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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; [...]

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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  • Media type: E-Article
  • Title: Magnetic Resonance Imaging of Iron Metabolism with T2* Mapping Predicts an Enhanced Clinical Response to Pharmacologic Ascorbate in Patients with GBM
  • Contributor: 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; [...]
  • Published: American Association for Cancer Research (AACR), 2024
  • Published in: Clinical Cancer Research, 30 (2024) 2, Seite 283-293
  • Language: English
  • DOI: 10.1158/1078-0432.ccr-22-3952
  • ISSN: 1557-3265; 1078-0432
  • Origination:
  • Footnote:
  • Description: 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