Geara F B, Peters L J, Ang K K, Wike J L, Brock W A
Department of Clinical Radiotherapy, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Int J Radiat Oncol Biol Phys. 1993 Dec 1;27(5):1173-9. doi: 10.1016/0360-3016(93)90540-c.
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.
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).
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.
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.
开展这项初步研究以评估不同正常细胞类型的体外放射敏感性与放疗后个体患者正常组织反应的类型和严重程度之间的关系。
对21例头颈癌患者进行前瞻性研究；对4例头颈癌患者和2例乳腺癌患者进行回顾性研究。选择回顾性病例是因为他们在放疗后表现出异常（严重或轻微）的正常组织反应。获取小的皮肤活检样本和血液样本，分别用于培养体外成纤维细胞和淋巴细胞。采用克隆形成试验测量高剂量率和低剂量率照射后体外成纤维细胞和淋巴细胞的放射敏感性。头颈癌患者接受常规、超分割或同步加量方案治疗，这些方案已被发现产生晚期正常组织反应的概率相同。使用计算机断层扫描治疗计划估计靶区内每个正常组织接受的最高剂量。患者的中位随访时间为19个月（范围：13 - 25个月）。
患者体外放射敏感性参数的分布和组织反应评分的等级在个体之间显示出广泛差异。当将体外参数与急性和晚期组织反应进行比较时，以高剂量率照射后2 Gy的存活分数衡量的成纤维细胞放射敏感性与晚期效应的最高等级显示出高度显著的相关性（整个组p < 0.0001，前瞻性研究的患者组p = 0.0013）。未发现成纤维细胞放射敏感性与急性效应的最高等级之间或淋巴细胞放射敏感性与急性或晚期效应之间存在显著相关性。
我们得出结论，个体的正常细胞放射敏感性存在差异，并且体外测量成纤维细胞放射敏感性可能预测放疗后晚期正常组织反应的程度。然而，这些初步结果需要在更大的患者群体中进行验证。
