ESTRO 37 Abstract book

S119

ESTRO 37

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 tumor response. However, assessment of tumor response following CRT and prior to radical surgery may identify patients with complete clinical response that could be managed by organ preserving strategies. These strategies may include transanal local excision (by endoscopic microsurgery platforms – TEMs) or even no immediate surgery (known as the Watch & Wait strategy). Local excision in this setting (in a complete clinical response) has the advantages of providing histological confirmation of complete primary tumor regression and still provide an organ-preservation alternative. However, the morbidity of local excision may be quite significant due to the risk of wound dehiscences and subsequent functional detrimental consequences. Even in patients with (unexpected) residual cancer, the need for completion TME may result in worse outcomes when compared to TME alone. On the other hand non-operative management requires a very strict follow-up (Watch & Wait Strategy). It avoids unnecessary postoperative morbidity, including long-term urinary, sexual, and fecal continence dysfunctions and the frequent need for temporary or definitive stomas associated with TME and TEMs. Critical aspects in this treatment strategy include timing and studies (clinical, endosopic and radiological) for the assessment of tumor response. Many studies have suggested that longer intervals between RT completion and assessment of tumor response were associated with increased rates of complete response even though one recent randomized study has challenged this assumption. Clinical and endoscopic assessment using strict criteria have been used for the selection of patients based on the presence of whitening of the mucosa, teleangiectasia and minimal loss of pliability of the rectal wall in the absence of any ulceration, stenosis or mass. Radiological studies with high-resolution magnetic resonance (MR) with or without diffusion-weighted series has been the preferred method of assessment of response and the presence of low-signal intensity areas are usually consistent with a complete response. With the use of these studies, selection of patients for a non-immediate surgical approach (without TME or TEMs) may provide good oncological outcomes and excellent functional results. Local recurrences may develop in nearly 25-30% after 3 years from initial tumor response assessment. Most local recurrences have an endoluminal component (90%) and are amenable to simple clinical and endoscopic detection. Even patients that do develop local recurrences may undergo salvage surgery with apparent no oncological compromise. In this setting, after a complete clinical response in selected patients and expert centers, the preferred initial approach should be non-immediate surgical resection and strict follow-up. SP-0230 Targeted imaging in rectal cancer A. Vahrmeijer 1 1 Leiden University Medical Center LUMC, Surgery, Leiden, The Netherlands Abstract text Tumor-targeted fluorescence imaging has the potential to revolutionize current practice of oncologic surgery by selectively highlighting malignant tissue during surgery and other minimal invasive procedures. Various targets were explored for real-time tumor visualization by

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 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

Abstract not received

Symposium: Novelties in organ-and function sparing treatment in rectal cancer

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