Abstract

Abstract BACKGROUND Within 3-6 months of completing initial chemoradiotherapy, up to 50% of glioblastomas (GBM) develop worsening contrast enhancement on surveillance imaging, which could represent early progression (EP) or pseudoprogression (PsP). Reports suggest EP is more common in MGMT unmethylated (uMGMT) cases. While multiple advanced imaging studies have tried to address this issue (including magnetic resonance with perfusion [MRP], with spectroscopy [MRS], and FDG-PET), no non-invasive test reliably differentiates EP from PsP, yet the distinction is critical for subsequent management. We aimed to develop a multiparametric score including advanced imaging and MGMT status to improve interpretation. METHODS We retrospectively reviewed records of patients diagnosed with GBM from 2016-2022 who had changes on anatomic imaging concerning for EP vs. PsP ≤6 months after chemoradiotherapy and underwent ≥ 2 advanced imaging sequences (MRP, MRS, FDG-PET); definitive distinction between EP and PsP was made by either histology from surgical resampling or subsequent clinico-radiographic evolution. Associations between clinical factors and EP were investigated with logistic regression. Sensitivity and specificity of each imaging modality and of a composite score (1 point each for MRP consistent with EP, MRS consistent with EP, and uMGMT) were calculated. RESULTS 46 evaluable patients (57% male; median age 58.5 years, range 31-80) were included; outcome (EP in 29 [63%], PsP in 17 [37%]) was determined histologically and clinically in 15 (33%) and 31 (67%) of cases, respectively. In multivariate analysis, uMGMT was predictive of EP (OR=2.63, 95% CI=1.29-37.55, p< 0.05). Sensitivity/specificity to predict EP were 78%/77% for uMGMT, 76%/29% for MRP, 85%/67% for MRS, 86%/0% for FDG-PET (8 patients) and 88%/75% for composite score of 2-3 (vs. 0-1). CONCLUSION Combining MRS, MRP and MGMT results can improve accuracy in distinguishing EP from PsP in GBM. MGMT status should be incorporated in the interpretation of advanced imaging to distinguish EP from PsP.

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