Nguyen J, Moteabbed M, Paganetti H
Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114 and Department of Physics, Ruprecht-Karls-Universität Heidelberg, Heidelberg 69117, Germany.
Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114 and Harvard Medical School, Boston, Massachusetts 02114.
Med Phys. 2015 Jan;42(1):81-9. doi: 10.1118/1.4903272.
Theoretical dose-response models offer the possibility to assess second cancer induction risks after external beam therapy. The parameters used in these models are determined with limited data from epidemiological studies. Risk estimations are thus associated with considerable uncertainties. This study aims at illustrating uncertainties when predicting the risk for organ-specific second cancers in the primary radiation field illustrated by choosing selected treatment plans for brain cancer patients.
A widely used risk model was considered in this study. The uncertainties of the model parameters were estimated with reported data of second cancer incidences for various organs. Standard error propagation was then subsequently applied to assess the uncertainty in the risk model. Next, second cancer risks of five pediatric patients treated for cancer in the head and neck regions were calculated. For each case, treatment plans for proton and photon therapy were designed to estimate the uncertainties (a) in the lifetime attributable risk (LAR) for a given treatment modality and (b) when comparing risks of two different treatment modalities.
Uncertainties in excess of 100% of the risk were found for almost all organs considered. When applied to treatment plans, the calculated LAR values have uncertainties of the same magnitude. A comparison between cancer risks of different treatment modalities, however, does allow statistically significant conclusions. In the studied cases, the patient averaged LAR ratio of proton and photon treatments was 0.35, 0.56, and 0.59 for brain carcinoma, brain sarcoma, and bone sarcoma, respectively. Their corresponding uncertainties were estimated to be potentially below 5%, depending on uncertainties in dosimetry.
The uncertainty in the dose-response curve in cancer risk models makes it currently impractical to predict the risk for an individual external beam treatment. On the other hand, the ratio of absolute risks between two modalities is less sensitive to the uncertainties in the risk model and can provide statistically significant estimates.
理论剂量反应模型为评估外照射治疗后诱发二次癌症的风险提供了可能。这些模型中使用的参数是根据流行病学研究的有限数据确定的。因此，风险估计存在相当大的不确定性。本研究旨在通过为脑癌患者选择特定治疗方案，说明在预测原发辐射野中器官特异性二次癌症风险时的不确定性。
本研究考虑了一个广泛使用的风险模型。利用各器官二次癌症发病率的报告数据估计模型参数的不确定性。随后应用标准误差传播来评估风险模型中的不确定性。接下来，计算了五名头颈部癌症患儿的二次癌症风险。对于每个病例，设计了质子和光子治疗的治疗方案，以估计（a）给定治疗方式的终生归因风险（LAR）中的不确定性，以及（b）比较两种不同治疗方式的风险时的不确定性。
几乎所有考虑的器官的风险不确定性都超过了100%。当应用于治疗方案时，计算出的LAR值具有相同量级的不确定性。然而，不同治疗方式的癌症风险比较确实能得出具有统计学意义的结论。在研究的病例中，脑癌、脑肉瘤和骨肉瘤患者质子治疗与光子治疗的平均LAR比值分别为0.35、0.56和0.59。根据剂量测定的不确定性，它们相应的不确定性估计可能低于5%。
癌症风险模型中剂量反应曲线的不确定性使得目前预测个体外照射治疗的风险不切实际。另一方面，两种治疗方式之间的绝对风险比值对风险模型中的不确定性不太敏感，并且可以提供具有统计学意义的估计。
