Journal article
Prospective biomarker study in newly diagnosed glioblastoma: Cyto-C clinical trial
Neuro-oncology advances, Vol.4(1), pp.vdab186-vdab186
01/2022
DOI: 10.1093/noajnl/vdab186
PMCID: PMC8788017
PMID: 35088051
Abstract
Abstract
Background
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.
Details
- Title: Subtitle
- Prospective biomarker study in newly diagnosed glioblastoma: Cyto-C clinical trial
- Creators
- Corinne E Griguer - University of IowaClaudia R Oliva - University of IowaChristopher S Coffey - University of IowaMerit E Cudkowicz - Massachusetts General HospitalRobin A Conwit - National Institutes of HealthAnna L Gudjonsdottir - University of IowaDixie J Ecklund - University of IowaJanel K Fedler - University of IowaTina M Neill-Hudson - University of IowaLouis B Nabors - University of Alabama at BirminghamMelanie Benge - University of Alabama at BirminghamJames R Hackney - University of Alabama at BirminghamMarianne Chase - Massachusetts General HospitalTimothy P Leonard - Massachusetts General HospitalToral Patel - The University of Texas Southwestern Medical CenterHoward Colman - University of UtahMacarena de la Fuente - University of MiamiRekha Chaudhary - University of CincinnatiKaren Marder - Columbia UniversityTeri Kreisl - Columbia UniversityNimish Mohile - University of RochesterMilan G Chheda - Department of Medicine and Neurology, Washington University School of Medicine, St. Louis, MO, 63110, USAKatharine McNeill - Montefiore Medical CenterPriya Kumthekar - Northwestern UniversityAclan Dogan - Oregon Health & Science UniversityJan Drappatz - University of PittsburghVinay Puduvalli - The Ohio State UniversityAgnes Kowalska - State University of New YorkJerome Graber - Swedish Medical CenterElizabeth Gerstner - Massachusetts General HospitalStephen Clark - Vanderbilt UniversityMichael Salacz - University of KansasJames Markert - University of Alabama at Birmingham
- Resource Type
- Journal article
- Publication Details
- Neuro-oncology advances, Vol.4(1), pp.vdab186-vdab186
- DOI
- 10.1093/noajnl/vdab186
- PMID
- 35088051
- PMCID
- PMC8788017
- NLM abbreviation
- Neurooncol Adv
- ISSN
- 2632-2498
- eISSN
- 2632-2498
- Publisher
- Oxford University Press
- Grant note
- DOI: 10.13039/100000065, name: National Institute of Neurological Disorders and Stroke; DOI: 10.13039/100000002, name: National Institutes of Health, award: U01 NS093663
- Language
- English
- Date published
- 01/2022
- Academic Unit
- Biostatistics; Radiation Oncology
- Record Identifier
- 9984227043302771
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