Radiation Epidemiology Group, INSERM U1018, Villejuif, France; Institut Gustave Roussy, Villejuif, France; Université Paris-Sud, Villejuif, France.
Lancet Oncol. 2012 Oct;13(10):1002-10. doi: 10.1016/S1470-2045(12)70323-6. Epub 2012 Aug 23.
Children and young adults treated with total body or abdominal radiotherapy have an increased risk of insulin resistance and diabetes mellitus. However, little is known of the effect of pancreas irradiation on the risk of diabetes. We assessed the relation between radiation exposure and occurrence of diabetes in a large cohort of long-term childhood cancer survivors.
We sent a questionnaire to 3468 survivors of a childhood cancer treated in eight centres in France and the UK between 1946 and 1985, of which 2520 were returned. Each self-declaration of diabetes was confirmed by contacting the patients' medical doctors. We estimated the radiation dose received by the tail, head, and body of the pancreas and 185 other anatomical sites during each course of radiotherapy from 1990 to 1995 for each child after reconstruction of the conditions in which irradiation was delivered. We investigated the relation between radiation dose to the pancreas and the risk of a subsequent diabetes diagnosis.
65 cases of diabetes were validated. The risk of diabetes increased strongly with radiation dose to the tail of the pancreas, where the islets of Langerhans are concentrated, up to 20-29 Gy and then reached a plateau for higher radiation doses. The estimated relative risk at 1 Gy was 1·61 (95% CI 1·21-2·68). The radiation dose to the other parts of the pancreas did not have a significant effect. Compared with patients who did not receive radiotherapy, the relative risk of diabetes was 11·5 (95% CI 3·9-34·0) in patients who received 10 Gy or more to the tail of the pancreas. Results were unchanged after adjustment for body-mass index, despite its strong independent effect (p<0·0001), and were similar between men and women. Children younger than 2 years at time of radiotherapy were more sensitive to radiation than were older patients (relative risk at 1 Gy 2·1 [95% CI 1·4-4·3] vs 1·4 [95% CI 1·1-2·2] in older patients; p=0·02 for the difference). For the 511 patients who had received more than 10 Gy to the tail of the pancreas, the cumulative incidence of diabetes was 16% (95% CI 11-24).
Our study provides evidence of a dose-response relation between radiation exposure of pancreas and subsequent risk of diabetes. Because of the risks observed and the frequency of diabetes in general population, this finding raises important public health issues. The pancreas needs to be regarded as a critical organ when planning radiation therapy, particularly in children. Follow-up of patients who received abdominal irradiation should include diabetes screening.
接受全身或腹部放射治疗的儿童和年轻人患胰岛素抵抗和糖尿病的风险增加。然而，对于胰腺照射对糖尿病风险的影响知之甚少。我们评估了在法国和英国的 8 个中心接受治疗的一大群长期儿童癌症幸存者中，辐射暴露与糖尿病发生之间的关系。
我们向 1946 年至 1985 年间在法国和英国 8 个中心接受治疗的 3468 名儿童癌症幸存者发送了一份调查问卷，其中 2520 名幸存者返回。每一例自我报告的糖尿病都通过联系患者的医生进行了确认。我们根据每个孩子的情况重建了放射治疗期间胰腺尾部、头部和体部以及 185 个其他解剖部位接受的辐射剂量，并在 1990 年至 1995 年期间对每个孩子进行了评估。我们研究了胰腺接受的辐射剂量与随后诊断出糖尿病的风险之间的关系。
65 例糖尿病得到验证。随着胰腺尾部（胰岛集中的部位）接受的辐射剂量增加，糖尿病的风险强烈增加，达到 20-29 Gy，然后达到更高剂量的辐射剂量 plateau。1 Gy 时的估计相对风险为 1.61（95%CI 1.21-2.68）。胰腺其他部位的辐射剂量没有显著影响。与未接受放疗的患者相比，接受 10 Gy 或更多胰腺尾部放疗的患者糖尿病的相对风险为 11.5（95%CI 3.9-34.0）。尽管身体质量指数（BMI）具有很强的独立影响（p<0.0001），但调整 BMI 后结果保持不变，且在男性和女性之间相似。放疗时年龄小于 2 岁的儿童比年龄较大的患者对辐射更敏感（1 Gy 时的相对风险分别为 2.1（95%CI 1.4-4.3）和 1.4（95%CI 1.1-2.2）；p=0.02）。对于 511 名接受胰腺尾部超过 10 Gy 照射的患者，糖尿病的累积发病率为 16%（95%CI 11-24）。
我们的研究提供了胰腺照射剂量与随后糖尿病风险之间存在剂量反应关系的证据。由于观察到的风险以及一般人群中糖尿病的发病率，这一发现引发了重要的公共卫生问题。在规划放射治疗时，胰腺需要被视为一个关键器官，特别是在儿童中。接受腹部照射的患者应进行糖尿病筛查。
