ESTRO 36 Abstract Book

S175 ESTRO 36 _______________________________________________________________________________________________

RT. RT total dose was 70 Gy (2 Gy/day, 5 days/week). Concurrent CT was 3 cycles of carboplatin 70mg/m²/d + 5FU 600mg/m²/d, D1-4. About 2/3 of the patients had oropharyngeal cancers (OPC) and HPV status was determined in these patients using p16 expression as a surrogate (immunohistochemistry). Smoking status was also collected. Primary endpoint was progression free survival (PFS). Results Between Feb 2008 and Feb 2014, 406 pts were randomized with 265 (65%) OPC. The median follow-up was 4.4 years. Overall, p16 was assessed in 236 OPC (89%) patients (115 pts in arm A and 121 in arm B), and p16+ was found in 21% of each arm (24 patients in arm A and 25 arm B). 15 out the 49 (31%) p16+ patients were non-smokers, while 5/187 (3%) p16- patients were non-smokers. A significant improvement in PFS was found in p16+ compared to p16- OPC (p= 0.0002). A significantly improved PFS was observed with cetux-CT/RT (arm B) compared with cetux- RT (arm A) in p16- OPC (HR: 0.63, 95% CI: 0.44 – 0.91) as well as in p16+ (HR: 0.23, 95% CI: 0.07 – 0.73), and the interaction between p16 and treatment modality was not significant (p=0.13). For loco-regional control, a similar effect was found in both p16- and p16+ OPC in favor of arm B (HR= 0.33 [95%CI 0.19 – 0.56] and 0.16 [95%CI 0.02 – 1.36] respectively; interaction test p=0.51). Conclusion The large majority of OPC patients randomized in this trial were p16- and smokers. The addition of concomitant chemotherapy to cetux-RT markedly improved PFS and LRC in patients with OPC regardless of p16 status. OC-0333 Prognostic impact of HPV and smoking in RT of oropharyngeal cancer: the MARCH-HPV project P. Lassen 1 , B. Lacas 2 , A. Trotti 3 , B. Zackrisson 4 , Q. Zhang 5 , J. Overgaard 1 , J.P. Pignon 2 , P. Blanchard 6 1 Aarhus University Hospital, Department of Experimental Clinical Oncology, Aarhus C, Denmark 2 Gustave-Roussy Paris-Saclay University Ligue Nationale Contre le Cancer meta-analysis platform, Biostatistics and Epidemiology Department, Villejuif, France 3 Moffitt Cancer Center, Department of Radiation Oncology, Tampa- Florida, USA 4 Umeå University, Department of Radiation Sciences - Oncology, Umeå, Sweden 5 NRG Oncology Statistics and Data Management Center formerly RTOG, NRG Oncology Statistics and Data Management Center formerly RTOG, Philadelphia- PA, USA 6 Gustave-Roussy Paris-Saclay University, Radiotherapy Department- INSERM-U1018-CESP, Villejuif, France Purpose or Objective HPV is a favorable prognostic factor in radiotherapy (RT) of HNSCC but whether HPV is predictive of response to altered fractionated RT remains controversial. We aimed to assess the potential prognostic and predictive impact of HPV in altered fractionated RT and moreover to evaluate the combined prognostic impact of HPV and smoking. Material and Methods The MARCH-HPV project is based on the first update of the Meta-Analysis of Radiotherapy in HNSCC (MARCH), which included 33 trials and 11833 patients. HPV status was determined according to p16 immunohistochemistry. The HPV analysis was restricted to oropharyngeal cancer (OPC) and performed using a Cox model stratified by trial and adjusted on gender, age, T-stage, N-stage, type of RT schedule, p16 (positive, negative) and smoking status (never/former, current). The potential prognostic and predictive effects of HPV-status were estimated for progression-free survival (PFS) and overall survival (OS). Moreover, the combined prognostic impact of HPV and smoking were assessed for PFS and OS. Results

Conclusion Our findings strongly favor use of cisplatin in CRT treatment of locally advanced p16+ OPC. Until results of randomized trials evaluating cisplatin versus cetuximab are available, off-trial use of C225 in this population as an effort to reduce morbidity should be discouraged, especially in patients with advanced tumor and nodal stage disease. In cases where cisplatin is contraindicated, the use of carboplatin as an alternative option may reduce DF compared to C225. When C225 is used, altered fractionation radiotherapy may be beneficial for LRC. OC-0332 Impact of HPV on effect of chemotherapy in SCCHN : results of the GORTEC 2007-01 randomized trial X. Sun 1 , Y. Tao 2 , A. Auperin 3 , C. Sire 4 , L. Martin 5 , C. Khoury 6 , P. Maingon 7 , E. Bardet 8 , M. Lapeyre 9 , Y. Pointreau 10 , N. Ollivier 3 , A. Cornely 2 , O. Casiraghi 11 , J. Bourhis 12 1 CHRU- Besançon and Hôpital du Nord Franche Comté-, radiotherapy, Montbéliard, France 2 Institut Gustave Roussy, Radiation Oncology, Villejuif, France 3 Institut Gustave Roussy, Biostatistics, Villejuif, France 4 CH de Bretagne Sud, radiotherapy, Lorient, France 5 Centre Le Conquerant, radiotherapy, Le Havre, France 6 Centre Saint Louis, radiotherapy, Toulon, France 7 Centre GF Leclerc, radiotherapy, Dijon, France 8 Centre Gauducheau, radiotherapy, Nantes, France 9 Centre Perrin, radiotherapy, Clermont, France 10 Jean Bernard centre - Victor Hugo clinic, radiotherapy, Le Mans, France 11 Institut Gustave Roussy, Pathology, Villejuif, France 12 CHUV, radiation oncology, Lausanne, Switzerland Purpose or Objective Chemo-radiotherapy (CT/RT) and cetuximab-RT (cetux- RT) were established as standard treatments in non- operated locally advanced (LA) SCCHN. The GORTEC 2007- 01 randomized trial was restricted to patients (pts) with no or limited nodal spread (N0-N2a and non palpable N2b). The results showed that the addition of concomitant CT with cetux-RT backbone markedly improved both PFS and LRC ( Bourhis et al ASCO 2016 ) with no significant benefit on overall survival. The impact of p16 expression on the treatment effect of these patients was not available at the time of the first presentation. Material and Methods The 1:1 randomization between cetux-RT (arm A) and cetux-CT/RT (arm B) was done by minimization on centers, N and T stages. Cetuximab was given as a loading dose of 400 mg/m2 followed by weekly 250 mg/m2 during