放疗前周围血淋巴细胞敏感性是骨盆放疗所致疾病的预示因素

摘要

目的探讨前列腺癌(PC)治疗前体外照射诱导的Go淋巴细胞微核量是否与放疗(xRT)相关疾病的发生有关.方法对38例PC周围血淋巴细胞(PBL)以细胞因子阻止的微核法进行前瞻性观察.患者平均年龄68.7±1.0岁.临床分期:T1 16例,T2 16例,T3 6例.治疗前前列腺癌特异性抗原(PSA)≤4ng*ml-1者5例,4～10ng*ml-1者19例,＞10ng*ml-1者14例.所有患者均接受标准的骨盆外xRT(41.4～50.4Gy),追加剂量(16.4～26Gy).平均随访32.8±4.6个月.随访末,按RTOG标准对胃肠道(GI)或泌尿生殖道(GU)xRT相关疾病的发生率进行评定.结果发生xRT相关疾病24例为高敏(HS),未发生者14例为正常敏感性(NS),HS患者均有GI(1～3级)或GU(1～2级) xRT相关疾病.体外照射暴露的血标本,与照射剂量相关的PBL微核量在HS 和NS患者之间有显著差异,特别是当剂量≥3Gy时.xRT相关疾病的发生与治疗前PBL微核量相关,而与病情无关.结论与xRT前体外照射剂量相关的PBL微核量是骨盆xRT的PC患者GI 或GU疾病发生的一个预示因素.%Objective To test the hypothesis that before treatment, prostate cancer(PC) patients who demonstrate a high yield of micronucleus (MN) in G0 lymphocytes induced by ex vivo irradiation represent a radiosensitive population with a higher-than-average risk of developing radiotherapy(xRT)-related morbidity. Methods The cytokinesis-block MN assay of peripheral blood lymphocytes(PBL) in 38 PC patients was prospectively conducted.Before the initiation of radiotherapy (xRT), PBL were irradiated(1～4 Gy) in each individual. The patients' mean age was 68.7±1.0 years.Clinical stage was T1(n=16),T2(n=16), and T3(n=6). The pre-operative prostate specific antigen (PSA) level was ≤4ng*ml-1(n=5), 4～10ng*ml-1(n=19), and＞10ng*ml-1(n=14).All patients received a standardized pelvic external beam xRT(41.4～50.4 Gy) and boost(16.4～26 Gy). The mean followed up was 32.8±4.6 months. At the end of follow-up times, the gastrointestinal (GI) or genitourinary (GU) morbidity were scored according to the RTOG criteria. Results PC patients who developed xRT-related morbidity were grouped as hyper-sensitive patients (HS,n=24);and did not develop morbidity were normal-sensitive patients(NS,n=14). HS patients all had GI(Grade 1～3) or GU (Grade 1～2) morbidity. After ex vivo radiation exposure(1～4 Gy) of pre-xRT blood samples, the differences of radiation dose-response relationship of MN yield in PBL between HS and NS patients were significant, especially when dose was ≥3 Gy; and the development of xRT-related morbidity correlated with radiation dose-response relationship of MN yield in PBL before treatment, but did not correlate with patients' clinical variables.Conclusion The pre-xRT ex vivo radiation dose-response relationship of MN yield in PBL was a significant predictive factor for the development of GI or GU morbidity in PC patients after pelvic xRT.