Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this gap in knowledge, an international cohort of 93 molecularly confirmed WNT MB was assembled, where 5-year progression-free survival is 0.84 (95%, 0.763-0.925) with 15 relapsed individuals identified. Maintenance chemotherapy is identified as a strong predictor of relapse, with individuals receiving high doses of cyclophosphamide or ifosphamide having only one very late molecularly confirmed relapse (p = 0.032). The anatomical location of recurrence is metastatic in 12 of 15 relapses, with 8 of 12 metastatic relapses in the lateral ventricles. Maintenance chemotherapy, specifically cumulative cyclophosphamide doses, is a significant predictor of relapse across WNT MB. Future efforts to de-escalate therapy need to carefully consider not only the radiation dose but also the chemotherapy regimen and the propensity for metastatic relapses.

• MeSH
• Cyclophosphamide therapeutic use   MeSH
• Child MeSH
• Progression-Free Survival MeSH
• Ifosfamide therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Recurrence, Local drug therapy   metabolism   MeSH
• Medulloblastoma drug therapy   metabolism   MeSH
• Adolescent MeSH
• Biomarkers, Tumor metabolism   MeSH
• Cerebellar Neoplasms drug therapy   MeSH
• Antineoplastic Combined Chemotherapy Protocols therapeutic use   MeSH
• Check Tag
• Child MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• Cyclophosphamide MeSH
• Ifosfamide MeSH
• Biomarkers, Tumor MeSH

INTRODUCTION: Medulloblastoma is the most frequent malignant brain tumour in children. Radiation-induced cavernous haemangiomas (RICHs) are a known late complication of radiation exposure, especially in young children. CASE REPORT: We present a patient who underwent subtotal resection of posterior fossa medulloblastoma with subsequent chemotherapy and radiotherapy at the age of 10 years. A new lesion in the region of the left foramen of Monro appeared 16 years later. Based on the imaging results, metastasis or radiation-induced cavernoma was considered. The lesion had the same appearance on imaging as a rarely published intraventricular cavernoma of the foramen of Monro. Unlike the cavernoma of the foramen of Monro, this lesion was subependymal and intraforniceal. Using electromagnetic navigation and neuroendoscopy, the lesion was completely removed. Histopathological examination revealed a cavernous haemangioma. CONCLUSION: This is a unique case of intraforniceal paraforaminal cavernoma that was successfully removed endoscopically using electromagnetic neuronavigation and without neurological sequelae.

• Keywords
• Electromagnetic neuronavigation, Foramen of Monro, Intraforniceal cavernoma, Medulloblastoma treatment, Neuroendoscopy, Radiation-induced cavernoma, Subependymal,
• MeSH
• Child MeSH
• Adult MeSH
• Electromagnetic Phenomena MeSH
• Hemangioma, Cavernous etiology   surgery   MeSH
• Humans MeSH
• Medulloblastoma radiotherapy   MeSH
• Cerebellar Neoplasms radiotherapy   MeSH
• Neoplasms, Radiation-Induced surgery   MeSH
• Neuroendoscopy methods   MeSH
• Neuronavigation methods   MeSH
• Radiotherapy adverse effects   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH

While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials.

• Keywords
• copy number, gene expression, integrative clustering, medulloblastoma, methylation, subgroups,
• MeSH
• Genomics MeSH
• Precision Medicine * MeSH
• Cohort Studies MeSH
• Humans MeSH
• Medulloblastoma classification   genetics   therapy   MeSH
• DNA Methylation MeSH
• Cluster Analysis MeSH
• Gene Expression Profiling MeSH
• DNA Copy Number Variations MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH