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

在放射治疗（RT）后的长期幸存者中，第二种癌症的发生是最严重的事件。本研究的目的是评估宫颈癌接受放射治疗后发生第二种癌症的风险。我们回顾了1961年至1986年间在国家放射科学研究所接受放射治疗的2167例宫颈癌患者。其中，单纯放疗组1702例（79%），术后放疗组465例（21%），平均年龄为60岁，术后放疗组49岁。腔内近距离放疗单独采用高剂量率源（82%）或低剂量率源（18%）。采用日本疾病预期表计算第二癌的相对危险度（RR）。此外，根据放疗时的年龄和放疗后随访时间计算第二癌的RR。随访总人数为25,771人-年，其中60例患者失去随访。在2167例患者中，1063例（49%）患者存活超过10年。210名患者发生第二种癌症，与可比的正常人群相比，风险显著增加（RR = 1.24, 95%CI = 1.08-1.42）。年龄小于60岁的患者在放疗时（RR = 1.33, 95%CI = 1.10-1.61）和放疗后随访5 - 15年的患者（RR = 1.31, 95%CI = 1.06-1.62）发生第二癌的RR显著升高。第二次癌症发生的累积概率在10年为6.7%，20年为15.6%，30年为23.8%。在宫颈癌放疗后的长期幸存者中观察到第二种癌症的风险显著增加。RR随放疗时年龄和放疗后随访时间的不同而不同，这有助于我们确定继发癌症的高危人群。

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.