ESTRO 36 Abstract Book

S530 ESTRO 36 _______________________________________________________________________________________________

After radiotherapy the level of MEG3 and PANDA expression increased. Conclusion The potential genetic association of the lncRNAs LINC00336 and PCAT1, and microRNA miR-146a with radiotherapy-induced late toxicity needs to be confirmed in larger breast cancer cohorts. The expression of lncRNAs can be a biomarker of radiotherapy response measurable in blood. Funding: This research was supported by a grant [FIS 05/2181] from ‘‘Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerio Español de Economía y Competitividad”. PO-0959 REQUITE: Radiation Induced Lymphocyte Apoptosis assay as a predictor for radiotherapy side effects C. Talbot 1 , A. Appanvel 2 , A. Botma 2 , T. Rancati 3 , A. Webb 1 , D. Azria 4 , T. Burr 5 , J. Chang-Claude 2 , C. Herskind 6 , D. De Ruysscher 7 , R. Elliott 8 , S. Gutiérrez Enríquez 9 , P. Lambin 7 , B. Rosenstein 10 , T. Rattay 11 , A. Vega 12 , F. Wenz 6 , R. Valdagni 3 , C. West 8 1 University of Leicester, Department of Genetics, Leicester, United Kingdom 2 German Cancer Research Centre DKFZ, Genetic Epidemiology Unit, Heidelberg, Germany 3 Fondazione IRCCS Istituto Nazionale dei Tumori, Prostate Cancer Program, Milan, Italy 4 University of Montpellier, Institut du cancer de Montpellier, Montpellier, France 5 Source Bioscience, R&D, Nottingham, United Kingdom 6 Heidelberg University, Department of Radiation Oncology, Mannheim, Germany 7 Maastricht University Medical Center, Department of Radiation Oncology MAASTRO clinic, Maastricht, The Netherlands 8 University of Manchester, Institute of Cancer Sciences, Manchester, United Kingdom 9 Vall d’Hebron Institute of Oncology-VHIO, Radiation Oncology Department, Barcelona, Spain 10 Mount Sinai School of Medicine, Department of Radiation Oncology, New York, USA 11 University of Leicester, Department of Cancer Studies, Leicester, United Kingdom 12 Universidade de Santiago de Compostela, Centro de Investigación Biomédica en Red de Enfermedades Raras CIBERER, Santiago de Compostela, Spain Purpose or Objective Recently the first replicated genetic associations for radiotherapy-induced adverse reactions were reported. The European Union funded REQUITE consortium aims to validate known predictors of adverse reactions to develop clinically useful tools. One such predictor is low levels of radiation induced lymphocyte apoptosis which has previously been found in patients experiencing increased rates of late radiation induced toxicity. Material and Methods REQUITE is a multi-centre, observational study. Enrolment was open for two and a half years in nine centres (eight in Europe and one in the United States), with another two years of follow-up still ongoing. The primary endpoints are change in breast appearance at two years (breast), rectal bleeding at two years (prostate) and breathlessness at 12 months (lung). Work Package 4 involves validation of biomarkers. This includes genetic polymorphisms and the radiation induced lymphocyte apoptosis assay (RILA). The RILA was carried out in three of the European centres using a standardised protocol which had been verified with inter lab testing; it assesses percentage radiation induced apoptosis in lymphocytes, detected by flow cytometry, 48 hours after ex-vivo irradiation of whole blood. Results More than 4300 patients have been enrolled in REQUITE. 1322 samples have been analysed using the apoptosis

assay. The levels of apoptosis 48 hours after ex-vivo irradiation increase over baseline in a range from 2.4% to 62.4%, confirming large inter-patient variability. In the Leicester cohort mean RILA is higher in the prostate patients compared to the breast patients (24.9% vs 20.3%; p=0.004). Analysis of predictive value for acute toxicity is being carried out. Conclusion Variation in percentage of lymphocyte apoptosis is in keeping with previous studies. This large scale prospective observational study will be the largest to date to assess the use of predictive biomarkers for assessing radiotherapy related toxicity. PO-0960 Radiobiological effectiveness and its role in modelling secondary cancer risk for proton therapy A. Madkhali 1,2 , C. Timlin 1 , M. Partridge 1 1 University of Oxford, Oncology, Oxford, United Kingdom 2 King Saud University, Medicine, Riyadh, Saudi Arabia Purpose or Objective In proton therapy, a radiobiological effectiveness ratio (RBE) of 1.1 (RBE 1.1 ) is often used. In reality, RBE depends on dose, linear energy transfer (LET), biological end point, and tissue type. Using a value of RBE that may be not accurate may affect dose calculation and hence, outcome. Material and Methods We used an in-house built code for modelling malignant induction probability (MIP) from voxel-by-voxel dose map (Timlin 2014) and implement a published model to calculate structure-specific RBE, recalculate dose and MIP, and compare the outcomes with initial calculations using RBE 1.1 . MIP was calculated using linear quadratic (LQ), linear (LIN), and linear-no-threshold (LNT) models for proton therapy plans for an adult and a teenage patient diagnosed with medulloblastoma (MB). The MIP was then re-calculated using the RBE model by Dale and Jones which is a function of dose (d), α and β and RBE min and RBE max: Poster: Radiobiology track: Radiobiology of proton and heavy ions

Results Results are shown in Table 1. The difference in MIP by using RBE 1.1 and RBE MinMax is ~2-3%. The effect on mean dose varies between different organs and is between 6% and 8%. Clinical implications due to difference in RBE depend on beam characteristics, dose, structures concerned, and the volume irradiated.