Data Support Whole Brain Irradiation Reduction in Pediatric Cancer Survivors

Results from a pooled case control study indicate that meninges are very radiosensitive in pediatric patients who were treated at prior to age 10 years, supporting reduced dose whole brain irradiation in this population.

High radiosensitivity of the meninges was observed in pediatric patients with cancer treated before 10 years of age, supporting the use of reduced dose whole brain irradiation and the prioritization of approaches that limit radiation exposure in healthy tissue, according to data from an international pooled case-control study.

In the analysis, which included 273 survivors of childhood cancer who developed subsequent meningioma and 738 survivors who did not, higher radiation doses were associated with an increased risk of meningioma (excess odds ratio [EOR]/Gy, 1.44; 95% CI, 0.62-3.61), with no evidence suggesting departure from linearity (P = .90). Patients who received 24 Gy or more of radiation therapy had more than 30-fold odds of developing meningioma compared with those who were not exposed to radiation therapy (OR, 33.66; 95% CI, 14.10-80.31).

Radiation dose-response associations were lower for treated patients 10 years and older compared with those younger than 10 years (EOR/Gy, 0.57; 95% CI, 0.18-1.91 vs 2.20; 95% CI, 0.87-6.31; P for heterogeneity = .03). Radiation-related risks remained significantly elevated 30 years following treatment (EOR/Gy, 3.76; 95% CI, 0.77-29.15), and there was an increased risk of meningioma among children who had received methotrexate (OR, 3.43; 95% CI, 1.56-7.57).

“These results support the reductions in whole brain irradiation over recent decades and the use of radiotherapy approaches that limit exposure of healthy tissue in children,” the investigators noted. “The persistence of elevated risk of meningioma for more than 30 years after cranial radiotherapy could help inform surveillance guidelines for those treated as young children.”

The pooled analysis included 4 case-control studies of subsequent brain and central nervous system (CNS) tumors in survivors of childhood cancer, which were conducted in North America, France, the United Kingdom, and Nordic countries. Cases involved individuals who were treated for first primary cancers between 1942 and 2000. Controls were survivors of childhood cancer who did not specifically develop subsequent meningioma and were matched based on age, sex, and duration of follow-up. Data were analyzed from July 2019 to June 2022. Investigators explored the role of chemotherapy in the development of meningioma and grouped agents into several major categories: alkylating agents, anthracyclines, epipodophyllotoxins, platinum-based compounds, and antimetabolites.

The main outcome of the analysis was the incidence of subsequent meningioma, assessed using odds ratios (ORs) and excess odds ratios per gray (EOR/Gy).

The study included a total of 1011 individuals. The most common first disease type in the cases population was CNS tumors (56.0%), whereas the most common types among controls were leukemia (15.7%), CNS (15.0%), and Wilms tumors (16.9%). Most patients in the case and control groups, respectively, were female (58.2% vs 59.6%). Additionally, most patients across both groups were 0 to 4 years of age upon their first cancer diagnosis (42.9% vs 45.8%) and the majority received their diagnosis from 1970 to 1979 (51.3% vs 53.0%). Moreover, the majority had received prior radiotherapy (96.0% vs 69.0%) and prior chemotherapy (50.9% vs 65.9%). The most frequent chemotherapy agents among the cases cohort included alkylating agents (33.0%), antimetabolites (31.1%), and intrathecal methotrexate (24.5%), whereas the most common agents among the control cohort included alkylating agents (41.3%), anthracyclines (26.1%), and antimetabolites (22.4%).

Investigators reported no significant difference in EOR/Gy for male patients (EOR/Gy, 2.82; 95% CI, 0.61-36.82) vs female patients (EOR/Gy, 1.11; 95% CI, 0.41-3.20; P = .34). Additionally, no differences were observed between survivors of CNS tumors (EOR/Gy, 0.63; 95% CI, 0.19-2.47) or leukemia (EOR/Gy, 0.51; 95% CI, 0.05-10.80) vs survivors of other first cancers (EOR/ Gy, 2.69; 95% CI, 0.94-8.79; P = .15). There was no evidence that a modified radiation dose response was associated with factors such as age, calendar year of follow-up, or class of chemotherapeutic agents.

Reference

Withrow DR, Anderson H, Armstrong GT, et al. Pooled analysis of meningioma risk following treatment for childhood cancer. JAMA Oncol. Published online October 06, 2022. doi:10.1001/jamaoncol.2022.4425