• Judith L Kok, Jop C Teepen, Flora E van Leeuwen, Tissing Wim J E WJE Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands. Department , Neggers Sebastian J C M M SJCMM Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands. , Helena J van der Pal, Jacqueline J Loonen, Dorine Bresters, Birgitta Versluys, Marry M van den Heuvel-Eibrink, Eline van Dulmen-den Broeder, Margriet van der Heiden-van der Loo, Aleman Berthe M P BMP Department of Radiation Oncology, the Netherlands Cancer Institute, Amsterdam, the Netherlands., Laurien A Daniels, Haasbeek Cornelis J A CJA Department of Radiation Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands., Bianca Hoeben, Geert O Janssens, John H Maduro, Foppe Oldenburger, Caroline van Rij, Robbert J H A Tersteeg, Michael Hauptmann, DCOG-LATER Study Group, Kremer Leontien C M LCM Department of Pediatric Oncology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. , and Cécile M Ronckers.
• Department of Pediatric Oncology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
• Neuro-oncology. 2019 Feb 19; 21 (3): 392-403.

BackgroundPediatric cranial radiotherapy (CrRT) markedly increases risk of meningiomas. We studied meningioma risk factors with emphasis on independent and joint effects of CrRT dose, exposed cranial volume, exposure age, and chemotherapy.MethodsThe Dutch Cancer Oncology Group-Long-Term Effects after Childhood Cancer (DCOG-LATER) cohort includes 5-year childhood cancer survivors (CCSs) whose cancers were diagnosed in 1963-2001. Histologically confirmed benign meningiomas were identified from the population-based Dutch Pathology Registry (PALGA; 1990-2015). We calculated cumulative meningioma incidence and used multivariable Cox regression and linear excess relative risk (ERR) modeling.ResultsAmong 5843 CCSs (median follow-up: 23.3 y, range: 5.0-52.2 y), 97 developed a benign meningioma, including 80 after full- and 14 after partial-volume CrRT. Compared with CrRT doses of 1-19 Gy, no CrRT was associated with a low meningioma risk (hazard ratio [HR] = 0.04, 95% CI: 0.01-0.15), while increased risks were observed for CrRT doses of 20-39 Gy (HR = 1.66, 95% CI: 0.83-3.33) and 40+ Gy (HR = 2.81, 95% CI: 1.30-6.08). CCSs whose cancers were diagnosed before age 5 versus 10-17 years showed significantly increased risks (HR = 2.38, 95% CI: 1.39-4.07). In this dose-adjusted model, volume was not significantly associated with increased risk (HR full vs partial = 1.66, 95% CI: 0.86-3.22). Overall, the ERR/Gy was 0.30 (95% CI: 0.03-unknown). Dose effects did not vary significantly according to exposure age or CrRT volume. Cumulative incidence after any CrRT was 12.4% (95% CI: 9.8%-15.2%) 40 years after primary cancer diagnosis. Among chemotherapy agents (including methotrexate and cisplatin), only carboplatin (HR = 3.55, 95% CI: 1.62-7.78) appeared associated with meningioma risk. However, we saw no carboplatin dose-response and all 9 exposed cases had high-dose CrRT.ConclusionAfter CrRT 1 in 8 survivors developed late meningioma by age 40 years, associated with radiation dose and exposure age, relevant for future treatment protocols and awareness among survivors and physicians.© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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