Risk of Second Primary Neoplasms of the Central Nervous System

Abstract

Purpose: Second primary (SP) neoplasms of the central nervous system (CNS) among cancer survivors are devastating but poorly understood processes. The absolute risk, or true incidence, of developing an SP CNS tumor among cancer survivors is not well characterized.

Methods and materials: Patients diagnosed with cancer between 1975 and 2016 were queried using the Surveillance, Epidemiology, and End Results Program. Cumulative incidence rates (CIRs) were estimated using competitive risk analysis. The effects of covariates were assessed using multivariate competitive risk regression.

Results: More than 3.8 million patient records were extracted. The absolute risk of developing an SP CNS neoplasm at 25 years was highest among long-term survivors of CNS cancers (CIR, 6.6%). Cranial radiation increased the incidence of SP tumors in pediatric patients (25-year CIR, 5.7% vs 1.1%; P = .0012) but not adults (25-year CIR, 5.8% vs 5.0%; P = .66). Multivariate cumulative risk regression identified radiation among pediatric patients as the greatest risk for an increased CIR (subdistribution hazard ratio, 2.50; 95% CI, 1.86-3.38; P = 2e-9). Meningiomas (42.9% vs 24.1%; P = 2e-7) and glioblastomas (20.5% vs 14.5%; P = .046) represented a greater proportion of the SP CNS tumors in those who received cranial irradiation. The median age of an SP diagnosis was decreased among those who received prior radiation (41 years [interquartile range (IQR), 30-65 years] vs 49 years [IQR, 30-65 years]; P = 7e-5).

Conclusions: The risk of developing a second primary CNS neoplasm is elevated in patients with a prior CNS cancer independent of treatment history. The association between cranial radiation therapy and risk for subsequent cancers may be limited to the pediatric population.

Fig. 1

Cumulative incidence of second primary CNS tumors among A, all survivors, B, long-term survivors, and C, long-term survivors with no history of radiation or chemotherapy. The group CNS (-meningiomas) refers to the incidence of second primary CNS tumors among nonmeningioma CNS primary tumors. Abbreviations: CNS = central nervous system; GI = gastrointestinal; GU = genitourinary; RT, radiation therapy.

Fig. 2

Cumulative incidence of A and C, second primary CNS tumors and B and D, mortality among long-term survivors of CNS cancers by whether radiation was part of the primary treatment regimen. Groups were matched by age, sex, year of diagnosis, tumor location, histology, and receipt of chemotherapy using propensity score–based exact algorithms and stratified by age of initial diagnosis. Intervals reflect 95% confidence intervals of cumulative incidence functions. Abbreviations: CNS = central nervous system; RT, radiation therapy.

Fig. 3

Multivariate cumulative risk regression on risk of developing a second CNS tumor among long-term CNS cancer survivors. Abbreviations: CI = confidence interval; CNS = central nervous system; PCNSL = primary CNS lymphoma; SHR = subdistribution hazard ratio, SPM = second primary malignancy.