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Accounting for Shared and Unshared Dosimetric Uncertainties in the Dose Response for Ultrasound-Detected Thyroid Nodules after Exposure to Radioactive Fallout

机译：在暴露于放射性尘埃后超声检测甲状腺结节的剂量反应中考虑共用和非共用剂量学的不确定性

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Dosimetic uncertainties, particularly those that are shared among subgroups of a study population, can bias, distort or reduce the slope or significance of a dose response. Exposure estimates in studies of health risks from environmental radiation exposures are generally highly uncertain and thus, susceptible to these methodological limitations. An analysis was published in 2008 concerning radiation-related thyroid nodule prevalence in a study population of 2,994 villagers under the age of 21 years old between August 1949 and September 1962 and who lived downwind from the Semi-palatinsk Nuclear Test Site in Kazakhstan. This dose-response analysis identified a statistically significant association between thyroid nodule prevalence and reconstructed doses of fallout-related internal and external radiation to the thyroid gland; however, the effects of dosimetric uncertainty were not evaluated since the doses were simple point “best estimates”. In this work, we revised the 2008 study by a comprehensive treatment of dosimetric uncertainties. Our present analysis improves upon the previous study, specifically by accounting for shared and unshared uncertainties in dose estimation and risk analysis, and differs from the 2008 analysis in the following ways: 1. The study population size was reduced from 2,994 to 2,376 subjects, removing 618 persons with uncertain residence histories; 2. Simulation of multiple population dose sets (vectors) was performed using a two-dimensional Monte Carlo dose estimation method; and 3. A Bayesian model averaging approach was employed for evaluating the dose response, explicitly accounting for large and complex uncertainty in dose estimation. The results were compared against conventional regression techniques. The Bayesian approach utilizes 5,000 independent realizations of population dose vectors, each of which corresponds to a set of conditional individual median internal and external doses for the 2,376 subjects. These 5,000 population dose vectors reflect uncertainties in dosimetric parameters, partly shared and partly independent, among individual members of the study population. Risk estimates for thyroid nodules from internal irradiation were higher than those published in 2008, which results, to the best of our knowledge, from explicitly accounting for dose uncertainty. In contrast to earlier findings, the use of Bayesian methods led to the conclusion that the biological effectiveness for internal and external dose was similar. Estimates of excess relative risk per unit dose (ERR/Gy) for males (177 thyroid nodule cases) were almost 30 times those for females (571 cases) and were similar to those reported for thyroid cancers related to childhood exposures to external and internal sources in other studies. For confirmed cases of papillary thyroid cancers (3 in males, 18 in females), the ERR/Gy was also comparable to risk estimates from other studies, but not significantly different from zero. These findings represent the first reported dose response for a radiation epidemiologic study considering all known sources of shared and unshared errors in dose estimation and using a Bayesian model averaging (BMA) method for analysis of the dose response.
机译：剂量学不确定性，尤其是在研究人群的亚组中共有的不确定性，可能会导致偏倚，扭曲或减少剂量反应的斜率或显着性。对环境辐射暴露造成的健康风险的研究中的暴露估计通常高度不确定，因此容易受到这些方法学限制。在1949年8月至1962年9月之间居住在哈萨克斯坦塞米-帕拉金斯克核试验场下风的2994名21岁以下村民中，2008年发表了有关辐射相关甲状腺结节患病率的分析。这项剂量反应分析确定了甲状腺结节患病率和与辐射有关的甲状腺内部和外部辐射重建剂量之间的统计学显着相关性。但是，由于剂量是简单的“最佳估计值”，因此未评估剂量学不确定性的影响。在这项工作中，我们通过全面处理剂量学不确定性修订了2008年的研究。我们目前的分析在先前的研究基础上进行了改进，特别是考虑了剂量估计和风险分析中共享和非共享的不确定性，并且在以下方面与2008年的分析有所不同：1.研究人口规模从2,994名减少到2,376名， 618名居住历史不确定的人； 2.使用二维蒙特卡洛剂量估算方法对多个总体剂量组（向量）进行仿真； 3.使用贝叶斯模型平均法评估剂量反应，明确考虑剂量估计中的大而复杂的不确定性。将结果与常规回归技术进行了比较。贝叶斯方法利用人口剂量向量的5,000个独立实现，每个剂量向量对应于2376名受试者的一组条件性个体中值内部和外部剂量。这5,000个人口剂量向量反映了研究人口个体成员之间剂量学参数的不确定性，部分参数是共享的，部分是独立的。内部辐射对甲状腺结节的风险估计高于2008年公布的结果，据我们所知，这是由于明确考虑了剂量不确定性而导致的。与早期发现相反，使用贝叶斯方法得出的结论是内部和外部剂量的生物有效性相似。男性（177例甲状腺结节病例）的单位剂量超额相对危险度（ERR / Gy）的估计值几乎是女性（571例）的30倍，与报道的与儿童期暴露于外部和内部来源相关的甲状腺癌的相似在其他研究中。对于确诊的甲状腺乳头状癌病例（男性3例，女性18例），ERR / Gy也可与其他研究的风险估计值相媲美，但与零值无显着差异。这些发现代表了辐射流行病学研究首次报告的剂量反应，其中考虑了剂量估计中所有已知的共享和非共享误差来源，并使用贝叶斯模型平均（BMA）方法来分析剂量反应。

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