The STEMRI trial: Magnetic resonance spectroscopy imaging can define tumor areas enriched in glioblastoma stem-like cells
Anthony Lemarié, V. Lubrano, Caroline Delmas, Amélie Lusque, Juan‐Pablo Cerapio, Marion Perrier, Aurore Siegfried, Florent Arnauduc, Yvan Nicaise, Perrine Dahan, Thomas Filleron, Muriel Mounier, Christine Toulas, Elizabeth Cohen‐Jonathan Moyal
Abstract
Despite maximally safe resection of the magnetic resonance imaging (MRI)–defined contrast-enhanced (CE) central tumor area and chemoradiotherapy, most patients with glioblastoma (GBM) relapse within a year in peritumoral FLAIR regions. Magnetic resonance spectroscopy imaging (MRSI) can discriminate metabolic tumor areas with higher recurrence potential as CNI+ regions (choline/ N -acetyl-aspartate index >2) can predict relapse sites. As relapses are mainly imputed to glioblastoma stem-like cells (GSCs), CNI+ areas might be GSC enriched. In this prospective trial, 16 patients with GBM underwent MRSI/MRI before surgery/chemoradiotherapy to investigate GSC content in CNI−/+ biopsies from CE/FLAIR. Biopsy and derived-GSC characterization revealed a FLAIR/CNI+ sample enrichment in GSC and in gene signatures related to stemness, DNA repair, adhesion/migration, and mitochondrial bioenergetics. FLAIR/CNI+ samples generate GSC-enriched neurospheres faster than FLAIR/CNI−. Parameters assessing biopsy GSC content and time-to-neurosphere formation in FLAIR/CNI+ were associated with worse patient outcome. Preoperative MRI/MRSI would certainly allow better resection and targeting of FLAIR/CNI+ areas, as their GSC enrichment can predict worse outcomes.