Prognostic IntraOperative Biomarkers ideNtification in Tumor rElatEd suRgery

Официальное название

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

Обзор

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.

Вмешательства

• Устройство Neuropixel probe recording
  Neuropixel recordings captures neuronal activity at the single-neuron level across the layers of the cortex.

Первичные конечные точки

• Number of Successful Neuropixels Probe Recordings During Glioma Surgeries [Срок оценки: From the beginning to end of tumor surgery]

Вторичные конечные точки (1)

• Prognostic Biomarker Identification (Unit: Number of Isolated Single Neurons with Tumor-Modulated Activity): [Срок оценки: From the beginning to end of surgery]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Оценка устройства

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Coughlin B, Munoz W, Kfir Y, Young MJ, Meszena D, Jamali M, Caprara I, Hardstone R, Khanna A, Mustroph ML, Trautmann EM, Windolf C, Varol E, Soper DJ, Stavisky SD, Welkenhuysen M, Dutta B, Shenoy KV, Hochberg LR, Mark Richardson R, Williams ZM, Cash SS, Paulk AC. Modified Neuropixels probes for recording human neurophysiology in the operating room. Nat Protoc. 2023 Oct;18(10):2927-2953. doi: 10.10 PMID 37697108
• Paulk AC, Kfir Y, Khanna AR, Mustroph ML, Trautmann EM, Soper DJ, Stavisky SD, Welkenhuysen M, Dutta B, Shenoy KV, Hochberg LR, Richardson RM, Williams ZM, Cash SS. Large-scale neural recordings with single neuron resolution using Neuropixels probes in human cortex. Nat Neurosci. 2022 Feb;25(2):252-263. doi: 10.1038/s41593-021-00997-0. Epub 2022 Jan 31. PMID 35102333
• Chung JE, Sellers KK, Leonard MK, Gwilliams L, Xu D, Dougherty ME, Kharazia V, Metzger SL, Welkenhuysen M, Dutta B, Chang EF. High-density single-unit human cortical recordings using the Neuropixels probe. Neuron. 2022 Aug 3;110(15):2409-2421.e3. doi: 10.1016/j.neuron.2022.05.007. Epub 2022 Jun 8. PMID 35679860
• Leonard MK, Gwilliams L, Sellers KK, Chung JE, Xu D, Mischler G, Mesgarani N, Welkenhuysen M, Dutta B, Chang EF. Large-scale single-neuron speech sound encoding across the depth of human cortex. Nature. 2024 Feb;626(7999):593-602. doi: 10.1038/s41586-023-06839-2. Epub 2023 Dec 13. PMID 38093008
• Krishna S, Choudhury A, Keough MB, Seo K, Ni L, Kakaizada S, Lee A, Aabedi A, Popova G, Lipkin B, Cao C, Nava Gonzales C, Sudharshan R, Egladyous A, Almeida N, Zhang Y, Molinaro AM, Venkatesh HS, Daniel AGS, Shamardani K, Hyer J, Chang EF, Findlay A, Phillips JJ, Nagarajan S, Raleigh DR, Brang D, Monje M, Hervey-Jumper SL. Glioblastoma remodelling of human neural circuits decreases survival. Natur PMID 37138086
• Venkataramani V, Yang Y, Schubert MC, Reyhan E, Tetzlaff SK, Wissmann N, Botz M, Soyka SJ, Beretta CA, Pramatarov RL, Fankhauser L, Garofano L, Freudenberg A, Wagner J, Tanev DI, Ratliff M, Xie R, Kessler T, Hoffmann DC, Hai L, Dorflinger Y, Hoppe S, Yabo YA, Golebiewska A, Niclou SP, Sahm F, Lasorella A, Slowik M, Doring L, Iavarone A, Wick W, Kuner T, Winkler F. Glioblastoma hijacks neuronal mec PMID 35914528
• Venkataramani V, Tanev DI, Strahle C, Studier-Fischer A, Fankhauser L, Kessler T, Korber C, Kardorff M, Ratliff M, Xie R, Horstmann H, Messer M, Paik SP, Knabbe J, Sahm F, Kurz FT, Acikgoz AA, Herrmannsdorfer F, Agarwal A, Bergles DE, Chalmers A, Miletic H, Turcan S, Mawrin C, Hanggi D, Liu HK, Wick W, Winkler F, Kuner T. Glutamatergic synaptic input to glioma cells drives brain tumour progression PMID 31534219

Идентификаторы

NCT: NCT06617208 · PaNaMa 12744

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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