Population-based analysis of radiation-induced gliomas after cranial radiotherapy for childhood cancers

Abstract

Background Cranial radiotherapy (RT) used for pediatric CNS cancers and leukemias carries a risk of secondary CNS malignancies, including radiation-induced gliomas (RIG). Our aim was to characterize the epidemiology of RIG. Methods This retrospective study used SEER data (1975-2016). Cohort 1 included patients diagnosed with glioma as a second malignancy > 2 years after receiving treatment for a first malignancy diagnosed at 0-19 years, either a primary CNS tumor (1a, n=57) or leukemia (1b, n=20). Cohort 2 included patients who received RT for a pediatric CNS tumor and died of presumed progressive disease > 7 years after diagnosis, since previous studies have documented many missed RIGs in this group (n=296). Controls (n=10,687) included all other patients ages 0-19 who received RT for a first CNS tumor or leukemia. Results For Cohort 1, 0.77% of patients receiving cranial RT developed RIG. 3.39% of patients receiving cranial RT for primary CNS tumors fell in Cohort 2. Median latency to RIG diagnosis was 11.1 years and was significantly shorter for Cohort 1b than 1a. Median OS for Cohort 1 was 9.0 months. Receiving surgery, radiation, or chemotherapy were all associated with a non-statistically significant improvement in OS (p 0.1-0.2). 1.8% of all brain tumor deaths fell in Cohort 1, with 7.9% in Cohort 2. Conclusion 1-4% of patients undergoing cranial RT for pediatric cancers later developed RIG, which can occur 3-35 years after RT. Given the substantial and likely underestimated impact on overall CNS tumor mortality, RIG is deserving of increased attention in preclinical and clinical studies.

Clinical and molecular study of radiation-induced gliomas

“…Because our cohort and other published cohorts reported patients developing RIG even 35 to 45 years 19 after radiation therapy, it is very likely that the actual risk of developing RIG exceeds 3% more than 15 years after the primary tumor RT. Consistent with our findings, the increasing cumulative incidence of RIG development was also demonstrated using SEER data 20 . Based on SEER data, the risk of RIG development was estimated to be between 1 and 4%, and RIG was responsible for 2 to 10% of all pediatric brain tumor deaths 20 .…”

“…Consistent with our findings, the increasing cumulative incidence of RIG development was also demonstrated using SEER data 20 . Based on SEER data, the risk of RIG development was estimated to be between 1 and 4%, and RIG was responsible for 2 to 10% of all pediatric brain tumor deaths 20 .…”

Characteristics of radiation-induced brain tumors: case series and systematic review

“…16 In previous studies that included patients with childhood cancer exposed to cranial RT, 0.77%-3.39% and 5.6% of patients developed RIG and RIM, respectively. 32,33 Increased radiation dose increased the risk of subsequent meningioma and glioma among childhood cancer survivors. 34 In addition, the dose-dependent risk was significant in younger patients, especially those < 5 years of age.…”

Germline Variants in Cancer Predisposition Genes in Pediatric Patients with Central Nervous System Tumors

“…However, they are prone to developing various secondary malignancies, including radiation-induced high-grade gliomas. As they occur in 1-4% of patients treated with cranial radiotherapy, the influence of the germline variants can be a subject of debate [41][42][43].…”

“…The discovered variant most probably plays a role in the development of the medulloblastomas in these patients. However, the impact of the ELP1 variant on the appearance of high-grade glioma cases is not so straightforward due to cranial irradiation, a known risk factor for secondary tumors of this type [43].…”