Radiation treatment of benign tumors in NF2-related-schwannomatosis: A national study of 266 irradiated patients showing a significant increase in malignancy/malignant progression
Authors: Evans D Gareth , Halliday Dorothy , Obholzer Rupert , Afridi Shazia , Forde Claire , Rutherford Scott A , Hammerbeck-Ward Charlotte , Lloyd Simon K , Freeman Simon M , Pathmanaban Omar N , Thomas Owen M , Laitt Roger D , Stivaros Stavros , Kilday John-Paul , Vassallo Grace , McBain Catherine , Lavin Timothy , Paterson Chay , Whitfield Gillian , McCabe Martin G , Axon Patrick R , Halliday Jane , Mackeith Samuel , Parry Allyson ,   English Specialist NF2 Research Group, Axon Patrick , Buttimore Juliette , Tysome James , Donnelly Neil , Borsetto Daniele , Whitworth James , Hensiek Anke , Jena Rajesh , Guilfoyle Mathew , Mannion Richard , Nicholson James , Muthusamy Brinda , Taylor Amy , Price Richard , Edme Karine , Gamazo Nicola , Vanat Zebunnisa , Scoffings Daniel , Scott Josh , Jefferies Sarah , Knight Richard , Lamb Tamara , Chuen Tam Yu , Foweraker Karen , Harris Fiona , Sanghera Paul , Meade Sara , Irving Richard , Monksfield Peter , Ragge Nicola , Murrell Melanie , Barwell Julian , English Martin , Trivedi Rikin , Afridi Shazia K , Ferner Rosalie E , Obholzer Rupert , Williams Victoria , Hammond Chris , Lascelles Karine , Skilbeck Chris , Shaw Adam , Swampillai Angela , Thomson Suki , Thomas Nick , Maratos Eleni , Barazi Sinan , Mullin Rebecca , Henley Susie , Smith Natalie , Carlton-Jones Lal , Baker Alison , Myers Mandy , Nunn Terry , Nduka Charles , Anup Raji , Duff Chris , Freeman Simon R , Jarvis Nicola , Kamaly-Asl Ian , King Andrew T , Kellett Mark , Kilday John-Paul , Lloyd Simon K , McBain Catherine , Laitt Roger , O’Driscoll Martin , McCabe Martin , Perry Mary , Rutherford Scott A , Henshaw Kirsty , Stivaros Stavros M , Thomas Owen , Vassallo Grace , Hammerbeck-Ward Charlotte L , Pathmanaban Omar N , Kurian Jincy , Lavin Tim , Harkness Elaine F , Buttimore Juliette , King Andrew T 
Published: March 2023

AbstractBackgroundRadiation 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).MethodsAll 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.ResultsIn 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 &lt; .001). Lifetime and 20-year CNS M/MP was ~6% in all irradiated patients—(4.9% for vestibular schwannomas [VS] radiotherapy) versus &lt;1% in the non-irradiated population (P &lt; .001/.01). Controls were well matched for age at NF2 diagnosis and treatment (Males = 133%–50%) and had no M/MP in the CNS post-index tumor treatment (P = .0016). Thirty-year survival from index tumor treatment was 45.62% (95% CI = 34.0–56.5) for cases and 66.4% (57.3–74.0) for controls (P = .02), but was nonsignificantly worse for VS radiotherapy.ConclusionNF2 patients should not be offered radiotherapy as first-line treatment of benign tumors and should be given a frank discussion of the potential 5% excess absolute risk of M/MP.