BACKGROUND
The current study builds on the hypothesis that cancer‐predisposing germline mutations are less common among patients with fusion‐positive (F+) sarcomas compared to those with fusion‐negative (F‐) sarcomas, resulting in a lower risk of developing second malignant neoplasms (SMNs) in those with F + sarcomas.
METHODS
Standardized incidence ratios (SIRs) for developing SMNs were evaluated in 4822 survivors of F + and 3963 survivors of F‐ sarcomas that were diagnosed between 1992 and 2012 in pediatric, adolescent, and young adult patients (aged birth‐39 years) and reported in the Surveillance, Epidemiology, and End Results (SEER) database. Cox proportional hazards models (adjusted hazard ratio [aHR]) and competing risk methods (subhazard ratio [sHR]) were used to evaluate SMN risk in those with F‐ versus F + sarcomas while controlling for demographic and clinical variables.
RESULTS
SMN risk was found to be nearly 2‐fold greater among survivors of F + sarcomas (SIR, 1.86; 95% confidence interval [95% CI], 1.48‐2.30) and nearly 3‐fold greater among survivors of F‐ sarcomas (SIR, 2.89; 95% CI, 2.30‐3.59) compared with the reference population. Although SMN types were noted to be similar between the fusion groups, the rate of any SMN was noted to be greater among survivors of F‐ sarcomas (aHR, 1.38 [95% CI, 1.01‐1.89] and sHR, 1.27 [95% CI, 0.94‐1.73]) when compared with survivors of F + sarcomas. The difference was most notable for solid tumor SMNs after index sarcomas were diagnosed between 2002 and 2012, for which rates of SMN were >2‐fold greater among survivors of F‐ sarcomas (aHR, 2.31 [95% CI, 1.20‐4.48] and sHR, 2.24 [95% CI, 1.13‐4.43]).
CONCLUSIONS
The findings of the current study highlight the increased SMN risk experienced by survivors of sarcoma and demonstrate higher SMN rates in survivors of F‐ sarcomas compared to those with a history of F + sarcomas. Cancer 2016;122:3492–3500. © 2016 American Cancer Society