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Florent de Vathaire, PhD; Claire Hardiman; Akthar Shamsaldin, PhD; Sarah Campbell; Emmanuel Grimaud, PhD; Mike Hawkins, PhD; Mariane Raquin, MD; Odile Oberlin, MD; Ibrahima Diallo, PhD; Jean-Michel Zucker, MD; Xavier Panis, MD; Jean Leon Lagrange, MD; Nicolas Daly-Schveitzer, MD; Jean Lemerle, MD; Jean Chavaudra, PhD; Martin Schlumberger, MD; Catherine Bonaïti, PhD, MD

Arch Intern Med. 1999;159:2713-2719.

Background  The thyroid gland is among the most radiosensitive organs. However, little is known about the long-term risk of developing a thyroid tumor after fractionated external radiotherapy for cancer during childhood.

Objective  To study the long-term risk of developing a thyroid tumor in 4096 three-year survivors of childhood cancer treated between May 1942 and December 1985 in 8 centers in France and the United Kingdom, 2827 of whom had received external radiotherapy.

Methods  A wide range of radiation doses were given to the thyroid: 1164 children received less than 0.5 Gy and 812 received more than 5.0 Gy, the average dose being 7.0 Gy.

Results  After mean follow-up of 15 years (range, 3-45 years), 14 patients—all of whom had received radiotherapy—developed a clinical thyroid carcinoma. Within the cohort, the relation between radiation dose to the thyroid and risk of thyroid carcinoma and adenoma was similar to that observed in patients who received radiotherapy during childhood for other reasons, such as an excess relative risk per gray of 4 to 8, up to a few gray. In contrast, compared with thyroid cancer incidence in the general population, the standardized incidence of thyroid carcinoma was much higher than expected from the dose-response relationship estimated within the cohort and from patients who received radiotherapy during childhood for other reasons: a dose of 0.5 Gy was associated with a standardized incidence ratio of 35 (90% confidence interval, 10-87) and a dose of 3.6 Gy with a standardized incidence ratio of 73 (90% confidence interval, 28-153). We did not show a reduction in excess relative risk per gray with use of an increasing number of fractions.

Conclusion  Although we cannot estimate the exact proportion, it is probable that some or all children who are treated for cancer are predisposed to developing a thyroid carcinoma.

From the Cancer Epidemiology Research Unit, National Institute for Health and Medical Research (Drs de Vathaire, Shamsaldin, Raquin, Oberlin, Diallo, and Bonatï and Mss Hardiman and Campbell), and Departments of Physics (Drs Shamsaldin, Grimaud, Diallo, and Chavaudra and Ms Hardiman) and Pediatrics (Dr Raquin , Oberlin, and Lemerle), and Nuclear Medicine Unit (Dr Schlumberger), Institut Gustave Roussy, Villejuif, France; Thames Cancer Registry, Sutton, England (Ms Campbell); Childhood Cancer Research Group, Radcliffe Infirmary, Oxford, England (Dr Hawkins); Department of Pediatrics, Institut Curie, Paris, France (Dr Zucker); Department of Radiotherapy, Institut Jean Godinot, Reims, France (Dr Panis); Department of Radiotherapy, Centre Lacassagne, Nice, France (Dr Lagrange); and Department of Radiotherapy, Centre Claudius-Regaud, Toulouse, France (Dr Daly-Schveitzer).

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