Evidence map›Paper›PMID 26830093›Full record

ArticleJournal of neuro-oncology2016

Valproic acid, compared to other antiepileptic drugs, is associated with improved overall and progression-free survival in glioblastoma but worse outcome in grade II/III gliomas treated with temozolomide.

Navid Redjal, Clemens Reinshagen, Andrew Le, Brian P Walcott, Erin McDonnell, Jorg Dietrich, Brian V Nahed

Abstract readComparative Study
PubMed Publisher
In one paragraph

Article in Journal of neuro-oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 2 pooled it
3.3field-weighted citation impact, top 8% of its field
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

32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 52 citations in OpenAlex.

  1. Guideline
  2. Management of epilepsy in brain tumors.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2019
    Guideline
  3. Pilot Trial of Perampanel on Peritumoral Hyperexcitability in Newly Diagnosed High-grade Glioma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Trial
  4. Review
  5. The molecular landscape of glioblastoma-associated epilepsy.Journal of molecular medicine (Berlin, Germany) · 2025
    Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Review
  16. Article
  17. Medical and Neurological Management of Brain Tumor Complications.Current neurology and neuroscience reports · 2021
    Review
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Navid RedjalDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, White Building Room, Gray 502, Boston, MA, 02114, USA. nredjal@gmail.com.
Clemens ReinshagenDepartment of Radiology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, 02114, Boston, MA, USA.
Andrew LeDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, White Building Room, Gray 502, Boston, MA, 02114, USA.
Brian P WalcottDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, White Building Room, Gray 502, Boston, MA, 02114, USA.
Erin McDonnellMGH Biostatistics Center, Massachusetts General Hospital, Harvard Medical School, 50 Staniford Street, Boston, MA, 02114, USA.
Jorg DietrichDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, 02114, MA, USA.
Brian V NahedDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, White Building Room, Gray 502, Boston, MA, 02114, USA.
Harvard University · USMassachusetts General Hospital · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Valproic acid (VPA) is an anti-epileptic drug with properties of a histone deacetylase inhibitor (HDACi). HDACi play a key role in epigenetic regulation of gene expression and have been increasingly used as anticancer agents. Recent studies suggest that VPA is associated with improved survival in high-grade gliomas. However, effects on lower grade gliomas have not been examined. This study investigates whether use of VPA correlates with tumor grade, histological progression, progression-free and overall survival (OS) in grade II, III, and IV glioma patients. Data from 359 glioma patients (WHO II-IV) treated with temozolomide plus an antiepileptic drug (VPA or another antiepileptic drug) between January 1997 and June 2013 at the Massachusetts General Hospital was analyzed retrospectively. After confounder adjustment, VPA was associated with a 28 % decrease in hazard of death (p = 0.031) and a 28 % decrease in the hazard of progression or death (p = 0.015) in glioblastoma. Additionally, VPA dose correlated with reduced hazard of death by 7 % (p = 0.002) and reduced hazard of progression or death by 5 % (p < 0.001) with each 100 g increase in total dose. Conversely, in grade II and III gliomas VPA was associated with a 118 % increased risk of tumor progression or death (p = 0.014), and every additional 100 g of VPA raised the hazard of progression or death by 4 %, although not statistically significant (p = 0.064). Moreover, grade II and III glioma patients taking VPA had 2.17 times the risk of histological progression (p = 0.020), although this effect was no longer significant after confounder adjustment. In conclusion, VPA was associated with improved survival in glioblastoma in a dose-dependent manner. However, in grade II and III gliomas, VPA was linked to histological progression and decrease in progression-free survival. Prospective evaluation of VPA treatment for glioma patients is warranted to confirm these findings.

Indexed as

AdolescentAdultAgedAged, 80 and overAnticonvulsantsAntineoplastic Agents, AlkylatingBrain NeoplasmsChildDacarbazineDrug Therapy, CombinationFemaleFollow-Up StudiesGlioblastomaHumansMaleMiddle AgedAnticonvulsantsAntineoplastic Agents, AlkylatingDacarbazineTemozolomideValproic AcidGlioblastomaGliomaHDACHistone deacetylase inhibitorLow-gradeProgressionSurvivalValproic acid

Identifiers

PMID26830093
OpenAlexW2260723971

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.