Risk of second primary thyroid cancer after radiotherapy for a childhood cancer in a large cohort study: an update from the childhood cancer survivor study.
Risk of second primary thyroid cancer after radiotherapy for a childhood cancer in a large cohort study: an update from the childhood cancer survivor study.
复制标题
DOI：
10.1667/rr2240.1
复制
发表时间：
2010-12
影响因子：
3.4
通讯作者：
Inskip PD
中科院分区：
文献类型：
--
作者：
Bhatti P;Veiga LH;Ronckers CM;Sigurdson AJ;Stovall M;Smith SA;Weathers R;Leisenring W;Mertens AC;Hammond S;Friedman DL;Neglia JP;Meadows AT;Donaldson SS;Sklar CA;Robison LL;Inskip PD
先前的研究表明，儿童期首次恶性肿瘤后患甲状腺癌的风险随辐射剂量呈曲线变化，在低至中等剂量时增加，在高剂量时减少。了解在整个治疗剂量范围内改变辐射剂量反应的因素具有挑战性，需要大量受试者。我们量化了12,547例儿童癌症5年生存者中与放射治疗相关的甲状腺癌长期风险（白血病、霍奇金淋巴瘤和非霍奇金淋巴瘤、中枢神经系统癌症、软组织肉瘤、肾癌、骨癌、神经母细胞瘤），其在1970年至1986年期间在儿童癌症幸存者研究中使用最新的队列随访至2005年。随后有119例经病理证实的甲状腺癌病例，并对整个队列的甲状腺个体辐射剂量进行了估计。这项队列研究建立在以前的病例对照研究，在这一人群（69例甲状腺癌病例随访至2000年），允许相对和绝对风险的评价。Poisson回归分析用于计算与辐射剂量相关的甲状腺癌的标准化发病率比（SIR）、超额相对危险度（ERR）和超额绝对危险度（RR）。评估了其他因素（如性别、首次癌症类型、达到的年龄、暴露于辐射时的年龄、自暴露于辐射后的时间和化疗（是/否））对描述剂量-反应关系的线性和指数二次项的影响。与之前的分析相似，甲状腺癌风险随着辐射剂量的增加而线性增加，直至约20戈伊，其中相对风险达到峰值14.6倍（95% CI，6.8-31.5）。在甲状腺辐射剂量>20戈伊时，观察到剂量-反应关系下降。最佳拟合数据的ERR模型是线性-指数二次型。我们发现，暴露时的年龄修改了ERR线性剂量项（年龄越小，辐射风险越高）（P < 0.001），性别（女性辐射风险越高）（P = 0.008）和暴露后的时间（时间越长，辐射风险越高）（P < 0.001）修改了ERR线性剂量项。这些因素均未改变指数二次（高剂量）项。研究发现，性别、受照射时的年龄和自受照射以来的时间是甲状腺癌辐射相关风险的重要修正因素，因此是在对儿童癌症幸存者进行临床随访和甲状腺癌风险估计时需要考虑的重要因素。
Previous studies have indicated that thyroid cancer risk after a first childhood malignancy is curvilinear with radiation dose, increasing at low to moderate doses and decreasing at high doses. Understanding factors that modify the radiation dose response over the entire therapeutic dose range is challenging and requires large numbers of subjects. We quantified the long-term risk of thyroid cancer associated with radiation treatment among 12,547 5-year survivors of a childhood cancer (leukemia, Hodgkin lymphoma and non-Hodgkin lymphoma, central nervous system cancer, soft tissue sarcoma, kidney cancer, bone cancer, neuroblastoma) diagnosed between 1970 and 1986 in the Childhood Cancer Survivor Study using the most current cohort follow-up to 2005. There were 119 subsequent pathologically confirmed thyroid cancer cases, and individual radiation doses to the thyroid gland were estimated for the entire cohort. This cohort study builds on the previous case-control study in this population (69 thyroid cancer cases with follow-up to 2000) by allowing the evaluation of both relative and absolute risks. Poisson regression analyses were used to calculate standardized incidence ratios (SIR), excess relative risks (ERR) and excess absolute risks (EAR) of thyroid cancer associated with radiation dose. Other factors such as sex, type of first cancer, attained age, age at exposure to radiation, time since exposure to radiation, and chemotherapy (yes/no) were assessed for their effect on the linear and exponential quadratic terms describing the dose–response relationship. Similar to the previous analysis, thyroid cancer risk increased linearly with radiation dose up to approximately 20 Gy, where the relative risk peaked at 14.6-fold (95% CI, 6.8–31.5). At thyroid radiation doses >20 Gy, a downturn in the dose–response relationship was observed. The ERR model that best fit the data was linear-exponential quadratic. We found that age at exposure modified the ERR linear dose term (higher radiation risk with younger age) (P < 0.001) and that sex (higher radiation risk among females) (P = 0.008) and time since exposure (higher radiation risk with longer time) (P < 0.001) modified the EAR linear dose term. None of these factors modified the exponential quadratic (high dose) term. Sex, age at exposure and time since exposure were found to be significant modifiers of the radiation-related risk of thyroid cancer and as such are important factors to account for in clinical follow-up and thyroid cancer risk estimation among childhood cancer survivors.