In a pooled analysis reported in JAMA Oncology, Withrow et al found that increased exposure of the meninges to radiation therapy was associated with an increased risk of developing meningioma in survivors of childhood cancer. Receipt of methotrexate was also associated with increased risk.
Study Details
The case-control study used pooled data from four nested case-control studies of survivors of childhood cancer diagnosed between 1942 and 2000, with follow-up through 2016. Cases were defined as survivors diagnosed with meningioma during follow-up; controls were those who did not develop meningioma matched with cases for sex, age at first cancer diagnosis, and duration of follow-up. Absorbed radiation doses to the meningioma location in the cases and the corresponding locations in controls were estimated.
Key Findings
The analysis included 273 cases and 738 controls. Median age at first cancer diagnosis was 5 years, and median time since first cancer was 21.5 years. For cases vs controls, first cancer was central nervous system cancer in 56% vs 15%, leukemia in 25% vs 16%, and other cancers in 19% vs 69%.
Increasing radiation dose was associated with an increased risk of meningioma (excess odds ratio per Gy [EOR/Gy] = 1.44, 95% confidence interval [CI] = 0.62–3.61, P < .001 for trend). No significant change in EOR/Gy with time since exposure was observed, with a significant EOR/Gy persisting at 30 years after exposure (EOR/Gy = 3.76, 95% CI = 0.77–29.15).
Compared with survivors who were not exposed to radiation therapy, those who received doses of 4 to 24 Gy had an odds ratio for development of meningioma of 14.44 (95% CI =5.73–36.39) and those who received > 24 Gy had an odds ratio of 33.66 (95% CI = 14.10–80.31).
The radiation dose-response association was significantly lower (P = .03) among patients treated at age ≥ 10 years (EOR/Gy = 0.57, 95% CI = 0.18–1.91) vs those treated at age < 10 years (EOR/Gy = 2.20, 95% CI = 0.87–6.31).
Any receipt of methotrexate was associated with an increased risk of meningioma (OR = 3.43, 95% CI = 1.56–7.57). Risks were similar for systemic (OR = 2.37) and intrathecal (OR = 2.90) use, and no dose-response association was observed overall or for systemic or intrathecal use. No interaction of risk associated with methotrexate with radiation dose was observed.
No significant associations with risk for meningioma were observed for chemotherapy overall, alkylating agents, anthracyclines, platinum-based compounds, or epipodophyllotoxins.
The investigators concluded, “These findings suggest that the meninges are highly radiosensitive, especially for children treated before age 10 years. These results support the reduction in whole-brain irradiation over recent decades and the prioritization of approaches that limit radiation exposure in healthy tissue for children. The persistence of elevated risks of meningiomas for 30 years after cranial radiotherapy could help inform surveillance guidelines.”
Lene H.S. Veiga, PhD, of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was funded by the Division of Cancer Epidemiology and Genetics, part of the Intramural Program of the National Cancer Institute. For full disclosures of the study authors, visit jamanetwork.com.
