Abstract 681: Prospective study for the identification of DNA repair radiotoxicity biomarkers in breast and prostate cancer patients: Cohort description and descriptive statistics

Abstract

Abstract Introduction: Radiotherapy (RT) can induce with short-term (acute) and long term toxicity. Although acute toxicity is generally well tolerated, long term toxicity might be irreversible and progressive over time. RT induces damage in healthy tissue, triggers inflammation and bystander effects in non-irradiated cells. The toxicity is dependent on many variables and precise knowledge on the responsible mechanisms is still lacking. Purpose: DNA damage, DNA repair and inflammation are known to interplay. Because of the specific involvement of Base Excision Repair (BER) in Reactive Oxygen and Nitrogen species (RONs)-induced lesions and inflammation, we monitored BER activities in patients receiving radiotherapy to investigate glycosylase/AP endonucleases activities as potential biomarkers of radiotoxicity. First, impact of gender, age, concomitant treatment, body mass index (BMI), smoking and alcohol consumption, on basal repair levels, and radiation-induced repair activities were evaluated. Methods: About 220 patients suffering from non-metastatic breast or prostate cancer and treated by radiotherapy (RT) were enrolled by Institut de Cancérologie Lucien Neuwirth. 8 mL of blood was collected prior to RT, 24h after the first radiation dose and before the 6th radiation dose. We then used the Glyco-SPOT assay to quantify BER activities, and nucleases level in lysates prepared from the patients' lymphocytes. Patients were followed-up for at least 6 months. Clinical and toxicity data were collected. All adverse events (AE; acute, sub-acute and late) were scored according to Common Terminology Criteria for Adverse Events. Results: Due to differences in the BER profile between prostate and breast cancer patients, the two groups were analyzed separately. We provide a descriptive overview of recorded AE for each group, according to time period. Some significant specific changes in BER activities where associated with smoking, alcohol consumption, BMI, treatment type and age. Conclusion: Known risk factors significantly affected some BER activities. Males and females should be considered independently for radiotoxicity biomarkers identification using glycosylase/AP endonuclease/nucleases related biomarkers. The identification of possible confounding factors is a prerequisite to any selection of radiotoxicity biomarkers. Citation Format: Sylvie Sauvaigo, Giovanna Muggiolu, Sarah Libert, Elisabeth Daguenet, Claire Rodriguez-Lafrasse, Thierry Maillet, Nicolas Magné. Prospective study for the identification of DNA repair radiotoxicity biomarkers in breast and prostate cancer patients: Cohort description and descriptive statistics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 681.