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Neurocognitive Consequences of Risk-Adapted Therapy for Childhood Medulloblastoma

Raymond K. Mulhern, Shawna L. Palmer, Thomas E. Merchant, Dana Wallace, Mehmet Kocak, Pim Brouwers, Kevin Krull, Murali Chintagumpala, Robyn Stargatt, David M. Ashley, Vida L. Tyc, Larry Kun, James Boyett, Amar Gajjar

From the Division of Behavioral Medicine, Division of Radiation Oncology, Department of Biostatistics, Division of Neuro-Oncology, Department of Hematology Oncology, St Jude Children's Research Hospital, Memphis TN; Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX; and Royal Children's Hospital, Melbourne, Australia

Address reprint requests to Amar Gajjar, MD, Division of Neuro-Oncology, St Jude Children's Research Hospital, 332 N Lauderdale, Memphis, TN 38105-2794; e-mail: amar.gajjar{at}stjude.org

PURPOSE: This prospective, longitudinal study examined the effects of risk-adapted craniospinal irradiation (CSI) dose and the interactions of dose with age and time from diagnosis on intelligence quotient (IQ) and academic achievement (reading, spelling, and math) among patients treated for medulloblastoma (MB).

PATIENTS AND METHODS: Patients received serial neurocognitive testing spanning from 0 to 6.03 years after diagnosis (median, 3.14 years). The multi-institutional study included 111 patients, who were 3 to 20 years of age at diagnosis (median age, 7.4 years), treated for MB with risk-adapted CSI followed by four cycles of high-dose chemotherapy (cyclophosphamide, cisplatin, and vincristine) with stem-cell support. High-risk patients (HR; n = 37) received CSI to 36 to 39.6 Gy and conformal boost treatment of the primary site to 55.8 to 59.4 Gy. Average-risk patients (AR; n = 74) received CSI to 23.4 Gy and conformal boost treatment of the posterior fossa to 36.0 Gy and primary site to 55.8 Gy.

RESULTS: Multivariate modeling revealed statistically significant declines in mean IQ (–1.59 points/yr; P = .006), reading (–2.95 points/yr; P < .0001), spelling (–2.94 points/yr; P < .0001), and math (–1.87 points/yr; P = .003) scores for the entire group. The effects of risk-adapted radiation therapy on IQ, reading, and spelling were moderated by age, with the greatest rates of decline observed for the HR patients who were younger (< 7 years old) at diagnosis.

CONCLUSION: Young age at diagnosis was the most prominent risk factor for neurocognitive deficits among survivors of MB despite reductions in CSI dosing and efforts to limit the boost volume. Younger patients exhibited substantial problems with the development of reading skills.

Deceased.

This research is supported by Musicians Against Childhood Cancer, the Noyes Foundation, the American Lebanese Syrian Associated Charities, National Cancer Institute grant Nos. R01CA78957 and U01CA81445, and Cancer Center Support grant No. P30CA21765.

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

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