GLIOBLASTOMA IN THE UK POST WHO CNS 5: INITIAL ﬁNDINGS FROM THE HISTO-MOL GBM COLLABORATIVE
Authors: Robinson Dr Stephen , Ryan Dr Katherine , Black Dr Louisa , Forner Dr Sam , Hatton Dr Nathaniel Luke , Hatton Dr Rebecca , Aktar Dr Nurjahan , Lathangue Mr Haydn , Conkey Dr David , Durage Dr Praveen , MacArthur Ms Rachel , Teoh Dr May , choudhury Dr mahbuba , Bowman Dr Miranda , Cavalli Dr Camilla , de Luna Mr Paolo , Christodoulou Dr Pavlos , Hill Dr Timothy , Williams Dr Adenike , Golten Dr Jennifer , Aghadiuno Dr Tasia , Yogalingam Dr Kohgulakuhan , Lau Dr Sue , Kahan Dr Jennifer , Dixit Dr Sanjay , Guglani Dr Samir , Williams Dr Matthew , Lewis Dr Rachel , Moleron Dr Rafael , Iqbal Dr Najmus , Wadd Dr Nick , Lord Dr Hannah , Bhat Dr Prashanth , Giamas Prof Georgios , Lorimer Dr Cressida , Chandy Dr Edward , Critchley Prof Giles 
Published: October 2024

Abstract

AIMS
The 2021 World Health Organisation Classiﬁcation (WHO CNS5) incorporated molecular diagnostic features for glioblastoma for the ﬁrst time. The Histo-Mol GBM collaborative is conducting a retrospective cohort study evaluating the outcomes of patients prospectively diagnosed with WHO CNS5 IDH wild type glioblastoma.

METHOD
Biopsy conﬁrmed glioblastoma patients diagnosed between 01/01-31/12/2021 were identiﬁed. Demographic, tumour, treatment, and survival data were collected. Descriptive statistics and Kaplan-Meier method were used to describe the cohort and for survival analysis respectively, assessed from surgery date.

RESULTS
So far, 363 glioblastoma patients were included from 13 centres (range: 11-61 patients/centre). Median age was 63.0, 65.8% were male, 77.4% had an ECOG performance status of 0-1 at diagnosis, and 28/333 had a molecular glioblastoma (8.4%). Biopsy was performed in 106/363 patients (29.2%), and gross total resection in 50/363 (13.8%). Adjuvant radiotherapy was performed in 290/363 (79.9%), and 71/290 (24.5%) had an additional pre-radiotherapy MRI with rapid early progression identiﬁed in 30/71 patients (42.3%). 128/269 (47.6%) patients received 2nd line treatment; most commonly systemic therapy (91/128, 71.1%) followed by re-resection (27/128, 21.1%). Second line systemic therapy was primarily lomustine (48/81, 52.7%). Median progression free survival was 7.7 months and median overall survival (OS) was 11.6 months. Median OS was 16.9 months with conventional fractionation chemoradiotherapy (n=169/363, 46.6%), 10.4 months with hypofractionated chemoradiotherapy (n=64/363, 17.6%), and 2.3 months with no oncological treatment (n=57/363, 15.7%). On univariate analysis age, gender, performance status, multifocality, MGMT promoter methylation, surgery extent, radiotherapy type (none, palliative, hypofractionated, conventional fractionation), larger planning target volume (PTV), receiving concurrent temozolomide, and receiving adjuvant temozolomide were statistically signiﬁcant. On multivariate analysis age, and receiving concurrent temozolomide remained signiﬁcant.

CONCLUSION
We describe the initial ﬁndings from a large real-world cohort of glioblastoma patients prospectively diagnosed according to WHO CNS5. Survival compares favourably with the practice changing phase 3 clinical trial outcomes.