ESTRO 38 Abstract book

S115 ESTRO 38

particular, liquid biopsies using circulating tumour DNA (ctDNA) are rapidly gaining acceptance in clinical settings. Current methods for the detection of ctDNA involve sequencing somatic mutations using cell-free DNA, but the sensitivity of these methods may be low among patients with localized cancer given the limited number of recurrent mutations. By contrast, large-scale epigenetic alterations—which are tissue- and cancer-type specific— are not similarly constrained and therefore potentially have greater ability to detect and monitor cancers in patients with localized disease. A prime example is DNA methylation, which differs between cancerous and normal tissues and between distinct cancer types. In this talk, I will describe current approaches to measuring methylated cell-free DNA. We have developed a new immunoprecipitation-based technique that addresses several limitations of previous assays. Our technique avoids chemical conversion of cell-free DNA (i.e., bisulfite treatment), therefore enabling genome-wide methylome analysis of small quantities of circulating cell-free DNA. We show that large-scale DNA methylation changes that are tumour-specific are enriched within cell-free DNA. Robust performance is seen in cancer detection and classification across an extensive collection of plasma samples from several tumour types. In a cohort of patients with head and neck squamous cell carcinoma, we demonstrate how methylated cell-free DNA analysis could be used for longitudinal monitoring and evaluating treatment response. SP-0228 Circulating biomarkers tumor immune response D. De Ruysscher 1 1 Maastro Clinic, Radiation Oncology, Maastricht, The Netherlands Abstract text Immunotherapy (IO) is increasingly used to treat a variety of cancers, both in the curative and palliative setting. In contrast to TKIs, where biomarkers are in use for over a decade, leading to increased success and insights in resistance mechanisms and new targets, the landscape in IO is more sober. Although many IO targets are being identified in pre-clinical models and in human material, robust and highly predictive biomarkers are still lacking. The reasons may partly due to the complexity and dynamic nature of the immune system. Ideally, all parts of the immune system as well as the inflammatory status of the tumor at a certain moment in time should be known from a blood sample. The cancer immunogram was developed to describe the cancer-immune system interaction including a framework of seven parameters that are known to affect the anticancer immune response and that can be interrogated in individual cancer patients. These parameters are: tumor mutational burden; the general immune status of the patient; presence of T cell immune infiltrates; tumor PD-L1 expression; sensitivity of tumor cells to T-cell killing (including MHC expression, functional IFN-gamma receptor pathway); a myeloid cell-mediated inflammation (high C-reactive protein (CRP) and IL-6 levels); and high serum lactate dehyrogenase (LDH) (reflecting both tumor burden and anaerobic glycolysis). PD-L1 expression, with all its shortcomings, is the most commonly used biomarker for IO, but is not usable as a circulating biomarker. In contrast, tumor mutational burden (MB), which is associated with response to IO, is experimentally detectable in the blood. The hypothesis is that the higher the number of mutations, the higher the probability of neo-antigen expression and thus the higher the likelihood that the tumor is being recognized as “foreign” by the immune system. Patients with either germline or somatic mutations in mismatch repair genes have a very high number of non- synonymous mutations. This is reflected by unstable

High complication rate. Currently there are some groups that are using BT for: Breast (second conservative approacch). The GEC-ESTRO Breast group experience (JM Hannoun-Levy) published their experience with the same local control as the primary treatment and with good cosmetic results; Prostate (Salvage HDR or LDR BT): the rate of biochemical control, survival and complications by differents groups are described. For Head&Neck, I will explain in detail Navarra’s experience (R Martinez-Monge) and Erlangen’s (V Strnad). I will also describe other indications, as Gynecology, Rectum, Chordoma, and other second primary cancers ocurring in previously treated in- field. And finally I will describe our results in Breast (40 cases), Prostate: (96 analised), Head&Neck: 13, Rectum: 14 and a miscellaneous. SP-0225 Blood biomarkers to predict radiotherapy response G. Hanna 1 1 Peter Maccallum Cancer Centre, Department of Radiation Oncology, Melbourne, Australia Abstract text The use of predictive biomarkers in radiation oncology is a field still very much in its infancy. Very few validated biomarkers exist which are used to select or modify the treatment of a patient scheduled to receive radiotherapy and which are in routine use in clinical practice. Moving towards a precision medicine based approach in radiation oncology, it is hoped that predictive biomarkers may be used in a range of scenarios to inform clinical decision making. It is hypothesised that biomarkers could select patients for treatment versus no treatment, for selection of a specific radiation technique or dose and/or fractionation schedule and perhaps they may be used to select patients for a specific systemic therapy agent in combination with radiotherapy. It is hoped that circulating biomarkers could be used in combination with or in place of tissue samples. This presentation will review these considerations and will suggest potential blood based biomarkers which may be of potential clinical benefit in the future. SP-0226 ctDNA as a non-invasive liquid biopsy for patient stratification and treatment monitoring D. Gale 1 1 University of Cambridge, Cancer Research UK Cambridge Institute- Li Ka Shing Centre, Cambridge, United Kingdom Abstract text This talk will focus on the use of circulating tumour DNA (ctDNA) as a non-invasive liquid biopsy for treatment monitoring and patient stratification. Different technologies will be discussed, including amplicon-based sequencing, exome sequencing, the use of patient-specific panels and digital PCR to monitor disease in advanced and early stage cancer in high-grade serous ovarian cancer, melanoma, breast and non-small cell lung cancer (NSCLC). SP-0227 Cancer detection using methylated cell-free DNA S. Bratman 1 1 Princess Margaret Cancer Centre, Radiation Oncology, Toronto, Canada Abstract text Circulating biomarkers play an important role in personalized cancer medicine and adaptive therapy. In Symposium: Circulating biomarkers for patient stratification and treatment monitoring