Retrograde longitudinal imaging analyses of IDH-wildtype glioblastoma reveal its clinical timeline from radiological birth to death

TL;DR

This study tracks the progression of a specific type of brain tumor from its earliest detectable stage to death, showing how long it takes to become visible on scans and how it evolves clinically.

Contribution

The study provides the first detailed longitudinal analysis of IDH-wildtype glioblastoma's clinical timeline from radiological birth to death.

Findings

Radiological birth of IDH-wildtype glioblastoma occurs about 0.83 years before diagnosis.

Tumors with certain genetic alterations progress more rapidly, while their absence delays progression.

The median time from radiological birth to death is 2.8 years.

Abstract

Glioblastoma (GB), IDH-wildtype, and low-grade glioma appear indistinguishable in their early pre-symptomatic phase, yet GB follows a far more aggressive clinical course. While genomic studies suggest a “biological birth” of GB years before diagnosis, when GB first becomes radiologically detectable (radiological birth) remains unknown.

We analyzed longitudinal imaging data from 67 early-stage glioblastoma (earlyGB) cases, characterized by small, asymptomatic lesions that later progressed to classic magnetic resonance imaging appearance of GB (classicGB), comprising 44 institutional and 23 from published reports. A mathematical model integrating tumor volume, radius, imaging intervals, clinical data, and molecular features estimated radiological birth and its modifiers.

The median interval from earlyGB to classicGB was 155 days (range: 35-1557) in our cohort and 113 days (range: 4-854) in the published cohort. Radiological birth occurred 0.83 years (95% CI: 0.66-1.10) before diagnosis in our cohort and 0.15-0.92 years in the published cohort. 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 2.27 years (95% CI: 0.79-100), indicating slower progression. Median overall survival of our cohort was 1.7 years, yielding a radiological-birth-to-death span of 2.8 years.

This largest earlyGB cohort defines the radiological birth and entire clinical trajectory of IDH-wildtype GB. These findings bridge the gap between biological and radiological birth and offer a benchmark for surveillance and early-intervention strategies.

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