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 be tween in vitro radiosensitivity of different normal cell types and the type and severity of normal tissue reactions in individual patients a fter radiotherapy. Methods and Materials: Twenty-one patients with hea d and neck cancer were studied prospectively; four with head and neck and two with breast cancer were studied retrospectively. The retrospec tive cases were chosen because they exhibited unusual (severe or minim al) normal tissue reactions after radiotherapy. Small skin biopsies an d 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 hig h- and low-dose rate irradiation. Head and neck patients were treated by conventional, hyperfractionated, or concomitant boost regimens, whi ch have been found to yield an equal probability of late normal tissue reactions. The highest dose received by each normal tissue in the tar get volume was estimated using computed tomography treatment plans. Th e median patient follow-up time was 19 months (range: 13-25). Results: The distributions of in vitro radiosensitivity parameters and the gra de of tissue reaction scores in the patients showed a broad range betw een individuals. When in vitro parameters were compared to the acute a nd late tissue reactions, the radiosensitivity of fibroblasts, measure d as surviving fraction at 2 Gy after high-dose rate irradiation, show ed a highly significant correlation with the maximum grade of late eff ects (p < 0.0001 for the whole group and p = 0.0013 for the group of p atients studied prospectively). No significant correlation was found b etween fibroblast radiosensitivity and maximum grade of acute effects or between lymphocyte radiosensitivity and either acute or late effect s. Conclusion: We conclude that individuals vary in normal cell radios ensitivity, and that in vitro measurements of fibroblast radiosensitiv ity may predict the magnitude of late normal tissue reactions after ra diotherapy. These preliminary results, however, need to be validated i n a larger group of patients.