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Molecular correlates of cerebellar mutism syndrome in medulloblastoma.
Molecular correlates of cerebellar mutism syndrome in medulloblastoma. Neuro-oncology Jabarkheel, R., Amayiri, N., Yecies, D., Huang, Y., Toescu, S., Nobre, L., Mabbott, D. J., Sudhakar, S. V., Malik, P., Laughlin, S., Swaidan, M., Al Hussaini, M., Musharbash, A., Chacko, G., Mathew, L. G., Fisher, P. G., Hargrave, D., Bartels, U., Tabori, U., Pfister, S. M., Aquilina, K., Taylor, M. D., Grant, G. A., Bouffet, E., Mankad, K., Yeom, K. W., Ramaswamy, V. 2019Abstract
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 five sites globally including Great Ormond Street Hospital, Christian Medical College and Hospital, Hospital for Sick Children, King Hussein Cancer Center, and Lucile Packard Children's Hospital. Age at diagnosis, sex, tumour 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 tumours (mean difference 10.25 cm3 ± 4.60, P=0.0010) that were more often midline (OR=5.72, P<0.0001). In a multivariable analysis adjusting for age, sex, midline location, and tumour volume, WNT (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=9.1x10-5) tumours were found to be independently associated with higher risk of CMS compared with SHH (Sonic Hedgehog) tumours.CONCLUSIONS: Medulloblastoma subgroup is a very strong predictor of CMS development, independent of tumour volume and midline location. These findings have significant implications for management of both the tumour and CMS.
View details for DOI 10.1093/neuonc/noz158
View details for PubMedID 31504816