OS12.6.A MOLECULAR GLIOBLASTOMAS - BETTER PROGNOSIS AFTER CORRECTING FOR TREATMENT DIFFERENCES
Authors: Robinson S D , Clark M , MacColl J , Forner S , Wong A , Srimat Tirumala L N K , Hatton N L , Lathangue H , Wontumi S , Conkey D , Rayner L , Patel K , de Boisanger J , Fullagar A , Lachmann E , Durage P T T , Edlmann E , Pillai V , de Luna P J , Teoh M , Choudhury M , Williams A , Norris T , Golten J , Murphy S , Kingdon S , Yogalingham K , Stewart G , Lau S E , Kahan J , Olukiran G , Heckelmann M , Giamas G , Critchley G , Chandy E ,   Histo-Mol Collaborative
Published: October 2024

Abstract

BACKGROUND
Molecular glioblastoma (mGBM), without classical histological features, was defined in the 2021 WHO classification based on select criteria (EGFR amplification, TERT promoter mutation (pTERT), chromosome 7+/10-). Subsequent validation relied on retrospective patient re-diagnosis and/or historical histological GBMs (hGBMs) controls. Whether pTERT only mGBMs also have a poor prognosis remains uncertain. We comprehensively characterised mGBMs compared to concurrently diagnosed hGBMs.

MATERIAL AND METHODS
We identified pathologically confirmed GBMs diagnosed in 2021 in a multicentre retrospective study. Patients were diagnosed and treated as per their centre’s standard practice. Most centres offered routine molecular testing. Demographic, tumour and treatment characteristic differences were assessed by unpaired t-test. Kaplan-Meier analysis was from surgery date and survival differences compared by log rank.

RESULTS
We identified 944 pathologically confirmed GBMs from 31 centres, and 61 were mGBM (9.3% of tested cases). For mGBM patients, median age was 62 (vs 63), 66% were male (vs 64%) and 84% were WHO performance status 0-1 (vs 76%). Seizures were the most common presentation (33 vs 26%, p=0.300), plus significantly more sensory deficits (21 vs 10%, p=0.043) but significantly less speech (13 vs 28%, p=0.002) and cognitive deficits (15 vs 26%, p=0.027). mGBM patients were more likely to have multifocal disease (36% vs 23%, p=0.011) and less likely to have contrast enhancement (69% vs 96%, p&lt;0.001). Lesions were mostly temporal (53 vs 45%, p=0.257). EGFR amplification was seen in 33% and pTERT in 74% (48% pTERT only). Chromosome 7+/10- was not routinely tested. 79% were grade 3. 41% were MGMT promoter unmethylated and 21% were highly (&gt;10%) methylated (p=0.840). There was a trend for delay from initial imaging to surgery (median 19 vs 15 days) and surgery to radiotherapy (RT) (median 46 vs 40 days), resulting in a significant delay from initial imaging to RT (median 77 vs 57 days, p&lt;0.01). There was significant difference in resection extent (biopsy 64 vs 29%, &gt;95% resected 15 vs 35%, p&lt;0.001). Similar proportions received any RT (75 vs 80%, p=0.537), chemotherapy (54 vs 56%, p=0.838), and conventional chemoRT (34 vs 41%, p=0.305). Median progression free (8.2 vs 7.4 months, p=0.211) and overall survival (OS) (13.8 vs 10.9 months, p=0.120) were not significantly different to histological GBMs. pTERT only mGBMs had numerically worse OS at 10.8 months (p=0.255). Histological grade did not impact OS of all mGBMs (p=0.302) or pTERT only mGBMs (p=0.518). However, stratifying based on imbalances in surgery extent, OS was significantly improved for mGBMs (Biopsy: 7.9 vs 6.5 months, Resection: 26.5 vs 13.0 months, p=0.003).

CONCLUSION
In our cohort of prospectively diagnosed and treated mGBMs, when stratifying by surgical extent, mGBMs had significantly better OS than hGBMs.