An Increased Risk of Second Malignant Neoplasms After Rhabdomyosarcoma: Population-based Evidence for a Cancer Predisposition Syndrome?

Background. Rhabdomyosarcoma survivors have an increased risk of developing second malignant neoplasms (SMN); this risk is traditionally attributed to the effects of multidisciplinary management required for cure. However, the impact of constitutional predisposition has not been properly analyzed. Methods. We analyzed the risk of SMN among 1,151 children diagnosed with rhabdomyosarcoma and reported to the Surveillance, Epidemiology, and End Results registries (SEER-9) from 1973 to 2010. Standardized incidence ratios (SIR) and corresponding 95% confidence intervals (CI) were calculated using SEERStat 8.1.2. Results. Children with pleomorphic and embryonal rhabdomyosarcoma had an increased risk of developing a SMN (SIR = 15.77, 95% CI 1.91-56.96 and SIR = 5.6, 95% CI 3.32-8.85, respectively). The risk was age-dependent; the highest was among children <2 years (SIR = 13.38, 95% CI 4.34-31.22) and the lowest was in children >10 years (SIR = 3.35, 95% CI 1.53-6.35). The risk for the youngest patients was higher for those with embryonal rhabdomyosarcoma (SIR = 14.72, 95% CI 4.01-37.70) compared to other histiotypes. Additionally, the risk of SMN was independent of the use of radiation to the primary (SIR = 6.50, 95% CI 3.97-10.03 and SIR = 4.57, 95% CI 2.09-8.68, for children receiving and not receiving radiation, respectively). The pattern of SMN observed was consistent with the Li-Fraumeni spectrum. Conclusions. Children with rhabdomyosarcoma are at high risk of developing SMN. This risk is higher for a subgroup of young children with pleomorphic and embryonal histologies, and is independent of the use of radiation. This suggests that a subgroup of children with pleomorphic and embryonal rhabdomyosarcoma may have a constitutional cancer predisposition. (c) 2015 Wiley Periodicals, Inc.