Lee Tung-Kwang, Allison Ron R, O'Brien Kevin F, Johnke Roberta M, Christie Karen I, Naves James L, Kovacs Charles J, Arastu Hyder, Karlsson Ulf L
Department of Radiation Oncology, Leo W. Jenkins Cancer Center, East Carolina University Brody School of Medicine, Greenville, NC 27858, USA.
Int J Radiat Oncol Biol Phys. 2003 Sep 1;57(1):222-9. doi: 10.1016/s0360-3016(03)00411-5.
To test the hypothesis that, before treatment, prostate cancer patients who demonstrate a high yield of ex vivo radiation-induced micronucleus (MN) in G(0) lymphocytes represent a patient population with a greater-than-average risk of developing radiotherapy (RT)-related morbidity.
We prospectively conducted the cytokinesis-block MN assay of peripheral blood lymphocytes (PBLs) in 38 prostate cancer patients. Before the initiation of RT, PBLs from each patient were irradiated (1-4 Gy). The mean patient age +/- SEM was 68.7 +/- 1.0 years. The clinical stage was T1 in 17, T2 in 15, and T3 in 6. The preoperative prostate-specific antigen level was < or =4 ng/mL in 5, 4-10 ng/mL in 18, and >10 ng/mL in 15. All patients underwent standardized pelvic external beam radiotherapy (range 41.4-50.4 Gy) and boost (range 16-26 Gy). The mean follow-up +/- SEM was 32.8 +/- 4.6 months. At the end of follow-up, a radiation oncologist scored the GI or GU morbidity according to the Radiation Therapy Oncology Group criteria without knowledge of the MN data.
We found that between the average reactors (n = 25; i.e., patients who had Grade 1 or less RT-related morbidity) and over reactors (n = 13; i.e., patients who developed Grade 2 or greater RT-related morbidity), the differences in the ex vivo radiation dose-response relationship of MN yield in PBLs were highly significant, especially at doses of > or =2 Gy. Also, the development of RT-related morbidity correlated with the radiation dose-response relationship of MN yield in PBLs before treatment, but did not correlate with any of the patients' clinical variables.
Our findings suggest that the pre-RT ex vivo radiation dose-response relationship of MN yield in PBLs may be a significant predictive factor for the development of GI or GU morbidity in prostate cancer patients after pelvic RT.
验证以下假设，即在治疗前，G(0)淋巴细胞中体外辐射诱导微核（MN）产量高的前列腺癌患者，其发生放疗（RT）相关并发症的风险高于平均水平。
我们前瞻性地对38例前列腺癌患者进行了外周血淋巴细胞（PBL）的胞质分裂阻滞微核试验。在开始放疗前，对每位患者的PBL进行照射（1 - 4 Gy）。患者的平均年龄±标准误为68.7±1.0岁。临床分期为T1期17例，T2期15例，T3期6例。术前前列腺特异性抗原水平≤4 ng/mL者5例，4 - 10 ng/mL者18例，>10 ng/mL者15例。所有患者均接受标准化盆腔外照射放疗（范围41.4 - 50.4 Gy）及加量照射（范围16 - 26 Gy）。平均随访时间±标准误为32.8±4.6个月。随访结束时，放疗肿瘤学家根据放射治疗肿瘤学组标准对胃肠道或泌尿生殖系统并发症进行评分，且不知晓微核数据。
我们发现，在平均反应者（n = 25，即RT相关并发症为1级或更低级别的患者）和过度反应者（n = 13，即发生2级或更高级别RT相关并发症的患者）之间，PBL中MN产量的体外辐射剂量反应关系差异非常显著，尤其是在剂量≥2 Gy时。此外，RT相关并发症的发生与治疗前PBL中MN产量的辐射剂量反应关系相关，但与患者的任何临床变量均无关联。
我们的研究结果表明，放疗前PBL中MN产量的体外辐射剂量反应关系可能是前列腺癌患者盆腔放疗后发生胃肠道或泌尿生殖系统并发症的一个重要预测因素。
