JS03.5.A DO PATIENTS WITH MOLECULARLY-DEFINED GLIOBLASTOMA SHARE THE SAME CLINICAL CHARACTERISTICS AND OUTCOME OF HISTOLOGICALLY-DEFINED GLIOBLASTOMA? A MULTICENTRIC STUDY FROM THE ITALIAN ASSOCIATION OF NEURO-ONCOLOGY (AINO)
Authors: Bruno F , Pellerino A , Bertero L , Silvani A , Pollo B , Ius T , Pizzolitto S , Conti Nibali M , Berzero G , Navarria P , Gurrieri L , Di Stefano A , Maccari M , Lombardi G , Internò V , Pronello E , Caffo M , D’Alessandris Q , Soffietti R , Garbossa D , Bello L , Rudà R 
Published: October 2024

Abstract

BACKGROUND
The 2021 WHO Classification defines IDH-wildtype (IDHwt) astrocytomas with either EGFR amplification, pTERT mutation or +7/-10 chromosomal changes as molecularly-defined glioblastomas (mGBMs), even if histologically grade 2. However, it is not clear whether mGBMs share the same clinical characteristics, response to treatments and prognosis of histologically-defined (grade 4) IDHwt GBMs (hGBMs). The Italian Association of Neuro-Oncology (AINO) performed a multicentric study to address this issue.

PATIENTS AND METHODS
A retrospective AINO database was created to collect clinical data of patients with mGBM with grade 2 histological features from 2010 to 2023. Exclusion criteria were the presence of mitoses, necrosis and/or microvascular proliferation in tumour specimens, and strong ring-enhancement on MRI at onset. A historical cohort of 66 hGBM patients was used for comparison.

RESULTS
We collected 70 patients with mGBMs. Median age was 59 years (vs 60 years of hGBM patients). All mGBM and hGBM patients had KPS&gt;70. 46/70 mGBMs (66%) and 13/66 hGBMs (20%) presented with seizures. Methylation of pMGMT was found in 23/53 mGBMs (43%) and 30/66 hGBMs (45%). Among mGBMs, EGFR amplification was found in 23/59 (39%), and pTERT mutation in 55/66 (83%). Gross-total resection was achieved in 20/70 mGBM (29%) patients, and 21/66 hGBMs (32%). Among mGBMs, post-surgical modalities were radiotherapy (RT) +/- concomitant temozolomide (TMZ) followed by TMZ in 39 (56%), observation in 15 (21%), upfront TMZ in 13 (19%); conversely, all hGBMs underwent concomitant RT/TMZ followed by TMZ. Patients with mGBMs vs hGBMs had longer median progression-free survival (mPFS) (13 vs 9 months, p=0.011) and overall survival (mOS) (27 vs 22 months, p=0.036). Unlike hGBMs, pMGMT methylation did not affect the outcome of mGBM patients undergoing chemoradiation, mPFS being 13 months for both pMGMT-methylated and unmethylated mGBM patients (p=0.471), and mOS 38 vs 25 months (p=0.291) - conversely, among hGBM patients with vs without pMGMT methylation, mPFS was 12 vs 8 months, p&lt;0.001, and mOS 32 vs 15 months, p&lt;0.001). Also, mGBM patients with isolated pTERT mutation, vs those with EGFR amplification, had similar mPFS (12 vs 8 months, p=0.780), and mOS (32 vs 22 months, p=0.175). However, mGBM patients with isolated pTERT mutation showed a trend for a better mOS after chemoradiation (45 months) as compared to TMZ upfront (17 months), p=0.06.

CONCLUSION
Although sharing some similar characteristics (median age, KPS), mGBM patients included in our study differed hGBMs: they had a higher incidence of seizures and significantly longer mPFS and mOS; also, pMGMT methylation did not affect the outcome of mGBMs. A trend for better mOS was seen in mGBM patients with isolated pTERT mutation after chemoradiation. The study is ongoing, to confirm these findings in a larger cohort.