# 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.

## Key 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.