title: White matter lesions detected by magnetic resonance imaging after radiotherapy and high-dose chemotherapy in children with medulloblastoma or primitive neuroectodermal tumor.
abstract: OBJECTIVE
  White matter lesions (WMLs) have been described as a delayed effect of cranial irradiation in children with brain tumors, or a transient subacute effect characterized by an intralesional or perilesional reaction. We report the occurrence of subacute WMLs detected by magnetic resonance imaging (MRI) in children treated for medulloblastoma or primitive neuroectodermal tumor (PNET) and document the associated clinical, radiologic, and neurocognitive findings.
  
  
  METHODS
  Among 134 patients with medulloblastoma or supratentorial PNET treated prospectively with risk-adjusted craniospinal irradiation and conformal boost to the tumor bed, followed by four high-dose chemotherapy (HDC) cycles with stem-cell rescue, 22 developed WMLs on T1-weighted imaging with and without contrast and/or T2-weighted imaging on MRI. Patients had > or = 12 months of follow-up. Neurocognitive assessments included intelligence quotient (IQ) tests and tests of academic achievement.
  
  
  RESULTS
  Twenty-two patients developed WMLs at a median of 7.8 months after starting therapy (range, 1.9 to 13.0 months). Lesions were predominantly in the pons (n = 8) and cerebellum (n = 6). Sixteen patients (73%) had WML resolution at a median of 6.2 months (range, 1.68 to 23.5 months) after onset; two patients developed necrosis and atrophy. Three developed persistent neurologic deficits. Cumulative incidence of WMLs at 1 year was 15% +/- 3%. Patients with WMLs had a significant decline in estimated IQ (-2.5 per year; P = .03) and math (-4.5 per year; P = .003) scores.
  
  
  CONCLUSIONS
  WMLs in medulloblastoma or PNET patients treated with conformal radiotherapy and HDC are typically transient and asymptomatic, and may mimic early tumor recurrence. A minority of patients with WMLs develop permanent neurologic deficits and imaging changes. Overall, the presence of WMLs is associated with greater neurocognitive decline.
authors.affiliation: Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN 38105-2794, USA. maryam.fouladi@stjude.org
authors.forename: Maryam
authors.initials: M
authors.lastname: Fouladi
authors.forename: Murali
authors.initials: M
authors.lastname: Chintagumpala
authors.forename: Fred H
authors.initials: FH
authors.lastname: Laningham
authors.forename: David
authors.initials: D
authors.lastname: Ashley
authors.forename: Stewart J
authors.initials: SJ
authors.lastname: Kellie
authors.forename: James W
authors.initials: JW
authors.lastname: Langston
authors.forename: Charles W
authors.initials: CW
authors.lastname: McCluggage
authors.forename: Shaio
authors.initials: S
authors.lastname: Woo
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kocak
authors.forename: Kevin
authors.initials: K
authors.lastname: Krull
authors.forename: Larry E
authors.initials: LE
authors.lastname: Kun
authors.forename: Raymond K
authors.initials: RK
authors.lastname: Mulhern
authors.forename: Amar
authors.initials: A
authors.lastname: Gajjar
mesh_terms: D000293:Adolescent; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D001932:Brain Neoplasms / Q000532:radiotherapy*; D016022:Case-Control Studies; D002528:Cerebellar Neoplasms / Q000532:radiotherapy*; D002648:Child; D003072:Cognition Disorders / Q000209:etiology; D016371:Cranial Irradiation / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015994:Incidence; D008279:Magnetic Resonance Imaging; D008297:Male; D008527:Medulloblastoma; D009336:Necrosis; D018242:Neuroectodermal Tumors, Primitive / Q000532:radiotherapy*; D011446:Prospective Studies; D011832:Radiation Injuries / Q000453:epidemiology* / Q000473:pathology*; D020266:Radiotherapy, Conformal; D012307:Risk Factors