FIBROBLAST RADIOSENSITIVITY VERSUS ACUTE AND LATE NORMAL SKIN-RESPONSES IN PATIENTS TREATED FOR BREAST-CANCER

Purpose/Objective: To determine if the radiosensitivity of normal huma n skin fibroblasts, measured in early passage cultures, is significant ly correlated with the degree of acute or late normal skin damage in p atients treated for breast cancer with radiotherapy. Methods and Mater ials: In the 1970s, a series of breast cancer patients was treated at the Department of Oncology in Gothenburg, Sweden with postoperative ir radiation to the parasternal region. Patients were treated bilaterally using different fractionation schedules and doses to the right and le ft fields. Peak acute reactions were scored on a six-point scale, and skin erythema was measured by reflectance spectrophotometry. Telangiec tasia was graded over time on a six-point scale. In April 1992, two sm all skin biopsies were obtained from 22 patients in two treatment grou ps (;i.e., four dose-fractionation schedules) and, using either delaye d or immediate plating, fibroblast radiosensitivity was measured in ea rly passage cultures by clonogenic survival, after high and low dose-r ate irradiations. Survival at 2.0 Gy (SF2) was calculated from complet e survival curves. Results: To test assay reproducibility, SF2 values derived from paired biopsies of the same patient (12 cases) were compa red. A reasonably good correlation (p = 0.075) was obtained for SF2s d etermined by high dose-rate irradiations with immediate plating, but n ot for delayed plating or low dose-rate treatments. The median coeffic ient of variation in the replicate SF2s after high dose-rate treatment and immediate plating was 13%, suggesting that the poor correlation I n paired SF2 values is due to the magnitude of the uncertainty in SF2 relative to the overall spread in SF2 values between patients (CV = 28 %). Individual SF2 values and averaged values from patients with data from two biopsies were compared with the acute and late clinical react ions. A significant negative correlation was found between SF2 and rel ative clinical response, but only when averaged high dose-rate SF2 val ues and telangiectasia scores were compared. There was no significant correlation between average SF2 values and acute responses or between individual SF2 measurements and either the acute or late clinical resp onse. Conclusion: The results of this study suggest that the degree of late telangiectasia is at least partially dependent upon the intrinsi c cellular radiosensitivity of normal fibroblasts, but the relationshi p is not clear cut. Multiple replicate assays are necessary to obtain reliable estimates of fibroblast SF2 values using current techniques.