Eveline Teresa Hidalgo1, Matija Snuderl2, Cordelia Orillac3, Svetlana Kvint3, Jonathan Serrano2, Peter Wu2, Matthias A Karajannis4,5, Sharon L Gardner4. 1. Division of Pediatric Neurosurgery, Department of Neurosurgery, Hassenfeld Children's Hospital, NYU Langone Health, New York, USA. teresa.hidalgo@nyumc.org. 2. Department of Pathology, NYU Langone Health, New York, USA. 3. Division of Pediatric Neurosurgery, Department of Neurosurgery, Hassenfeld Children's Hospital, NYU Langone Health, New York, USA. 4. Pediatric Neuro-Oncology, Department of Pediatrics, Hassenfeld Children's Hospital, NYU Langone Health, New York, USA. 5. Pediatric Neuro-Oncology Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center (MSKCC), New York, USA.
Abstract
PURPOSE: Molecular subgroups of pediatric brain tumors associated with divergent biological, clinical, and prognostic features have been identified. However, data regarding the impact of subgroup affiliation on the outcome of children with malignant brain tumors treated with radiation-sparing protocol is limited. We report long-term clinical outcomes and the molecular subgroups of malignant brain tumors in young children whose first-line treatment was high-dose chemotherapy without irradiation. METHODS: Tumor subclassification was performed using the Illumina HumanMethylation450 BeadChip (450k) genome-wide methylation array profiling platform. Clinical information was obtained from chart review. RESULTS: Methylation array profiling yielded information on molecular subgroups in 22 children. Median age at surgery was 26 months (range 1-119 months). Among medulloblastomas (MB), all 6 children in the infant sonic hedgehog (SHH) subgroup were long-term survivors, whereas all 4 children in subgroup 3 MB died. There was one long-term survivor in subgroup 4 MB. One out of five children with ependymoma was a long-term survivor (RELPOS). Both children with primitive neuroectodermal tumors died. One child with ATRT TYR and one child with choroid plexus carcinoma were long-term survivors. CONCLUSIONS: The efficacy of high-dose chemotherapy radiation-sparing treatment appears to be confined to favorable molecular subgroups of pediatric brain tumors, such as infant SHH MB. Identification of molecular subgroups that benefit from radiation-sparing therapy will aid in the design of prospective, "precision medicine"-driven clinical trials.
PURPOSE: Molecular subgroups of pediatric brain tumors associated with divergent biological, clinical, and prognostic features have been identified. However, data regarding the impact of subgroup affiliation on the outcome of children with malignant brain tumors treated with radiation-sparing protocol is limited. We report long-term clinical outcomes and the molecular subgroups of malignant brain tumors in young children whose first-line treatment was high-dose chemotherapy without irradiation. METHODS: Tumor subclassification was performed using the Illumina HumanMethylation450 BeadChip (450k) genome-wide methylation array profiling platform. Clinical information was obtained from chart review. RESULTS: Methylation array profiling yielded information on molecular subgroups in 22 children. Median age at surgery was 26 months (range 1-119 months). Among medulloblastomas (MB), all 6 children in the infantsonic hedgehog (SHH) subgroup were long-term survivors, whereas all 4 children in subgroup 3 MB died. There was one long-term survivor in subgroup 4 MB. One out of five children with ependymoma was a long-term survivor (RELPOS). Both children with primitive neuroectodermal tumors died. One child with ATRT TYR and one child with choroid plexus carcinoma were long-term survivors. CONCLUSIONS: The efficacy of high-dose chemotherapy radiation-sparing treatment appears to be confined to favorable molecular subgroups of pediatric brain tumors, such as infantSHH MB. Identification of molecular subgroups that benefit from radiation-sparing therapy will aid in the design of prospective, "precision medicine"-driven clinical trials.
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