IMG-129. Combination of advanced imaging, <i>MGMT</i> status and time since chemoradiation to optimize distinction between early progression and pseudoprogression in glioblastoma

Abstract BACKGROUND Distinguishing early progression (EP) from pseudoprogression (PsP) following radiochemotherapy for glioblastoma is important but remains a significant clinical challenge. EP is more common in MGMT unmethylated (uMGMT) than methylated (mMGMT) cases. We aimed to develop a multiparametric scoring system that integrates advanced imaging techniques (magnetic resonance perfusion [MRP] and spectroscopy [MRS]) with MGMT status and time since radiochemotherapy to aid in the interpretation of anatomic imaging findings. METHODS We retrospectively reviewed records of glioblastoma patients diagnosed from 2016-2025 who had worsening contrast enhancement ≤ 6 months after radiochemotherapy and underwent MRS and MRP. Definitive distinction between EP and PsP was made by either histology from surgical resampling or subsequent clinico-radiographic evolution. Optimal cutoff for time since radiochemotherapy was calculated for uMGMT and mMGMT using receiver operating characteristic (ROC) curve; a time-MGMT prediction was determined for each case (PsP if time since radiochemotherapy was below the cutoff for their MGMT status, EP if above). Sensitivity, specificity and accuracy of MGMT status, of each imaging modality, and of a composite score (1 point for each of the following consistent with EP: MRP, MRS, and time-MGMT prediction) were calculated. RESULTS 78 MRS/MRP instances from 65 patients (26 mMGMT, 39 uMGMT) were included; outcome (EP 49 [63%], PsP 29 [37%]) was determined histologically in 21 (27%) and clinically in 57 (73%) cases. Sensitivity/specificity/accuracy to predict EP were 65%/79%/71% for uMGMT, 82%/41%/67% for MRP, 78%/62%/72% for MRS, and 82%/69%/77% for composite score of 2-3 (vs. 0-1). In 21 cases with discordant MRS and MRP, the time-MGMT prediction correctly identified the outcome in 17 cases (81%). CONCLUSION Incorporating clinical parameters—including MGMT status and time since radiochemotherapy—to imaging results improves accuracy in distinguishing EP from PsP, but challenges remain. Ongoing work will incorporate CSF cell-free DNA and nuclear imaging into the model.