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

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Abstract

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.

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Acknowledgement

We thank The “Associazione per la ricerca sui Tumori Cerebrali del Bambino” and The “Fondazione Berlucchi” for supporting our research.

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Authors and Affiliations

  1. Neuro-Oncology, Istituto Giannina Gaslini, Genova, Italy

    Angela Di Giannatale, Claudia Milanaccio & Maria Luisa Garrè

  2. Neuroradiology Operative Unit, Istituto Giannina Gaslini, Genova, Italy

    Giovanni Morana & Andrea Rossi

  3. Neurosurgery, Istituto Giannina Gaslini, Genova, Italy

    Armando Cama & Alessandro Consales

  4. Epidemiology and Biostatistics, Istituto Giannina Gaslini, Genova, Italy

    Luisella Bertoluzzo

  5. Radio-Oncology Department, IRCCS AOU San Martino, IST, National Institute for Cancer Research, Genova, Italy

    Salvina Barra

  6. Anatomo-pathology Department, Istituto Giannina Gaslini, Genova, Italy

    Paolo Nozza

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  1. Angela Di Giannatale
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  2. Giovanni Morana
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  3. Andrea Rossi
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  4. Armando Cama
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  5. Luisella Bertoluzzo
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  8. Claudia Milanaccio
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  9. Alessandro Consales
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  10. Maria Luisa Garrè
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Correspondence to Angela Di Giannatale.

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Di Giannatale, A., Morana, G., Rossi, A. et al. Natural history of cavernous malformations in children with brain tumors treated with radiotherapy and chemotherapy. J Neurooncol 117, 311–320 (2014). https://doi.org/10.1007/s11060-014-1390-9

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  • DOI: https://doi.org/10.1007/s11060-014-1390-9

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