TY - JOUR
T1 - Molecular correlates of long survival in IDH-Wildtype glioblastoma cohorts
AU - Galbraith, Kristyn
AU - Kumar, Ashwani
AU - Abdullah, Kalil G.
AU - Walker, Jamie M.
AU - Adams, Steven H.
AU - Prior, Timothy
AU - Dimentberg, Ryan
AU - Henderson, Fraser C.
AU - Mirchia, Kanish
AU - Sathe, Adwait Amod
AU - Viapiano, Mariano S.
AU - Chin, Lawrence S.
AU - Corona, Robert J.
AU - Hatanpaa, Kimmo J.
AU - Snuderl, Matija
AU - Xing, Chao
AU - Brem, Steven
AU - Richardson, Timothy E.
N1 - Funding Information:
Matija Snuderl is supported in part by grants from the Friedberg Charitable Foundation and the Making Headway Foundation. The authors would like to thank Rena Pacheco at the University of Pennsylvania for her assistance with Institutional Review Board (IRB) and data transfer. They would also like to thank the University of Pennsylvania, Department of Neurosurgery Clinical Research Division for allowing us access to their collected glioblastoma data.
Publisher Copyright:
© 2020 American Association of Neuropathologists, Inc. All rights reserved.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - IDH-wildtype glioblastoma is a relatively common malignant brain tumor in adults. These patients generally have dismal prognoses, although outliers with long survival have been noted in the literature. Recently, it has been reported that many histologically lower-grade IDH-wildtype astrocytomas have a similar clinical outcome to grade IV tumors, suggesting they may represent early or under-sampled glioblastomas. cIMPACT-NOW 3 guidelines now recommend upgrading IDH-wildtype astrocytomas with certain molecular criteria (EGFR amplifications, chromosome 7 gain/10 loss, and/or TERT promoter mutations), establishing the concept of a “molecular grade IV” astrocytoma. In this report, we apply these cIMPACT-NOW 3 criteria to 2 independent glioblastoma cohorts, totaling 393 public database and institutional glioblastoma cases: 89 cases without any of the cIMPACT-NOW 3 criteria (GBM-C0) and 304 cases with one or more criteria (GBM-C1-3). In the GBM-C0 groups, there was a trend toward longer recurrence-free survival (median 12-17 vs 6-10 months), significantly longer overall survival (median 32-41 vs 15-18 months), younger age at initial diagnosis, and lower overall mutation burden compared to the GBM-C1-3 cohorts. These data suggest that while histologic features may not be ideal indicators of patient survival in IDH-wildtype astrocytomas, these 3 molecular features may also be important prognostic factors in IDH-wildtype glioblastoma.
AB - IDH-wildtype glioblastoma is a relatively common malignant brain tumor in adults. These patients generally have dismal prognoses, although outliers with long survival have been noted in the literature. Recently, it has been reported that many histologically lower-grade IDH-wildtype astrocytomas have a similar clinical outcome to grade IV tumors, suggesting they may represent early or under-sampled glioblastomas. cIMPACT-NOW 3 guidelines now recommend upgrading IDH-wildtype astrocytomas with certain molecular criteria (EGFR amplifications, chromosome 7 gain/10 loss, and/or TERT promoter mutations), establishing the concept of a “molecular grade IV” astrocytoma. In this report, we apply these cIMPACT-NOW 3 criteria to 2 independent glioblastoma cohorts, totaling 393 public database and institutional glioblastoma cases: 89 cases without any of the cIMPACT-NOW 3 criteria (GBM-C0) and 304 cases with one or more criteria (GBM-C1-3). In the GBM-C0 groups, there was a trend toward longer recurrence-free survival (median 12-17 vs 6-10 months), significantly longer overall survival (median 32-41 vs 15-18 months), younger age at initial diagnosis, and lower overall mutation burden compared to the GBM-C1-3 cohorts. These data suggest that while histologic features may not be ideal indicators of patient survival in IDH-wildtype astrocytomas, these 3 molecular features may also be important prognostic factors in IDH-wildtype glioblastoma.
KW - Astrocytoma
KW - GBM
KW - Glioblastoma
KW - IDH1/2
KW - Long survival
KW - Prognosis
KW - TCGA
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U2 - 10.1093/jnen/nlaa059
DO - 10.1093/jnen/nlaa059
M3 - Article
C2 - 32647886
AN - SCOPUS:85088494645
VL - 79
SP - 843
EP - 854
JO - Journal of Neuropathology and Experimental Neurology
JF - Journal of Neuropathology and Experimental Neurology
SN - 0022-3069
IS - 8
ER -