de Vathaire Florent, Haddy Nadia, Allodji Rodrigue S, Hawkins Mike, Guibout Catherine, El-Fayech Chiraz, Teinturier Cécile, Oberlin Odile, Pacquement Hélène, Diop Fara, Kalhouche Amar, Benadjaoud Mohamedamine, Winter David, Jackson Angela, Bezin Mai-Quynh Giao, Benabdennebi Aymen, Llanas Damien, Veres Cristina, Munzer Martine, Nguyen Tan Dat, Bondiau Pierre-Yves, Berchery Delphine, Laprie Anne, Deutsch Eric, Lefkopoulos Dimitri, Schlumberger Martin, Diallo Ibrahima, Rubino Carole
Radiation Epidemiology Group (F.d.V., N.H., R.S.A., C.G., C.E.-F., C.T., F.D., A.K., M.B., A.J., G.B.M.-Q., A.B., D.L., C.V., I.D., C.R.), INSERM U1018 Villejuif, F-94805, France; Institut Gustave Roussy (F.d.V., N.H., R.S.A., C.G., C.E.-F., C.T., O.O., F.D., A.K., M.B., A.J., G.B.M.-Q., A.B., D.L., C.V., E.D., D.L., M.S., I.D., C.R.), Villejuif, F-94805, France; Université Paris-Sud (F.d.V., N.H., R.S.A., C.G., C.E.-F., C.T., O.O., F.D., A.K., M.B., A.J., G.B.M.-Q., A.B., D.L., C.V., E.D., M.S., I.D., C.R.), Villejuif, F-94800, France; Centre for Childhood Cancer Survivor Studies, Department of Public Health & Epidemiology (M.H., D.W.), University of Birmingham, Birmingham B15 2TT, United Kingdom; Institut Curie (H.P.), Paris F-75005 Paris, France; Institut Jean Godinot (M.M., T.D.N.), F-51092 Reims, France; Centre Antoine Lacassagne (P.-Y.B.), F-06100 Nice, France; and Centre Claudius Régaud (D.B., A.L.), F-51100 Toulouse, France.
J Clin Endocrinol Metab. 2015 Nov;100(11):4282-90. doi: 10.1210/jc.2015-1690. Epub 2015 Sep 1.
Thyroid carcinoma is a frequent complication of childhood cancer radiotherapy. The dose response to thyroid radiation dose is now well established, but the potential modifier effect of other factors requires additional investigation.
This study aimed to investigate the role of potential modifiers of the dose response.
We followed a cohort of 4338 5-year survivors of solid childhood cancer treated before 1986 over an average of 27 years. The dose received by the thyroid gland and some other anatomical sites during radiotherapy was estimated after reconstruction of the actual conditions in which irradiation was delivered.
Fifty-five patients developed thyroid carcinoma. The risk of thyroid carcinoma increased with a radiation dose to the thyroid of up to two tenths of Gy, then leveled off for higher doses. When taking into account the thyroid radiation dose, a surgical or radiological splenectomy (>20 Gy to the spleen) increased thyroid cancer risk (relative risk [RR] = 2.3; 95% confidence interval [CI], 1.3-4.0), high radiation doses (>5 Gy) to pituitary gland lowered this risk (RR = 0.2; 95% CI, 0.1-0.6). Patients who received nitrosourea chemotherapy had a 6.6-fold (95% CI, 2.5-15.7) higher risk than those who did not. The excess RR per Gy of radiation to the thyroid was 4.7 (95% CI, 1.7-22.6). It was 7.6 (95% CI, 1.6-33.3) if body mass index at time of interview was equal or higher than 25 kg/m(2), and 4.1 (95% CI, 0.9-17.7) if not (P for interaction = .1).
Predicting thyroid cancer risk following childhood cancer radiation therapy probably requires the assessment of more than just the radiation dose to the thyroid. Chemotherapy, splenectomy, radiation dose to pituitary gland, and obesity also play a role.
甲状腺癌是儿童癌症放射治疗的常见并发症。甲状腺辐射剂量的剂量反应现已明确，但其他因素的潜在调节作用需要进一步研究。
本研究旨在探讨剂量反应潜在调节因素的作用。
我们对1986年前接受治疗的4338名5岁实体儿童癌症幸存者进行了队列研究，平均随访27年。在重建放疗实际条件后，估计甲状腺及其他一些解剖部位在放疗期间接受的剂量。
55例患者发生甲状腺癌。甲状腺癌风险随甲状腺辐射剂量增加至0.2 Gy而增加，更高剂量时趋于平稳。考虑甲状腺辐射剂量时，手术或放射脾切除术（脾脏辐射剂量>20 Gy）会增加甲状腺癌风险（相对风险[RR]=2.3；95%置信区间[CI]，1.3 - 4.0），垂体高辐射剂量（>5 Gy）会降低此风险（RR = 0.2；95% CI，0.1 - 0.6）。接受亚硝基脲化疗的患者风险比未接受者高6.6倍（95% CI，2.5 - 15.7）。甲状腺每Gy辐射的额外RR为4.7（95% CI，1.7 - 22.6）。如果访谈时体重指数等于或高于25 kg/m²，则为7.6（95% CI，1.6 - 33.3），否则为4.1（95% CI，0.9 - 17.7）（交互作用P值 = 0.1）。
预测儿童癌症放射治疗后的甲状腺癌风险可能不仅需要评估甲状腺的辐射剂量。化疗、脾切除术、垂体辐射剂量和肥胖也起作用。
