Cellular radiosensitivity and complication risk after curative radiotherapy

Purpose: To test for an association between in vitro fibroblast radiosensit ivity and complication risk in a case-control study of breast cancer patien ts treated under standard conditions in a clinical trial of radiotherapy do se fractionation. Patients and methods: A cohort of patients participating in a randomised cl inical trial of radiotherapy dose fractionation was selected on the basis o f treatment-induced changes in the breast several years later. Thirty-nine cases with marked normal tissue changes were matched on several variables w ith 65 controls with no changes attributable to radiotherapy. Dermal fibrob last strains were established from duplicate skin biopsies, and clonogenic cell survival assays performed in triplicate after both high (similar to 1. 6 Gy/min) and low (similar to 1 cGy/min) dose-rate irradiation. Laboratory studies were blind to patient identity, treatment outcome and radiotherapy schedule. Results: Analysis of 1128 clonogenic survival curves confirmed significant inter-patient variation in fibroblast radiosensitivity as measured by clono genic survival. However, no association between fibroblast radiosensitivity and the development of late radiotherapy normal tissue effects was detecte d. Conclusions: Inter-individual variation in cellular radiosensitivity may no t be the main determinant of complication risk in patients undergoing radio therapy for breast cancer. Other biological and technical factors may be mo re important in explaining the marked interpatient differences in normal ti ssue damage evident several years after curative radiotherapy. (C) 2000 Els evier Science Ireland Ltd. All rights reserved.