ESTRO 38 Abstract book

S282 ESTRO 38

to get insights on new possible immunotherapeutic strategies. Material and Methods From May to November 2017 20 untreated patients affected by moderately to advance stage OSCC and treated by radiotherapy or chemo/bio-radiotherapy have been enrolled in the study. Peripheral blood and tumor biopsies were collected and evaluated by multiparametric flow cytometry panels to delineate: CD4+ and CD8+ T cell maturation stages, frequency of CD4+ and CD8+ T regulatory cells (Treg), expression of exhaustion/immune checkpoints (CD39, PD-1, CTLA-4, TIM3). Results The results showed: a) CD4+ and CD8+ effector memory cells were the most represented population among tumor infiltrating lymphocytes (TIL) but not among peripheral blood lymphocytes; b) CD4+ and CD8+ TIL showed decreased expression of co-activatory receptors, as CD28 molecule, and increased expression of inhibitory receptors, as PD-1, TIM-3, CTLA-4, than circulating CD4+ and CD8+ T cells; c) intratumoral CD4+ and CD8+Treg frequencies resulted statistically increased in cancer specimens with respect to blood; d) Treg exhibited an active functional phenotype, as demonstrated by their elevated FoxP3, CTLA-4 and CD39 expression and high expression of immune checkpoints (PD1, CTLA-4 and TIM3). Conclusion Collectively, the results highlight expansion in the tumor of T cells in advanced stage of maturation, characterized by high expression of immune checkpoints and enrichment of Treg, suggesting a pressure by tumor toward regulatory function induction. Interestingly, immune checkpoint expression only partially overlapped in the different intratumoral T cell subsets indicating that immunotherapy by immune checkpoint inhibitors might develop new combinatorial protocols associating at least 3 different agents targeting CTLA-4, PD1-PDL1 and TIM3-Galectin-9 axes in order to be effective in HNSCC patients. PV-0536 On the impact of HPV status and radiation dose on survival in a large cohort of anal cancer patients R. Kabarriti 1 , P. Brodin 2 , R. Narang 3 , R. Huang 3 , J. Chuy 3 , L. Rajdev 3 , S. Kalnicki 2 , C. Guha 2 , M. Garg 2 1 Montefiore Medical Center- Albert Einstein College, Radiation Oncology, New York, USA ; 2 Montefiore Medical Center, Radiation Oncology, Bronx, USA; 3 Montefiore Medical Center, Oncology, Bronx, USA Purpose or Objective To determine whether patients with anal cancer with human papilloma virus (HPV) infections have different overall survival compared to those without HPV infections, and to elucidate the radiation dose-response relationship in a large retrospective cohort of anal cancer patients. Material and Methods We utilized the National Cancer Database (NCDB) registry to identify a cohort of non-metastatic anal cancer patients treated with curative intent between 2008 – 2015 with available treatment data and follow-up for vital status. HPV status was dichotomized into positive vs. negative for those with available HPV markers from diagnostic work- up. For patients receiving definitive radiation therapy (RT), the total dose delivered to the tumor was used for analysis. Multivariable Cox proportional hazards regression models were used to determine the association between HPV status and overall survival (OS), as well as varying levels of total RT dose delivered. Kaplan-Meier survival analysis with log-rank test was used to illustrate and compare actuarial survival estimates between groups. Results We identified 33,537 patients for this analysis, of which 5,961 patients had information on HPV infection. Of those, 3,550 (59.6%) were HPV positive and 2,411 (40.4%) were

Conclusion Overall, our findings show that photons and carbon ions may modulate the expression of different miRNAs still affecting the same biological processes. While photon radiobiology has been extensively characterized, a deeper understanding of the biological dynamic underlying the modus operandi of carbon ions might contribute to the design of more precise and honed hadrontherapy treatment schedules on the basis of patient miRNA expression patterns. In addition, miRNAs may be envisaged as a novel class of predictive biomarkers also for this promising frontier in radiotherapy. PV-0535 Pilot study on immunomodulation role of radiotherapy in oropharyngeal cancer: preliminary results L. Belgioia 1 , A. Bacigalupo 2 , F. Missale 3 , S. Negrini 4 , G. Filaci 4 , D. Fenoglio 4 , F. Incandela 3 , S. Vecchio 5 , G. Peretti 3 , R. Corvò 1 1 University of Genoa and IRCCS Ospedale Policlinico San Martino, Department of Health Science DISSAL and Radiation Oncology, Genoa, Italy; 2 IRCCS Ospedale Policlinico San Martino, Department of Radiation Oncology-, Genoa, Italy; 3 University of Genoa, Department of Otorinolaringology- Head and Neck Surgery-, Genoa, Italy; 4 University of Genoa and IRCCS Ospedale Policlinico San Martino, U.O. Immunologia Clinica and Centro di Eccellenza per le Ricerche Biomediche CEBR, Genoa, Italy; 5 IRCCS Ospedale Policlinico San Martino, Department of Medical Oncology, Genoa, Italy Purpose or Objective The discovery of the key role of the immune system in the pathogenesis of tumors prompted studies aimed at identifying immunological prognostic biomarkers. The encouraging results of immunotherapy in recurrent non- resectable head and neck cancer may indicate its potential efficacy, combined to conventional therapies, also as primary treatment. The aim of our prospective study is to perform a comprehensive analysis of the circulating and intratumoral T cell compartments in patients affected by Oropharyngeal Squamous Cell Carcinoma (OSCC) to search for new prognosticators and