ESTRO 2025 - Abstract Book

S3952

Radiobiology - Normal tissue radiobiology

ESTRO 2025

References: Toyomasu, Y.; Matsui, K.; Omori, K.; Takada, A.; Imanaka-Yoshida, K.; Tawara, I.; Shimamoto, A.; Takao, M.; Kobayashi, H.; Tomaru, A.; et al. Tenascin C in radiation-induced lung damage: Pathological expression and serum level elevation. Thorac. Cancer 2022, 13, 2904–2907.

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Proffered Paper Treatment time and circadian genotype interact to alter the severity of radiotherapy side-effects in prostate cancer patients Christopher J Talbot 1 , Adam Webb 1 , David Azria 2 , Ananya Choudhury 3 , Dirk De Ruysscher4 4 , Alison Dunning 5 , Sarah Kerns 6 , Maarten Lambrecht 7 , Tiziana Rancati 8 , Barry Rosenstein 9 , Petra Seibold 10 , Elena Sperk 11 , Ana Vega 12 , Liv Veldeman 13 , Jenny Chang-Claude 14 , Catharine West 3 , Tim Rattay 1 , Raymond P Symonds 1 1 Genetics, Genomics & Cancer Sciences, University of Leicester, Leicester, United Kingdom. 2 Department of Radiation Oncology, Montpellier Cancer Institute, Montpellier, France. 3 Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom. 4 Department of Radiation Oncology, 4Maastricht University Medical Center, Maastricht, Netherlands. 5 Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, United Kingdom. 6 Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, USA. 7 Radiation Oncology, UZ Leuven, Leuven, Belgium. 8 Prostate Cancer Program, 8Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 9 Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, USA. 10 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. 11 Radiation Oncology, Medical Faculty Mannheim, Mannheim, Germany. 12 Instituto de Investigación Sanitaria, 12Fundación Pública Galega Medicina Xenómica, Santiago de Compostela, Spain. 13 Radiation Oncology, Ghent University Hospital, Ghent, Belgium. 14 University Cancer Center, 14University Medical Center Hamburg-Eppendorf, Hamburg, Germany Purpose/Objective: Circadian rhythm influences a range of biological processes, including efficacy and side effects of cancer treatment. Evidence disagrees whether risk of radiotherapy side-effects is affected by treatment time, probably due to differences in organs irradiated and time analysis methods. We previously showed an interactive effect of time and genotype of circadian rhythm genes on late toxicity after breast radiotherapy (1-3). This study aimed to replicate those results in a different cancer type. Material/Methods: We collected time of each radiotherapy fraction from patients in REQUITE prostate cancer cohorts. REQUITE was a multi-centre, prospective study in Europe and US. Enrolment was open for 2.5 years through 26 centres in eight countries. Radiotherapy toxicity data was collected at baseline, after radiotherapy and one & two years later. Genome-wide SNP data was available typed with Illumina OncoArrays. The primary endpoints used were late rectal bleeding and urinary incontinence assessed by CTCAE v4. 861 prostate cancer patients were included in the analysis. Local date-times for each fraction were converted into solar times as continuous predictors. Genetic chronotype markers were included in LASSO regression analyses with random forest feature selection to identify predictors of each end-point. Results: For rectal bleeding at 24m, significant predictors include spread of treatment times (OR=1.57, 95%CI=1.2-2), BMI (OR=0.9, 95%CI=0.85-0.96), alpha blockers (OR=2.3, 3 95%CI=1.2-4.2) and PER3 SNP rs696305 (OR=0.37, 95%CI=0.16 0.84). Treatment time (hours after sunrise) was non-significant but a significant interaction exists between the SNP and treatment time (P<0.001), suggesting that circadian genotype modifies the time of peak radiotoxicity risk. Models achieve a ROC AUC of 0.66.