Radiation treatment of benign tumors in NF2-related-schwannomatosis: A national study of 266 irradiated patients showing a significant increase in malignancy/malignant progression

Abstract Background Radiation treatment of benign tumors in tumor predisposition syndromes is controversial, but short-term studies from treatment centers suggest safety despite apparent radiation-associated malignancy being reported. We determined whether radiation treatment in NF2-related schwannomatosis patients is associated with increased rates of subsequent malignancy (M)/malignant progression (MP). Methods All UK patients with NF2 were eligible if they had a clinical/molecular diagnosis. Cases were NF2 patients treated with radiation for benign tumors. Controls were matched for treatment location with surgical/medical treatments based on age and year of treatment. Prospective data collection began in 1990 with addition of retrospective cases in 1969. Kaplan–Meier analysis was performed for malignancy incidence and survival. Outcomes were central nervous system (CNS) M/MP (2cm annualized diameter growth) and survival from index tumor treatment. Results In total, 1345 NF2 patients, 266 (133-Male) underwent radiation treatments between 1969 and 2021 with median first radiotherapy age of 32.9 (IQR = 22.4–46.0). Nine subsequent CNS malignancies/MPs were identified in cases with only 4 in 1079 untreated (P < .001). Lifetime and 20-year CNS M/MP was ~6% in all irradiated patients—(4.9% for vestibular schwannomas [VS] radiotherapy) versus