Prognostic IntraOperative Biomarkers ideNtification in Tumor rElatEd suRgery

Prognostic IntraOperative Biomarkers ideNtification in Tumor rElatEd suRgery (PIONEER Study)

INTRODUCTION AND RATIONALE

Aggressive brain tumors like glioma have the ability to infiltrate the surrounding healthy brain tissue, disrupting normal neuronal activities and leading to impaired motor and cognitive functions, as well as causing epilepsy. This malignant brain tumor is considered one of the most challenging cancers to treat, with a median survival of 12 to 15 months. Recent findings on direct neuron-tumor interactions indicate that abnormal brain activity in the regions surrounding brain tumors may contribute to develop epilepsy and accelerating tumor growth. Tumors tend to 'fuel' themselves with neurotransmitters released during its 'daily' neuronal firing. Hyperactive neurons in the peritumoral cortex can form excitatory electrochemical synapses with surrounding tumor cells, creating direct communication pathways within the peritumoral microenvironment, which aids in the progression and proliferation of tumor cells via direct and paracrine signalling pathways. However, the specific features of this abnormal brain activity in the peritumoral cortex have not been fully clarified and information on the pathological changes of neuronal activity in glioma patients is largely lacking. To advance more effective treatment strategies, it is crucial to better understand the complex interactions between the tumor and the brain.

This is especially important for the group of patients of which many perceive diminished quality of life because of epilepsy, cognitive functioning and language problems after tumor surgery. Furthermore, a thorough understanding is lacking of what tumor resection does to the original hyperactive peritumoral cortex and if resecting this is beneficial for improving postoperative outcome both for epilepsy as well as regarding survival. Therefore, identifying the hyperactive peritumoral cortex and directly addressing its impacts on the brain function and long-term surgical outcome could be a promising novel therapeutic strategy for treating glioma patients.

STUDY AIM

The measurement focuses on capturing neuronal activity at single-neuron resolution in the peritumoral cortex of glioma patients using cortical depth electrodes. It is well-established that gliomas can remodel the surrounding brain tissue, leading to abnormal neuronal hyperactivity, which contributes to tumor progression and epilepsy. However, the specific neuronal patterns and underlying mechanisms of these changes are not yet fully understood. This study will aim to collect detailed single-neuron recordings in this context, enabling us to map the precise neurophysiological disruptions caused by gliomas. On the long term, this research could lay the groundwork in identifying novel therapeutic approaches by providing critical in-sights into how gliomas alter brain function.

Inclusion Criteria:

• Age between 18 yrs and 90 yrs old with radiologically diagnosed GBM
• Eligible for surgery according to standard practices. If suitable and necessary according to standard practices, awake surgery is also permitted.
• Written Informed consent.

Exclusion Criteria:

• Inability to give consent because of or language barrier
• Psychiatric history
• Previous brain tumour surgery or radiotherapy
• Severe aphasia or dysphasia
• Patient has pacemaker or other implanted electrical device such as vagal nerve stimulator or other