Iron-based biomarkers for personalizing pharmacological ascorbate therapy in glioblastoma: insights from a phase 2 clinical trial

M S Petronek; K L Bodeker; C Y Lee; N Teferi; K L Eschbacher; K A Jones; B T Loeffler; B J Smith; J M Buatti; V A Magnotta; B G Allen

doi:10.1007/s11060-024-04571-z

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Iron-based biomarkers for personalizing pharmacological ascorbate therapy in glioblastoma: insights from a phase 2 clinical trial

Journal article

Peer reviewed

Iron-based biomarkers for personalizing pharmacological ascorbate therapy in glioblastoma: insights from a phase 2 clinical trial

M S Petronek, K L Bodeker, C Y Lee, N Teferi, K L Eschbacher, K A Jones, B T Loeffler, B J Smith, J M Buatti, V A Magnotta, …

Journal of neuro-oncology, Vol.166(3), pp.493-501

02/2024

DOI: 10.1007/s11060-024-04571-z

PMCID: PMC13105400

PMID: 38285244

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Abstract

Pharmacological ascorbate (intravenous delivery reaching plasma concentrations ≈ 20 mM; P-AscH ) has emerged as a promising therapeutic strategy for glioblastoma. Recently, a single-arm phase 2 clinical trial demonstrated a significant increase in overall survival when P-AscH was combined with temozolomide and radiotherapy. As P-AscH relies on iron-dependent mechanisms, this study aimed to assess the predictive potential of both molecular and imaging-based iron-related markers to enhance the personalization of P-AscH therapy in glioblastoma participants. Participants (n = 55) with newly diagnosed glioblastoma were enrolled in a phase 2 clinical trial conducted at the University of Iowa (NCT02344355). Tumor samples obtained during surgical resection were processed and stained for transferrin receptor and ferritin heavy chain expression. A blinded pathologist performed pathological assessment. Quantitative susceptibility mapping (QSM) measures were obtained from pre-radiotherapy MRI scans following maximal safe surgical resection. Circulating blood iron panels were evaluated prior to therapy through the University of Iowa Diagnostic Laboratory. Through univariate analysis, a significant inverse association was observed between tumor transferrin receptor expression and overall and progression-free survival. QSM measures exhibited a significant, positive association with progression-free survival. Subjects were actively followed until disease progression and then were followed through chart review or clinical visits for overall survival. This study analyzes iron-related biomarkers in the context of P-AscH therapy for glioblastoma. Integrating molecular, systemic, and imaging-based markers offers a multifaceted approach to tailoring treatment strategies, thereby contributing to improved patient outcomes and advancing the field of glioblastoma therapy.

Iron metabolism

Quantitative susceptibility mapping

Transferrin receptor

Glioblastoma

Pharmacological ascorbate

Details

Title: Subtitle: Iron-based biomarkers for personalizing pharmacological ascorbate therapy in glioblastoma: insights from a phase 2 clinical trial
Creators: M S Petronek - University of Iowa
K L Bodeker - University of Iowa
C Y Lee - University of Iowa
N Teferi - University of Iowa
K L Eschbacher - University of Iowa
K A Jones - Duke University
B T Loeffler - University of Iowa
B J Smith - University of Iowa
J M Buatti - University of Iowa
V A Magnotta - University of Iowa
B G Allen - University of Iowa
Resource Type: Journal article
Publication Details: Journal of neuro-oncology, Vol.166(3), pp.493-501
DOI: 10.1007/s11060-024-04571-z
PMID: 38285244
PMCID: PMC13105400
NLM abbreviation: J Neurooncol
ISSN: 0167-594X
eISSN: 1573-7373
Grant note: P01 CA217797 / NIH HHS
Language: English
Electronic publication date: 01/29/2024
Date published: 02/2024
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Psychiatry; Pathology; Iowa Neuroscience Institute; Biostatistics; Radiation Oncology; Neurosurgery; Otolaryngology; Holden Comprehensive Cancer Center
Record Identifier: 9984554859302771

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