Abstract Book

S120

ESTRO 37

Abstract text Over the last decade tremendous progresses have been made in the understanding on how immune system dysfunction plays a role in both the development and the progression of head and neck squamous cell carcinoma (HNSCC). Down-regulation of HLA class I molecules, development of T-cells tolerance, inhibition of cytokine production and increased expression of programmed death receptor-1 (PD-1) and/or its ligand (PD-L1) have been shown to impair the host immune response. In this context, checkpoint inhibitors of CTLA-4 (T-cells surface receptor) such as ipilimumab, of PD-1 such as nivolumab and pembrolizumab, and of PD-L1 such as avelumab have been developed and tested in the clinics. In second line metastatic or recurrent HNSCC progressing after platinum-based chemotherapy, a randomized study (Checkmate-141) has demonstrated a significant increase in overall survival with a significantly lower toxicity profile in patients treated with nivolumab compared to standard of care. A similar trial has been conducted with pembrolizumab (Keynote-040) and the results are awaited. Such positive data prompted the design of clinical trials in first line metastatic or recurrent tumors. Several pre-clinical studies have highlighted the potential synergism between ionizing radiation and anti-PD-1 or PD-L1. Radiotherapy triggers an upregulation of PD-L1 at the tumor cell surface and enhance the release of damage associated molecular patterns (DAMPs) such as calreticulin, ATP, HMGB1 and cytokines. After binding to their respective receptors on dendritic cells (DCs), these DAMPs facilitate the uptake and processing of tumor antigens and their presentation to naïve CD8+T cells. This immune response appears however to be dependent on the total radiation dose and the fractionation regimen used, emphasizing on the need for a better understanding of the synergism between immune blockers and radiotherapy. This is required for an optimal translation into the clinics. Several clinical trials (phase I to III) combining immune blockers with concomitant chemo- radiotherapy are already ongoing in HNSCC, either in the primary setting for locally advanced disease or in the post-operative setting for high risk patients. SP-0228 The role of immunotherapy for recurrent/metastatic disease with emphasis on the complications L. Licitra Fondazione IRCCS Istituto Nazionale dei Tumori, Italy SP-0229 TME, TEM or Wait and See? The surgeon’s perspective R. Perez 1 1 Ludwig Institute for Cancer Research, Angelita & Joaquim Gama Institute - Colorectal Surgery, Sao Paulo, Brazil Abstract text Incorporation of new treatment modalities has significantly increased the complexity of decision making for patients with locally advanced rectal cancer. Neoadjuvant chemoradiation (CRT) is considered one of the preferred treatment strategies for these patients. In addition, this treatment strategy may lead to significant tumor regression, ultimately leading to complete pathological response in up to 42% of patients. Routine total mesorectal excision after neoadjuvant CRT has been the recommended practice for many years regardless of Abstract not received Symposium: Novelties in organ-and function sparing treatment in rectal cancer

predict clinical outcomes is being improved through mouse humanization strategies and implementation of co-clinical trials, within which patients and PDXs reciprocally inform therapeutic decisions. Here, aspects of PDX modelling that are relevant to these questions will be discussed. Byrne AT et al. Interrogating open issues in cancer medicine with patient-derived xenografts. Nat Rev Cancer. 2017 Sep 15;17(10):632 SP-0225 Studying normal tissue damage using small animal high-precision irradiators P. Van Luijk 1 1 University of Groningen- University Medical Center Groningen, Radiation Oncology, Groningen, The Netherlands Abstract text Understanding radiation-induced complications is vital to the further optimization of radiotherapy treatment. With the introduction of high-precision small-animal irradiators, the field of in vivo radiobiology has regained interest and is growing. Novel high-precision irradiators offer a variety of equipment making them technologically similar, or sometimes even more advanced, than clinical machines. Though these technological advancements bring many new opportunities to the field, the rationale of their use in in vivo studies for normal tissue is not straight- forward. Using animal models is usually justified by their ability to facilitate better possibilities for controlled experiments, reduced variation in outcome measures due to better resemblance of study subjects and treatment conditions, and the possibility to test conditions beyond clinically accepted. Examples of such studies and features contributing to their clinical translation will be described. Finally, the potential of recent high-precision technology to improve and extend these studies will be discussed. SP-0226 Role of the immune system in radiation therapy M. Pruschy 1 1 University Hospital Zürich, Department of Radiation Oncology, Zurich, Switzerland Abstract text The relevance of the immune system for the radiation response of the tumor has been strongly investigated during the last decade and has been recognized to be an important determinant for the overall tumor response to radiotherapy. As such, “Tumor (R)ejection by the Immune System” might be defined as an additional “R of Radiotherapy”. Here we will outline the major general players and processes of the immune response to radiotherapy, including specific aspects related to head and neck cancer. Furthermore, we will discuss the most relevant preclinical approaches to determine and investigate the most promising combined treatment modalities of immunotherapy in combination with external radiotherapy and indicate putative resistance mechanisms existing for head and neck cancer. SP-0227 The immune landscape and immunotherapy for head and neck cancer V. Grégoire 1 1 UCL Cliniques Univ. St.Luc, Radiation Oncology, Brussels, Belgium Symposium: Immunotherapy to complement chemoradiation for head and neck cancer