Rapid early progression of glioblastoma: evaluation of a novel prognostic radiologic biomarker

Objectives: Rapid Early Progression (REP) in glioblastoma occurs when there is tumor growth between the immediate postoperative MRI and the radiotherapy planning MRI. We reviewed a large multicenter series to determine the frequency, predictors, and impact of REP. Methods: Patients treated with radiotherapy for newly-diagnosed glioblastoma between 2014 and 2023 were reviewed. Preoperative/postoperative MRIs were individually reviewed to determine radiographic extent of resection (EOR) as either gross-total (GTR), near-total (NTR), subtotal (STR), or biopsy. Radiotherapy-planning MRIs were evaluated for REP and classified as clear, mild, or none; and REP location as local, distant, or both. Progression-free survival (PFS), overall survival (OS), and predictors for REP were analyzed and compared. Results: Four hundred and one (401) patients met inclusion criteria. REP was seen in 62.1% of patients. Compared to patients with GTR, increased REP was seen in patients with NTR (OR = 7.94, p < 0.001), STR (OR = 15.12, p < 0.001), and biopsy (OR = 6.52, p < 0.001). Time from resection to radiotherapy-planning MRI was not associated with REP (p = 0.611). REP predicted inferior PFS (p = 0.011) with further decrease seen in clear REP (HR = 1.713, 95% CI: 1.202–2.441) as compared to mild REP (HR = 1.511, 95% CI: 1.046–2.183). Conclusion: These data support REP as a common and practical biomarker suggestive of more aggressive tumor phenotype. REP was strongly associated with EOR (although not with delays to radiotherapy) and associated with decreased PFS. Novel strategies are needed to integrate REP into clinical trial stratification, predict for REP a priori, reduce its frequency, and/or tailor adjuvant therapy.