O39. In vitro cellular radiosensitivity assays as predictor of radiotherapy related late toxicity in breast cancer patients

Introduction About 5% of cancer patients receiving radiation therapy (RT) exhibit severe normal tissue reactions. The prediction of late toxicity in cancer patients would enable individualized and optimized radiation dose prescription. In this study, four different candidate in vitro cellular radiosensitivity assays for prediction of late normal tissue reactions were evaluated in a retrospective matched case-control set-up of breast cancer patients. Materials and methods Breast cancer patients expressing severe radiation toxicity (12 cases) and no or minimal reactions (12 controls) with a follow-up of at least 3 years were selected for this study. Case and control patients were matched for therapy and patient related variables. After in vitro irradiation of patient blood samples, case and control radiation responses were compared for the following biological end points: radiation-induced CD8+ late apoptosis, residual DNA double strand breaks (DSB), G0 and G2+caf micronucleus assay. Results Despite a substantial overlap in standard deviations, all cellular assays showed a significant difference between cases and controls. Less radiation-induced apoptosis was observed in CD8+ lymphocytes of cases (14.45%) compared to the matched controls (30.64%) ( p  0.01). The number of residual DNA DSB was higher in cases (9.92 foci/cell) compared to their matched controls (9.17 foci/cell) ( p  0.01). The average dose response curve of the G0 MN assay for cases lies above the average dose response curve of the controls. Finally, a pairwise comparison of the G2+caf MN results showed a higher MN yield for cases (351 MN/1000BN) compared to controls (219 MN/1000BN) ( p  0.01). Conclusion Current results suggest that intrinsic radiosensitivity is involved in the development of late radiotoxic effects. Larger prospective studies are warranted to validate the retrospective findings in order to use in vitro cellular assays in the future to predict late normal tissue radiosensitivity in clinical practice.