Metabolic Tumor Volume Response Assessment Using (11)C-Methionine Positron Emission Tomography Identifies Glioblastoma Tumor Subregions That Predict Progression Better Than Baseline or Anatomic Magnetic Resonance Imaging Alone

Abstract

To evaluate whether response assessment of newly diagnosed glioblastoma at 3 months using 11 C-methionine-positron emission tomography (MET-PET) is better associated with patient outcome compared with baseline MET-PET or anatomic magnetic resonance imaging alone. Methods and Materials: Patients included were participants in a phase I/II trial of dose-escalated chemoradiation based on anatomic magnetic resonance imaging. Automated segmentation of metabolic tumor volume (MTV) was performed at a threshold of 1.5 times mean cerebellar uptake. Progression-free (PFS) and overall survival were estimated with the Kaplan-Meier method and compared with log-rank tests. Multivariate analysis for PFS and overall survival was performed using Cox proportional hazards, and spatial overlap between imaging and recurrence volumes were analyzed. Results: Among 37 patients, 15 had gross total resection, of whom 10 (67%) had residual MTV, 16 subtotal resection, and 6 biopsy alone. Median radiation therapy dose was 75 Gy (range, 66-81). Median baseline T1 Gd-enhanced tumor volume (GTV-Gd) was 38.0 cm 3 (range, 8.0-81.5). Median pre-CRT MTV was 4.9 cm 3 (range, 0-43.8). Among 25 patients with 3-month MET-PET, MTV was only 2.4 cm 3 (range, 0.004-18.0) in patients with uptake. Patients with MTV Z 0 cm 3 at 3 months had superior PFS (18.2 vs 10.1 months,

Simultaneous Mapping of Vasculature, Hypoxia, and Proliferation Using Dynamic Susceptibility Contrast MRI, 18F-FMISO PET, and 18F-FLT PET in Relation to Contrast Enhancement in Newly Diagnosed Glioblastoma

“…The hotspots analysis showed that all tumors had hyperproliferative area that extended outside the CE volume, while hypervascularized or severe hypoxic areas were mostly included within the CE volume. This result concurs with a recent publication using 11 C-Methionine and demonstrating the presence of metabolic tumor volume following gross tumor resection (43).…”

“…These results strengthen the fact that tumor cells have already infiltrated the non-enhancing tissue and ought to be included in the surgical treatment or in the definition of the Biological Target Volume for radiotherapy (43).…”

Value of PET imaging for radiation therapy

“…In contrast to [ 18 F]FDG, which is not valuable for the response prediction to radiotherapy [23,24], early [ 18 F]FETor [ 11 C]MET-PET changes are predictors for progressionfree survival (PFS) and overall survival (OS) [25][26][27][28][29].…”

Artificial intelligence in tumor subregion analysis based on medical imaging: A review

“…Threshold algorithms are also suitable to separate tumor subregions based on imaging characteristics. Miller et al 147 investigated whether three month treatment response of newly diagnosed GBM based on C‐methionine‐positron emission tomography (MET‐PET) could predict prognosis better than baseline MET‐PET or anatomic magnetic resonance imaging alone. A threshold set at 150% of mean cerebellar uptake was used to automatically segment the metabolic tumor volume (MTV).…”