SURG-39. Retrograde Longitudinal Imaging Analyses of IDH-Wildtype Glioblastoma Reveal Its Clinical Timeline from Radiological Birth to Death

Abstract BACKGROUND Early surgery vs watch-and-wait remains a debated strategy for incidental low-grade gliomas (iLGG). In the early preclinical phase, glioblastoma (GB), IDH-wildtype, and LGG are radiologically indistinguishable, yet GB follows a much more aggressive clinical course. Therefore, understanding the clinical course of iLGG with IDH-wildtype, potential future GB, is necessary. METHODS We analyzed longitudinal imaging data from 68 early-stage glioblastoma (earlyGB) cases, characterized by small, asymptomatic lesions that later progressed to classic MRI appearance of GB (classicGB), comprising 45 institutional and 23 published cases. A mathematical model integrating tumor volume, radius, imaging intervals, clinical data, and molecular features was used to estimate the timing of radiological birth and its modifiers. RESULTS The median interval from earlyGB to classicGB was 158 days (range: 35–1557) in our cohort and 113 days (range: 4–854) in the published cohort. Radiological birth, when GB first becomes radiologically detectable, occurred 0.85 years (95% CI: 0.68–1.13) before classicGB detection, consistent with the estimates from the published cases (0.15–0.92 years). Rapid progression correlated with age < 65 years, MIB1 labeling index > 30%, and copy-number alterations (CNAs) in EGFR, PTEN, or CDKN2A, but not with TERT promoter status. Absence of these CNAs prolonged the radiological birth to 2.24 years, indicating slower progression. Median overall survival was 1.71 years, yielding a radiological-birth-to-death span of 3.0 years, reflecting outcomes when surgery is delayed until classicGB appearance. From our retrospective institutional data, early surgery for suspected earlyGB (n = 12) resulted in no death with sustained KPS over a median follow-up of 86 months (range 8–125). CONCLUSIONS This largest earlyGB cohort defines the radiological birth and entire clinical trajectory of IDH-wildtype GB. Our findings provide outcomes without early surgery and support risk-adapted management, offering a benchmark for surveillance and early-intervention.