P17.12.b Investigating Short Term (<6 Months) Survivors of Glioblastoma - An Analysis of the Histo-Mol GBM Collaborative Database.

BACKGROUND Population level survival for glioblastoma (GBM) remains limited at only 9-12 months. However, whilst a minority of patients have extended survival >24 months (long term survivors, LTS), a significant proportion survive <6 months (short term survivors, STS) and the characteristics of STS are poorly defined. Further, the survival benefit with concurrent temozolomide seen in clinical trials only emerges >6 months, with no separation in the survival curves before this. MATERIAL AND METHODS Using a large multicentre retrospective database of pathologically confirmed IDH wildtype (IDHwt) GBMs diagnosed in 2021, we investigated differences in the clinical and treatment characteristics of STS compared to LTS. Differences were assessed by independent samples T-test and survival was assessed using Kaplan-Meier methodology. RESULTS Of 1612 GBM patients, there were 520 STS (32%) and 243 LTS (15%). Age at diagnosis was increased in STS compared to LTS (median 65 [interquartile range: 59-72] vs 58 years [interquartile range: 50-67], p<0.001), whilst gender balance was not changed. STS presented with more motor (47% vs 30%, p<0.001), cognitive (30% vs 21%, p=0.007) and behavioural (10% vs 4%, p=0.002) symptoms, but fewer seizures (20% vs 30%, p=0.003) and headaches (31% vs 39%, p=0.027). Performance status (PS) significantly differed (p<0.001) with a greater proportion of PS>2 (36% vs 9%) and a lower proportion of PS0 (18% vs 47%) in STS. STS tumours were more commonly midline (10% vs 3%, p<0.001), multifocal (30% vs 14%, p<0.001) and contrast enhancing (97% vs 92%, p=0.002), but less frequently MGMT promoter methylated (40% vs 69%, p<0.001). Surgical strategy differed (p<0.001), with more biopsies (50% vs 13%) and fewer gross total resections (20% vs 56%) in STS. Oncological treatment also differed (p<0.001), with less STS receiving oncological treatment (37% vs 98%) and fewer patients received chemoradiotherapy (hypofractionated 10% vs 14%, or conventional 12% vs 80%). In STS who underwent adjuvant radiotherapy (n=206), there was an increase in the size of the planning target volume (median 386cc vs 268cc, p<0.001) and an increased proportion of patients had evidence of progression between surgery and radiotherapy (20% vs 11%, p<0.001). In STS patients who received radical radiotherapy (60Gy/30# or 40Gy/15#, n=156), there was improved survival with the addition of concurrent temozolomide (median survival 4.2 months vs 4.9 months, p=0.002). CONCLUSION We present a well characterised clinical cohort of pathologically confirmed IDHwt GBM STS, demonstrating clear differences from LTS. STS represent a third of pathologically confirmed GBM patients, plus additional patients who were not felt suitable for pathological confirmation. Further research to reliably predict STS at diagnosis would help patients make more informed decisions about their treatment.