Parametric Response Mapping of FLAIR MRI Provides an Early Indication of Progression Risk in Glioblastoma

Rationale and Objectives: Glioblastoma image evaluation utilizes Magnetic Resonance Imaging contrast-enhanced, T1-weighted, and noncontrast T2-weighted fluid-attenuated inversion recovery (FLAIR) acquisitions. Disease progression assessment relies on changes in tumor diameter, which correlate poorly with survival. To improve treatment monitoring in glioblastoma, we investigated serial voxel-wise comparison of anatomically-aligned FLAIR signal as an early predictor of GBM progression. Materials and Methods: We analyzed longitudinal normalized FLAIR images (rFLAIR) from 52 subjects using voxel-wise Parametric Response Mapping (PRM) to monitor volume fractions of increased (PRMrFLAIR+), decreased (PRMrFLAIR-), or unchanged (PRMrFLAIR0) rFLAIR intensity. We determined response by rFLAIR between pretreatment and 10 weeks posttreatment. Risk of disease progression in a subset of subjects (N = 26) with stable disease or partial response as defined by Response Assessment in Neuro-Oncology (RANO) criteria was assessed by PRMrFLAIR between weeks 10 and 20 and continuously until the PRMrFLAIR+ exceeded a defined threshold. RANO defined criteria were compared with PRM-derived outcomes for tumor progression detection. Results: Patient stratification for progression-free survival (PFS) and overall survival (OS) was achieved at week 10 using RANO criteria (PFS: p <0.0001; OS: p <0.0001), relative change in FLAIR-hyperintense volume (PFS: p = 0.0011; OS: p <0.0001), and PRMrFLAIR+ (PFS: p <0.01; OS: p <0.001). PRMrFLAIR+ also stratified responding patients' progression between weeks 10 and 20 (PFS: p <0.05; OS: p = 0.01) while changes in FLAIR-volume measurements were not predictive. As a continuous evaluation, PRMrFLAIR+ exceeding 10% stratified patients for PFA after 5.6 months (p<0.0001), while RANO criteria did not stratify patients until 15.4 months (p <0.0001). Conclusion: PRMrFLAIR may provide an early biomarker of disease progression in glioblastoma.