Vinnikov Volodymyr, Hande Manoor Prakash, Wilkins Ruth, Wojcik Andrzej, Zubizarreta Eduardo, Belyakov Oleg
S.P. Grigoriev Institute for Medical Radiology and Oncology, National Academy of Medical Science of Ukraine, 61024 Kharkiv, Ukraine.
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, MD9, 2 Medical Drive, Singapore 117593, Singapore.
J Pers Med. 2020 Dec 16;10(4):285. doi: 10.3390/jpm10040285.
A search for effective methods for the assessment of patients' individual response to radiation is one of the important tasks of clinical radiobiology. This review summarizes available data on the use of ex vivo cytogenetic markers, typically used for biodosimetry, for the prediction of individual clinical radiosensitivity (normal tissue toxicity, NTT) in cells of cancer patients undergoing therapeutic irradiation. In approximately 50% of the relevant reports, selected for the analysis in peer-reviewed international journals, the average ex vivo induced yield of these biodosimetric markers was higher in patients with severe reactions than in patients with a lower grade of NTT. Also, a significant correlation was sometimes found between the biodosimetric marker yield and the severity of acute or late NTT reactions at an individual level, but this observation was not unequivocally proven. A similar controversy of published results was found regarding the attempts to apply G- and γH2AX foci assays for NTT prediction. A correlation between ex vivo cytogenetic biomarker yields and NTT occurred most frequently when chromosome aberrations (not micronuclei) were measured in lymphocytes (not fibroblasts) irradiated to relatively high doses (4-6 Gy, not 2 Gy) in patients with various grades of late (not early) radiotherapy (RT) morbidity. The limitations of existing approaches are discussed, and recommendations on the improvement of the ex vivo cytogenetic testing for NTT prediction are provided. However, the efficiency of these methods still needs to be validated in properly organized clinical trials involving large and verified patient cohorts.
寻找评估患者个体辐射反应的有效方法是临床放射生物学的重要任务之一。本综述总结了关于使用通常用于生物剂量测定的离体细胞遗传学标记物来预测接受治疗性照射的癌症患者细胞中个体临床放射敏感性（正常组织毒性，NTT）的现有数据。在同行评审的国际期刊中选择用于分析的约50%的相关报告中，这些生物剂量测定标记物的平均离体诱导产量在有严重反应的患者中高于NTT等级较低的患者。此外，有时在个体水平上发现生物剂量测定标记物产量与急性或晚期NTT反应的严重程度之间存在显著相关性，但这一观察结果尚未得到明确证实。关于应用G-和γH2AX焦点分析进行NTT预测的尝试，也发现已发表结果存在类似争议。当在不同晚期（而非早期）放疗（RT）发病率的患者中，对淋巴细胞（而非成纤维细胞）进行相对高剂量（4-6 Gy，而非2 Gy）照射后测量染色体畸变（而非微核）时，离体细胞遗传学生物标志物产量与NTT之间的相关性最为常见。讨论了现有方法的局限性，并提供了关于改进用于NTT预测的离体细胞遗传学检测的建议。然而，这些方法的有效性仍需在涉及大量经过验证的患者队列的适当组织的临床试验中得到验证。
