Risk of benign meningioma after childhood cancer in the DCOG-LATER cohort: contributions of radiation dose, exposed cranial volume, and age

DCOG-LATER Study Group, Judith L Kok, Jop C Teepen, Flora E van Leeuwen, Wim J E Tissing, Sebastian J C M M Neggers, 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, Berthe M P Aleman, Laurien A Daniels, Cornelis J A Haasbeek, Bianca Hoeben, Geert O Janssens, John H Maduro, Foppe OldenburgerCaroline van Rij, Robbert J H A Tersteeg, Michael Hauptmann, Leontien C M Kremer, Cécile M Ronckers

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Scopus)
181 Downloads (Pure)

Abstract

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.

The Dutch Cancer Oncology GroupLong-Term Effects after Childhood Cancer (DCOG-LATER) cohort includes 5-year childhood cancer survivors (CCSs) whose cancers were diagnosed in 19632001. Histologically confirmed benign meningiomas were identified from the population-based Dutch Pathology Registry (PALGA; 19902015). We calculated cumulative meningioma incidence and used multivariable Cox regression and linear excess relative risk (ERR) modeling.

Among 5843 CCSs (median follow-up: 23.3 y, range: 5.052.2 y), 97 developed a benign meningioma, including 80 after full- and 14 after partial-volume CrRT. Compared with CrRT doses of 119 Gy, no CrRT was associated with a low meningioma risk (hazard ratio [HR] = 0.04, 95% CI: 0.010.15), while increased risks were observed for CrRT doses of 2039 Gy (HR = 1.66, 95% CI: 0.833.33) and 40+ Gy (HR = 2.81, 95% CI: 1.306.08). CCSs whose cancers were diagnosed before age 5 versus 1017 years showed significantly increased risks (HR = 2.38, 95% CI: 1.394.07). In this dose-adjusted model, volume was not significantly associated with increased risk (HR full vs partial = 1.66, 95% CI: 0.863.22). Overall, the ERR/Gy was 0.30 (95% CI: 0.03unknown). 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: 1.627.78) appeared associated with meningioma risk. However, we saw no carboplatin dose-response and all 9 exposed cases had high-dose CrRT.

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.

Original languageEnglish
Pages (from-to)392-403
Number of pages12
JournalNeuro-Oncology
Volume21
Issue number3
Early online date7-Aug-2018
DOIs
Publication statusPublished - Mar-2019

Keywords

  • meningioma
  • cranial radiotherapy
  • childhood cancer survivors
  • radiation dose
  • radiation volume
  • ACUTE LYMPHOBLASTIC-LEUKEMIA
  • CENTRAL-NERVOUS-SYSTEM
  • TERM-FOLLOW-UP
  • SUBSEQUENT NEOPLASMS
  • INTENSIVE TREATMENT
  • 5-YEAR SURVIVORS
  • RADIOTHERAPY
  • PROTOCOL
  • TUMORS
  • CNS

Cite this