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White Matter Lesions Detected by Magnetic Resonance Imaging After Radiotherapy and High-Dose Chemotherapy in Children With Medulloblastoma or Primitive Neuroectodermal Tumor

From the Departments of Hematology-Oncology, Biostatistics and Epidemiology, Radiological Sciences, Behavioral Medicine, St Jude Children's Research Hospital; Departments of Pediatrics and Radiology, University of Tennessee, Memphis, TN; Department of Pediatrics, Baylor College of Medicine, Houston, TX; Department of Hematology-Oncology, Royal Children's Hospital, Melbourne; and the Children's Hospital at Westmead, and the University of Sydney, Sydney, Australia

Address reprint requests to Maryam Fouladi, MD, Department of Hematology-Oncology, St Jude Children's Research Hospital, 332 N Lauderdale, Memphis, TN 38105-2794; e-mail: maryam.fouladi{at}stjude.org

PURPOSE: 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.

PATIENTS AND 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 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.

CONCLUSION: 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.

Supported in part by Center of Research Excellence support grant no. CA21765, American Lebanese Syrian Associated Charities (ALSAC).

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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