Magnetic resonance imaging of iron metabolism with T2 mapping predicts an enhanced clinical response to pharmacological ascorbate in patients with GBM

Michael S. Petronek; Varun Monga; Kellie L Bodeker; Michael A Kwofie; Chu-Yu Lee; Kranti Mapuskar; Jeffrey M Stolwijk; Amira Zaher; Brett A Wagner; Mark C Smith; Sandy A Vollstedt; Heather Brown; Meghan Chandler; Amanda C Lorack; Jared S Wulfekuhle; Jann N Sarkaria; Ryan T Flynn; Jeremy D W Greenlee; Matthew A Howard; Brian J Smith; Karra A Jones; Garry R Buettner; Joseph J Cullen; Joel St-Aubin; John M Buatti; Vincent A Magnotta; Douglas R Spitz; Bryan G Allen

doi:10.1158/1078-0432.CCR-22-3952

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Magnetic resonance imaging of iron metabolism with T2 mapping predicts an enhanced clinical response to pharmacological ascorbate in patients with GBM

Journal article

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Magnetic resonance imaging of iron metabolism with T2 mapping predicts an enhanced clinical response to pharmacological ascorbate in patients with GBM

Michael S. Petronek, Varun Monga, Kellie L Bodeker, Michael A Kwofie, Chu-Yu Lee, Kranti Mapuskar, Jeffrey M Stolwijk, Amira Zaher, Brett A Wagner, Mark C Smith, …

Clinical cancer research, Vol.30(2), pp.283-293

01/17/2024

DOI: 10.1158/1078-0432.CCR-22-3952

PMCID: PMC10841843

PMID: 37773633

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https://pmc.ncbi.nlm.nih.gov/articles/PMC10841843/pdf/nihms-1936466.pdfView

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Abstract

Abstract Purpose: Pharmacological ascorbate (P-AscH-) is hypothesized to be an Fe-dependent tumor-specific adjuvant to chemo-radiation in treating glioblastoma (GBM). The current study determined the efficacy of combining P-AscH- with radiation and temozolomide in a phase 2 clinical trial while simultaneously investigating a mechanism-based, non-invasive biomarker in T2* mapping to predict GBM response to P-AscH- in humans. Patients and Methods: The single-arm phase 2 clinical trial (NCT02344355) enrolled 55 subjects with analysis performed 12 months following the completion of treatment. Overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan-Meier method and compared across patient subgroups with log-rank tests. 49 of 55 subjects were evaluated using T2*-based MRI to assess its utility as an Fe-dependent biomarker. Results: Median OS was estimated to be 19.6 months (90% CI: 15.7 – 26.5 months), a statistically significant increase compared to historic control patients (14.6 months). Subjects with initial T2* relaxation < 50 ms were associated with a significant increase in PFS compared to T2*high subjects (11.2 months vs. 5.7 months, p<0.05) and a trend towards increased OS (26.5 months vs. 17.5 months). These results were validated in pre-clinical in vitro and in vivo model systems. Conclusions: P-AscH- combined with temozolomide and radiotherapy has the potential to significantly enhance GBM survival. T2*-based MRI assessment of tumor iron content is a prognostic biomarker for GBM clinical outcomes.

Details

Title: Subtitle: Magnetic resonance imaging of iron metabolism with T2 mapping predicts an enhanced clinical response to pharmacological ascorbate in patients with GBM
Creators: Michael S. Petronek - University of Iowa
Varun Monga - University of Iowa, Hematology, Oncology, and Blood & Marrow Transplantation
Kellie L Bodeker - University of Iowa
Michael A Kwofie - University of Iowa, Radiology
Chu-Yu Lee - University of Iowa, Radiology
Kranti Mapuskar - University of Iowa, Radiation Oncology
Jeffrey M Stolwijk
Amira Zaher
Brett A Wagner - University of Iowa, Radiation Oncology
Mark C Smith - University of Iowa, Radiation Oncology
Sandy A Vollstedt
Heather Brown - University of Iowa
Meghan Chandler - University of Iowa
Amanda C Lorack - University of Iowa
Jared S Wulfekuhle - University of Iowa
Jann N Sarkaria
Ryan T Flynn - University of Iowa, Radiation Oncology
Jeremy D W Greenlee - University of Iowa, Iowa Neuroscience Institute
Matthew A Howard - University of Iowa, Iowa Neuroscience Institute
Brian J Smith - University of Iowa, Biostatistics
Karra A Jones - Duke University
Garry R Buettner - University of Iowa, Radiation Oncology
Joseph J Cullen - University of Iowa, Surgery
Joel St-Aubin - University of Iowa, Radiation Oncology
John M Buatti - University of Iowa, Radiation Oncology
Vincent A Magnotta - University of Iowa, Iowa Neuroscience Institute
Douglas R Spitz - University of Iowa, Fraternal Order of Eagles Diabetes Research Center
Bryan G Allen - University of Iowa, Radiation Oncology
Resource Type: Journal article
Publication Details: Clinical cancer research, Vol.30(2), pp.283-293
DOI: 10.1158/1078-0432.CCR-22-3952
PMID: 37773633
PMCID: PMC10841843
NLM abbreviation: Clin Cancer Res
ISSN: 1078-0432
eISSN: 1557-3265
Grant note: DOI: 10.13039/100000054, name: National Cancer Institute, award: T32 CA078586; DOI: 10.13039/100000054, name: National Cancer Institute, award: P01 CA217797; DOI: 10.13039/100000054, name: National Cancer Institute, award: P01 CA244091; DOI: 10.13039/100001634, name: Gateway for Cancer Research, award: G-17-1500; DOI: 10.13039/100000054, name: National Cancer Institute, award: R21 CA270742; DOI: 10.13039/100000054, name: National Cancer Institute, award: P30 CA086862
Language: English
Electronic publication date: 09/29/2023
Date published: 01/17/2024
Academic Unit: Neurology; Psychiatry; Pathology; Biostatistics; Surgery; Otolaryngology; Roy J. Carver Department of Biomedical Engineering; Radiology; Hematology, Oncology, and Blood & Marrow Transplantation; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Holden Comprehensive Cancer Center; Internal Medicine
Record Identifier: 9984473475202771

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