A pooled analysis of thyroid cancer incidence following radiotherapy for childhood cancer

Lene H.S. Veiga, Jay H. Lubin*, Harald Anderson, Florent De Vathaire, Margaret Tucker, Parveen Bhatti, Arthur Schneider, Robert Johansson, Peter Inskip, Ruth Kleinerman, Roy Shore, Linda Pottern, Erik Holmberg, Michael M. Hawkins, M. Jacob Adams, Siegal Sadetzki, Marie Lundell, Ritsu Sakata, Lena Damber, Gila NetaElaine Ron

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Childhood cancer five-year survival now exceeds 7080. Childhood exposure to radiation is a known thyroid carcinogen; however, data are limited for the evaluation of radiation dose-response at high doses, modifiers of the dose-response relationship and joint effects of radiotherapy and chemotherapy. To address these issues, we pooled two cohort and two nested case-control studies of childhood cancer survivors including 16,757 patients, with 187 developing primary thyroid cancer. Relative risks (RR) with 95 confidence intervals (CI) for thyroid cancer by treatment with alkylating agents, anthracyclines or bleomycin were 3.25 (0.914.9), 4.5 (1.417.8) and 3.2 (0.810.4), respectively, in patients without radiotherapy, and declined with greater radiation dose (RR trends, P 0.02, 0.12 and 0.01, respectively). Radiation dose-related RRs increased approximately linearly for <10 Gy, leveled off at 1015-fold for 1030 Gy and then declined, but remained elevated for doses >50 Gy. The fitted RR at 10 Gy was 13.7 (95 CI: 8.024.0). Dose-related excess RRs increased with decreasing age at exposure (P < 0.01), but did not vary with attained age or time-since-exposure, remaining elevated 25 years after exposure. Gender and number of treatments did not modify radiation effects. Thyroid cancer risks remained elevated many decades following radiotherapy, highlighting the need for continued follow up of childhood cancer survivors.

Original languageEnglish
Pages (from-to)365-376
Number of pages12
JournalRadiation Research
Issue number4
StatePublished - Oct 2012


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