P18.23.A GLIOBLASTOMA IN OLDER ADULTS, A NEED FOR BOLDER TREATMENT IN SELECTED PATIENTS?
Authors: Robinson S D , Hooper C , MacColl J , Ryan K , Ajah H , Williams S T , Aktar N J , Lathangue H , Carter T , Conkey D , Rayner L , Theodoulou M , Kalra B , Fullagar A , Sen R , Durage P T T , Edlmann E , Winfield K , Hill T , MacArthur R , Cavalli C , Williams A , Norris T , Aghadiuno T , Lavelle G , Kingdon S , Yogalingham K , Stewart G , Lau S E , Kahan J , Walsh L , Mazarakis N , Giamas G , Chandy E , Critchley G ,   Histo-Mol Collaborative
Published: October 2024

Abstract

BACKGROUND
Glioblastoma (GBM) is a disease of older adults with peak incidence at 65-74 years. Treatment of this group is challenging and varies significantly. We sought to define treatment patterns and outcomes for patients aged &gt;65 with GBM diagnosed by WHO CNS 5.

MATERIAL AND METHODS
We identified pathologically confirmed older GBMs diagnosed in 2021 in a multicentre retrospective study. Patients were diagnosed and treated as per centre’s routine practice. Demographic, tumour and treatment characteristics were recorded and survival calculated from surgery date.

RESULTS
We identified 408 patients with pathologically confirmed GBM from 29 centres (age range 65-85 years old). 173 were 65-69 years old, 147 were 70-74, 71 were 75-79, and 17 were ≥80 years old. At diagnosis, WHO performance status (PS) was 0-1 in 70%, PS2 in 23% and PS3+ in 5%. 77% required dexamethasone and 46% required anti-epileptic medication. MGMT was unmethylated in 43% and methylated (&gt;10%) in 23%. Similar distributions were seen in each 5-year age range. Biopsy most frequently occurred (35%) and only 29% had &gt;95% resection. Radiotherapy (RT) was given to 74% (n=303). For patients 65-69, 66% received conventional RT and 32% hypofractionated RT, whilst for patients &gt;70, 78% received hypofractionated RT and 14% conventional RT. 192 received concurrent temozolomide (TMZ) (63%) and completed by 91%. 172 received adjuvant TMZ (median 5 cycles, range 1-12), stopped mostly for completion (41%), followed by progression (41%), and 18% due to toxicity. 105 patients received conventional chemoRT (26%), 85 received hypofractionated chemoRT (21%), 88 received hypofractionated RT (22%), 13 received TMZ alone (3%), and 90 received no oncology treatment (22%). For patients receiving TMZ alone 7/13 were strongly methylated and 1/13 was unmethylated. Median overall survival (mOS) was 8.8 months. OS decreased with age but increased with greater resection extent (mOS 6.0 months for biopsy vs 16.4 months for gross total resection, p&lt;0.001). mOS increased with increasing oncological treatment - 17.1 months with conventional chemoRT, 12.5 months with hypofractionated chemoRT, 8.4 months with hypofractionated RT, 7.1 months with TMZ alone, and 2.7 months with no oncological treatment. In the highly selected cohort of patients with PS 0-1, underwent a gross total resection and received chemoRT (n=38, 9%) mOS was 22.3 months. On multivariate analysis PS, greater MGMT methylation, greater surgery extent, greater RT intensity and adjuvant TMZ were associated with better OS.

CONCLUSION
In this population of older patients fit enough to have pathological confirmation of GBM, we identify that increasing treatment intensity is correlated with better OS. This might suggest that more intensive treatment strategies are appropriate in properly selected older patients with GBM. Better stratification tools (ie frailty assessments) may be useful.