyd RV, Douglas BR, Young WF. Endocrine Diseases. Atlas of Tumor Pathology. Washington DC: Armed Forces Institute of Pathology, 2002. 236 B Parathyroidectomy specimens 1 Indications Removal of hyperfunctioning parathyroid tissue in primary, secondary or tertiary hyperparathyroidism. The surgeon may request intra-operative confirmation of tissue type by frozen section. 2 Staffing and workload Confirmation of the nature of the tissue at frozen section can be performed by any consultant pathologist. For reporting of paraffin histology, there should ideally be two consultant pathologists with a special interest or experience in endocrine pathology. It is recognised that this may be difficult in small departments and, if there is only one, there should be a network for referral/review. There is currently no EQA scheme. 3 Specimen submission These are often received fresh for intra-operative frozen sections. After frozen sectioning has been completed, the whole gland is placed in formalin. If no intra-operative consultation is required, the gland is received in formalin, which should be of adequate volume. 4 Specimen dissection For each parathyroid gland, the site, weight, dimensions, colour and consistency are noted. Small glands are bisected. Larger glands are cut into parallel slices, cutting through the vascular pole where possible. Glands should have margins inked prior to frozen section if the diagnosis of carcinoma is being considered. This would be more usual in large glands with a thick capsule or where the surgeon has indicated difficulty in removing the gland. For frozen section, one representative block is taken. All tissue is processed to paraffin blocks after the frozen section. Where no frozen section is required, all tissue is embedded. Some parathyroid glands are intrathyroidal. If a thyroid lobectomyor partial lobectomy specimen is received, it is weighed and measured. The specimen is sliced and any nodule(s) embedded. If no nodules are identified, all slices are embedded. 5 Sectioning and staining A single H&E stained section per block is adequate for examination, provided the blocks taken are fully represented on the slide. If there is tangential sectioning, deeper levels may be necessary. 6 Further investigations None is usually required. 7 Report content For each parathyroid gland it is noted whether or not the gland is enlarged, has a diffuse or nodular pattern or is encapsulated. The presence or absence of fat is noted. The cell types are documented. Other specimens may be submitted as parathyroid glands (e.g. thyroid or lymph node). The tissue type present and any abnormality are reported. The report indicates whether the histological appearances favour adenoma or hyperplasia. It is also useful to identify whether there is single gland or multigland parathyroid disease. This is usually easy in secondary or tertiary hyperparathyroidism. However, with the current trend for targeted removal of a single gland in primary hyperparathyroidism without the surgeon viewing the others, it is difficult to be certain.1 Where intra-operative frozen section has been performed, the report should document who gave the result to whom and should specify the date and time. More detailed instructions on handling can be found in the following references.1,2 8 References 1. Johnson SJ, Sheffield EA, McNicol AM. Best practice no 183. Examination of parathyroid gland specimens. J Clin Pathol 2005;58:338–342. 2. The Royal College of Pathologists. Dataset for parathyroid cancer histopathology reports. The Royal College of Pathologists, 2006. www.rcpath.org/publications C Thyroidectomy and thyroid lobectomy specimens 1 Indications To relieve compressive symptoms or for cosmetic reasons in multinodular goitre or Hashimoto’s thyroiditis. As treatment, where medical therapy has been unsuccessful in Graves’ disease. 2 Staffing and workload Ideally, there should be two consultant pathologists with a special interest or experience in endocrine pathology. It is recognised that this may be difficult in small departments and, if there is only one, there should be a network for referral/review. There is currently no dedicated EQA scheme, although thyroid cases may be included in general EQA schemes and the specialist head and neck pathology EQA scheme. 3 Specimen submission Usually received in formalin, which should be of adequate volume. If received fresh, formalin is added. 4 Specimen dissection The nature of the specimen and side (in lobectomy specimens) are noted. If possible, the specimen is orientated. A search is made for parathyroid glands. The thyroid capsule is examined to assess whether it appears intact. The resection margins are inked. The specimen is weighed and the dimensions of each lobe noted. The specimen is cut into 5 mm slices i n the horizontal plane. Any parathyroid glands or lymph nodes identified are processed. In some cases, it can be useful to have photographs of the gross and dissected specimen for orientation and discussion. a) Multinodular disease Submit one block from representative nodules, up to a maximum of five from each lobe. Any encapsulated nodule should be treated as a potential follicular tumour and sampled according to The Royal College of Pathologists’ guidelines for thyroid tumours.1 Any unusual foci are also processed. b) Inflammatory disease Submit three representative blocks from each lobe and one from the isthmus, if present. Any unusual foci are also processed. 5 Sectioning and staining A single H&E stained section is adequate for examination provided the sections represent the full face of the blocks. If there is tangential sectioning, deeper levels may be necessary. 6 Further investigations None is usually required. However, if the histological features in a case of Hashimoto’s thyroiditis raise the possibility of lymphoma, appropriate immunohistochemical and molecular analyses are performed. 7 Report content2,3 The report summarises the gross and histological features and includes a diagnosis. 8 References 1. The Royal College of Pathologists. Dataset for thyroid cancer histopathology reports. The Royal College of Pathologists 2006. www.rcpath.org/publications 2. Lloyd RV, Douglas BR, Young WF. Endocrine diseases. Atlas of Nontumor Pathology. Washington, DC: Armed Forces Institute of Pathology, 2002. 3. Rosai J, Carcangiu ML, DeLellis RA. Tumors of the Thyroid Gland. Atlas of Tumor Pathology, Third Series, Fascicle 5. Washington DC: Armed Forces Institute of Pathology, 1992. London and South East Sarcoma Network London and South East Sarcoma Network Shared Care Pathway for Soft Tissue Sarcomas Presenting to Site Specialised MDTs Head and Neck sarcomas Background This guidance is to provide direction for the management of patients with sarcomas that may present through Head and Neck cancer services and to define the relationship that should exist with the specialist sarcoma MDT. This guidance refers to the care of patients in the London and South East Sarcoma Network and therefore recognises that specialist services for soft tissue sarcomas are provided by the Sarcoma Unit at The London Sarcoma Service provided through joint working of UCLH and RNOH. All bone sarcomas are managed by the London Sarcoma Service. The local control rate for intermediate and high grade soft tissue sarcoma of the head and neck is markedly inferior to that of sarcoma of the limbs. This is largely related to the extent and nature of the excisions possible. The surgical factors associated with higher control rate in the limb are (i) primary, en bloc, rather than piecemeal, resection and (ii) resection with negative margins. These goals are difficult to achieve in the head and neck. Furthermore, although post operative radiotherapy reduces the local relapse rate, this still remains high when surgical margins are positive. For surgery to be sufficient local treatment alone, margins must be wide. Where radiotherapy is used with surgery the width of the margin is less important provided that the margins are negative. The first aim of this pathway is to ensure early discussion with a specialist head and neck sarcoma MDT so that the chances of the first surgical intervention resulting in negative margins are maximised. Where possible the surgery should be en bloc. Surgery alone may be sufficient when sarcomas are small (2 cm or less) and can be excised en bloc with a wide margin (minimum 0.5 cm of uninvolved tissue or across an intact fascial plane). In all other cases combined modality treatment with surgery and radiotherapy is indicated. For high grade sarcomas, adjuvant chemotherapy will also be considered in all cases. The sequence has usually been surgery followed by radiotherapy but increasingly pre-operative radiotherapy +/- chemotherapy may be preferred. The major rationale for neoadjuvant chemotherapy is that in overview studies of adjuvant chemotherapy in STS as a whole, use of chemotherapy is associated with a reduction in local recurrence. While this may be insignificant in sarcomas of the limb, where the local relapse rate is 10-15% with surgery and radiotherapy, the impact of chemotherapy may be greater where the expected local relapse rate is of the order of 25-50%. Therefore, for patients without contraindications to both chemotherapy and pre–operative radiotherapy (where it will not significantly compromise long term morbidity) both modalities are considered before surgery. The rarity of head and neck sarcomas, their clinical diversity, the poor outcomes referred to above and the important differences compared with squamous carcinomas of the head and neck argue for close co-operation between head and neck and sarcoma MDTs and for centralisation of care. Where patients are receiving combined modality treatment, especially with pre-operative chemotherapy and/or radiotherapy, receiving all treatments at a single institution has many advantages for patients and treating teams. Regular multidisciplinary clinical review when patients are on treatment and co-ordination between surgeon and oncologist is essential. Principals This guidance is being developed in accordance with the relevant measures in the Manual for Cancer Services: Sarcoma Measures and the Manual for Cancer Services: Head and Neck Measures. They are also written in accordance with the LSESN referral guidelines (see www.lsesn.nhs.uk) and the LSESN Patient Management Policy. 1) Notification All sarcoma patients presenting to a specialist Head and Neck MDT should be notified to the sarcoma MDT nominated in the local network Head and Neck cancer operational policy. 2) Review by Sarcoma MDT a) Pathology All sarcomas arising in the head and neck will have pathology review undertaken by the nominated specialist sarcoma pathology service (for details see MDT operational policies). b) Management Management of all new soft tissue sarcomas sarcomas will be discussed with the sarcoma MDT. Early referral from the time of suspicion or biopsy is recommended. All new bone sarcomas will be referred at time of suspicion to UCLH Sarcoma Unit. 3) Site of Definitive Treatment Discussion between MDT’s will take place to determine the appropriate hospital for definitive excision. In general, primary surgical excision at the sarcoma centre is preferred. All patients undergoing pre-operative chemotherapy or radiotherapy will be managed at the sarcoma centre. All craniofacial bone sarcomas will be managed at UCLH. Chemotherapy and radiotherapy will be undertaken by designated practitioners as agreed by the SAG. 4) Recurrence All recurrent head and neck sarcomas will be discussed and reviewed by the sarcoma MDT. Presentation Diagnosis Treatment Follow up Role and Responsibility Specialist Head and Neck Sarcoma MDT/Clinic MDT/Clinic Assess new cases of suspected head and neck cancer Notify Sarcoma MDT of all new cases of head and neck sarcoma Refer all cases of head and neck Review pathology of all new cases sarcoma for pathology review. of head and neck sarcoma Refer all new cases of head and neck Clinical review of all new cases sarcoma for review by sarcoma MDT Excision when agreed by head and Consider definitive excision of all neck and sarcoma MDT’s head and neck sarcomas; need for adjuvant chemotherapy and/or radiotherapy; re-excision of all incompletely excised or recurrent sarcomas. All radical chemotherapy and radical radiotherapy except agreed by sarcoma and head and neck MDT’s that individual factors determine otherwise Follow up according to agreed Follow up in accordance with guidelines of selected patients agreed sarcoma follow up guidelines of all by MDT’s patients treated by the sarcoma MDT Pathway Summary: Suspected head and neck sarcoma Specialist Head & Neck MDT Assess new cases of suspected head & neck cancer Notify sarcoma MDT of all new cases of head & neck sarcoma Suspected/biopsy-proven soft tissue sarcoma LSS MDT Coordinator Contact details: Ucl-tr.LondonSarcomaService:nhs.net Tel: 020 3447 4821 suspected bone sarcoma Sarcoma MDT UCLH All histology reviewed by Specialist Sarcoma Pathologist Register patient Review diagnosis Plan management Patients under 24 will also be referred to the teenage and young adult or paediatric MDTs as appropriate Treatment Follow-Up Pre-operative chemo and/or radiotherapy e.g < 2cm; low grade at sarcoma centre* Definitive Excision Discussion between MDTs to determine appropriate hospital for definitive excision* Excision or palliation by local team by local team Follow Up Follow Up according to agreed head & neck MDT guidelines and LSESN sarcoma follow-up guidelines (for those patients treated by sarcoma MDT) Recurrence Follow Up