Natural history of cavernous malformations in children with brain tumors treated with radiotherapy and chemotherapy

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Cavernous malformations (CM) are cerebral irradiation-related late complications. Little is known about their natural history and the pathogenetic role of concomitant chemotherapy. We present a retrospective, single-institution study of 108 children affected with medulloblastoma, ependymoma, or germinoma treated with radio- and chemotherapy. The frequency, clinical and radiological presentations, and outcomes were analyzed to investigate the relationship among radiation dose, associated chemotherapy, age, latency and localization of radiation-induced CM. 100 out of 108 children were treated with radiotherapy for primary brain tumor; 34 (27 with medulloblastoma and 7 with other histologies) out of 100 patients developed CM. No significant relationship was found between CM and gender (p = 0.70), age (p = 0.90), use of specific chemotherapy (standard versus high-dose, p = 0.38), methotrexate (p = 0.49), and radiation dose (p = 0.45). However, CM developed more frequently and earlier when radiotherapy was associated with methotrexate (70 % of cases). Radiation-induced CM prevailingly occurred in the cerebral hemispheres (p = 0.0001). Only 3 patients (9 %) were symptomatic with headache. Three patients underwent surgery for intra- or extra-lesional hemorrhage. CM was confirmed by histopathology for all 3 patients. The vast majority of radiation-induced CM is asymptomatic, and macro-hemorrhagic events occur rarely. Concomitant therapy with methotrexate seems to favor their development. We recommend observation for asymptomatic lesions, while surgery should be reserved to symptomatic growth or hemorrhage.

Original languageEnglish
Pages (from-to)311-320
Number of pages10
JournalJournal of Neuro-Oncology
Issue number2
Publication statusPublished - 2014


  • Brain tumors
  • Cavernous malformation
  • Methotrexate
  • Radiation therapy

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neurology
  • Medicine(all)


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