A Multi-Institutional Pilot Clinical Trial of Spectroscopic MRI-guided Radiation Dose Escalation for Newly-Diagnosed Glioblastoma. Issue 1 (27th January 2022)

• Record Type: Journal Article
• Authors: Ramesh, Karthik; Mellon, Eric A; Gurbani, Saumya S; Weinberg, Brent D; Schreibmann, Eduard; Sheriff, Sulaiman A; Goryawala, Mohammed; de le Fuente, Macarena; Eaton, Bree R; Zhong, Jim; Voloschin, Alfredo D; Sengupta, Soma; Dunbar, Erin M; Holdhoff, Matthias; Barker, Peter B; Maudsley, Andrew A; Kleinberg, Lawrence R; Shim, Hyunsuk; Shu, Hui-Kuo G
• Is Part Of: Neuro-oncology advances. Volume 4:Issue 1(2022)
• Publication Date: 2022-01-27
• Subjects: glioblastoma -- spectroscopic MRI -- MRSI -- radiation dose-escalation; 616.99481
• DOI: 10.1093/noajnl/vdac006
• Languages: English
• ISSNs: 2632-2498

Abstract

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 U, U Miami, Johns Hopkins U) from 9/2017 to 6/2019. 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) ≥ 2x 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 on study. 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 OS and PFS 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 one 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.