Impact of Radiation Avoidance on Survival and Neurocognitive Outcome in Infant Medulloblastoma

Abstract

PurposeConcerns about radiotherapy-related neurocognitive sequelae in young children have led to deferral or avoidance of radiation in contemporary treatment for this fragile group of patients. We compared survival and neurocognitive outcome in two groups of infants with medulloblastoma who received adjuvant conventional craniospinal irradiation (csi) or reduced or no radiotherapy during an era of change in the philosophy of infant medulloblastoma treatment.Patients and MethodsFrom 1985 to 2007, 29 patients 3 years of age or younger were diagnosed and treated with curative intent in our institution. Children treated before 1994 received adjuvant radiation with chemotherapy; subsequently, radiation was prescribed essentially for disease progression or relapse.ResultsMedian age at diagnosis was 24 months (range: 1–36 months); 15 patients (52%) presented with metastatic disease at diagnosis. As part of initial treatment, 8 children received adjuvant radiotherapy with chemotherapy, and 21 children received postoperative chemotherapy only. Five children treated with chemotherapy alone are in prolonged remission. The 5-year event-free and overall survivals were 35.9% ± 9.8% and 50.2% ± 9.6% respectively. Extent of resection, metastatic status, and desmoplastic histology were not found to be significant prognostic factors.On serial neurocognitive evaluations, patients treated with chemotherapy with or without reduced radiotherapy demonstrated improvement of intellectual function over time. Patients treated with conventional csi exhibited significantly lower intelligence quotient scores and academic performance, with the exception of receptive vocabulary.ConclusionsAvoidance of conventional csi in treatment of very young children with medulloblastoma appears to be associated with a preserved neurocognitive profile. Neurocognitive evaluation should be integrated into the primary objectives of future infant protocols.

Therapeutic implications of CD1d expression and tumor-infiltrating macrophages in pediatric medulloblastomas

“…Various treatment strategies have been employed to improve survival rates of infants with MB and to delay or avoid craniospinal radiotherapy, including systemic chemotherapy and high-dose chemotherapy, followed by radiotherapy at relapse, systemic and intraventricular chemotherapy, systemic chemotherapy and local conformal radiotherapy [39][40][41][42]. Some patients have been cured by postoperative chemotherapy alone, but survival rates after chemotherapy, with or without radiotherapy, remain unsatisfactory at 25-45 % [43][44][45]. The identification of marked CD1d-expressing tumors in a subset of infantile MBs, despite the lack of statistical significance due to the small sample size, provides new understanding of the immunobiology of this disease and supports the rationale for developing novel NKT cell based therapy that could lead to potential new modality of treatment and personalized therapy for this specific group of patients.…”

Practical Molecular Pathology and Histopathology of Embryonal Tumors

“…[9][10][11] With current therapeutic management, including surgical resection, craniospinal radiation, and chemotherapy, a majority of patients can be cured of their tumor, even though most have long-term disabilities. [12][13][14] These disabilities can be attributed to both their underlying disease and to the treatment.…”

Time perception in children treated for a cerebellar medulloblastoma

“…Apart from motor deficits, children with medulloblastoma also exhibit poor performance in numerous cognitive tasks. After the excision of a cerebellar tumor, there is a decline in intellectual functions as revealed by low scores on different neuropsychological tests assessing working memory, processing speed, and attention/concentration (Callu, Viguier, et al, 2009;Lafay-Cousin, Bouffet, Hawkins Amid, Huang, & Mabbott, 2009;Puget et al, 2009;Ribi et al, 2005;Silverman et al, 1984). Among the different cognitive deficits, one may expect that children with medulloblastoma would also have difficulty within the perception of time, as the cerebellum is thought to be critically involved in time perception, at least in the sub-second range.…”