Abstract Book

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ESTRO 37

Material and Methods Between June, 2010 and February, 2014, patients were randomly allocated to receive either 60 Gy in split course over 11 weeks combined with concomitant 5FU and hydroxyurea according to the previously reported Vokes protocol (VP arm), or 60 Gy and 1.2 Gy per fraction twice daily combined with cetuximab (Hyper-Fractionated Radiotherapy: HFR arm). Eligibility criteria were: recurrence or a second primary in a previously irradiated area, no major sequelae due to the first radiotherapy, no distant metastasis, salvage surgery with macroscopic complete resection. Results twenty six patients were included in VP arm and 27 in HFR arm. There was no imbalance in the distribution of the main tumor and patients characteristics. Only one patient in VP arm experienced more than 15 days of treatment interruption due to toxicity, and none in HFR arm (primary endpoint). In both arms, all patients received at least 60 Gy. In VP arm 8/ 26 patients had delay and/or dose reduction of chemotherapy. In HFR arm, 4/27 patients had less than 6 cycles of cetuximab. There was an improved overall survival in HFR arm than in VP arm, however the difference was not significant between the 2 arms (Median OS 37.4 months [95% CI: 16.1 - NA] vs 21.9 months [95% CI: 12.9 - 33], p = 0.12). Acute and late toxicities and disease-free survival were not statistically different between the 2 arms. Conclusion the twice daily schedule of re-irradiation of 60Gy/ 5 weeks with concomitant weekly cetuximab is well tolerated and can be proposed after salvage surgery of recurrent HNSCC. However the twice daily schedule can be difficult to organize. It was the main raison for the slow accrual of patients in this trial. OC-0273 Phase II Trial of De-intensified Chemoradiotherapy for HPV-associated Oropharyngeal Cancer B. Chera 1 , R. Amdur 2 , X. Tan 3 , N. Hayes 4 , J. Weiss 5 , J. Grilley-Olson 5 , A. Zanation 6 , T. Hackman 6 , J. Zevallos 7 , S. Patel 6 , N. Sheets 8 , M. Weissler 6 , W. Mendenhall 2 1 The University of North Carolina, Radiation Oncology, Chapel Hill NC, USA 2 University of Florida, Radiation Oncology, Gainesville, USA 3 University of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill, USA 4 University of Tennessee Health Science Center, Hematology/Oncology, Memphis, USA 5 University of North Carolina, Hematology/Oncology, Chapel Hill, USA 6 University of North Carolina, Otolaryngology, Chapel Hill, USA 7 Washington University, Otolaryngology, St Louis, USA 8 Rex/UNC Healthcare, Radiation Oncology, Raleigh, USA Purpose or Objective To report initial results from a prospective phase II clinical trial of highly de-intensified chemoradiotherapy (CRT) for patients with favorable risk HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Material and Methods The major inclusion criteria were: 1) T0-T3, N0-N2c, M0, 2) HPV or p16 positive, and 3) minimal/remote smoking history. Treatment was limited to 60 Gy intensity modulated radiotherapy with concurrent weekly intravenous cisplatin 30 mg/m 2 (second choice was cetuximab). Patients received neither induction chemotherapy nor definitive surgery. Patients with T0-T2 N0-1 disease did not receive chemotherapy (i.e. received 60 Gy alone). All patients had a 10 to 12-week post- treatment PET/CT to determine need for planned neck dissection. The primary study endpoint is 2 year progression free survival (PFS). Secondary endpoint

were randomized to control-arm or zalutumumab-arm. The control-arm was primary accelerated RT, predominantly 66-68Gy, 2Gy/fx, 6fx/wk and concomitant daily hypoxic radiosensitisation with nimorazole. Stage III-IV carcinomas received weekly cisplatinum 40 mg/m2 during RT. Elective neck-dissection was not performed. The zalutumumab-arm was identical with the control-arm plus zalutumumab 8 mg/kg. First dose was given the week before start of RT and continued weekly during irradiation. Analyses were performed as intention-to- treat. Primary endpoint was Loco-Regional Control (LRC). Secondary endpoints were Disease Specific Survival (DSS) and Overall Survival (OS). Results Median observation time was 59 months. 608 patients were eligible for analysis. 307 pts were in the control- arm and 301 in the zalutumumab-arm. Patient and tumor parameters were well balanced. The 5-year LRC rate was 70% in the zalutumumab-arm vs. 74% in the control-arm, HR: 1.10 [95% CI: 0.81-1.50]. This outcome was also reflected in DSS: HR 1.12 [0.79-1.60] and in OS: HR 1.17 [0.89-1.52]. There was no benefit of adding zalutumumab to C-RT nor RT alone for any of the endpoints. Treatment was generally well tolerated, but 94% of the pts in the zalutumumab-arm experienced a skin-rash (29% grade 3+4 rash), and pts treated with zalutumumab experienced significantly more frequent confluent mucositis (70% vs. 56%, p=0.001) and grade 3+4 in-field skin reaction (27% vs. 4%, p<0.0001). The 5-year update did not reveal any significant increase in late morbidity between the zalutumumab-arm and control-arm: severe dysphagia (19% vs. 16%), severe dryness of the mouth (20% vs. 18%), severe late oedema (3% vs. 5%), severe atrophia (8% vs. 6%) and severe fibrosis (20% vs. 16%). Conclusion Treatment with zalutumumab was generally well tolerated, but the addition of concomitant zalutumumab to primary C-RT or RT and nimorazole for HNSCC did not increase loco-regional control nor disease specific or overall survival at 5 years. Acute toxicities, but not late morbidity, were increased in the zalutumumab-arm. OC-0272 Twice daily reirradiation with cetuximab vs once daily chemoRT after surgery in head and neck cancer Y. Tao 1 , L. Faivre 2 , A. Laprie 3 , P. Boisselier 4 , C. Ferron 5 , G. Jung 6 , S. Racadot 7 , B. Gery 8 , C. Even 9 , I. Breuskin 9 , J. Bourhis 10 , F. Janot 9 1 Institut Gustave Roussy, radiation oncology, Villejuif, France 2 Institut Gustave Roussy, biostatistics, Villejuif, France 3 Institut Claudius Regaud, radiotherapy, toulouse, France 4 Institut du Cancer Val d’Aurelle, radiotherapy, Montpellier, France 5 Centre Hospitalier Universitaire de Nantes, head and neck surgery, Nantes, Franc 6 Centre Paul Strauss, radiotherapy, Strasbourg, France 7 Centre Léon Berard, radiotherapy, Lyon, France 8 Centre François Baclesse, radiotherapy, Caen, France 9 Institut Gustave Roussy, Head and neck oncology, Villejuif, France 10 CHUV, Radiation oncology, Lausanne, Switzerland Purpose or Objective A previously published randomized trial of patients with recurrent Head and Neck squamous cell carcinoma (HNSCC) has shown that full-dose re-irradiation combined with chemotherapy after salvage surgery significantly improved disease free survival (DFS), but had no significant impact on overall survival. The GETTEC and GORTEC groups performed a randomized phase 2 trial to compare two methods of re-irradiation (once-daily split- course with chemotherapy vs twice-daily with cetuximab) in terms of toxicity and survival.