Spectroscopic MRI-Based Biomarkers Predict Survival for Newly Diagnosed Glioblastoma in a Clinical Trial

• Type of Material: Article
• Authors: Anuradha G Trivedi, Emory University; Karthik K Ramesh, Emory University; Vicki Huang, Emory University; Eric A Mellon, University of Miami; Peter B Barker, Johns Hopkins University; Lawrence R Kleinberg, Johns Hopkins University; Brent D Weinberg, Emory University; Hui-Kuo G Shu, Emory University; Hyunsuk Shim, Emory University
• Language: English
• Date: 2023-07-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2023 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/cancers15133524
• Title of Journal or Parent Work: CANCERS
• Volume: 15
• Issue: 13
• Grant/Funding Information: This research was funded by NIH U01 CA264039 (E.A.M. and H.S.) and NIH F31 CA247564 (K.K.R.).
• Keywords: EXTENT; radiation therapy; BEVACIZUMAB; ADJUVANT TEMOZOLOMIDE; survival biomarkers; dose-escalation; RADIOTHERAPY; Science & Technology; DISTRIBUTIONS; spectroscopic MRI; TUMOR VOLUME; RESECTION; CONCOMITANT; Oncology; Life Sciences & Biomedicine; glioblastoma
• Research Categories: Engineering, Biomedical; Health Sciences, Oncology; Biology, Radiation

Abstract

Despite aggressive treatment, glioblastoma has a poor prognosis due to its infiltrative nature. Spectroscopic MRI-measured brain metabolites, particularly the choline to N-acetylaspartate ratio (Cho/NAA), better characterizes the extent of tumor infiltration. In a previous pilot trial (NCT03137888), brain regions with Cho/NAA ≥ 2x normal were treated with high-dose radiation for newly diagnosed glioblastoma patients. This report is a secondary analysis of that trial where spectroscopic MRI-based biomarkers are evaluated for how they correlate with progression-free and overall survival (PFS/OS). Subgroups were created within the cohort based on pre-radiation treatment (pre-RT) median cutoff volumes of residual enhancement (2.1 cc) and metabolically abnormal volumes used for treatment (19.2 cc). We generated Kaplan–Meier PFS/OS curves and compared these curves via the log-rank test between subgroups. For the subgroups stratified by metabolic abnormality, statistically significant differences were observed for PFS (p = 0.019) and OS (p = 0.020). Stratification by residual enhancement did not lead to observable differences in the OS (p = 0.373) or PFS (p = 0.286) curves. This retrospective analysis shows that patients with lower post-surgical Cho/NAA volumes had significantly superior survival outcomes, while residual enhancement, which guides high-dose radiation in standard treatment, had little significance in PFS/OS. This suggests that the infiltrating, non-enhancing component of glioblastoma is an important factor in patient outcomes and should be treated accordingly.