MBCL-06. RISK STRATIFICATION IMPROVEMENT OF THE HIT2000 AND I-HIT-MED COHORTS USING MOLECULAR SUBTYPES I-VIII OF GROUP 3/4 MEDULLOBLASTOMAS. (4th December 2020)

• Record Type: Journal Article
• Authors: Mynarek, Martin; Obrecht, Denise; Sill, Martin; Selt, Florian; von Hoff, Katja; Jones, David; Sturm, Dominic; Juhnke, B - Ole; Ecker, Jonas; Pietsch, Torsten; von Deimling, Andreas; Sahm, Felix; Pfister, Stefan M; Witt, Olaf; Bockmayr, Michael Ludwig; Schüller, Ulrich; Rutkowski, Stefan; Milde, Till
• Is Part Of: Neuro-oncology. Volume 22(2020)Supplement 3
• Page Start: iii388
• Page End: iii388
• Publication Date: 2020-12-04
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noaa222.482
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: OBJECTIVE: Molecular subtypes of Group 3/4 medulloblastoma have been identified by unsupervised clustering methods in different studies. We hypothesized that risk stratification using these subtypes I-VIII improves outcome prediction. PATIENTS AND METHODS: n=340 patients with Group 3 or Group 4 medulloblastoma defined by DNA methylation array profiling enrolled into the HIT2000 study and HIT-MED registries were subtyped by the Heidelberg Medulloblastoma Classifier. The discovery cohort consisted of n=162 previously published samples, the validation cohort of n=178 newly analyzed samples. RESULTS AND DISCUSSION: n=300/340 (88%) MBs could be assigned to one of the subtypes with confidence (score >0.8; Heidelberg Medulloblastoma classifier). Subtype II, III and V showed a poor PFS and OS and were classified as HR (discovery:5y-PFS 45%[95%-CI:33–62], 5y-OS 50%[37–67]; validation:5y-PFS 32%[20–50], 5y-OS 40%[27–61]). Subtypes I, IV, VI-VIII fared better (discovery:5y-PFS 67%[58–77], 5y_OS 84%[77–91]; Validation:5y-PFS 70%[58–83], 5y-OS 89%[81–99]). Survival prediction by subtype-based risk assessment was improved compared to Group 3 versus 4 differentiation in both cohorts in univariate and multivariable Cox regression models (PFS:Hazard ratio HR versus LR 2.474, p<0.001; Group 3 versus Group 4 1.842, p=0.003; adjustment for anaplasia, age and metastatic disease). Patients older than 4 with subtype IV tumors (mainly Group 3) treated with radiotherapy achieved a 100% PFS, while subtype V patients (mainly Group 4) had poor survival. CONCLUSION: We showed that molecular subtypes I-VIII improved risk stratification of Group 3/4 medulloblastomas. Group 3 subtype IV MB treated with RT had very high cure rates.