FIBROBLAST RADIOSENSITIVITY VERSUS ACUTE AND LATE NORMAL SKIN-RESPONSES IN PATIENTS TREATED FOR BREAST-CANCER
FIBROBLAST RADIOSENSITIVITY VERSUS ACUTE AND LATE NORMAL SKIN-RESPONSES IN PATIENTS TREATED FOR BREAST-CANCER
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DOI：
10.1016/0360-3016(95)00068-a
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发表时间：
1995-07-30
影响因子：
7
通讯作者：
PETERS, LJ
中科院分区：
文献类型：
--
作者：
BROCK, WA;TUCKER, SL;PETERS, LJ
目的/目的：确定在早期传代培养物中测量的正常人类皮肤成纤维细胞的放射敏感性是否与接受放射治疗的乳腺癌患者的急性或晚期正常皮肤损伤程度显着相关。方法和材料：20世纪70年代，瑞典哥德堡肿瘤科对一系列乳腺癌患者进行了术后胸骨旁区域放射治疗。患者使用不同的分割方案和左右视野的剂量进行双侧治疗。按六分制对峰值急性反应进行评分，并通过反射分光光度法测量皮肤红斑。随着时间的推移，毛细血管扩张按照六分制进行分级。 1992年4月，从两个治疗组（即四个剂量分割方案）的22名患者中获得了两个小皮肤活检组织，并使用延迟或立即铺板，通过高剂量率和低剂量率照射后的克隆存活率在早期传代培养物中测量成纤维细胞放射敏感性。根据完整的生存曲线计算 2.0 Gy (SF2) 下的生存率。结果：为了测试测定的再现性，比较了同一患者（12 例）的配对活检中的 SF2 值。通过高剂量率照射与立即电镀确定的 SF2 获得了相当好的相关性 (p = 0.075)，但对于延迟电镀或低剂量率处理则没有这种相关性。高剂量率治疗和立即接种后重复 SF2 的变异系数中位数为 13%，表明配对 SF2 值相关性较差是由于 SF2 相对于患者之间 SF2 值总体分布的不确定性程度（CV = 28%）。将来自两次活检数据的患者的个体 SF2 值和平均值与急性和晚期临床反应进行比较。 SF2 与相对临床反应之间存在显着负相关，但仅当比较平均高剂量率 SF2 值和毛细血管扩张评分时。平均 SF2 值与急性反应之间或个体 SF2 测量值与急性或晚期临床反应之间没有显着相关性。结论：本研究的结果表明晚期毛细血管扩张的程度至少部分取决于正常成纤维细胞的固有细胞放射敏感性，但这种关系并不明确。为了使用当前技术获得成纤维细胞 SF2 值的可靠估计，需要进行多次重复测定。
Purpose/Objective: To determine if the radiosensitivity of normal human skin fibroblasts, measured in early passage cultures, is significantly correlated with the degree of acute or late normal skin damage in patients treated for breast cancer with radiotherapy.Methods and Materials: In the 1970s, a series of breast cancer patients was treated at the Department of Oncology in Gothenburg, Sweden with postoperative irradiation to the parasternal region. Patients were treated bilaterally using different fractionation schedules and doses to the right and left fields. Peak acute reactions were scored on a six-point scale, and skin erythema was measured by reflectance spectrophotometry. Telangiectasia was graded over time on a six-point scale. In April 1992, two small skin biopsies were obtained from 22 patients in two treatment groups (;i.e., four dose-fractionation schedules) and, using either delayed or immediate plating, fibroblast radiosensitivity was measured in early passage cultures by clonogenic survival, after high and low dose-rate irradiations. Survival at 2.0 Gy (SF2) was calculated from complete survival curves.Results: To test assay reproducibility, SF2 values derived from paired biopsies of the same patient (12 cases) were compared. A reasonably good correlation (p = 0.075) was obtained for SF2s determined by high dose-rate irradiations with immediate plating, but not for delayed plating or low dose-rate treatments. The median coefficient of variation in the replicate SF2s after high dose-rate treatment and immediate plating was 13%, suggesting that the poor correlation In 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 reactions. A significant negative correlation was found between SF2 and relative clinical response, but only when averaged high dose-rate SF2 values 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 response.Conclusion: The results of this study suggest that the degree of late telangiectasia is at least partially dependent upon the intrinsic cellular radiosensitivity of normal fibroblasts, but the relationship is not clear cut. Multiple replicate assays are necessary to obtain reliable estimates of fibroblast SF2 values using current techniques.