Fang Liu1, Nadia Scantlebury1, Uri Tabori1, Eric Bouffet1, Suzanne Laughlin1, Douglas Strother1, Dina McConnell1, Juliette Hukin1, Chris Fryer1, Marie-Eve Brière1, Isabelle Montour-Proulx1, Daniel Keene1, Frank Wang1, Donald J Mabbott1. 1. Neurosciences & Mental Health, The Hospital for Sick Children, Toronto, Ontario, Canada (F.L., N.S., F.W., D.J.M.); Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada (U.T., E.B.); Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada (U.T., E.B.); Diagnostic Imaging, The Hospital for Sick Children, Toronto, Ontario, Canada (S.L.); Medical Imaging, University of Toronto, Toronto, Ontario, Canada (S.L.); Departments of Oncology and Pediatrics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada (D.S.); Independent practice, Montréal area, Québec, Canada (M.-E.B.); Department of Psychology, Division of Oncology, British Columbia Children's Hospital, Vancouver, British Columbia, Canada (D.M.); Divisions of Neurology and Oncology, British Columbia Children's Hospital, Vancouver, British Columbia, Canada (J.H.); Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada (J.H., C.F.); Division of Hematology and Oncology, British Columbia Children's Hospital, Vancouver, British Columbia, Canada (C.F.); Division of Ambulatory Care/Oncology, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada (I.M.-P., D.K.); Department of Pediatrics, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada (D.K.); Department of Psychology, The Hospital for Sick Children, Toronto, Ontario, Canada (D.J.M.); Department of Psychology, University of Toronto, Toronto, Ontario, Canada (D.J.M.).
Abstract
BACKGROUND: While the impact of cranial radiation on white matter following treatment for pediatric brain tumor has been the focus of many recent studies, the effect of treatment in the absence of radiation has received little attention. The relations between white matter and cognitive outcome have not been explored in patients who have undergone radiation-free treatment. As most patients treated without cranial radiation survive long after their diagnosis, it is critical to identify factors that may impact structural and neurocognitive outcomes. METHODS: Using diffusion tensor imaging, we examined white matter structure in 32 patients with pediatric low-grade glioma (PLGG) (19 with subtentorial location and 13 with supratentorial location) and 32 healthy participants. Indices of intellectual functioning were also evaluated. Radiation was not used to treat this cohort, aged 8-19 years. RESULTS: We detected evidence of deficits in IQ and compromised supra- and subtentorial white matter in patients relative to healthy children (P < .05). Compromise of supratentorial white matter mediated the impact of treatment for PLGG on IQ. Greater white matter compromise was observed in patients who presented without multiple symptoms, were treated with biopsy/no surgery, had positive neurofibromatosis 1 status, were younger age at diagnosis, and whose parents had lower levels of education (P < .05). CONCLUSIONS: Our findings provide evidence of increased risk of intellectual and white matter compromise in patients treated for PLGG without radiation. We identify a neural origin of cognitive deficit useful for predicting outcome and mitigating long-term adverse effects in pediatric brain tumor patients treated without cranial radiation.
BACKGROUND: While the impact of cranial radiation on white matter following treatment for pediatric brain tumor has been the focus of many recent studies, the effect of treatment in the absence of radiation has received little attention. The relations between white matter and cognitive outcome have not been explored in patients who have undergone radiation-free treatment. As most patients treated without cranial radiation survive long after their diagnosis, it is critical to identify factors that may impact structural and neurocognitive outcomes. METHODS: Using diffusion tensor imaging, we examined white matter structure in 32 patients with pediatric low-grade glioma (PLGG) (19 with subtentorial location and 13 with supratentorial location) and 32 healthy participants. Indices of intellectual functioning were also evaluated. Radiation was not used to treat this cohort, aged 8-19 years. RESULTS: We detected evidence of deficits in IQ and compromised supra- and subtentorial white matter in patients relative to healthy children (P < .05). Compromise of supratentorial white matter mediated the impact of treatment for PLGG on IQ. Greater white matter compromise was observed in patients who presented without multiple symptoms, were treated with biopsy/no surgery, had positive neurofibromatosis 1 status, were younger age at diagnosis, and whose parents had lower levels of education (P < .05). CONCLUSIONS: Our findings provide evidence of increased risk of intellectual and white matter compromise in patients treated for PLGG without radiation. We identify a neural origin of cognitive deficit useful for predicting outcome and mitigating long-term adverse effects in pediatric brain tumorpatients treated without cranial radiation.
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