Table S1 from Magnetic Resonance Imaging of Iron Metabolism with T2* Mapping Predicts an Enhanced Clinical Response to Pharmacologic Ascorbate in Patients with GBM

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

doi:10.1158/1078-0432.25011398.v1

ccr-22-3952_table_s1_suppts1.pdf (152.09 kB)

Table S1 from 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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posted on 2024-01-17, 08:21 authored by Michael S. Petronek, Varun Monga, Kellie L. Bodeker, Michael Kwofie, Chu-Yu Lee, Kranti A. Mapuskar, Jeffrey M. Stolwijk, Amira Zaher, Brett A. Wagner, Mark C. Smith, Sandy Vollstedt, Heather Brown, Meghan L. 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

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ARTICLE ABSTRACT

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. 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. 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. 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

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Biomarkers Imaging biomarkers Clinical Trial Results Phase II clinical trials Precision Medicine

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