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OG CANCER CLINICAL GUIDELINES OG NSSG on behalf of NECN Signatures: Position: Name: Organisation: Date Agreed: Chair of the Network Board Karen Straughair Chief Executive of Gateshead PCT, South Tyneside PCT and Sunderland TPCT 10.08.12 Position: Name: Organisation: Date Agreed: Chair of the OG NSSG Mr Samuel Dresner South Tees Hospitals NHS Foundation Trust 30.04.12 Title: Authors: Circulation List: Contact Details: NECN OG Cancer Clinical Guidelines OG NSSG members OG NSSG Ann Bassom, Network Co-ordinator, North of England Cancer Network, Waterfront 4, Goldcrest Way, Newcastle NE15 8NY 0191 275 4748 Telephone: Version History: Date: September 2012 1.9 March 2013 1 Contents Introduction .............................................................................................................................. 3 Primary Care Referral Pathways ............................................................................................ 4 GP Referral Guidelines .............................................................................................................. 5 NSSG Guidelines for Teenage and Young Adults ................................................................ 6 Appendix 1 – Teenage and Young Adult Pathway for initial Management ................................ 7 Appendix 2 – Contact Details .................................................................................................... 8 Appendix 3 – NHS Specialised Services Pathway..................................................................... 9 Oesophageal & Stomach Cancer Background Information ............................................... 11 Agreed Network Model (Upper GI) ....................................................................................... 11 Specialist Teams ..................................................................................................................... 12 Operational Policy for named key worker for cancer patients .......................................... 13 Referral in to the Specialist MDM ......................................................................................... 13 Follow Up................................................................................................................................. 13 Upper GI Pathology Guidelines ............................................................................................ 13 Upper GI Radiology Guidelines ............................................................................................ 17 Optimal T-Stage....................................................................................................................... 18 Optimal N-Stage ...................................................................................................................... 19 Other Investigations ................................................................................................................. 20 Current Staging algorithm ........................................................................................................ 21 Treatment Options In Oesophageal Cancer ........................................................................ 23 Treatment Options In Gastric Cancer .................................................................................. 24 Clinical Trials ......................................................................................................................... 25 Cancer Peer Review and Clinical Trials................................................................................... 26 Guidelines For Genetic Risk Assessment And Surveillance Of Individuals With A Family History Of Gastric Or Oesophageal Cancer ............................................................ 27 NECN Chemotherapy Treatment Algorithm ........................................................................ 32 2 Introduction These guidelines have been developed by the Upper GI Cancer Network Site Specific Group of the North of England cancer Network. The North of England NSSG for UGI OG cancers has adopted in their entirety the comprehensive national guidelines for UGI oesophago-gastric cancers; these are to be used in collaboration with NICE 2005 referral guidance. To support local implementation of these, each section included below provides the clinician with information on referral pathways and clinical team. 3 Primary Care Referral Pathways PCT Referral Pathways Diagnostic Services Designated MDT Lead Clinician Case Mix Newcastle Upon Tyne Hospitals Foundation NHS Trust Royal Victoria Infirmary Prof S M Griffin 0191 2336161 UGI cancers Specialist MDT Wansbeck General Hospital UGI cancers North Tyneside General Hospital Queen Elizabeth Hospital Sunderland Royal Hospital Miss S Robinson 01670 529331 Miss S Robinson 0191 2934079 Mr R Farrell 0191 4820000 Dr J Painter 0191 5656256 Royal Victoria Infirmary University Hospital of North Durham Mr K Wynne 0191 4041000 Dr D Kejariwal 0191 3332333 UGI cancers Darlington Memorial Hospital Bishop Auckland Hospital James Cook University Hospital South - Dr A Dhar 01325 380100/ext 55170 University Hospital of North Tees Cumberland Infirmary Dr J Vasani 01642 617617 Mr J Wayman 01228 814144 Area Population* Newcastle 292,200 Northumberland 312,000 North Tyneside 198,500 Gateshead 191,700 Gateshead Health NHS FT Sunderland *Easington (60%) 283,500 55,700 City Hospitals Sunderland NHS Foundation Trust South Tyneside 153,700 South Tyneside NHS FT Co Durham North *60% Easington split inc in Sunderland pathway 237,854 Co Durham (South) 217,246 Darlington 100,800 Redcar & Cleveland Middlesbrough North Yorkshire & York Stockton on Tees Hartlepool 137,400 142,400 133,165 South Tees Hospitals Trust 192,400 91,300 North Tees & Hartlepool NHS FT Cumbria 321,854 North Cumbria University Hospital NHS Trust Northumbria Health Care NHS FT County Durham and Darlington NHS FT Mr P Davis 01642 850850 UGI Cancers UGI cancers UGI cancers UGI cancers UGI cancers Specialist MDT UGI cancers UGI cancers *2010 Mid-year population estimates 4 GP Referral Guidelines Dyspepsia: Epigastric pain Heartburn Bloating Nausea With alarm symptoms No alarm symptoms On NSAID must continue Alarm Symptoms: Dysphagia Unintentional weight loss Epigastric Mass Recent Onset >55 Persistent vomiting Iron Deficiency Anaemia Yes Gastroscopy Yes No Test for H Pylori & try PPI -ve H pylori >55 + ve H pylori Responds Request for gastroscopy outside of guidelines Fax 2 week rule referral Review possible diagnosis No very unlikely to have peptic ulcer disease/malignancy - reassure & treat symptomatically or consider refer to Gastroenterologist/Upper GI Surgeon if clinically concerned No/relapse Yes Manage in Primary Care. No further investigations Alarm Symptoms: Dysphagia Unintentional weight loss Epigastric mass Recent onset dyspepsia >55 Persistent vomiting Iron deficiency anaemia * Iron Deficient Anaemia: Hb < 11.0 g/dl in men or <10.0 g/dl in post-menopausal women Low Ferritin on its own or Low/normal ferritin + low MCV/M. If not iron deficient anaemia then endoscopy is not required 5 NSSG Guidelines for Teenage and Young Adults Teenage and Young Adults Peer Review Measures Topic 11-1C (Functions of the Network Site Specific Groups for TYA) 1. Teenage and Young Adult Pathway for initial Management The NSSG has received the document named ‘NECN Teenage and Young Adult Cancer Pathway Guidance Paper’ and agrees to follow the generic TYA Pathway with any site specific variations to be documented. Please see Appendix A for pathway. 2. Teenage and Young Adult Pathway for Follow up on completion of first line treatment Patients aged 19-24 years will adopt the site specific adult follow up pathway on completion of first line treatment. It is acknowledged by both the CYPCG and NSSGs across NECN that further work is required to develop these pathways for this age group and partly in response a TYA working group has been established to take this work forward. If advice is required regarding the follow up care of a 19-24 year old patient, then the Lead TYA Clinician at the designated hospital or PTC should be contacted. Please see Appendix B for contact details. Patients age 16-18 years will continue to adopt the paediatric and adolescent follow up protocol of the PTC and all advice should be sought direct from the On Call Paediatric Oncologist at Royal Victoria Infirmary 0191 2336161. Paediatric Follow Up Protocols can be found on the CCLG website (2005 second edition) with the exception of trial specific protocols which can be requested via the Children’s Trial Co-ordinator based at the RVI. 3. Pathways for cases involving Specialised NHS services (Only Gynae and Sarcoma) The Gynae NSSG and SAG reviewed and agreed the Specialised NHS Service pathway for patient’s age 16-24 years. This is attached in Appendix C 6 Appendix 1 – Teenage and Young Adult Pathway for initial Management 7 Appendix 2 – Contact Details List of designated MDTs at Principal Treatment Centre and TYA Designated Hospitals (19 - 24 years) Name of NHS Trust and designated hospital site Name of MDT TYA Lead Clinician Acute oncology Breast TYA Lead Nurse Contact Number Cancer of Unknown Primary (CUP) Colorectal Gynaeoncology Haematology Head & Neck Lung Principal Treatment Centre MDTs for 19 - 24 year olds at Newcaslte upon Tyne NHS Foundation Trust - at Freeman Hospital Neurooncology (Brain/Spinal, Pituitary, Skull Base) Sarcoma Dr Emma Lethbridge Mrs Suzanne Brand 0191 2138464 Gateshead Health NHS Foundation Trust – QE Hospital Upper GI Urology Gynaeoncology Mr Richard Edmondson Mrs Alison Guest 0191 4456148 City Hospitals Sunderland NHS Foundation Trust - at Sunderland Royal Hospital leukaemia and lymphoma (Haematology MDT) Dr Scott Marshall Ms Faye Laverick North Tees and Hartlepool NHS Foundation Trust - at University Hospital of North Tees leukaemia and lymphoma (Haematology MDT) Dr Philip Mounter to be confirmed Dr Dianne Plews to be confirmed Skin Specialist pancreatic T-cell Lymphoma Teenage and Young Adult MDT testicular Thyroid 0191 5656256 01642 624458 Gynaeoncology Breast Colorectal Haematology South Tees Hospital NHS Foundation Trust - at Janes Cook University Hospital Head & Neck Lung 01642 854381 Neurooncology Skin Thyroid Upper GI Urology 8 Appendix 3 – NHS Specialised Services Pathway 9 10 NB – please refer routinely to Gastroenterologist or Upper GI Surgeon for outpatient review if there are clinical concerns Oesophageal & Stomach Cancer Background Information The incidence of oesophageal cancer and proximal gastric cancer has increased dramatically. An average GP practice would now expect to see 1 to 2 such cancers every year. The prognosis for oesophageal and gastric cancer remains poor unless identified early (overall 5 year survival 17% and <10% respectively). These cancers are uncommon under the age of 45 but presentation is often with vague and commonly occurring dyspeptic symptoms... Surgical resection offers a chance of cure for only a minority of patients with the majority requiring palliation of their symptoms. This may include the placement of an endoscopic stent, radiotherapy or chemotherapy. The management of these cancers is multidisciplinary through upper GI surgeons, gastroenterologists, radiologists, oncologists, hospital and community based palliative care teams, dieticians and Primary Care teams. Please note: Gastroscopy is more accurate at establishing a diagnosis when acid suppression has not been taken (early cancers can be missed). Agreed Network Model (Upper GI) Patient Pathway Three levels of care are identified in the Upper GI Improving Guidance document, published in January 2001. 1. The diagnostic process 2. Local care – i.e. palliation and support, including certain local stenting procedures 3. Specialist care – any definitive anti-cancer treatment: palliative or curative including debulking or resection and palliative surgical bypass procedures. Objectives of Specialist MDT: To ensure that designated specialists work together effectively such that decisions regarding all aspects of diagnosis and treatment of individual patients and decisions regarding the team’s operational policies are entirely multidisciplinary. To ensure that care is given according to recognised guidelines (including guidelines for onward referrals), with appropriate information being collected to inform clinical decision making and to support Clinical Governance / Audit. To ensure that mechanisms are in place to support entry of eligible patients into clinical trials, subject to patients giving fully informed consent. 11 Figure 2.1: Operable Patients: Specialist Teams PCT Populations Designated Hospital Area Population* Newcastle 292,200 Royal Victoria Infirmary Northumberland 312,000 North Tyneside 198,500 Total Population Gateshead 191,700 2,047,008 South Tyneside 153,700 Sunderland 283,500 Co Durham (North) 293,554 Cumbria 321,854 Co Durham (South) 217,246 James Cook University Middlesbrough 142,400 Hospital Redcar & Cleveland 137,400 Darlington 100,800 Total Population Hartlepool 91,300 1,014,711 Stockton on Tees 192,400 North Yorkshire & 133,165 York *2010 Mid-year population estimates Lead Clinician Professor S M Griffin 0191 2336161 Mr P Davis 01642 850850 12 Operational Policy for named key worker for cancer patients Each patient will have a named key worker who will be identified and recorded at the appropriate MDT meeting. The Upper GI tumour site has clearly identified patient pathways with the key worker role apparent throughout. The Clinical Nurse Specialist will perform this role, however when appropriate, any MDT member can act in this capacity if contacted by a patient or carer. The Key Worker / Clinical Nurse Specialist will act as the co-ordinator of cases and be the single common contact for patients and carers. This will enable patients to have access to the MDT to discuss problems or concerns. Referral in to the Specialist MDM All referral and follow up practice adheres to national guidelines. All patients are either discussed by the Specialist Multi-Disciplinary Team or in their local Multi-Disciplinary Meeting attended by core members of the Specialist Multi-Disciplinary Team. All patients with suspected oesophago-gastric malignancies are referred in to the Specialist MDT. Patients for palliation are discussed with the representative core members of the central MDT in order to manage their disease in as local a setting as is possible, however, these cases should also discussed in the Specialist MDT if further Specialist input is required. Follow Up The specialist MDT will arrange and organise for any further investigations and followup of all patients referred by diagnostic / local care teams. Upper GI Pathology Guidelines These guidelines are supplementary to the following national guidance: Minimum dataset for gastric and oesophageal cancer histopathology reports issued by the Royal College of Pathologists. All upper GI cancer cases should be reviewed by an Upper GI Cancer multidisciplinary team which had a nominated Lead upper GI pathologist for the service. All pathologists reporting upper GI cancer specimens should participate in local audit (including an assessment of consistency of reporting, as appropriate to the site). If there is a significant discrepancy with the clinical/radiological findings the pathological material from diagnostic upper GI specimens should be reviewed, if possible by a second pathologist with an interest in upper GI cancer. All biopsy diagnoses of squamous or glandular dysplasia should be reviewed by at least one other pathologist with a GI interest before report authorisation. Their name will normally be included in the report as a reviewing pathologist. Where further treatment is being considered e.g. surgery, EMR etc the case should be reviewed at a Specialist MDT meeting and the diagnosis confirmed by at least two pathologists. Specimens should be reported to an agreed timeframe so as to allow appropriate clinical decision making at a planned upper GI MDT meeting. 13 Specimen Examination Each pathology service should establish a defined protocol for each type of diagnostic and therapeutic upper GI specimen type received by the laboratory, taking into account the above guidance. The protocols should be regularly reviewed and updated by the lead upper GI pathologist in consultation with other pathologists who participate in service delivery. Where appropriate protocols should include a code for specimen orientation as agreed with the local upper GI surgical team. Upper GI tissue should only be removed and stored for the purposes of research if it is surplus to the requirements of the diagnostic process. Appropriate patient consent and ethical approval should be obtained. Minimum Dataset for Reporting Diagnostic specimens: For upper GI biopsies Tumour type Presence of associated epithelial dysplasia when identified Assessment of minimum depth of invasion ie.identification of submucosal invasion when this is present in the biopsy (level, not measurement) Therapeutic resections: Relevant RCPath Dataset with local modifications Specimen type Length of specimen Site of tumour Macroscopic appearance of tumour Dimensions of tumour Distance to margins Invasive tumour type Invasive tumour grade of differentiation Character of the invasive margin ie. expansile or infiltrative [Gastric] Depth of invasion Serosal involvement Vascular invasion Number regional lymph nodes examined Number of involved regional lymph nodes Number and site(s) of distant (non-regional) lymph nodes submitted and number involved (M1) Distance to circumferential margin and status of this margin (<1mm regarded as involved) [oesophagus]. Local dissection of lymph nodes will compromise the estimation of the circumferential margin but the distance to the remaining margin should be stated. Status of proximal and distal margins Other relevant pathology (Barrett’s or intestinal metaplasia, background dysplasia, chronic gastritis, H pylori status etc) TMN staging system, including R status The dataset items may be reported in a proforma either within or instead of the free text part of the pathology report, or recorded as a separate proforma. Trusts and MDTs 14 should work towards recording and storing the dataset items as individually categorised items in a relational database, so as to allow electronic retrieval and to facilitate the use of pathology data in clinical audit, service planning and monitoring, research and quality assurance. Laboratories should use an agreed diagnostic coding system (eg. SNOMED). All malignancies must be reported to the Cancer Registry, in accordance with the service level agreement with their host Trust. Grading and Staging Conventions Dysplasia grading: Revised Vienna classification of gastrointestinal epithelial neoplasia Tumour grading: WHO invasive carcinoma grade system Tumour staging: TNM classification of malignant tumours (6th edition) Use of Ancillary Laboratory Techniques All laboratories providing a Pathology service in the network must have at least conditional laboratory (eg CPA) accreditation and ensure participation an appropriate external quality assurance programme which demonstrates satisfactory laboratory performance. Immunohistochemical procedures which may be of value include the following: Diagnostic Scenario Intra-abdominal malignancy, ? primary Neuroendocrine differentiation GIST Immunohistochemical markers CK7, CK20, CEA, CA125, CA19-9 CD 56, Synaptophysin, Chromogranin, Ki 67 Notes Treatment instituted on proliferative index of >8% CD117, CD34, Desmin, SMA, S100 Audit All pathologists reporting upper GI cancer specimens should participate in a relevant EQA scheme and in local audit (including an assessment of consistency where more than one pathologist participates in service provision). Audit may take the form of: review of compliance with procedures for specimen examination and reporting completeness of datasets systematic logging of diagnostic agreement/disagreement during review of cases for MDTMs 15 review of diagnostic consistency between pathologists using data from cases in EQA circulations or blind circulations. The results of the audit process should be discussed with all pathologists who participate in service delivery and used to inform the development of reporting protocols. Referral for Review or Specialist Opinion 1. Referral for treatment All patients referred for treatment at a hospital within the North of England Cancer Network following diagnosis elsewhere must be reviewed and discussed at the treating hospital’s multidisciplinary team meeting (MDTM). The complete diagnostic pathology report must be available at the MDTM, and when appropriate, the histological/cytological material should be reviewed prior to the meeting. This is particularly important if there is a significant discrepancy with the clinical/radiological findings. Pathological material should be requested at least five working days before and received at least three working days before the relevant MDTM to allow sufficient time for review. A formal report should be issued by the reviewing pathologist to the clinician or pathologist initiating the referral. The report of the reviewing pathologist should also be sent to the original pathologist and the clinician responsible for the patients care at the treating hospital, when they are not responsible for initiating the referral. Where patients have been referred for oncology treatment, requests for specialist biomarker studies will be co-ordinated between the treating oncology service, their local pathology service and the referring hospital’s pathology service, as appropriate. The oncology service must agree a mechanism for requesting tests and the relevant pathological material with their local pathology service. Requests for pathological material should be made in good time to ensure that results are available at the MDTM where the patient is to be discussed. 2. Referral for specialist opinion In cases of diagnostic difficulty, referral will usually be made to the lead pathologist of the relevant specialist MDT in the network, although referral to other specialists within or outwith the network may be appropriate in individual cases. Cases referred for individual specialist or second opinion will be dealt with by the individual pathologist and a report issued by them. Where relevant, tissue blocks should be made available to allow any further investigations that are deemed appropriate. The result of the review should be communicated to the referring pathologist by letter and also by fax/telephone as appropriate. In instances when the patient is referred for an opinion by a specialist multidisciplinary team the case should be referred to the Lead Pathologist of the appropriate MDT and dealt with according to specialist team/Cancer centre MDT guidelines. 16 There is no need for routine review of diagnoses of carcinoma made outside the Cancer Centre (specialist MDT) when the patient is referred to an oncologist/surgeon at the Cancer centre for further treatment. Individual cases may be reviewed at the request of the responsible clinician. External diagnoses of dysplasia where further treatment is being considered, e.g. radical surgery, EMR, etc should be reviewed at a Specialist MDT meeting and the diagnosis confirmed by at least two GI pathologists. Unusual tumours, e.g. lymphoma, melanoma, carcinoid, small cell carcinoma, GIST should be reviewed in the course of a Specialist MDT meeting. All suspected upper GI lymphomas should be referred to the Haematological Malignancy Diagnostic Service for phenotypic analysis and confirmation of diagnosis. Internal review of cases reported in the Cancer centre does not require the issue of another report unless a correction/modification or addition is needed. This should only be done with the knowledge and agreement of the original reporting pathologist. Review of material from outside the Cancer centre should lead to a formal report by the reviewing pathologist to the clinician or pathologist initiating the referral. The report of the reviewing pathologist should also be sent to the original pathologist and the clinician responsible for the patients care at the treating hospital, when they are not responsible for initiating the referral. Upper GI Radiology Guidelines Preoperative Staging Aim Accurate staging of gastro-oesophageal tumours is essential to formulate appropriate treatment options and thus to allow a well informed treatment decision to be made. In addition, advances in non-surgical management of advanced tumours demand accurate anatomical staging, such as the increasing use of endoscopic mucosal resection which requires accurate pre-procedure depth of tumour data and exclusion of distant spread. Precise stage-management should also limit inappropriate investigative pathways that do not influence management decisions and unnecessary exploratory surgery. Accurate tumour staging is also clearly important when comparing outcomes of non-surgical interventions as there is no histopathological “gold standard” stage of disease. Methods Essential modalities for the staging of gastro-oesophageal cancer are: Spiral Computed Tomography (CT) Endoscopic Ultrasound (EUS) Modalities and techniques that should be available for use in selected cases include: Chest radiography Trans-abdominal ultrasound 17 Neck ultrasound Magnetic Resonance Imaging (MRI) Bronchoscopy Laparoscopy Positron Emission Tomography (PET-CT) Computed Tomography Technique Spiral contrast enhanced scans with thin collimation (5mm) is optimal. In the oesophagus, prone scanning may help to clarify mediastinal invasion but has not been routinely adopted. Tumours in the cardia and within the stomach are best demonstrated following gastric distension with 600-800ml water. Distal body and antral tumours are best evaluated in the prone position. Optimal T-Stage CT Scanning a) Oesophagus CT cannot delineate the component layers of the oesophageal wall and therefore is unable to differentiate between T1 and T2 lesions. Microscopic T3 tumours cannot be detected by CT and differentiating macroscopic T3 from focal tumour bulging or juxtalesional lymphadenopathy can be impossible, particularly in a cachectic individual. Under-staging is more common than over staging. CT findings suggesting T4 involvement of aorta, tracheo-bronchial tree and crura are well documented but the signs are “soft” leading to poor sensitivity when compared with EUS. However, CT can predict mediastinal invasion in over 80% of patients. b) Stomach Adequate gastric distension is required for CT to identify the primary lesion and determine the extent of the abnormal wall thickness. Achieving this distension can be problematic in patients with advanced gastric carcinoma. CT cannot differentiate between T1 and T2 lesions. T3 lesions can be suggested by identifying stranding into the adequate peri-gastric fat but differentiating between transmural extension and perigastric lymphadenopathy can be difficult. Most contemporary studies report accuracy between 80-88% in identification of patients with advanced disease. T4 diagnosis on CT relies upon the presence of contact between tumour and contagious organs, a focal loss of intervening fat plane, or clear CT evidence of direct organ invasion. These signs may again be difficult to evaluate in a cachectic patient. Endoscopic Ultrasound 1. Fit and potentially operable oesophageal cancer patients with T2 or greater disease on staging CT scan. 2. Fit and resectable patients with non-regional lymphadenopathy (M1a) on staging CT scan with a view to do EUS FNA of non regional nodes. If these nodes are positive on cytology the same would preclude an unnecessary radical resection. 3. Identification of local invasion of organs e.g. pancreas/liver/aorta 4. Identification of low volume ascites can help identify peritoneal dissemination. 18 Optimal N-Stage CT Scanning Size is the only criterion for assessment of lymph nodes and is a poor predictor of involvement, particularly in the chest, where large nodes may be reactive. As such, the accuracy of CT diagnosis of mediastinal node involvement ranges greatly. If nodes over 8mm in diameter are considered abnormal in the coeliac axis, a sensitivity of 78% and a specificity of 93% are achieved. The identification of more distant nodal groups is of particular importance as these nodal groups may not be amenable to evaluation with EUS and will often be outside the borders of even a radical resection. The revised TNM classification has changed the classification of nodal involvement in gastric cancer. Previous classifications emphasised the importance of the distance of the involved nodes from the primary tumour. However, the current classification places emphasis on the number of involved nodes. Stage N1 refers to metastases in 1 to 6 regional nodes, N2 7 to 15 nodes and N3 involvement of more than 15 nodes. All published papers addressing the accuracy of EUS and CT in the staging of gastric cancer utilise the “old” TNM classification. The impact of these changes on the accuracy of current imaging modalities remains to be seen. Endoscopic Ultrasound Local lymphadenopathy is well characterised by EUS and certain features correlate accurately with malignant infiltration. Round nodes with well-defined margins, of greater than 1cm in diameter and with hypoechoic centres are likely to be involved. However, malignant nodes may not demonstrate all four features and large benign, reactive nodes are also recognised. EUS guided fine-needle node aspiration cytology may be helpful in these situations though the limitations of a negative result must be understood. Involved coeliac axis lymph nodes suggesting M1a disease from an oesophageal primary can be readily identified. A recent NHS Health Technology Assessment Systematic Review of Endoscopic Ultrasound in gastro-oesophageal cancer confirms the high accuracy of EUS for T and N-staging of oesophageal and gastric cancer. Initial indications suggest that the performance for T-staging at the cardia is less good. Radial probes performed better than linear probes in staging gastric cancer, although, in staging oesophageal cancer there was no significant difference between the two. Staging for metastases using EUS alone is not satisfactory. Optimal M-Stage A review of 838 cases of newly diagnosed oesophageal cancers revealed that 18% have metastases at presentation. 45% of metastases were in abdominal lymph nodes, 35% hepatic, 20% pulmonary, 18% cervical lymph nodes, 9% bone, 5% adrenal, 2% peritoneal and 2% cerebral. In this series, all patients with bone and brain metastases were associated with metastatic disease in the abdomen and thorax. Hence, in the absence of clinical indication, evaluation of metastatic disease should be focused in the examination of the thorax and abdomen. The revised TNM classification includes some important changes relating to metastatic disease in gastro-oesophageal carcinomas. Tumours in the lower oesophagus with involved coeliac axis nodes or tumours in the upper oesophagus with involved cervical 19 nodes are classified as M1a. Tumours of any region with other more distant metastases are classified as M1b. There is therefore “overlap” in the process between N and M-Staging. Spiral CT has significantly improved the detection of hepatic metastases by the introduction of techniques using thinner collimation, overlapping slices and dual phase imaging and will detect 75-80% of metastases. However, in patients with known malignancy, only 50% of lesions less than 1.5cm and 12% of lesions less than 1cm are metastatic deposits Small volume ascites can also be readily demonstrated with EUS alerting the surgeon to the possibility of diffuse peritoneal spread. Other Investigations Chest Radiography A chest x-ray should only be requested in accordance with the Royal College of Radiologists guidelines and whilst the presence of a known malignancy suggests such a requirement, CT will be performed as part of the routine staging procedure and is far more sensitive for the detection of pulmonary metastases. Trans-abdominal ultrasound Liver ultrasound may be more appropriate than CT when there is good clinical evidence of liver metastases and treatment options are so limited that confirmation is all that is required prior to palliation. Ultrasound may also be used in conjunction with or as an alternative to MRI to help characterise indeterminate liver lesions identified using CT. Its routine use is not recommended. MRI To date there is no evidence that MR has advantages over spiral CT in T stage assessment of either oesophageal or gastric carcinoma. MR imaging of the liver may be used in specific cases such as in patients with documented allergy to intravascular contrast agents or to help characterise indeterminate liver lesions identified using CT. Reports of the use of endoluminal MR are largely laboratory based and the few clinical studies have shown no advantage over EUS. PET-CT The current role of linked fluoro-deoxyglucose positron emission tomography – computed tomography in the staging of oesophago-gastric cancers is under evaluation. Up until recently, PET-CT was used by the Specialist Centre MDT on a individual basis to problem solve in cases of patients with potentially resectable disease stage T3 N1 with unusual lymph node or other lesions appearances that are not resolvable using conventional imaging including EUS with biopsy. However, as a result of the advancing body of evidence supporting its use for patients diagnosed with oesophageal and junctional carcinoma and it’s increased availability this is now included in our initial staging investigations. PET-CT is now used in all cases of fit patients with an oesophageal or oesophago-gastric junction cancer which is suitable for radical treatment or to detect occult stage IV disease. We are hoping that the resolution of the CT part of the PET-CT scan will be such that PET-CT plus EUS will become the staging strategy of choice in patients fit for radical treatment. Based on current evidence of staging accuracy, patients with gastric cancer will not routinely have PET-CT performed at initial staging. 20 Bronchoscopy CT and EUS combined are highly accurate in the assessment of tracheo-bronchial invasion from oesophageal tumours and bronchoscopy is not routinely required. It should however be available for use in patients where such imaging has raised suspicion of such invasion. Laparoscopy Laparoscopic assessment of the peritoneal cavity is the most sensitive investigation for the presence of peritoneal metastatic disease which is otherwise difficult to detect with conventional imaging. Laparoscopy is its routinely use following CT and EUS in patients with T2 or greater gastric cancer prior to radical treatment. It is also considered in any patients where there is suspicion of peritoneal spread on CT or EUS such as in the presence of small volume ascites. Bone Scan Patients with advanced disease (>T2N0) who have not undergone full body PET-CT require a Bone Scan to exclude bony metastases. Current Staging algorithm Spiral CT Centre MDT Discussion No Metastases "Problem solving" Histologically proven gastro-oesophageal carcinoma Bronchoscopy Trans abdominal Ultrsound MRI Laparoscopy EUS Stage Dependent Management Pre-operative Fitness Assessment The benefit derived from a particular therapy depends not only on the stage of the oesophageal or gastric disease but also on the fitness of the patient. The patient’s preoperative physiological status is a major factor in determining outcome after major surgery. Comprehensive pre-operative evaluation and assessment of the patient is mandatory before assigning the patient to a particular therapeutic option. Where potential 21 problems have been identified early communication with the anaesthetic/intensive care team is essential. Preoperative assessment and optimisation may necessitate a multidisciplinary approach. Anaesthesia for oesophageal surgery should only undertaken by anaesthetists familiar with the complexities of one lung ventilation. In such patients perioperative invasive monitoring should be routine (5). 22 Treatment Options In Oesophageal Cancer Surgery Surgery remains the mainstay of curative treatment for patients with oesophageal cancer and should be considered for all patients with potentially curable disease. The standard surgical approach is a two phase (Ivor-Lewis) oesophagectomy with a two field lymphadenectomy. Preoperative chemotherapy should be considered for patients undergoing surgery with T3 and/or node positive disease. The MRC OE02 trial reported an improved survival for patients who had 2 courses of preoperative chemotherapy with cisplatin and 5flurouracil compared to those patients who had surgery alone. Patients should be restaged after chemotherapy to ensure the disease remains resectable. Patients with adenocarcinoma of the oesophagus should be considered for appropriate trials. Radical chemoradiotherapy This treatment should be considered for all patients with squamous carcinoma of the oesophagus and for other patients with inoperable localised disease or who are unfit for surgery. The site and extent of the primary tumour are determined by endoscopy, CT scan and EUS. The length of the target volume is chosen to allow a 3-cm margin superior and inferior to the tumour limits as detected on endoscopy. Extra-oesophageal spread is determined by CT scans and is 2-cm. The spinal cord, lungs and heart are defined as critical structures. Palliative chemotherapy 75% of patients present with metastatic or locally advanced disease. The majority of patients with localised oesophageal cancer eventually relapse with local recurrence or metastatic disease. Chemotherapy is often used to palliate symptoms and to attempt to improve survival. There are no current National trials open for patients with locally advanced or metastatic gastro-oesophageal carcinoma. There is no useful second line chemotherapy regimen. Single agent irinotecan appears to be a possible option but this is not yet licensed. Fit patients could be considered for phase 1 trials in Newcastle. Palliative radiotherapy Dysphagia and chest pain are very common symptoms in patients with oesophageal cancer. Short courses of radiotherapy can be used to palliate these symptoms. Radiotherapy is of benefit in 70% of patients. 23 Treatment Options In Gastric Cancer Surgery Surgery is the only curative treatment in patients with gastric cancer and should be considered for all patients with potentially respectable disease. The standard surgery that is undertaken is either total or subtotal gastrectomy with radical lymphadenectomy. Adjuvant chemotherapy has been evaluated in a number of clinical trials but recent overviews suggest that it is associated with only a small survival advantage. A recent trial of postoperative chemo-radiotherapy has demonstrated a significant survival advantage. However it remains unclear whether this can be extrapolated into general clinical practise in the UK where surgery is more radical and when radiotherapy fields are not reviewed by a central team. The UK MRC ST02 MAGIC trial reported a significant 5 year survival advantage for those patients receiving 3 courses of neoadjuvant ECF chemotherapy. These patients had a 5 year survival of 36% compared to 26% for those patients having surgery alone. Following the publication of this trial we now offer all suitable patients neoadjuvant ECF chemotherapy. Chemotherapy 75% of patients present with metastatic or locally advanced disease. The majority of patients with localised gastric cancer eventually relapse with local recurrence or metastatic disease. Chemotherapy is often used to palliate symptoms and to attempt to improve survival. There have been a number of small trials comparing chemotherapy with best supportive care which show average survival is increased from 3-6 to 9-12 months with chemotherapy. There is no useful second line chemotherapy regimen. Single agent Irinotecan appears to be a possible option but this is not yet licensed. Fit patients could be considered for phase 1 trials in Newcastle. In locally advanced disease surgical opinion should be sought if disease responds to treatment to ensure that resection is not possible. Radiotherapy Radiotherapy may be used to palliate symptoms. Most commonly radiotherapy is used to treat tumours at the gastro-oesophageal junction causing dysphagia and is of benefit in 70% of patients. Less commonly it is used to treat pyloric tumours causing gastric outflow obstruction or to prevent blood loss from bleeding gastric tumours. Disease Recurrence “Routine” tests for disease recurrence will not be conducted. If patients are suspected on clinical ground of having recurrent cancer, all appropriate investigations will be ordered and results discussed in the MDM. Proven recurrent disease will then be offered treatment according to MDT meeting advice following assessment of symptoms and fitness. 24 Clinical Trials The Cancer Reform Strategy states that “in order to ensure that we build for the future of cancer services there is a need for increased support for research.” This statement underpins the need for promoting research to fill the gaps in the evidence and spreading good practice. The NECN Research Networks will work with the Service Network to promote integration of research into routine practice. Both NECN Research Networks will be meeting the performance based working proposals for the National Cancer Research Network (NCRN). This includes maintaining overall accrual and improving accrual into randomised controlled studies, (RCT’s) with the aim being to provide as wide reaching a portfolio as possible across the NECN. There is a need to ensure that the Networks portfolios are inclusive of trials for all disease groups and that there is an expansion of pre-malignancy and non-cancer screening trials. Both Networks believe it is important that patients within the NECN have equity of access to trials open. New initiatives to strengthen research into prevention of cancer are underway. The Research Networks will work with key stake holders and the Primary Care Research Networks to ensure that patients in the North East and Cumbria have access to these trials. The CRS states that there is funding for screening trials and the Research Networks will support the setting up and coordination of screening trials. The NCRN has an important role in identifying potential new therapies and making sure that clinical trials are undertaken in a timely manner. NCRN engages with Industry and NICE with the aim of maximising the impact of NCRN trials on subsequent NHS Practice. There will be further investment over the next 10 years into researching cures and treatments of the future. The Research Networks will ensure they maintain a wide reaching balanced portfolio and promote industry trials. Access to high quality information is a prerequisite for patients to be able to participate in decision making about their care and this includes research trials. All staff need to be aware of research portfolios so they can ensure they provide patients with relevant information. Reducing inequalities in equity of access to cancer trials. Promoting research proposals on cancer in equalities – encouraging more trials which include older people and ensuring that children and young adults are treated at centres where a complete portfolio of relevant trials is supported. NCRI will help fund research on data collected by the National Cancer Intelligence network (NCIN), facilitating a more informed analysis of cancer services. To ensure research is incorporated in World Class Commissioning for cancer. To work more closely with our Patient and Carer Group, particularly in relation to equity of access for patients to clinical trials. We hope they will be able to help us provide a patients perspective and help support us raise awareness. 25 The Cancer Reform Strategy supports the need for promoting integration of research into routine practice and the NECN Research Networks are keen to advance this concept. Cancer Peer Review and Clinical Trials The Manual of Measures 2008 for OG has a number of measures relating to clinical trials. Network Board measures for all NSSGs include the requirement for: A member of the NSSG responsible for ensuring recruitment into clinical trials and other well designed studies is integrated into the function of the NSSG; For the NECN OG group this is Dr Kate Sumpter, Consultant Medical Oncologist. For the Network Site Specific group, it is a requirement that: There is an agreed list of clinical trials and/or studies There is an agreed NSSG remedial action plan for recruitment into clinical trials. For the Specialist and Local Multidisciplinary Teams: Provide the names of core team members for named roles in the team. The core team specific to OG should include: A member of the core team nominated as the person responsible for ensuring recruitment into clinical trials and other well designed studies is integrated in to the function of the MDT. There is an agreed NSSG/MDT list of approved trials There is MDT/NSSG remedial action from the MDT’s recruitment results An agreed list of clinical trials for the Network can be found on the following website: www.cancernorth.nhs.uk/hpSite/home/necrnnorthsouth/portfolio. To review the current National Cancer research Network portfolio of Lung trials access the following website: http://public.ukcrn.org.uk/search/ 26 Guidelines For Genetic Risk Assessment And Surveillance Of Individuals With A Family History Of Gastric Or Oesophageal Cancer Introduction Most upper GI cancer occurs by chance. In general, 5-10% of all cancer has a significant genetic aetiology. Most families in which an inherited predisposition is suspected do not meet the currently accepted criteria for known genetic syndromes (e.g. HNPCC) and may be due to other genes as yet unidentified. Alternatively they may be accounted for by gene/environment interaction, polygenic inheritance or chance. An inherited tendency to upper GI cancer can be difficult to diagnose. Current evidence regarding surveillance comes from a variety of sources but – apart from screening recommendations for those with HNPCC (1) – are not yet conclusive. Guidelines are thus likely to change as more evidence emerges. Aim / scope The aim is to outline a risk assessment and surveillance strategy for families worried about an inherited tendency to upper GI cancer. It is possible that other types of cancer may be present in the family, and an experienced cancer genetics team should undertake the interpretation of these family histories. This guideline does not attempt to cover all possible permutations of family history, nor can it replace clinical judgement. Family structure can influence the weight attached to any particular diagnosis within a family. Genetic risk assessment is a skilled process for which there is a specific service in this cancer network. In general, the following features are suggestive, but not absolutely diagnostic, of an inherited predisposition to upper GI malignancies: early age of onset (and at diagnosis) multiple primary cancers in the same person (synchronous / metachronous tumours) multiple upper GI cancers in one family upper GI cancer associated with other characteristic tumours in the same individual / family There are 2 well-characterised and reasonably common inherited causes of upper GI cancer. Diagnosis should only be made after full genetic risk assessment. They are: syndrome HNPCC* BRCA2-related HBOC** * ** characteristic tumour (s) Stomach Pancreas Biliary tract upper Stomach Pancreas Biliary tract hereditary non-polyposis colon cancer hereditary breast/ovarian cancer GI Other tumours Colon Endometrium Urothelial Brain (glioma) Breast Ovary Melanoma 27 [Note: in addition, duodenal carcinoma may occur in Familial Adenomatous Polyposis (FAP), but remains rare and the benefit of upper GI surveillance has not been established (1).] Upper GI cancers may also occur as a site-specific familial cancer cluster (e.g. familial pancreatic cancer / hereditary pancreatitis; familial intestinal or diffuse gastric cancer; and familial oesophageal cancer / Barrett oesophagus). There are in addition a number of rare cancer predisposition syndromes, the diagnosis of which is beyond the remit of this guideline (e.g. Peutz-Jeghers syndrome, Juvenile Polyposis, Li Fraumeni syndrome, Familial Atypical Multiple Mole/Melanoma syndrome). Surveillance guidelines are offered for PJS and JP. 1. Genetic risk assessment pathway 1.1 Referral to the Cancer Family History Service : suggested criteria For individuals presenting to primary or secondary care, the following criteria identify those whose lifetime upper GI cancer risk is possibly elevated above the background population risk: multiple primary upper GI tumours in one individual 2 or more close relatives (fdr or sdr*) with pancreatic adenocarcinoma, gastric adenocarcinoma or oesophageal carcinoma anyone with oesophageal or gastric cancer with any of the following histories (either personal or familial): o o o o o o o colorectal stomach small bowel pancreas biliary tract endometrium ovary o o o o o o o breast renal / urothelial brain (glioma, haemangioblastoma) skin (melanoma) gastrointestinal polyposis leukaemia sarcoma * fdr = first degree relative (parent, sibling or child) ; sdr = second degree relative (grandparent, aunt / uncle or grandchild) Individuals who fulfil the above criteria – or those with a more complex family history that does not fulfil the criteria – should be referred to the Cancer Family History Service, Teesside Genetics Unit, James Cook University Hospital for further assessment and can be provided with the leaflet “I’ve got a family history of cancer - What happens next?” leaflet (available at http://www.cancercarealliance.nhs.uk/). 28 1.2 Risk assessment 2. on receipt of a referral, all patients will be sent an information leaflet informing them about the process of genetic risk assessment and a Family History Questionnaire (FHQ). when the completed FHQ is returned all relevant diagnoses will be confirmed in deceased relatives, where possible, with the UK Cancer Registries. Confirmation of diagnoses in living relatives will require informed consent; this will be sought where relevant. Histological sub-diagnosis will be sought in all reported gastric carcinomas. a risk assessment will then be made using standardised guidelines by a Genetic Risk Assessment Practitioner, usually in discussion with a cancer genetics counsellor or Consultant in Clinical Genetics. if the risk is assessed as LOW, the patient will be reassured by letter and the referring clinician will be informed. The patient will also be sent the leaflet “Family history of cancer – Low risk” (available at http://www.cancercarealliance.nhs.uk/professional/pubs/). Low risk patients are unlikely to receive an appointment in the genetics clinic. if the risk is assessed as possibly HNPCC or HBOC, the patient will be offered an appointment with a genetic counsellor or consultant clinical geneticist based at JCUH in the Teesside Genetics Unit. Where possible they will be seen in a hospital near to them. They will be given standard information about their family diagnosis, risk and risk reduction strategies such as site-specific disease surveillance, chemoprophylaxis [not currently an issue outside HNPCC] and risk reducing surgery where there is an evidence base. Patients will be referred for appropriate disease surveillance and for discussion about prophylaxis if appropriate. Consideration will also be given to genetic testing. Those individuals for whom no accurate risk assessment can be made, or who have extremely rare cancer predisposition syndromes, will be seen by the Consultant Clinical Geneticist. Their management will be tailored to their need according to evidence based guidelines where they exist. Consideration will be given to DNA testing/storage and suitability for research. Individuals should not be entered into a surveillance programme on the basis of their family history without a genetic risk assessment, especially given the paucity of evidence to justify surveillance. Genetic analysis Where possible, diagnostic mutation analysis will be offered to families with known cancer predisposition syndromes where the gene(s) is/are also known. This requires a lymphocyte DNA sample from a living affected individual. Mutation analysis is now routinely available for HNPCC (see below), FAP, hereditary diffuse gastric cancer (CDH1), BRCA2, TP53 (LFS), with other genes on a research basis in some labs. 29 Microsatellite instability testing will be routinely offered when: the family history suggests HNPCC other rare predispositions have been excluded on clinical grounds and tumour tissue and ideally lymphocyte DNA are available with consent from living affected relative or tumour tissue and normal tissue are available from a deceased relative with consent from the next of kin. Consideration will also be given to mutation analysis in an accredited NHS diagnostic DNA laboratory in a consenting living affected individual [or deceased affected individual who has previously stored DNA, with their consent or with that of the next of kin]: 3. in hMLH1 & hMSH2 in families with MSI-high tumours in hMLH1 & hMSH2 in modified Amsterdam / Amsterdam / Amsterdam II criteria positive families in hMSH6 where there is a preponderance of endometrial cancer in other HNPCC-associated genes when indicated and where technology allows Predictive genetic testing will be routinely offered to all individuals with a first degree relative in whom a germline mutation in a colorectal cancer predisposition gene has been identified, unless there are compelling psychiatric, psychological or medical reasons not to do so. Surveillance Gastric 1 Specific situation Surveillance recommendation Hereditary diffuse gastric cancer 50% risk (i.e. first degree relative) 2 yearly upper GI endoscopy with multiple random biopsies* Consideration given to prophylactic gastrectomy H.pylori eradication Hereditary diffuse gastric cancer CDH1 mutation carrier Annual upper GI endoscopy with multiple random biopsies* Consideration given to prophylactic gastrectomy H.pylori eradication Familial intestinal 2 yearly upper GI endoscopy gastric cancer 50% H.pylori eradication risk (i.e. first degree relative) Definitions Hereditary diffuse gastric cancer 2 or more first or second degree relatives with histologically proven 30 diffuse gastric cancer, at least one case diagnosed below 50, OR three or more first or second degree relatives with histologically proven diffuse gastric cancer at any age any individual with non-diffuse histology is considered not to be a ‘carrier’ [mixed or signet cell histology should be counted as diffuse] Familial intestinal gastric cancer 2 or more first or second degree relatives with histologically proven diffuse gastric cancer, at least one case diagnosed below 50, OR three or more first or second degree relatives with histologically proven diffuse gastric cancer at any age any individual with non-intestinal histology is considered not to be a ‘carrier’ HNPCC 50% risk** 2 yearly upper GI endoscopy from age 50 to 75 or (gastric cancer until predictive genetic testing possible present in family) H.pylori eradication HNPCC mutation carriers** (gastric cancer present in family) FAP PJS 50% affected JPS 50% affected 2 yearly upper GI endoscopy from age 50 (or 5 years before youngest gastric cancer in family) to 75 H.pylori eradication No evidence-based recommendations for upper gastrointestinal surveillance risk / 2 yearly upper GI endoscopy from age 25 risk / 2 yearly upper GI endoscopy from age 25 FAP: familial adenomatous polyposis; PJS: Peutz-Jeghers syndrome; JPS: juvenile polyposis syndrome * this approach has yet to be validated; in confirmed CDH1 families prophylactic gastrectomy may be more effective in reducing cancer risk 3,4 ** this is currently an area of controversy 2 3.2 Oesophagus In the rare families with a clear cluster of histologically identical oesophageal tumours the relative risk of oeasophageal cancer is increased. It would seem reasonable to offer 1-2 yearly endoscopic surveillance to at-risk relatives on pragmatic grounds, but there is no published evidence to support his. 4. References Dunlop MG. Guidance on gastrointestinal surveillance for hereditary nonpolyposis colorectal cancer, familial adenomatous polyposis, and Peutz-Jeghers syndrome. Gut 2002;51(suppl V): v21-v27 31 NECN Chemotherapy Treatment Algorithm NECN CHEMOTHERAPY TREATMENT ALGORITHM FOR OESPHAGOGASTRIC (OG) “Quality and safety for every patient every time” Document Control Prepared By NSSG Issue Date Approved By Chemotherapy group Review Date Version Contributors 1.1 Network Pharmacists Comments/ Amendment For more information regarding this document, please contact: NSSG Chair: Mr S Dresner 32 INTRODUCTION The 2011 Peer Review Chemotherapy Measures require each Network Site Specific group (NSSG) to agree in consultation with the Network Chemotherapy Group (NCG) a set of site specific chemotherapy treatment algorithms for the Network. Peer Review Definitions Chemotherapy treatment algorithm A guideline which specifies the acceptable ranges of regimen options for named steps on the patient pathway. Treatment algorithms are cancer site-specific. Thus, the treatment algorithm for the OG NSSG includes a statement of the range of regimens agreed as acceptable. Chemotherapy The term 'chemotherapy' refers to the use of those cytotoxic agents commonly understood and accepted as being covered by this term and includes other agents such as, biological therapy and small molecule tyrosine kinase inhibitors used for the systemic treatment of cancer. In NECN Treatment Algorithms are included in each NSSG’s Clinical Guidelines which can be found under the tumour specific page of the guidelines section of the website, e.g. for Lung Cancer http://www.cancernorth.nhs.uk/hpSite/home/guidelines/ SUPPORTING DOCUMENTS As new regimens are approved by NICE / NECDAG protocols for use of the new treatment will be uploaded to the chemotherapy site specific pages. The NSSG will be asked to update their algorithm with each new treatment approval. The availability of the Cancer Drug Fund (CDF) has increased the number of treatments potentially available to patients. CDF funded drugs may not be included in the NSSG clinical guidelines due to the dynamic nature of CDF funding (i.e. treatments can be removed as well as added). Any deviation from the algorithm should be recorded by the local Trust clinical chemotherapy service and brought to the NCG for discussion. The Network Policy on managing deviations from approved protocols/ algorithms is on the website: http://www.cancernorth.nhs.uk/hpSite/groups/networkcrosscuttinggroups/chemotherapy/ documents LIST OF APPROVED REGIMENS The NECN website provides the most up to date list of approved regimens and should be regularly checked. Appendix One below summarises the OG regimens on the website. 33 OG ALGORITHIM OESOPHAGEAL CANCER Preoperative chemotherapy Preoperative chemotherapy should be considered for patients undergoing surgery with T3 and/or node positive disease. The MRC OE02 trial reported an improved survival for patients who had 2 courses of preoperative chemotherapy with cisplatin and 5flurouracil compared to those patients who had surgery alone. Patients should be restaged after chemotherapy to ensure the disease remains resectable. Patients with adenocarcinoma of the lower oesophagus/GOJ can be considered for treatment with ECX ( see gastric cancer guidance ). Radical chemoradiotherapy This treatment should be considered for all patients with squamous carcinoma of the oesophagus and for other patients with inoperable localised disease or who are unfit for surgery. The site and extent of the primary tumour are determined by endoscopy, CT scan and EUS. The length of the target volume is chosen to allow a 3-cm margin superior and inferior to the tumour limits as detected on endoscopy. Extra-oesophageal spread is determined by CT scans and is 2-cm. The spinal cord, lungs and heart are defined as critical structures. Palliative chemotherapy 75% of patients present with metastatic or locally advanced disease. The majority of patients with localised oesophageal cancer eventually relapse with local recurrence or metastatic disease. Chemotherapy is often used to palliate symptoms and to attempt to improve survival. There are no current National trials open for patients with locally advanced or metastatic gastro-oesophageal carcinoma. There is no useful second line chemotherapy regimen. Single agent irinotecan appears to be a possible option but this is not yet licensed. Fit patients could be considered for phase 1 trials in Newcastle. Gastric Cancer Adjuvant chemotherapy Adjuvant chemotherapy has been evaluated in a number of clinical trials but recent overviews suggest that it is associated with only a small survival advantage. A recent trial of postoperative chemo-radiotherapy has demonstrated a significant survival advantage. However it remains unclear whether this can be extrapolated into general clinical practise in the UK where surgery is more radical and when radiotherapy fields are not reviewed by a central team. The UK MRC ST02 MAGIC trial reported a significant 5 year survival advantage for those patients receiving 3 courses of neoadjuvant ECF chemotherapy. These patients had a 5 year survival of 36% compared to 26% for those patients having surgery alone. Following the publication of this trial we now offer all suitable patients neoadjuvant chemotherapy. ( ECF can still be used but has generally been superceded by the more patient friendly ECX regimen ). 34 Chemotherapy 75% of patients present with metastatic or locally advanced disease. The majority of patients with localised gastric cancer eventually relapse with local recurrence or metastatic disease. Chemotherapy is often used to palliate symptoms and to attempt to improve survival. There have been a number of small trials comparing chemotherapy with best supportive care which show average survival is increased from 3-6 to 9-12 months with chemotherapy. There is no useful second line chemotherapy regimen. Single agent paclitaxol appears to be a possible option but this is not yet licensed. Fit patients could be considered for phase 1 trials in Newcastle. In locally advanced disease surgical opinion should be sought if disease responds to treatment to ensure that resection is not possible. Disease Recurrence “Routine” tests for disease recurrence will not be conducted. If patients are suspected on clinical ground of having recurrent cancer, all appropriate investigations will be ordered and results discussed in the MDM. Proven recurrent disease will then be offered treatment according to MDT meeting advice following assessment of symptoms and fitness. 35 APPENDIX ONE: NECN APPROVED LIST OF REGIMENS FOR OG Doc No. Upper GI & Hepato-biliary Cancers CRP-08-UGI001 Protocol for EOX (Epirubicin, Oxaliplatin & Capecitabine) CRP-09-UGI002 Protocol for ECX (Epirubicin, Cisplatin & Capecitabine) CRP-09-UGI003 Protocol for ECF (Epirubicin, Cisplatin & Fluorouracil) CRP-09-UGI004 Protocol for ECarboX (Epirubicin, Carboplatin & Capecitabine) CRP-09-UGI005 Protocol for ECarboF (Epirubicin, Carboplatin & Fluorouracil) CRP-09-UGI006 Protocol for Docetaxel Cisplatin CRP-09-UGI007 Protocol for Gemcitabine (Adjuvant and Metastatic) CRP-09-UGI008 Protocol for Cisplatin-Gemcitabine (Biliary Tract) CRP-09-UGI009 Protocol for Streptazocin and Capecitabine CRP-10-UGI010 Protocol for HCX (Trastuzumab, Capecitabine & Cisplatin) 36
