Prospective biomarker study in newly diagnosed glioblastoma: Cyto-C clinical trial

dc.contributor.authorGriguer, Corinne E.
dc.contributor.authorOliva, Claudia R.
dc.contributor.authorCoffey, Christopher S.
dc.contributor.authorCudkowicz, Merit E.
dc.contributor.authorConwit, Robin A.
dc.contributor.authorGudjonsdottir, Anna L.
dc.contributor.authorEcklund, Dixie J.
dc.contributor.authorFedler, Janel K.
dc.contributor.authorNeill-Hudson, Tina M.
dc.contributor.authorNabors, Louis B.
dc.contributor.authorBenge, Melanie
dc.contributor.authorHackney, James R.
dc.contributor.authorChase, Marianne
dc.contributor.authorLeonard, Timothy P.
dc.contributor.authorPatel, Toral
dc.contributor.authorColman, Howard
dc.contributor.authorde la Fuente, Macarena
dc.contributor.authorChaudhary, Rekha
dc.contributor.authorMarder, Karen
dc.contributor.authorKreisl, Teri
dc.contributor.authorMohile, Nimish
dc.contributor.authorChheda, Milan G.
dc.contributor.authorMcNeill, Katharine
dc.contributor.authorKumthekar, Priya
dc.contributor.authorDogan, Aclan
dc.contributor.authorDrappatz, Jan
dc.contributor.authorPuduvalli, Vinay
dc.contributor.authorKowalska, Agnes
dc.contributor.authorGraber, Jerome
dc.contributor.authorGerstner, Elizabeth
dc.contributor.authorClark, Stephen
dc.contributor.authorSalacz, Michael
dc.contributor.authorMarkert, James
dc.contributor.departmentNeurology, School of Medicine
dc.date.accessioned2025-03-11T10:37:55Z
dc.date.available2025-03-11T10:37:55Z
dc.date.issued2021-12-24
dc.description.abstractBackground: Glioblastoma (GBM) has a 5-year survival rate of 3%-5%. GBM treatment includes maximal resection followed by radiotherapy with concomitant and adjuvant temozolomide (TMZ). Cytochrome C oxidase (CcO) is a mitochondrial enzyme involved in the mechanism of resistance to TMZ. In a prior retrospective trial, CcO activity in GBMs inversely correlated with clinical outcome. The current Cyto-C study was designed to prospectively evaluate and validate the prognostic value of tumor CcO activity in patients with newly diagnosed primary GBM, and compared to the known prognostic value of MGMT promoter methylation status. Methods: This multi-institutional, blinded, prospective biomarker study enrolled 152 patients with newly diagnosed GBM who were to undergo surgical resection and would be candidates for standard of care. The primary end point was overall survival (OS) time, and the secondary end point was progression-free survival (PFS) time. Tumor CcO activity and MGMT promoter methylation status were assayed in a centralized laboratory. Results: OS and PFS did not differ by high or low tumor CcO activity, and the prognostic validity of MGMT promoter methylation was confirmed. Notably, a planned exploratory analysis suggested that the combination of low CcO activity and MGMT promoter methylation in tumors may be predictive of long-term survival. Conclusions: Tumor CcO activity alone was not confirmed as a prognostic marker in GBM patients. However, the combination of low CcO activity and methylated MGMT promoter may reveal a subgroup of GBM patients with improved long-term survival that warrants further evaluation. Our work also demonstrates the importance of performing large, multi-institutional, prospective studies to validate biomarkers. We also discuss lessons learned in assembling such studies.
dc.eprint.versionFinal published version
dc.identifier.citationGriguer CE, Oliva CR, Coffey CS, et al. Prospective biomarker study in newly diagnosed glioblastoma: Cyto-C clinical trial. Neurooncol Adv. 2021;4(1):vdab186. Published 2021 Dec 24. doi:10.1093/noajnl/vdab186
dc.identifier.urihttps://hdl.handle.net/1805/46298
dc.language.isoen_US
dc.publisherOxford University Press
dc.relation.isversionof10.1093/noajnl/vdab186
dc.relation.journalNeuro-Oncology Advances
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourcePMC
dc.subjectBiomarker
dc.subjectCytochrome C oxidase
dc.subjectGlioblastoma
dc.subjectMGMT
dc.subjectProspective clinical trial
dc.titleProspective biomarker study in newly diagnosed glioblastoma: Cyto-C clinical trial
dc.typeArticle
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