ESTRO 36 Abstract Book

S602 ESTRO 36 _______________________________________________________________________________________________

EP-1097 P16 expression: a predictive marker for treatment-related outcomes in oropharyngeal cancer patients? A. Modesto 1 , T. Galissier 2 , A. Lusque 3 , E. Uro-Coste 2 , J. Delord 4 , A. Laprie 1 , J. Sarini 5 , P. Graff 1 , P. Vergez 5 , M. Rives 1 1 Institut Universitaire du Cancer, radiation therapy, Toulouse, France 2 Institut Universitaire du Cancer, Pathology, Toulouse, France 3 Institut Universitaire du Cancer, Biostatistics, Toulouse, France 4 Institut Universitaire du Cancer, Medical Oncology, Toulouse, France 5 Institut Universitaire du Cancer, Head and Neck Surgery, Toulouse, France Purpose or Objective Treatment strategies in oropharyngeal squamous cell carcinomas (OSCC) consist in either surgery followed by adjuvant radio(chemo)therapy or definitive radio(chemo)therapy. P16 overexpression (p16+) is considered as a surrogate marker for HPV-induced tumors that are associated with improved outcome whichever treatment modality is considered in comparison with p16 negative (p16-) OSCC. To date no predictive factors are known to guide treatment decision. Material and Methods All consecutive patients treated for an OSCC with a curative intend at a single tertiary cancer center between 2009 and 2013 were eligible to this study. P16 status was determined by immunochemistry and centrally reviewed. Late toxicities incidence ie: dysphagia, xerostomia, painful shoulder, osteoradionecrosis or nerve paralysis were registrated and graded according to CTCAE v4 in patients alive without loco-regional evolution at least 6 months after treatment completion. Three-year disease free survival (DFS) and late severe toxicity occurrence were compared according to p16 expression and treatment modality: initial surgical treatment or definitive radio(chemo)therapy. Results Among the 167 patients included in this study, 77 (44%) presented a tumoral p16 overexpression (p16+). Initial surgery was performed in 51 (66%) and 48 (53%) cases and definitive radiochemotherapy was performed in 26 (34%) and 42 (47%) cases among p16 + and p16 - patients respectively (p=0.05). 99 patients (60%) underwent initial surgery followed by adjuvant radio (chemo) therapy in 51 cases (91 %). After a 51-month of median follow-up [47-54 months], the 3-year DFS was 82% and 42% among overall p16 + and p16 - patients respectively (p=0.01). Among p16 – patients, the 3-year DFS after initial surgery or definitive radiochemotherapy was 62% and 32% respectively (p=0.003). Among p16 + patients, the 3-year DFS was 85% and 77% (p=0.16) whereas severe delayed toxicity occurred in 42% vs. 18% after initial surgery or definitive radiochemotherapy respectively (p=0.05). Conclusion Whereas p16- OSSC are at high risk of loco-regional failure and highly benefited from aggressive multimodal treatment including surgery and adjuvant radio(chemo)therapy, p16+ OSCC didn’t harbour the same benefit from the combinative approach that was associated with a significant increase of delayed severe toxicity. The benefit of initial surgery or definitive radio(chemo) therapy seemed not equivalent among OSSC patients according to p16 status that might be a useful tool to guide initial treatment decision.

Case details are given in Table 1. Oral cavity primary disease accounted for 15% of cases in the original cohort available for review (prior to exclusions), but half of patients who relapsed loco-regionally. Mean time to relapse was 18 weeks (Std. error +/- 2.4 weeks). 10 of 12 patients (83%) had residual or relapsed disease ipsilateral to the primary site. 2 (both lateral tongue SCCs who underwent primary surgery followed by RT +/- chemo to the primary site and ipsilateral neck) relapsed early (8 and 20 weeks respectively) in the contralateral, un-irradiated neck.

Figure 1 describes the volume of rGTV covered by pertinent isodose contours and target CTV/PTVs. According to our criteria, 9 of 12 relapses were in-field (75%), 1 (8.3%) was marginal and 2 (16.7%) were in deliberately un-irradiated contralateral neck nodes as described. Conclusion Oral cavity tumours appeared at highest risk of relapse in our cohort. Using DIR to map disease relapse to treatment volumes and dose, we found most relapsed HNSCC (75%) occurred within the high dose volume, in keeping with previous studies, and suggesting that unfavourable biology rather than inadequate RT is the predominant reason for loco-regional HNSCC relapse. Our results will be used to inform review of our neck irradiation policy, particularly for SCCs of the oral cavity.