title: A pooled analysis of thyroid cancer incidence following radiotherapy for childhood cancer.
abstract: Childhood cancer five-year survival now exceeds 70-80%. 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 (0.9-14.9), 4.5 (1.4-17.8) and 3.2 (0.8-10.4), 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 10-15-fold for 10-30 Gy and then declined, but remained elevated for doses >50 Gy. The fitted RR at 10 Gy was 13.7 (95% CI: 8.0-24.0). 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.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland 20892, USA.
authors.forename: Lene H S
authors.initials: LH
authors.lastname: Veiga
authors.forename: Jay H
authors.initials: JH
authors.lastname: Lubin
authors.forename: Harald
authors.initials: H
authors.lastname: Anderson
authors.forename: Florent
authors.initials: F
authors.lastname: de Vathaire
authors.forename: Margaret
authors.initials: M
authors.lastname: Tucker
authors.forename: Parveen
authors.initials: P
authors.lastname: Bhatti
authors.forename: Arthur
authors.initials: A
authors.lastname: Schneider
authors.forename: Robert
authors.initials: R
authors.lastname: Johansson
authors.forename: Peter
authors.initials: P
authors.lastname: Inskip
authors.forename: Ruth
authors.initials: R
authors.lastname: Kleinerman
authors.forename: Roy
authors.initials: R
authors.lastname: Shore
authors.forename: Linda
authors.initials: L
authors.lastname: Pottern
authors.forename: Erik
authors.initials: E
authors.lastname: Holmberg
authors.forename: Michael M
authors.initials: MM
authors.lastname: Hawkins
authors.forename: M Jacob
authors.initials: MJ
authors.lastname: Adams
authors.forename: Siegal
authors.initials: S
authors.lastname: Sadetzki
authors.forename: Marie
authors.initials: M
authors.lastname: Lundell
authors.forename: Ritsu
authors.initials: R
authors.lastname: Sakata
authors.forename: Lena
authors.initials: L
authors.lastname: Damber
authors.forename: Gila
authors.initials: G
authors.lastname: Neta
authors.forename: Elaine
authors.initials: E
authors.lastname: Ron
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D009369:Neoplasms / Q000532:radiotherapy*; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology*; D016609:Neoplasms, Second Primary / Q000453:epidemiology*; D011878:Radiotherapy / Q000009:adverse effects; D013964:Thyroid Neoplasms / Q000453:epidemiology*