Second cancer after radiotherapy for malignant neoplasm: Epidemiological and molecular biological analysis.

第二次癌症的发生是放射治疗(RT)后长期幸存者中最严重的事件。这项研究的目的是评估宫颈癌放疗后发生第二次癌症的风险。我们回顾了1961年至1986年在美国国家放射科学研究所接受放射治疗的2,167例宫颈癌患者。其中单纯放疗组1702例(79%)，术后放疗组465例(21%)。单纯放疗组和术后放疗组的平均年龄分别为60岁和49岁。单纯采用高剂量率源(82%)或低剂量率源(18%)进行腔内近距离放射治疗。使用日本疾病期望表计算第二次癌症的相对风险(RR)。此外，根据放疗时的年龄和放疗后的随访时间计算第二癌的RR。总共随访了25,771人年，有60名患者失去了随访。在2,167名患者中，1,063名患者(49%)存活超过10年。在210名患者中发生了第二次癌症，与可比的正常人群相比，他们的风险显著增加(RR=1.24，95%CI=1.08-1.42)。放疗时年龄在60岁以下的患者发生第二癌的RR显著升高(RR=1.33，95%CI=1.10~1.61)，放疗后随访5~15年的患者发生第二癌的RR显著升高(RR=1.31，95%CI=1.06~1.62)。估计发生第二次癌症的累积概率在10年时为6.7%，20年时为15.6%，30年时为23.8%。观察到宫颈癌放疗后长期存活者发生二次癌症的风险显著增加。放疗时的年龄和放疗后的随访间隔不同，RR也不同，这有助于我们确定发生二次癌症的高危人群。

Occurrence of a second cancer is the most serious event among long-term survivors after radiotherapy (RT). The purpose of this study was to evaluate the risk of second cancers after cervical cancer treated with RT. We reviewed 2,167 patients with uterine cervical cancer undergoing RT between 1961 and 1986 at the National Institute of Radiological Sciences. Among them, 1,702 (79%) patients were treated with RT-alone group and 465 (21%) received postoperative RT. Their mean age was 60 years in the RT alone and 49 years in the postoperative RT group. Intracavitary brachytherapy was performed with high-dose rate source (82%) or low-dose rate source (18%) for RT alone. Relative risk (RR) of second cancer was calculated using the Japanese disease expectancy table. In addition, RR of second cancer was calculated by age at RT and the post-RT duration of follow-up. The total number of person-years of follow-up was 25,771, with 60 patients being lost to follow-up. Among 2,167 patients, 1,063 patients (49%) survived more than 10 years. Second cancers developed in 210 patients, which represented a significant increase in risk compared with a comparable normal population (RR = 1.24, 95%CI = 1.08-1.42). RR of developing a second cancer was significantly elevated for patients younger than 60 years at RT (RR = 1.33, 95%CI = 1.10-1.61) and for patients with post-RT follow-up between 5 and 15 years (RR = 1.31, 95%CI = 1.06-1.62). The estimated cumulative probability for development of a second cancer was 6.7% at 10 years, 15.6% at 20 years, and 23.8% at 30 years. Significant increased risk of second cancers was observed among long-term survivors after RT for cervical cancer. RR differed by age at RT and interval of follow-up after RT, helping us to identify a high-risk population for the development of second cancers.