Cancer stem cell assay-guided chemotherapy improves survival of patients with recurrent glioblastoma in a randomized trial

Tulika Ranjan; Soma Sengupta; Michael J Glantz; Richard M Green; Alexander Yu; Dawit Aregawi; Rekha Chaudhary; Ricky Chen; Mario Zuccarello; Christine Lu-Emerson; Hugh D Moulding; Neil Belman; Jon Glass; Aaron Mammoser; Mark Anderson; Jagan Valluri; Nicholas Marko; Jason Schroeder; Steven Jubelirer; Frances Chow; Pier Paolo Claudio; Anthony M Alberico; Seth T Lirette; Krista L Denning; Candace M Howard

doi:10.1016/j.xcrm.2023.101025

Cancer stem cell assay-guided chemotherapy improves survival of patients with recurrent glioblastoma in a randomized trial

Cell Rep Med. 2023 May 16;4(5):101025. doi: 10.1016/j.xcrm.2023.101025. Epub 2023 May 2.

Authors

Tulika Ranjan¹, Soma Sengupta², Michael J Glantz³, Richard M Green⁴, Alexander Yu⁵, Dawit Aregawi³, Rekha Chaudhary⁶, Ricky Chen⁷, Mario Zuccarello⁸, Christine Lu-Emerson⁹, Hugh D Moulding¹⁰, Neil Belman¹⁰, Jon Glass¹¹, Aaron Mammoser¹², Mark Anderson¹³, Jagan Valluri¹⁴, Nicholas Marko¹⁵, Jason Schroeder¹⁶, Steven Jubelirer¹⁷, Frances Chow¹⁸, Pier Paolo Claudio¹⁹, Anthony M Alberico²⁰, Seth T Lirette²¹, Krista L Denning²², Candace M Howard²³

Affiliations

¹ Department of Neuro-Oncology, Allegheny Health Network, Pittsburgh, PA, USA; Department of Neuro-Oncology, Cancer Center Southern Florida, Tampa General Hospital, Tampa, FL, USA.
² Department of Neurology and Rehabilitation Medicine, University of Cincinnati, Cincinnati, OH, USA.
³ Department of Neurosurgery, Penn State Neuroscience Institute, Hershey, PA, USA.
⁴ Department of Neuro-Oncology, Southern California Permanente Medical Group, Los Angeles, CA, USA.
⁵ Department of Neurosurgery, Allegheny Health Network, Pittsburgh, PA, USA.
⁶ Department of Internal Medicine, Division of Hematology-Oncology, University of Cincinnati, Cincinnati, OH, USA.
⁷ Department of Neuro-Oncology, Providence Brain & Spine Institute, Portland, OR, USA.
⁸ Department of Neurosurgery, University of Cincinnati, Cincinnati, OH, USA.
⁹ Department of Neuro-Oncology, Maine Medical Center, Scarborough, ME, USA.
¹⁰ Department of Neuroscience, St. Luke's University Hospital & Health Network, Bethlehem, PA, USA.
¹¹ Departments of Neurology and Neurological Surgery, Thomas Jefferson University, Philadelphia, PA, USA.
¹² Department of Neurosurgery, LSU Health Sciences Center, New Orleans, LA, USA.
¹³ Department of Neurology, University of Mississippi Medical Center, Jackson, MS, USA.
¹⁴ Cordgenics, LLC, Huntington WV, USA.
¹⁵ Department of Neurosurgery, LewisGale Regional Health System, Salem, VA, USA.
¹⁶ Department of Neurosurgery, University of Toledo, Toledo, OH, USA.
¹⁷ Department of Neuro-Oncology, Charleston Area Medical Center, Charleston, WV, USA.
¹⁸ Departments of Neurological Surgery and Neurology, University of Southern California, Los Angeles, CA, USA.
¹⁹ Cordgenics, LLC, Huntington WV, USA; Department of Pharmacology & Toxicology, University of Mississippi Medical Center, Jackson, MS, USA.
²⁰ Department of Neurosurgery, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA.
²¹ Department of Data Science, University of Mississippi Medical Center, Jackson, MS, USA.
²² Department of Pathology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA.
²³ Department of Radiology, University of Mississippi Medical Center, Jackson, MS, USA. Electronic address: cmhoward@umc.edu.

Abstract

Therapy-resistant cancer stem cells (CSCs) contribute to the poor clinical outcomes of patients with recurrent glioblastoma (rGBM) who fail standard of care (SOC) therapy. ChemoID is a clinically validated assay for identifying CSC-targeted cytotoxic therapies in solid tumors. In a randomized clinical trial (NCT03632135), the ChemoID assay, a personalized approach for selecting the most effective treatment from FDA-approved chemotherapies, improves the survival of patients with rGBM (2016 WHO classification) over physician-chosen chemotherapy. In the ChemoID assay-guided group, median survival is 12.5 months (95% confidence interval [CI], 10.2-14.7) compared with 9 months (95% CI, 4.2-13.8) in the physician-choice group (p = 0.010) as per interim efficacy analysis. The ChemoID assay-guided group has a significantly lower risk of death (hazard ratio [HR] = 0.44; 95% CI, 0.24-0.81; p = 0.008). Results of this study offer a promising way to provide more affordable treatment for patients with rGBM in lower socioeconomic groups in the US and around the world.

Keywords: ChemoID; assay-guided chemotherapy; cancer stem cells; chemotherapy; drug response assay; functional assay; glioblastoma; overall survival; personalized medicine; recurrent glioblastoma.

Publication types

Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents* / therapeutic use
Brain Neoplasms* / drug therapy
Glioblastoma* / drug therapy
Humans
Neoplastic Stem Cells
Treatment Outcome

Substances

Antineoplastic Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding