TY - JOUR
T1 - Risk of benign meningioma after childhood cancer in the DCOG-LATER cohort
T2 - contributions of radiation dose, exposed cranial volume, and age
AU - DCOG-LATER Study Group
AU - Kok, Judith L
AU - Teepen, Jop C
AU - van Leeuwen, Flora E
AU - Tissing, Wim J E
AU - Neggers, Sebastian J C M M
AU - van der Pal, Helena J
AU - Loonen, Jacqueline J
AU - Bresters, Dorine
AU - Versluys, Birgitta
AU - van den Heuvel-Eibrink, Marry M
AU - van Dulmen-den Broeder, Eline
AU - van der Heiden-van der Loo, Margriet
AU - Aleman, Berthe M P
AU - Daniels, Laurien A
AU - Haasbeek, Cornelis J A
AU - Hoeben, Bianca
AU - Janssens, Geert O
AU - Maduro, John H
AU - Oldenburger, Foppe
AU - van Rij, Caroline
AU - Tersteeg, Robbert J H A
AU - Hauptmann, Michael
AU - Kremer, Leontien C M
AU - Ronckers, Cécile M
AU - van den Berg, M. H.
AU - Bruggink, A. H.
AU - Caron, H. N.
AU - Dolsma, W. V.
AU - Grootenhuis, M. A.
AU - den Hartogh, J. G.
AU - Hollema, N.
AU - Jongmans, M. C.
AU - Jaspers, M. W. M.
AU - Postma, A.
AU - van de Vijver, M. J.
N1 - © 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.
PY - 2019/2/19
Y1 - 2019/2/19
N2 - BACKGROUND: Pediatric 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.METHODS: The 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.RESULTS: Among 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.CONCLUSION: After 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.
AB - BACKGROUND: Pediatric 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.METHODS: The 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.RESULTS: Among 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.CONCLUSION: After 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85065808893&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30099534
U2 - https://doi.org/10.1093/neuonc/noy124
DO - https://doi.org/10.1093/neuonc/noy124
M3 - Article
C2 - 30099534
SN - 1522-8517
VL - 21
SP - 392
EP - 403
JO - Neuro-oncology
JF - Neuro-oncology
IS - 3
ER -