Cellular radiosensitivity and complication risk after curative radiotherapy

Abstract

Purpose: To test for an association between in vitro fibroblast radiosensitivity and complication risk in a case-control study of breast cancer patients treated under standard conditions in a clinical trial of radiotherapy dose fractionation.

Patients and methods: A cohort of patients participating in a randomised clinical trial of radiotherapy dose fractionation was selected on the basis of treatment-induced changes in the breast several years later. Thirty-nine cases with marked normal tissue changes were matched on several variables with 65 controls with no changes attributable to radiotherapy. Dermal fibroblast strains were established from duplicate skin biopsies, and clonogenic cell survival assays performed in triplicate after both high ( approximately 1.6 Gy/min) and low ( approximately 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 clonogenic survival. However, no association between fibroblast radiosensitivity and the development of late radiotherapy normal tissue effects was detected.

Conclusions: Inter-individual variation in cellular radiosensitivity may not be the main determinant of complication risk in patients undergoing radiotherapy for breast cancer. Other biological and technical factors may be more important in explaining the marked inter-patient differences in normal tissue damage evident several years after curative radiotherapy.