White matter lesions detected by magnetic resonance imaging after radiotherapy and high-dose chemotherapy in children with medulloblastoma or primitive neuroectodermal tumor

Maryam Fouladi, Murali Chintagumpala, Fred H. Laningham, David Ashley, Stewart J. Kellie, James W. Langston, Charles W. McCluggage, Shaio Woo, Mehmet Kocak, Kevin Krull, Larry E. Kun, Raymond K. Mulhern, Amar Gajjar

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)4551-4560
Number of pages10
JournalJournal of Clinical Oncology
Volume22
Issue number22
DOIs
StatePublished - Dec 1 2004
Externally publishedYes

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Primitive Neuroectodermal Tumors
Medulloblastoma
Radiotherapy
Magnetic Resonance Imaging
Drug Therapy
Neurologic Manifestations
Craniospinal Irradiation
White Matter
Cranial Irradiation
Conformal Radiotherapy
Intelligence Tests
Pons
Intelligence
Brain Neoplasms
Cerebellum
Atrophy
Neoplasms
Necrosis
Stem Cells

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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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. / Fouladi, Maryam; Chintagumpala, Murali; Laningham, Fred H.; Ashley, David; Kellie, Stewart J.; Langston, James W.; McCluggage, Charles W.; Woo, Shaio; Kocak, Mehmet; Krull, Kevin; Kun, Larry E.; Mulhern, Raymond K.; Gajjar, Amar.

In: Journal of Clinical Oncology, Vol. 22, No. 22, 01.12.2004, p. 4551-4560.

Research output: Contribution to journalArticle

Fouladi, M, Chintagumpala, M, Laningham, FH, Ashley, D, Kellie, SJ, Langston, JW, McCluggage, CW, Woo, S, Kocak, M, Krull, K, Kun, LE, Mulhern, RK & Gajjar, A 2004, 'White matter lesions detected by magnetic resonance imaging after radiotherapy and high-dose chemotherapy in children with medulloblastoma or primitive neuroectodermal tumor', Journal of Clinical Oncology, vol. 22, no. 22, pp. 4551-4560. https://doi.org/10.1200/JCO.2004.03.058
Fouladi, Maryam ; Chintagumpala, Murali ; Laningham, Fred H. ; Ashley, David ; Kellie, Stewart J. ; Langston, James W. ; McCluggage, Charles W. ; Woo, Shaio ; Kocak, Mehmet ; Krull, Kevin ; Kun, Larry E. ; Mulhern, Raymond K. ; Gajjar, Amar. / White matter lesions detected by magnetic resonance imaging after radiotherapy and high-dose chemotherapy in children with medulloblastoma or primitive neuroectodermal tumor. In: Journal of Clinical Oncology. 2004 ; Vol. 22, No. 22. pp. 4551-4560.
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title = "White matter lesions detected by magnetic resonance imaging after radiotherapy and high-dose chemotherapy in children with medulloblastoma or primitive neuroectodermal tumor",
abstract = "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.",
author = "Maryam Fouladi and Murali Chintagumpala and Laningham, {Fred H.} and David Ashley and Kellie, {Stewart J.} and Langston, {James W.} and McCluggage, {Charles W.} and Shaio Woo and Mehmet Kocak and Kevin Krull and Kun, {Larry E.} and Mulhern, {Raymond K.} and Amar Gajjar",
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T1 - White matter lesions detected by magnetic resonance imaging after radiotherapy and high-dose chemotherapy in children with medulloblastoma or primitive neuroectodermal tumor

AU - Fouladi, Maryam

AU - Chintagumpala, Murali

AU - Laningham, Fred H.

AU - Ashley, David

AU - Kellie, Stewart J.

AU - Langston, James W.

AU - McCluggage, Charles W.

AU - Woo, Shaio

AU - Kocak, Mehmet

AU - Krull, Kevin

AU - Kun, Larry E.

AU - Mulhern, Raymond K.

AU - Gajjar, Amar

PY - 2004/12/1

Y1 - 2004/12/1

N2 - 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.

AB - 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.

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