Evidence mapPaperPMID 38645003Full record

ArticlemedRxiv : the preprint server for health sciences2024

Pilot trial of perampanel on peritumoral hyperexcitability and clinical outcomes in newly diagnosed high-grade glioma.

Steven Tobochnik, Michael S Regan, Maria K C Dorotan, Dustine Reich, Emily Lapinskas, Md Amin Hossain, Sylwia Stopka, Sandro Santagata, Melissa M Murphy, Omar Arnaout and 9 more

Open access · greenAbstract readPreprint
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 3 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 3 institutions in 1 country.

Steven TobochnikDepartment of Neurology, Brigham and Women's Hospital, Boston, MA, USA.ORCID 0000-0001-9071-8398
Michael S ReganDepartment of Neurosurgery, Brigham and Women's Hospital, Boston, MA, USA.
Maria K C DorotanDepartment of Neurology, Brigham and Women's Hospital, Boston, MA, USA.ORCID 0000-0002-0073-4982
Dustine ReichWeill Cornell Medical College, New York, NY, USA.
Emily LapinskasDepartment of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
Md Amin HossainDepartment of Neurosurgery, Brigham and Women's Hospital, Boston, MA, USA.
Sylwia StopkaDepartment of Neurosurgery, Brigham and Women's Hospital, Boston, MA, USA.ORCID 0000-0003-3761-6899
Sandro SantagataDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Melissa M MurphyDepartment of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
Omar ArnaoutDepartment of Neurosurgery, Brigham and Women's Hospital, Boston, MA, USA.
Wenya Linda BiDepartment of Neurosurgery, Brigham and Women's Hospital, Boston, MA, USA.ORCID 0000-0002-4635-0247
E Antonio ChioccaDepartment of Neurosurgery, Brigham and Women's Hospital, Boston, MA, USA.
Alexandra J GolbyDepartment of Neurosurgery, Brigham and Women's Hospital, Boston, MA, USA.
Michael A MooneyDepartment of Neurosurgery, Brigham and Women's Hospital, Boston, MA, USA.
Timothy R SmithDepartment of Neurosurgery, Brigham and Women's Hospital, Boston, MA, USA.
Keith L LigonDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.ORCID 0000-0002-7733-600X
Patrick Y WenDepartment of Medical Oncology, Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Nathalie Y R AgarDepartment of Neurosurgery, Brigham and Women's Hospital, Boston, MA, USA.ORCID 0000-0003-3149-3146
Jong Woo LeeDepartment of Neurology, Brigham and Women's Hospital, Boston, MA, USA.ORCID 0000-0001-5283-7476
Brigham and Women's Hospital · USCenter for Neuro-Oncology · USCornell University · US

Funding

TRD 3 - Enabling Technologies for Intraprocedural GuidanceP41EB028741 · NIBIB · BRIGHAM AND WOMEN'S HOSPITAL · 2022 to 2025
$6.8M
Targeted Therapies for GliomaP50CA165962 · BRIGHAM AND WOMEN'S HOSPITAL · 2025 to 2025
$2.4M
NCI NIH HHS P50 CA165962NCI NIH HHS U54 CA210180NIBIB NIH HHS P41 EB015898NIBIB NIH HHS P41 EB028741
6 · The paper itself

Abstract

Background: Glutamatergic neuron-glioma synaptogenesis and peritumoral hyperexcitability promote glioma growth in a positive feedback loop. The objective of this study was to evaluate the feasibility and estimated effect sizes of the AMPA-R antagonist, perampanel, on intraoperative electrophysiologic hyperexcitability and clinical outcomes. Methods: An open-label trial was performed comparing perampanel to standard of care (SOC) in patients undergoing resection of newly-diagnosed radiologic high-grade glioma. Perampanel was administered as a pre-operative loading dose followed by maintenance therapy until progressive disease or up to 12-months. SOC treatment involved levetiracetam for 7-days or as clinically indicated. The primary outcome of hyperexcitability was defined by intra-operative electrocorticography high frequency oscillation (HFO) rates. Seizure-freedom and overall survival (OS) were estimated by the Kaplan-Meier method. Tissue concentrations of perampanel, levetiracetam, and metabolites were measured by mass spectrometry. Results: HFO rates were similar between perampanel-treated and SOC cohorts. The trial was terminated early after interim analysis for futility, and outcomes assessed in 11 patients (7 perampanel-treated, 4 SOC). Over a median 281 days of post-enrollment follow-up, 27% of patients had seizures, including 14% treated with perampanel and 50% treated with SOC. OS in perampanel-treated patients was similar to a glioblastoma reference cohort (p=0.81). Glutamate concentrations in surface biopsies were positively correlated with HFO rates in adjacent electrode contacts and were not significantly associated with treatment assignment or drug concentrations. Conclusions: A peri-operative loading regimen of perampanel was safe and well-tolerated, with similar peritumoral hyperexcitability as in levetiracetam-treated patients. Maintenance anti-glutamatergic therapy was not observed to impact survival outcomes.

Identifiers

PMID38645003
PMCPMC11030478
OpenAlexW4394785270

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.