Radiation treatment of benign tumors in NF2-related-schwannomatosis: A national study of 266 irradiated patients showing a significant increase in malignancy/malignant progression
D. Gareth Evans, Dorothy Halliday, Rupert Obholzer, Shazia Afridi, Claire Forde, Scott Rutherford, Charlotte Hammerbeck-Ward, Simon Lloyd, Simon Freeman, Omar Pathmanaban, Owen Thomas, Roger Laitt, Stavros Stivaros, John‐Paul Kilday, Grace Vassallo, Catherine McBain, Timothy Lavin, Chay Paterson, Gillian Whitfield, Martin G. McCabe, Patrick Axon, Jane Halliday, Samuel MacKeith, Allyson Parry, Patrick Axon, Juliette Buttimore, James R. Tysome, Neil Donnelly, Daniele Borsetto, James Whitworth, Anke Hensiek, Rajesh Jena, Mathew R. Guilfoyle, Richard Mannion, James Nicholson, Brinda Muthusamy, Amy Taylor, Richard D. Price, Karine Edme, Nicola Gamazo, Zebunnisa Vanat, Daniel Scoffings, Josh Scott, Sarah Jefferies, Richard Knight, Tamara Lamb, Yu Chuen Tam, K. Foweraker, Fiona Harris, Paul Sanghera, Sara Meade, Richard Irving, Peter Monksfield, Nicola Ragge, Melanie Murrell, Julian Barwell, Martin English, Rikin Trivedi, Shazia Afridi, Rosalie E. Ferner, Rupert Obholzer, Victoria Williams, Chris Hammond, Karine Lascelles, Chris Skilbeck, Adam Shaw, Angela Swampillai, Suki Thomson, Nick Thomas, Eleni Maratos, Sinan Barazi, Rebecca Mullin, Susie M.D. Henley, Natalie Smith, Lal Carlton-Jones, Alison Baker, Mandy Myers, Terry Nunn, Charles Nduka, Raji Anup, Chris Duff, Simon Freeman, Nicola Jarvis, Ian Kamaly-Asl, Andrew T. King, Mark Kellett, John‐Paul Kilday, Simon Lloyd, Catherine McBain, Roger Laitt, Martin O’Driscoll, Martin G. McCabe, Mary Perry, Scott Rutherford, K. Henshaw, Stavros Stivaros, Owen Thomas, Grace Vassallo, Charlotte Hammerbeck-Ward, Omar Pathmanaban
Abstract
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 <1% in the non-irradiated population (P < .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. Conclusion NF2 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.