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Head and Neck cancer: Risk factors, imaging, treatment concepts, follow-up Frank Zimmermann Klinik für Strahlentherapie und Radioonkologie Universitätsspital Basel Petersgraben 4 CH – 4031 Basel www.radioonkologiebasel.ch Histopathology Squamous cell carcinoma ! • Laryngeal cancer • Oropharyngeal cancer • Hypopharyngeal cancer • Oral cancer • Nasopharyngeal cancer (non-ceratonized) Adeno- / Adenoidcystic carcinoma • Tumors of nose and paranasal sinus • Tumor of the glands Others: Melanoma, Lymphoma, Sarcome a.o. LN-Level IA and IB submental / submandibular along ventral digastricus II A and II B upper jugular along V. jugularis III middle jugular between hyoid and membrana cricothyroidea IV lower jugular between membrana Membrana cricothyroidea and clavicula V A and VB posterior cervical between M scm and trapezius VI anterior pretracheal between hyoid and jugulum LN-Level LN level and CT-based boundaries Lymphatic spread Nasopharyngeal Parotid LN Most cover from ca. 5 % likelyhood of infiltration Maxilla Hard palate ALL Oral cavity Oropharynx Imaging Techniques: - Clinical evaluation - Ultrasound - Endoscopy - CT-scan - MRI - (FDG)-PET Staging Type of imaging depending on initial stage and site 1. Laryngeal cancer vocal cord cT1 2. Nasopharyngeal cancer cT2 G3 3. Hypopharyngeal cancer cT2 cN1 T-Staging TX T0 Tis T1 T2 T3 T4 primary not measurable No primary Carcinoma in situ largest tumor extension < 2 cm tumor extension 2-4cm Largest tumor extension > 4 cm Infiltration of neighbored structures N-Staging NX N0 N1 N2a N2b N2c N3 Regional LN-metastases not measurable No regional LN-metastases Isolated ipsilateral metastase < 3 cm Isolated ipsilateral metastase 3-6 cm Multiple ipsilateral metastasis < 6 cm Bilateral / contralateral metastasis < 6cm Metastase(n) > 6 cm UICC-Staging Stage 0 I II III IVA IVB IVC T Tis T1 T2 T1, T2 T3 T1, T2, T3 T4a T4b each T each T N N0 N0 N0 N1 N0, N1 N2 N0, N1, N2 each N N3 each N M M0 M0 M0 M0 M0 M0 M0 M0 M0 M1 Further characteristics L0 vs. L1 V0 vs. V1 vs. V2 G1 vs. G2 vs. G3 vs. G4 Rx vs. R0 vs. R1 vs. R2 Treatments concepts: When for whom? Resection Radiation therapy Combined radio-chemotherapy Fractionation of radiation therapy Beitler et al. IJROBP 2014 Results of fractionation Pats. Fract. Weeks TD (Gy) GD (Gy) DFS OS 268 35 7 1 x 2,0 70 31,7 46,1 263 68 7 2 x 1,2 81,6 37,6 54,5 274 42 8 2 x 1,6 67,2 33,2 46,2 268 42 6 1 x 1,8 1,8 + 1,5 72 39,3 50,9 Fu et al, Int J Rad Oncol Biol Phys 2000; Beitler et al. IJROBP 2014 Fractionation of radiation therapy Beitler et al. IJROBP 2014 Fractionation of radiation therapy Beitler et al. IJROBP 2014 Fractionation of radiation therapy Beitler et al. IJROBP 2014 Only hyperfractionation superior Beitler et al. IJROBP 2014 Radiation treatment planning Marking of tumor resection borders improve radiation treatment planning after free flap reconstruction in head neck cancer surgery: titanium clips to reduce the dose in the center of the flap by IMRT Bittermann et al. J Cranio-Max Fac Surg 2015 Radiochemotherapy Standard: simultaneous RCT with Cisplatin (2 x 5 x 20 mg/m2 or 2-3 x 100 mg/m2) Simultaneous RCT Significant advantage of combined simultaneous Radiochemotherapy vs. pure radiotherapy (British Medical Journal, Budach et al. 2006) Radiochemotherapy (DAHANCA 18) 227 pats. with stage III / IVa HNC RT: 66-68 Gy in 6 weeks (6 x 2 Gy/week) CTx: 40 mg Cisplatin weekly + Nimorazole Results: 66 % full treatment; LRC 80 %; OS 72 % Tube feeding during RCT: 64 %, at 1-year 6 % Bentzen et al. Acta oncol 2015 Radiochemotherapy (DAHANCA 18) Bentzen et al. Acta oncol 2015 Radiochemotherapy (DAHANCA 18) Bentzen et al. Acta oncol 2015 Combined radiochemotherapy (GORTEC) 109 pats. with stage III / IVa HNC (cN2b-3): RT: 64 Gy in 5 weeks CTx: 3 x 100 mg Cisplatin + 2 x 5 x 1000 mg 5-FU Vs. RT: 64 Gy in 3 weeks Bourhis et al. Radiother Oncol 2011 Combined radiochemotherapy (GORTEC) Bourhis et al. Radiother Oncol 2011 Combined radiochemotherapy (GORTEC) Bourhis et al. Radiother Oncol 2011 Combined radiochemotherapy (GORTEC) Bourhis et al. Radiother Oncol 2011 Combined radiochemotherapy (GORTEC) Locoregional control and distant metastases better with RCT (p=0.005) Significant higher toxicity No advantage in OS / DFS (p=0.70 / 0.16) Conclusion: clear limits of dose intesification; no accelerated RT + CT Bourhis et al. Radiother Oncol 2011 Combined radiochemotherapy (RTOG0522) 891 pats. with stage III / IVa HNC (site/N-stage/PS/ IMRT/PET-CT-planning): RT: 70-72 Gy in 6 weeks CTx: 2 x 100 mg Cisplatin +/- Cetuximab PFS in intent-to treat: no advantage for Cetuximab Ang et al. J Clin Oncol 2014 Ang et al. J Clin Oncol 2014 Combined radiochemotherapy (ARO-95-06) 384 pats. with stage (III) / IVa HNC RT: 15 x 2.0 Gy + 29 x 1.4 Gy to 70.6 Gy in 6 weeks CTx: Mitomycin C + 5-FU vs. RT: 8 x 2.0 Gy + 34 x 1.4 Gy to 77.6 Gy in 6.5 weeks LRC significantly better with RCT: 38 % vs. 26 % Budach et al. IJROBP 2015 Combined radiochemotherapy (ARO-95-06) Budach et al. IJROBP 2015 Combination besides chemotherapy Radiotherapy plus Cetuximab (rand.) Improved survival with Cetuximab (57 % vs. 44 % 3-J-OS) Advantage: good toxicity profile (but severe dermatitis) Disadvantage: only 1 positive, pharma-supported trial No advantage to classical RCT Osteonecrosis ? Vermorken et al. 2008, Cohen et al. Bonner et al. Proc ASCO 2005 Intra-arterial chemotherapy (RADPLAT) 237 pats. with stage III / IVa HNC RT: 70 Gy in 7 weeks CTx: 4 x 150 mg Cisplatin i.a. Vs. CTx: 3 x 100 mg Cisplatin i.v. LRC not better with RCT: 60 % vs. 50 % Heukelom et al. Head Neck 2015 Intra-arterial chemotherapy (RADPLAT) Heukelom et al. Head Neck 2015 Laryngeal cancer T1a-tumors: Transoral laser surgery vs. radiotherapy - Similar local control rate - Similar voice quality - Higher laryngeal preservation with initial limited surgery Abdurehim et al. Head Neck 2010 Laryngeal cancer Abdurehim et al. Head Neck 2010 Laryngeal cancer: Overall survival Abdurehim et al. Head Neck 2010 Laryngeal cancer: Local control Abdurehim et al. Head Neck 2010 Laryngeal cancer: Larynx preservation Abdurehim et al. Head Neck 2010 Laryngeal cancer: Phonation time Abdurehim et al. Head Neck 2010 Laryngeal cancer T1-2-tumors: Transoral laser surgery vs. radiotherapy - Similar local control rate - Similar voice quality - Similar larynx preservation - No advantage for either therapy Feng et al. Head Neck 2010 Laryngeal cancer: treatment of cN0-neck Retrospective trials on 792 pats: - Neck dissection - Neck radiation - Neck dissection and radiation - Wait and see No significant difference in OS / DFS ! Goudakos et al. EJSO 2009 Laryngeal cancer Man, born 1939, with coronar heart disease, cardial insufficiency NYHA II, COPD Gold II, Diabetes IIb, 100 py Laryngeal carcinoma left vocal cord, cT2 cN0 cM0 G2, infiltrating into the supraglottis and into the sinus piriformis, infiltration of paraglottic tissue, no vocal cord fixation Laryngeal cancer Laryngeal cancer Laryngeal cancer Laryngeal cancer Laryngeal cancer Laryngeal cancer Laryngeal cancer Laryngeal cancer Man, born 1961, 60 py, alcohol abuse Advanced glottic cancer, pT4 pN2c (2/66) ECE, cM0, L0, V0, R0, Stage IVA After laryngectomy, bilateral Neck dissection, Provox Vega 8 mm Laryngeal cancer Laryngeal cancer Laryngeal cancer Laryngeal cancer Laryngeal cancer Laryngeal cancer Oral cancer 5 % of all cancer 95 % squamous cell carcinoma Risk factors: nicotin abuse and alcohol (6-fold, together 30-fold), for lip cancer contact with cigarette, HPV 16 Positive factors: nutrition (lemon, vegetables, oil of olives and fish) Precancerous: squamous intraepithelial neoplasia (SIN) (grade 1-3) Oral cancer: symptoms and prognosis Symptoms: white or red spots; ulceration; mucosal defect; pain; difficulties during speeking; thumbness of tongue, teeth, lips; bleeding; cervical or oral tumor; foetor Prognosis: - Margin < 1 mm - Basaloide/spindle cell tumors - Non continuous tumor spread Oral cancer: first steps Screening by dentists, but not systematically (Kujan et al. Cochrane 2003) Prevention: information of patients (Humphris et al. Oral Oncol 2001) Diagnostic: - Early diagnostic improves prognosis (Pitiphat et al. J Dental Res 2002) - Inspection (for all mucosal alterations for more than 2 weeks) Oral cancer: Imaging - CT-scan or MRI (67-69;94) (before biopsy) (with suspected metall artefacts MRI) (Van Cann et al. Int J Oral Max Surg 2008) - Panorama scan of mandibula - Value of FDG-PET-CT only for LN-staging (Kim et al. Eur J Surg Oncol 2008) - Ultrasound and LN-staging improved by fineneedle-biopsy (Takes et al. IJROBP 1998) - In stage III/IVa: CT-scan of thorax (US of liver) Oral cancer: therapy - Early stages: resection: 3 mm margins and preservation of contuinity of mandibula (when no infiltration of bone) (Sutton et al. Int J Oral Max Surg 2003; Wolff et al. J Craniomax Surg 2004) - Advanced stages: resection plus adjuvant radiotherapy/radiochemotherapy or definitive radiochemotherapy (Soo et al. Br J Cancer 2005) (risk of osteonecrosis) - Nutritional support - Dental support Oral cancer: therapy - Neck dissection of level I-III (~ 30 % subclinical metastasis) (elective – radical dissection) - In cN+ selective ND Level I-IV (skip lesions), sometimes modified radical ND - Adjuvant RT / RCT in cN2a or cN2b (Vikram et al. Head Neck Surg 1984; Bernier et al. N Engl J Med 2004) - Salvage ND reasonable but results poor (Mabanta et al. Head Neck 1999) - No superiority of brachytherapy - RCT with Cisplatin Oral cancer: therapy - Pure RT hyperfractionated - No superiority of additional brachytherapy - RCT with Cisplatin, not with Cetuximab - Adjuvant RT / RCT in pT3-4, R1, close margins, perinueral infiltration, vascular invasion, pN2 with 54-66 Gy - Whole treatment within 11 weeks Oral cancer: therapy - Pure RT hyperfractionated - No superiority of additional brachytherapy - RCT with Cisplatin, not with Cetuximab - Adjuvant RT / RCT in pT3-4, R1, close margins, perinueral infiltration, vascular invasion, pN2 with 54-66 Gy - Whole treatment within 11 weeks Oropharyngeal cancer 105 pats., stage III/IV oropharyngeal cancer RCT: 65-70 Gy, sim. Cisplatin (35 mg/sqm weekly) Rand. 2-3 cycles neoadjuvant Cisplatin (75mg/sqm) / 5-FU (3x800 mg/sqm) Results: Improved 2-years DFS with neoadjuvant CTx But: high drop-out rate in experimental arm (35 %) Gupta et al. Cancer Biol Ther 2009 Oropharyngeal cancer Gupta et al. Cancer Biol Ther 2009 Oropharyngeal cancer Gupta et al. Cancer Biol Ther 2009 Oropharynxkarzinom: shortened RT-time? Normal: ~ 45 % 5-y-overall survival with 76 Gy Local recurrence problem No. 1 Is increasing aggressiveness with shorter overall treatment time feasible ? Hyperfractionated-accelerated RT: 2 x 1,6 Gy to 64 Gy in stage III and IVA: 65 % 5-y-OS Waldron et al. Radiother Oncol 2008 HPV-status Important in oropharyngeal cancer, increasing in other sites 5-20 % of all HNC, 40-90 % of oropharyngeal HPV-16, but different staining and definition Middle-aged, white men; non-smokers; non- to moderate-drinkers; higher socioeconomic status; better performance status Boscolo-Rizzo et al. Acta otorhinlaryngol ital 2013; Larsen et al. BJC 2014 HPV-status Lower T- but higher N-status; non-keratinizing; poorly differentiated Better treatment response and better modalityindependent outcome So far no de-escalation in treatment ! Boscolo-Rizzo et al. Acta otorhinlaryngol ital 2013 Hypopharyngeal cancer Nasopharyngeal cancer Risk factors: latent Epstein-Barr-Virus infection (IgA and IgG; EBV-DNA) Chemicals (i.e. salted dried fish) Genetic disposition (Deletion chromosom 3p and 9p; HLA-Antigen A2, B17, Bw46) Chan Teo; Tsao Nasopharyngeal cancer Symptoms: Bleeding Serotympanon (Tuba Eustachii) Breathing through nose hindered Loss of smell sensation Pain Enlarged LN (> 60 %) Lee et al 2014 Nasopharyngeal cancer Risk factors: latent Epstein-Barr-Virus infection (IgA and IgG; EBV-DNA) Chemicals (i.e. salted dried fish) Genetic disposition (Deletion chromosom 3p and 9p; HLA-Antigen A2, B17, Bw46) Nasopharyngeal cancer Staging: Inspection, palpation (LN) Panendoscopy (with biopsy – CUP) MRI, if suspecious for infiltration CT-scan, too Sonography of LN X-ray lung / CT-scan /FDG-PET-CT-scan NCCN 2014; Ng Chan 2008 Nasopharyngeal cancer Treatment: cT1-2 cN0-1: RT or RCT (simultaneous or sequential) cT3-4 or cN 2: simultaneous RCT (CisplatinM Oxaliplatin) NCCN 2014; Baujat et al.; Zhang Zhao et al. IMRT in nasoparyngeal cancer Significant improvement of Xerostomia (CTC °II) 64 % - After 3 Months: 2,5 % - After 24 Months: IMRT vs. conventional planning - After 24 Months: 12 % vs. 67 % Xerostomia > °I No increased recurrence rate Chao et al. 2003; Lee et al. 2006; Liu et al. 2006; Wolden et al. 2006 Nasopharyngeal cancer Treatment: IMRT 70-74 Gy, 5 x 2 Gy per week; Cisplatin 100 mg/m2 day 1, 22, 43; and up to 3 cycles Cisplatin 80 mg/m2 and 5-FU 4 x 1000 mg/m2 IMRT 70-74 Gy, 5 x 2 Gy per week; Cisplatin 40 mg/m2 day 1, 8, 15, 22, 29, 36 NCCN 2014; Baujat et al.; Zhang Zhao et al. Postop. radiochemotherapy 2 randomized trials Indication for simultaneous combined RCT: - T3-4 R1 - ECE in LN Concept: up to 64 Gy plus Cisplatin Postop. radiochemotherapy (RTOG 0234) 238 pats., stage III-IVa, with R1/ECE,>2LN+ RT: 60 Gy CTx: Cetuximab + Cisplatin 30 mg or Taxol 15 mg 2-y-OS: Cis 69 % vs. 79 % Tax (better than with RTOG 9501 Cis-RT) Conclusion: phase-II/III trial ongoing, not standard ! Harari et al. J Clin Oncol 2014 Follow-up Clinically: inspection, palpation (oral, LN), compliance Imaging: none proven superior (respect financial aspects) Endoscopy: to detect early secondary cancer Schedule: 1. year – 3-monthly 2. year – 6-monthly 3.-5. year – 1-yearly Treatment planning Management of contralateral N0 neck Pyriform sinus: only in N+ ipsilateral or tumor accross the midline Oral cavity: only in N+ ipsilateral or tumor accross the midline or pT3 Koo et al. Laryngosope 2006; Koo et al. Head Neck 2006 Intensity modulated radiotherapy Intensity modulated radiotherapy Intensity modulated radiotherapy Randomized: IMRT vs. 3-D-CRT Trials on head neck or nasopharyngeal cancer Toxicity RTOG>°1 or local control All in favor of IMRT Less xerostomia with IMRT Same or better tumor control rates IMRT superior ! Gupta et al. Radiother Oncol 2012; Peng et al. Radiother Oncol 2012 Randomized: IMRT vs. 3-D-CRT Gupta et al. Radiother Oncol 2012 Proven advantage of IMRT IMRT reasonable Higher quality of life No increased recurrence rates Less than 2 % recurrences at the PTV-margin High demand on quality assurance Variation of GTV-definition in 14 pats. Anderson et al. J Radiat Oncol 2014 Variation of GTV-definition Anderson et al. J Radiat Oncol 2014 Radiation treatment planning Bittermann et al. J Cranio-Max Fac Surg 2015 Tomotherapy • Combination of MV-CT and Linear accelerator • 85 cm Gantry-opening • Treatment volumen diameter up to 40cm length up to 160cm • 6 MV Photons • Megavolt CT (3MV) • Proven efficious in head and neck cancer with good dose distribution Tomotherapy Spiral irradiation Precise axial table movement Pitch 0.0 – 1.0 Protontherapy at PSI Web-Seite in Internet Technique and physics of radiation Dose depth curves of proton Adenoidcystic carcinoma Primary: tongue Recurrence (6 y.): base of skull Problem with variabel dense tissues Perineural invasion with centripetal spread and recurrences Protontherapy Adenoid-zystisches carcinoma of the lacrimal gland (from Massachusetts General Hospital) Dose distribution of Carbon-Ions Schulz-Ertner et al., 2003 Dose distribution of Carbon-Ions Schulz-Ertner et al., 2003 Neutron therapy Garching Web-Seite im Internet Neutron therapy Garching Neutron therapy Garching Advantages in radiation biology: independent of oxygenation, more double-strand breaks Indication: glandular adenoid-cystic carcinoma Side effects Acute Mucositis Likelyhood of side effects Acute side effects - Mucositis - Severe Mucositis - Dysgeusia - Xerostomia - Dermatitis 100 % > 50 % up to 100 % bis 100 % bis 100 % Late side effects: - Xerostomia - Osteonecrosis - Dental loss - Dysgeusia > 50 % up to 10 % up to 50 % up to 100 % No protection Vitamins Growth factors (GSF, Epo) Selen Misteltoe Lambin et al., Cochrane 2009 Dental defects Walker et al., 2011 Caries and Osteomyelitis Causes of osteonecrosis Insufficient compliance of the patient - deficient oral hygiene - inadequate use of fluor support - pre-damaged teeth - soft diet with high carbohydrate contents Direct teeth damage by irradiation Indirect teeth damage by caries - Xerostomia - Alteation of oral microflora - more azidogene / cariogene bacteries In > 50 % dentogene, trauma-induced causes for contaminated osteonecrosis Explanation for osteonecrosis Care of clinically asymptomatic bone: - No consequent care by dentists before and after radiotherapy - Insufficient experience in care of radiationaltered mandibulae - Inadequate therapy at teeth extraction Prophylaxis of radiation sequelae • Avoid alcohol, nicotine, hot food • Before radiation: dental preparation, (caries, filling, pouches) • Fluor support under prosthesis (10-30 min. per day, break during RT) • During radiation: intensification of oral hygiene (to clean the mouth with water, tee, NaClsolution) • Benzydamin (Tantum) prophylactic, compliance problematic • Avoid weight loss (PEG, PORT) Prophylaxis of radiation sequelae • Xerostomia prophylaxis: IMRT, stimulation of saliva (z.B. oral gum, liquids), consider Amifostine in pure radiation therapy • Avoid definite prosthesis during RT and for further 6 months • Dental prosthesis during RT • Soormucositis: top. antimykosis • evtl. antibiotics • Analgesics: according to WHO-schedule Supportive care Antioxidant with calendula officinalis: randomized trial with less mucositis Low-level laser: randomized trial with no benefit Babaee et al. J Pharmaceut Sciences 2013; De Lima IJROBP 2012 With optimal care (273/639) Complications Percent No complications 77.5% Radiogen induced caries 19% Extractions after RT 8% Candidosis 3.5% Radiogen induced osteonecrosis 3% Risk factor: multimodal therapy ! Therapy of osteonekrose/xerostomia • In severe late reactions: HBO ? • In xerostomia: try pilocarpin when some function of glandulae exists; oral liquids • No artificial saliva support with products of cellulose (more caries) • Logopedie, swallowing training Therapy of soft tissue/bone necrosis • Chronic soft tissue necrosis: Pentoxifyllin (Trental), Vitamine E • Evtl. OP, evtl. HBO • Test with Bisphosphonates (Take care: mandibular necrosis !) Conclusion Modern tchniques allow higher dosis, but this is not allways necessary Perfect coordination of multimodal therapy and supportive treatments Critical considerations: Indication / aim of treatment ? What is acchievable ? Resourcen vs. Waiting time Treament of tumor recurrenes Locoregional failure in more than 50 % Re-treatment Chemotherapy (Cisplatin/5-FU, Carboplatin/5FU, MTX, Cisplatin/Taxol, Cisplatin/Cetuximab, Docetaxel/Gefintib): 5 – 10 months med. surv. Radiotherapy/Radiochemotherapy (50-65 Gy; ): 6 – 27.6 months med. surv. Resection plus RT/RCT: curative option ! Cacicedo et al. Cancer Treat Rev 2014 Re-treatment: recommendations No severe sequelae in previous radiation treatments and no significant comorbidities PET-CT for staging Whenever feasible initial surgery and doses > 60 Gy Re-irradiation beyond 6 months after initial treatment Tumors < 30 cm3 GTV plus margin IMRT or SBRT Cacicedo et al. Cancer Treat Rev 2014 Stereotactic radiotherapy Fixation with - mask Navigation with - frame - pure imaging Nasopharynx Med. FU 20,3 months; 5,7 (0,8-24,7) ml Pat., after RCT Dose 34 < 6 Months 3 x 6 Gy 56 > 6 Months 6 x 8 Gy Wu et al. IJROBP 2007 Nasopharynx Pat., after RCT 34 < 6 Months 56 > 6 Months Dose 3 x 6 Gy 6 x 8 Gy CR 66 % 63 % 3-JPFS 72,3 % 42,9 % 3-JLRSur 89,4 % 75,1 % 17 pats. complications: 6 mucosa-necrosis, 2 deadly bleeding; 9 brain necrosis, 0 deadly Wu et al. IJROBP 2007 Head neck cancer Pats.: 18 resp. 14; med. FU 30,4 vs. 25,6 for liv. RT: only GTV; 28 x 1,8 Gy vs. 6 x 6 Gy; CTx: Cetuximab 400/250 mg/m2 Balermpas et al. IJROBP 2012; Comet et al. IJROBP 2012 Head Neck Cancer PFS 7,3 vs. 8,8 Months; 47 % vs. 75 % Remission 5 Dermatitis °III, 5 Trismus °III vs. 2 Dermatitis °III Balermpas et al. IJROBP 2012; Comet et al. IJROBP 2012 Concepts and Dosis • • • • • Curative vs. palliative Large vs. small target volume 20-75 Gy total dose 1,2-6,0 Gy single dose Defintive, postoperative or simultaneous with chemotherapy Palliative radiotherapy Palliative: 2 x 6,0 Gy / pro week to 30 Gy TD 4 x 3,5 Gy / 2 days, each month to 42 Gy TD Results: 80 % Remission > 60 % symptom improvement Median survival 6 months 2-year survival ca. 15 % Low risk of osteonecrosis ! Radiotherapy in NHL Definitive curative radiotherapy 24 – 40 Gy - Total dose: - Local control: > 90 % 33-72 % - 10-year recurrence free: Pure palliative radiation therapy: - Total dose: 4,0 Gy - Remission rate: > 80 % - Local control: > 50 % Low risk of osteonecrosis ! Tumors at the base of skull Fixation with - Frame - Mask Adenoidcystic carcinoma Adenoid-cystic carcinoma with invasion of the base of skull 5-jahres Tumorkontrolle (%) Protonen: 100 Pommier et al. MGH, 2006 80 Kohlenstoff-Ionen 60 Neutronen 40 Photonen 20 20 40 60 80 Dosis [ Gy (RBE)] 100 Results of protontherapy Paul Scherrer Institute: Tu-control 5 years Chordoma 81 % Chondrosarcoma 94 % 0.2 0.4 0.6 0.8 1.0 Time to control local failure Local Chordoma Chondrosarcoma 0.0 P=0.25 0 20 40 60 80 months Severe toxicity: 5 – 7 % Mass. General Hospital: Tu-control 5 years Chordoma 73 % Chondrosarcoma 98 % Chordoma before and after Carbon-Ions Schulz-Ertner et al., 2003 Chordoma of the skull base 5-years tumor control (%) Photons small chordoma chondrosarcoma 100 Romero 1993 Zorlu 2000 Debus 2000 80 Protons 60 Munzenrider 1999 Ares 2007 Hug 1999 40 C-Ions 20 Schulz-Ertner 20 40 60 80 Dose [ Gy (RBE)] 100 Results of Carbon-Ions-therapy Chordoma and chondrosarcoma of skull base Schulz-Ertner et al., 2003 Phase-II trials 236 pats., 16 x 4 Gy or 16 x 3,6 5-y. loc.reg. control Melanoma Adenoidcyst. Ca. Adenocarcinoma SC-Ca. Sarcoma 75 % 73 % 73 % 61 % 24 % Late side effects Grade II mucositis Grade II dermatitis 2% 3% Mizoe et al. 2012 Chordoma-/Chondrosarcoma-Therapy Pharyngeal tumors In total 4 trials with 531 pats. neutrons vs. photons and 1 trial with 327 pats. neutrons plus photons vs. photons: No significant difference Cochrane database 2010, Griffin et al. 1984, MacDougall et al. 1990, Maor et al. 1986, Maor et al. 1995, Griffin et al. 1989) Summary: concepts Definitive radiochemotherapy: simultaneous Cisplatinum-based If contra-ind.: Cetuximab or Mito/5-FU or else Radiation therapy alone: in stage I: conventional fractionation in stage III-IVa: altered fractionation Postoperative radiochemotherapy: R1 or ECE Larynx preservation: concept open (neoadj. CTx vs. RCT) Summary: techniques In squamous cell carcinoma: IMRT (Linac or tomotherapy) Different techniques: in selected cases only In adenoidcystic carcinoma: Neutrons or protons In chordoma / chondrosarcoma: protons / ions In early stage oral cancer: brachytherapy For tumor recurrences: consider hypofractionated schedules in palliation and aggressive retreatment in curative options