Rashad Jabarkheel1, Nisreen Amayiri2,3, Derek Yecies1, Yuhao Huang1, Sebastian Toescu4, Liana Nobre3, Donald J Mabbott3,5,6, Sniya V Sudhakar7, Prateek Malik7, Suzanne Laughlin8, Maisa Swaidan9, Maysa Al Hussaini10, Awni Musharbash11, Geeta Chacko12, Leni G Mathew13, Paul G Fisher14, Darren Hargrave4, Ute Bartels1, Uri Tabori1, Stefan M Pfister15, Kristian Aquilina16, Michael D Taylor17,18,19, Gerald A Grant1, Eric Bouffet3, Kshitij Mankad20, Kristen W Yeom21, Vijay Ramaswamy3,18,19. 1. Department of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA. 2. Department of Oncology, King Hussein Cancer Center, Amman, Jordan. 3. Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada. 4. University College London, Great Ormond Street Institute of Child Health, London, UK. 5. Department of Psychology, University of Toronto, Toronto, Ontario, Canada. 6. Programme in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada. 7. Department of Radiology, Christian Medical College, Vellore, Tamil Nadu, India. 8. Division of Neuroradiology, Hospital for Sick Children, Toronto, Ontario, Canada. 9. Department of Diagnostic Radiology, King Hussein Cancer Center, Amman, Jordan. 10. Department of Pathology, King Hussein Cancer Center, Amman, Jordan. 11. Department of Surgery, King Hussein Cancer Center, Amman, Jordan. 12. Department of Pathology, Christian Medical College, Vellore, Tamil Nadu, India. 13. Department of Pediatrics, Christian Medical College, Vellore, Tamil Nadu, India. 14. Departments of Neurology & Pediatrics, Stanford University, Palo Alto, California, USA. 15. Hopp Children's Cancer Center Heidelberg, Division of Pediatric Neurooncology, German Cancer Research Center, German Cancer Consortium, and Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany. 16. Neurosurgery Department, Great Ormond Street Hospital for Children, London, UK. 17. Division of Neurosurgery, Hospital for Sick Children, Toronto, Ontario, Canada. 18. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. 19. Programme in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada. 20. Department of Radiology, Great Ormond Street Hospital for Children, London, UK. 21. Department of Radiology, Lucile Packard Children's Hospital, Stanford University School of Medicine, Palo Alto, California, USA.
Abstract
BACKGROUND: Cerebellar mutism syndrome (CMS) is a common complication following resection of posterior fossa tumors, most commonly after surgery for medulloblastoma. Medulloblastoma subgroups have historically been treated as a single entity when assessing CMS risk; however, recent studies highlighting their clinical heterogeneity suggest the need for subgroup-specific analysis. Here, we examine a large international multicenter cohort of molecularly characterized medulloblastoma patients to assess predictors of CMS. METHODS: We assembled a cohort of 370 molecularly characterized medulloblastoma subjects with available neuroimaging from 5 sites globally, including Great Ormond Street Hospital, Christian Medical College and Hospital, the Hospital for Sick Children, King Hussein Cancer Center, and Lucile Packard Children's Hospital. Age at diagnosis, sex, tumor volume, and CMS development were assessed in addition to molecular subgroup. RESULTS: Overall, 23.8% of patients developed CMS. CMS patients were younger (mean difference -2.05 years ± 0.50, P = 0.0218) and had larger tumors (mean difference 10.25 cm3 ± 4.60, P = 0.0010) that were more often midline (odds ratio [OR] = 5.72, P < 0.0001). In a multivariable analysis adjusting for age, sex, midline location, and tumor volume, Wingless (adjusted OR = 4.91, P = 0.0063), Group 3 (adjusted OR = 5.56, P = 0.0022), and Group 4 (adjusted OR = 8.57 P = 9.1 × 10-5) tumors were found to be independently associated with higher risk of CMS compared with sonic hedgehog tumors. CONCLUSIONS: Medulloblastoma subgroup is a very strong predictor of CMS development, independent of tumor volume and midline location. These findings have significant implications for management of both the tumor and CMS.
BACKGROUND:Cerebellar mutism syndrome (CMS) is a common complication following resection of posterior fossa tumors, most commonly after surgery for medulloblastoma. Medulloblastoma subgroups have historically been treated as a single entity when assessing CMS risk; however, recent studies highlighting their clinical heterogeneity suggest the need for subgroup-specific analysis. Here, we examine a large international multicenter cohort of molecularly characterized medulloblastomapatients to assess predictors of CMS. METHODS: We assembled a cohort of 370 molecularly characterized medulloblastoma subjects with available neuroimaging from 5 sites globally, including Great Ormond Street Hospital, Christian Medical College and Hospital, the Hospital for Sick Children, King Hussein Cancer Center, and Lucile Packard Children's Hospital. Age at diagnosis, sex, tumor volume, and CMS development were assessed in addition to molecular subgroup. RESULTS: Overall, 23.8% of patients developed CMS. CMSpatients were younger (mean difference -2.05 years ± 0.50, P = 0.0218) and had larger tumors (mean difference 10.25 cm3 ± 4.60, P = 0.0010) that were more often midline (odds ratio [OR] = 5.72, P < 0.0001). In a multivariable analysis adjusting for age, sex, midline location, and tumor volume, Wingless (adjusted OR = 4.91, P = 0.0063), Group 3 (adjusted OR = 5.56, P = 0.0022), and Group 4 (adjusted OR = 8.57 P = 9.1 × 10-5) tumors were found to be independently associated with higher risk of CMS compared with sonic hedgehog tumors. CONCLUSIONS:Medulloblastoma subgroup is a very strong predictor of CMS development, independent of tumor volume and midline location. These findings have significant implications for management of both the tumor and CMS.
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