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

Autor: Petronek MS; Department of Radiation Oncology, Division of Free Radical and Radiation Biology, University of Iowa, Iowa City, IA, USA. michael-petronek@uiowa.edu., Bodeker KL; Department of Radiation Oncology, Division of Free Radical and Radiation Biology, University of Iowa, Iowa City, IA, USA., Lee CY; Department of Radiology, University of Iowa, Iowa City, IA, USA., Teferi N; Department of Radiation Oncology, Division of Free Radical and Radiation Biology, University of Iowa, Iowa City, IA, USA., Eschbacher KL; Department of Pathology, University of Iowa, Iowa City, IA, USA., Jones KA; Department of Pathology, Division of Neuropathology, Duke University, Durham, NC, USA., Loeffler BT; Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA., Smith BJ; Department of Biostatistics, University of Iowa, Iowa City, IA, USA., Buatti JM; Department of Radiation Oncology, Division of Free Radical and Radiation Biology, University of Iowa, Iowa City, IA, USA., Magnotta VA; Department of Radiology, University of Iowa, Iowa City, IA, USA., Allen BG; Department of Radiation Oncology, Division of Free Radical and Radiation Biology, University of Iowa, Iowa City, IA, USA.
Jazyk: angličtina
Zdroj: Journal of neuro-oncology [J Neurooncol] 2024 Feb; Vol. 166 (3), pp. 493-501. Date of Electronic Publication: 2024 Jan 29.
DOI: 10.1007/s11060-024-04571-z
Abstrakt: Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
(© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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