title: Development of cystic malacia after high-dose cranial irradiation of pediatric CNS tumors in long-term follow-up.
abstract: OBJECTIVE
  The purpose of this study is to investigate the incidence of cystic malacia in long-term survivors of pediatric brain tumors treated with high-dose cranial irradiation.
  
  
  METHODS
  Between 1997 and 2015, we treated 41 pediatric patients (26 males, 15 females; age ranging from 3.3 to 15.7 years, median 9-year-old) of pediatric brain tumors [17 medulloblastomas, 7 primitive neuroectodermal tumors (PNET), 3 pineoblastomas, 6 non-germinomatous germ cell tumors (NGGCT), 8 gliomas (including 4 ependymomas, 1 anaplastic astrocytoma, 1 oligodendroglioma, 1 pilocytic astrocytoma, 1 astroblastoma)] with high-dose craniospinal irradiation. Follow-up ranged from 14.0 to 189.2 months (median 86.0 months, mean 81.5 months), the irradiation dose to the whole neural axis ranged from 18 to 41.4 Gy, and the total local dose from 43.2 to 60.4 Gy. All patients underwent follow-up magnetic resonance imaging (MRI) studies at least once a year. Diagnosis of cystic malacia was based solely on MRI findings. Of the 41 patients, 31 were censored during their follow-up due to recurrence of the primary disease (n = 5), detection of secondary leukemia after development of cystic malacia (n = 1), or the absence of cystic malacia on the last follow-up MRI study (n = 25). We also evaluated the development of post-irradiation cavernous angioma and white matter changes.
  
  
  RESULTS
  Following irradiation treatment, 11 patients developed 19 cystic malacia during a median course of 30.8 months (range 14.9 to 59.3 months). The site of predilection for cystic malacia was white matter around trigone of lateral ventricles with an incidence of 47.4% (9 of 19 lesions, 7 in 11 patients). Patients with supratentorial tumors developed cystic malacia statistically earlier than the patients with infratentorial tumors (P = 0.0178, log-rank test). Among the same patient group, incidence of post-irradiation cavernous angioma increased progressively, while the incidence of post-irradiation cystic malacia did not increase after 5 years. White matter degeneration developed earlier than cystic malacia or cavernous angioma, and these three clinical entities developed mutually exclusive of each other.
  
  
  CONCLUSIONS
  We attribute the higher incidence of post-irradiation cystic malacia, in our long-term follow-up study, to the cranial irradiation for pediatric brain tumors, particularly supratentorial brain tumors, and recommend a regular, long-term follow-up of brain tumor patients treated with cranial irradiation.
authors.affiliation: Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. fyama@hiroshima-u.ac.jp.
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Yamasaki
authors.affiliation: Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Takayasu
authors.affiliation: Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Nosaka
authors.affiliation: Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.|Department of Radiation Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan.
authors.forename: Ikuno
authors.initials: I
authors.lastname: Nishibuchi
authors.affiliation: Department of Pediatrics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawaguchi
authors.affiliation: Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Manish
authors.initials: M
authors.lastname: Kolakshyapati
authors.affiliation: Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Shumpei
authors.initials: S
authors.lastname: Onishi
authors.affiliation: Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Taiichi
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Clinical Oncology & Neuro-oncology Program, Hiroshima University Hospital, Hiroshima, 734-8551, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Sugiyama
authors.affiliation: Department of Pediatrics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kurisu
mesh_terms: D000293:Adolescent; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D016543:Central Nervous System Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy; D002648:Child; D002675:Child, Preschool; D016371:Cranial Irradiation / Q000009:adverse effects* / Q000639:trends; D005500:Follow-Up Studies; D006801:Humans; D056784:Leukoencephalopathies / Q000000981:diagnostic imaging* / Q000209:etiology*; D012189:Retrospective Studies; D013997:Time Factors
keywords: Cavernous angioma; Cystic malacia; Irradiation; Leukoencephalopathy