Schwartz Boris, Benadjaoud Mohamed Amine, Cléro Enora, Haddy Nadia, El-Fayech Chiraz, Guibout Catherine, Teinturier Cécile, Oberlin Odile, Veres Cristina, Pacquement Hélène, Munzer Martine, N'guyen Tan Dat, Bondiau Pierre-Yves, Berchery Delphine, Laprie Anne, Hawkins Mike, Winter David, Lefkopoulos Dimitri, Chavaudra Jean, Rubino Carole, Diallo Ibrahima, Bénichou Jacques, de Vathaire Florent
Radiation Epidemiology Group, Unit 1018 INSERM, Institut Gustave Roussy, Rue Camille Desmoulins, 94805, Villejuif, France,
Radiat Environ Biophys. 2014 May;53(2):381-90. doi: 10.1007/s00411-013-0510-9. Epub 2014 Jan 14.
Bone sarcoma as a second malignancy is rare but highly fatal. The present knowledge about radiation-absorbed organ dose-response is insufficient to predict the risks induced by radiation therapy techniques. The objective of the present study was to assess the treatment-induced risk for bone sarcoma following a childhood cancer and particularly the related risk of radiotherapy. Therefore, a retrospective cohort of 4,171 survivors of a solid childhood cancer treated between 1942 and 1986 in France and Britain has been followed prospectively. We collected detailed information on treatments received during childhood cancer. Additionally, an innovative methodology has been developed to evaluate the dose-response relationship between bone sarcoma and radiation dose throughout this cohort. The median follow-up was 26 years, and 39 patients had developed bone sarcoma. It was found that the overall incidence was 45-fold higher [standardized incidence ratio 44.8, 95 % confidence interval (CI) 31.0-59.8] than expected from the general population, and the absolute excess risk was 35.1 per 100,000 person-years (95 % CI 24.0-47.1). The risk of bone sarcoma increased slowly up to a cumulative radiation organ absorbed dose of 15 Gy [hazard ratio (HR) = 8.2, 95 % CI 1.6-42.9] and then strongly increased for higher radiation doses (HR for 30 Gy or more 117.9, 95 % CI 36.5-380.6), compared with patients not treated with radiotherapy. A linear model with an excess relative risk per Gy of 1.77 (95 % CI 0.6213-5.935) provided a close fit to the data. These findings have important therapeutic implications: Lowering the radiation dose to the bones should reduce the incidence of secondary bone sarcomas. Other therapeutic solutions should be preferred to radiotherapy in bone sarcoma-sensitive areas.
骨肉瘤作为第二种恶性肿瘤虽罕见但致死率很高。目前关于辐射吸收器官剂量反应的知识不足以预测放射治疗技术所引发的风险。本研究的目的是评估儿童癌症后治疗诱发骨肉瘤的风险，尤其是放疗相关风险。因此，对1942年至1986年在法国和英国接受实体儿童癌症治疗的4171名幸存者进行了前瞻性随访。我们收集了儿童癌症治疗期间所接受治疗的详细信息。此外，还开发了一种创新方法来评估该队列中骨肉瘤与辐射剂量之间的剂量反应关系。中位随访时间为26年，有39名患者发生了骨肉瘤。结果发现，总体发病率比一般人群预期的高45倍[标准化发病率比44.8，95%置信区间（CI）31.0 - 59.8]，绝对超额风险为每10万人年35.1（95%CI 24.0 - 47.1）。与未接受放疗的患者相比，骨肉瘤风险在累积辐射器官吸收剂量达到15 Gy之前缓慢增加[风险比（HR）= 8.2，95%CI 1.6 - 42.9]，而对于更高的辐射剂量则大幅增加（30 Gy及以上的HR为117.9，95%CI 36.5 - 380.6）。每Gy超额相对风险为1.77（95%CI 0.6213 - 5.935）的线性模型与数据拟合良好。这些发现具有重要的治疗意义：降低骨骼的辐射剂量应能降低继发性骨肉瘤的发病率。在骨肉瘤敏感区域，应优先选择其他治疗方案而非放疗。
