Dataset Information

Magnetic Resonance Imaging of Iron Metabolism with T2* Mapping Predicts an Enhanced Clinical Response to Pharmacologic Ascorbate in Patients with GBM.

ABSTRACT:

Purpose

Pharmacologic ascorbate (P-AscH-) is hypothesized to be an iron (Fe)-dependent tumor-specific adjuvant to chemoradiation in treating glioblastoma (GBM). This study determined the efficacy of combining P-AscH- with radiation and temozolomide in a phase II clinical trial while simultaneously investigating a mechanism-based, noninvasive biomarker in T2* mapping to predict GBM response to P-AscH- in humans.

Patients and methods

The single-arm phase II 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. Forty-nine 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% confidence interval (CI), 15.7-26.5 months], a statistically significant increase compared with historic control patients (14.6 months). Subjects with initial T2* relaxation < 50 ms were associated with a significant increase in PFS compared with T2*-high subjects (11.2 months vs. 5.7 months, P < 0.05) and a trend toward increased OS (26.5 months vs. 17.5 months). These results were validated in preclinical 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. See related commentary by Nabavizadeh and Bagley, p. 255.

SUBMITTER: Petronek MS

PROVIDER: S-EPMC10841843 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

Magnetic Resonance Imaging of Iron Metabolism with T2* Mapping Predicts an Enhanced Clinical Response to Pharmacologic Ascorbate in Patients with GBM.

Petronek Michael S MS Monga Varun V Bodeker Kellie L KL Kwofie Michael M Lee Chu-Yu CY Mapuskar Kranti A KA Stolwijk Jeffrey M JM Zaher Amira A Wagner Brett A BA Smith Mark C MC Vollstedt Sandy S Brown Heather H Chandler Meghan L ML Lorack Amanda C AC Wulfekuhle Jared S JS Sarkaria Jann N JN Flynn Ryan T RT Greenlee Jeremy D W JDW Howard Matthew A MA Smith Brian J BJ Jones Karra A KA Buettner Garry R GR Cullen Joseph J JJ St-Aubin Joel J Buatti John M JM Magnotta Vincent A VA Spitz Douglas R DR Allen Bryan G BG

Clinical cancer research : an official journal of the American Association for Cancer Research 20240101 2

<h4>Purpose</h4>Pharmacologic ascorbate (P-AscH-) is hypothesized to be an iron (Fe)-dependent tumor-specific adjuvant to chemoradiation in treating glioblastoma (GBM). This study determined the efficacy of combining P-AscH- with radiation and temozolomide in a phase II clinical trial while simultaneously investigating a mechanism-based, noninvasive biomarker in T2* mapping to predict GBM response to P-AscH- in humans.<h4>Patients and methods</h4>The single-arm phase II clinical trial (NCT023443 ...[more]

PMID: 37773633

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Dataset Information

Magnetic Resonance Imaging of Iron Metabolism with T2* Mapping Predicts an Enhanced Clinical Response to Pharmacologic Ascorbate in Patients with GBM.

Purpose

Patients and methods

Results

Conclusions

Publications

Magnetic Resonance Imaging of Iron Metabolism with T2* Mapping Predicts an Enhanced Clinical Response to Pharmacologic Ascorbate in Patients with GBM.

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