In:
Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_3 ( 2020-12-04), p. iii388-iii388
Abstract:
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 & gt;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 & lt;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.
Type of Medium:
Online Resource
ISSN:
1522-8517
,
1523-5866
DOI:
10.1093/neuonc/noaa222.482
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2020
detail.hit.zdb_id:
2094060-9
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