LAUSR

BACKGROUND Few studies in North America have quantified the risks of second malignant neoplasms (SMNs) among survivors of childhood non-central nervous system (non-CNS) embryonal tumours due to their rarity. We aimed to investigate these risks by combining population-based data from the United States of America and Canada. METHODS We evaluated patients with childhood non-CNS embryonal tumours reported to the Surveillance Epidemiology and End Results program and eight Canadian cancer registries from 1969 to 2010. Standardised incidence ratio (SIR) and cumulative incidence of SMNs were calculated. Subgroup analyses were conducted by the type of first primary cancer, age at first primary diagnosis and follow-up duration. FINDINGS Of the 13,107 survivors, 190 SMNs were reported over 134,548 person-years of follow-up. The SIR for all SMNs combined was 6.4 (95% confidence interval [CI]: 5.5-7.4). Most site-specific SIRs were significantly increased, ranging from 36 (95% CI: 26-49) for bone and joint cancer to 3.1 (95% CI: 1.5-5.2) for brain tumour. The risk for second malignancies declined as the time elapsed from the first primary diagnosis and was less prominent for patients first diagnosed at age 1-4 years. Notably, rhabdomyosarcoma survivors had a higher risk for SMNs than those with other first primaries. The overall cumulative incidence of SMNs was 1.0% at 10 years, increasing to 2.2% at 20 years and 4.1% at 30 years. INTERPRETATION Survivors with childhood non-CNS embryonal tumours faced an increased risk for SMNs compared to the general population. The risk variations observed in different patient categories may help target prevention strategies in high-risk subgroups.