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J Clin Endocrinol Metab. 2015 Nov;100(11):4282-90. doi: 10.1210/jc.2015-1690. Epub 2015 Sep 1.

Thyroid Radiation Dose and Other Risk Factors of Thyroid Carcinoma Following Childhood Cancer.

Author information

1
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.

Abstract

CONTEXT:

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.

OBJECTIVE:

This study aimed to investigate the role of potential modifiers of the dose response.

DESIGN:

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.

RESULTS:

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).

CONCLUSION:

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01620372.

PMID:
26327481
DOI:
10.1210/jc.2015-1690
[Indexed for MEDLINE]

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