Risk of Subsequent Primary Cancers After External Beam Radiotherapy Treatment of Pediatric Low Grade Gliomas: A Surveillance, Epidemiology, and End Results Analysis 1973 to 2015

Abstract

Abstract INTRODUCTION Past studies have associated external beam radiotherapy (EBRT) with higher incidences of subsequent primary malignancies (SPMs). This link has been documented for leukemias, and prostate, thyroid, and bone cancers. However, the effects of EBRT on SPM development from low grade gliomas (LGGs) are not well understood. The aim of the present study was to characterize the risk of SPM development after EBRT treatment of LGGs. METHODS A total of 1439 pediatric (age 0-17) records between 1973 and 2015 were assembled from the Surveillance, Epidemiology, and End Results (SEER) database. Univariable and multivariable Cox regressions were used to evaluate the prognostic impact of demographic, tumor, and treatment-related covariates. Propensity score matching was used to balance baseline characteristics. Survival and cumulative hazard analyses measured the time to, and risk of, SPM development, stratified by receipt of EBRT. RESULTS Of the 1439 pediatric patients we analyzed, 450 received EBRT and 989 did not. A total of 65 pediatric patients were identified who developed SPMs after LGG diagnosis, and 35 of these patients received EBRT (OR: 2.70). Unadjusted Cox regressions revealed a significantly elevated SPM risk in EBRT-treated pediatric patients with LGGs (HR: 2.22, CI: 1.34-3.67). After adjusting for covariates such as race, gender, income, chemotherapy, and grade (World Health Organization I vs II), there was still a clear association between EBRT and the development of SPMs (HR: 2.52, CI: 1.50-4.23). Propensity score matching across covariates did not significantly impact the hazard ratio. Time-to-event Kaplan Meier curves demonstrated earlier SPM development in the EBRT-treated LGG pediatric population, and Nelson–Aalen cumulative hazard estimates showed higher incidences of SPM development at all time points. CONCLUSION EBRT treatment for LGGs is associated with an elevated incidence of SPMs, even after controlling for available covariates. This suggests less aggressive EBRT use in the pediatric LGG population may be warranted.