PROSPECTIVE COMPARISON OF IN-VITRO NORMAL-CELL RADIOSENSITIVITY AND NORMAL TISSUE-REACTIONS IN RADIOTHERAPY PATIENTS

Purpose: This pilot study was undertaken to assess the relationship between in vitro radiosensitivity of different normal cell types and the type and severity of normal tissue reactions in individual patients after radiotherapy. Methods and Materials: Twenty-one patients with head and neck cancer were studied prospectively; four with head and neck and two with breast cancer were studied retrospectively. The retrospective cases were chosen because they exhibited unusual (severe or minimal) normal tissue reactions after radiotherapy. Small skin biopsies and blood samples were obtained and used to generate in vitro fibroblast and lymphocyte cultures, respectively. Clonogenic assays were used to measure in vitro fibroblast and lymphocyte radiosensitivity after high- and low-dose rate irradiation. Head and neck patients were treated by conventional, hyperfractionated, or concomitant boost regimens, which have been found to yield an equal probability of late normal tissue reactions. The highest dose received by each normal tissue in the target volume was estimated using computed tomography treatment plans. The median patient follow-up time was 19 months (range: 13-25). Results: The distributions of in vitro radiosensitivity parameters and the grade of tissue reaction scores in the patients showed a broad range between individuals. When in vitro parameters were compared to the acute and late tissue reactions, the radiosensitivity of fibroblasts, measured as surviving fraction at 2 Gy after high-dose rate irradiation, showed a highly significant correlation with the maximum grade of late effects (p < 0.0001 for the whole group and p = 0.0013 for the group of patients studied prospectively). No significant correlation was found between fibroblast radiosensitivity and maximum grade of acute effects or between lymphocyte radiosensitivity and either acute or late effects. Conclusion: We conclude that individuals vary in normal cell radiosensitivity, and that in vitro measurements of fibroblast radiosensitivity may predict the magnitude of late normal tissue reactions after radiotherapy. These preliminary results, however, need to be validated in a larger group of patients.