A multi-institutional pilot clinical trial of spectroscopic MRI-guided radiation dose escalation for newly diagnosed glioblastoma

Karthik Ramesh, Eric A. Mellon, Saumya S. Gurbani, Brent D. Weinberg, Eduard Schreibmann, Sulaiman A. Sheriff, Mohammed Goryawala, Macarena De Le Fuente, Bree R. Eaton, Jim Zhong, Alfredo D. Voloschin, Soma Sengupta, Erin M. Dunbar, Matthias Holdhoff, Peter B. Barker, Andrew A. Maudsley, Lawrence R. Kleinberg, Hyunsuk Shim, Hui Kuo G. Shu

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Glioblastomas (GBMs) are aggressive brain tumors despite radiation therapy (RT) to 60 Gy and temozolomide (TMZ). Spectroscopic magnetic resonance imaging (sMRI), which measures levels of specific brain metabolites, can delineate regions at high risk for GBM recurrence not visualized on contrast-enhanced (CE) MRI. We conducted a clinical trial to assess the feasibility, safety, and efficacy of sMRI-guided RT dose escalation to 75 Gy for newly diagnosed GBMs. Methods: Our pilot trial (NCT03137888) enrolled patients at 3 institutions (Emory University, University of Miami, Johns Hopkins University) from September 2017 to June 2019. For RT, standard tumor volumes based on T2-FLAIR and T1w-CE MRIs with margins were treated in 30 fractions to 50.1 and 60 Gy, respectively. An additional high-risk volume based on residual CE tumor and Cho/NAA (on sMRI) ≥2× normal was treated to 75 Gy. Survival curves were generated by the Kaplan-Meier method. Toxicities were assessed according to CTCAE v4.0. Results: Thirty patients were treated in the study. The median age was 59 years. 30% were MGMT promoter hypermethylated; 7% harbored IDH1 mutation. With a median follow-up of 21.4 months for censored patients, median overall survival (OS) and progression-free survival were 23.0 and 16.6 months, respectively. This regimen appeared well-tolerated with 70% of grade 3 or greater toxicity ascribed to TMZ and 23% occurring at least 1 year after RT. Conclusion: Dose-escalated RT to 75 Gy guided by sMRI appears feasible and safe for patients with newly diagnosed GBMs. OS outcome is promising and warrants additional testing. Based on these results, a randomized phase II trial is in development.

Original languageEnglish (US)
Article numbervdac006
JournalNeuro-Oncology Advances
Volume4
Issue number1
DOIs
StatePublished - Jan 1 2022

Keywords

  • MRSI
  • glioblastoma
  • radiation dose-escalation
  • spectroscopic MRI

ASJC Scopus subject areas

  • Clinical Neurology
  • Oncology
  • Surgery

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