Evidence map›Paper›PMID 34467991›Full record

SynthesisNeuro-oncology2021

MGMT promoter methylation testing to predict overall survival in people with glioblastoma treated with temozolomide: a comprehensive meta-analysis based on a Cochrane Systematic Review.

Sebastian Brandner, Alexandra McAleenan, Claire Kelly, Francesca Spiga, Hung-Yuan Cheng, Sarah Dawson, Lena Schmidt, Claire L Faulkner, Christopher Wragg, Sarah Jefferies and 2 more

Open access · bronzeAbstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in Neuro-oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 1 pooled it
7.0field-weighted citation impact, top 2% 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

54 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 1 country.

Sebastian BrandnerDivision of Neuropathology and Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.ORCID 0000-0002-9821-0342
Alexandra McAleenanPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.ORCID 0000-0003-2119-5604
Claire KellyPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Francesca SpigaPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.ORCID 0000-0002-6904-2247
Hung-Yuan ChengPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.ORCID 0000-0002-6162-4146
Sarah DawsonPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Lena SchmidtPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.ORCID 0000-0003-0709-8226
Claire L FaulknerBristol Genetics Laboratory, Pathology Sciences, Southmead Hospital, Bristol, UK.
Christopher WraggBristol Genetics Laboratory, Pathology Sciences, Southmead Hospital, Bristol, UK.ORCID 0000-0001-5960-742X
Sarah JefferiesDepartment of Oncology, Addenbrooke's Hospital, Cambridge, UK.ORCID 0000-0001-7660-4466
Julian P T HigginsPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.ORCID 0000-0002-8323-2514
Kathreena M KurianBristol Medical School, Brain Tumour Research Centre, Population Health Sciences, University of Bristol, Bristol, UK.ORCID 0000-0003-0303-3716
University of Bristol · GBSouthmead Hospital · GBAddenbrooke's Hospital · GBNational Hospital for Neurology and Neurosurgery · GB

Funding

Cancer Research UK 29019Cancer Research UK C18281/A19169
6 · The paper itself

Abstract

backgroundThe DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) causes resistance of tumor cells to alkylating agents. It is a predictive biomarker in high-grade gliomas treated with temozolomide, however, there is no consensus on which test method, methylation sites, and cutoff values to use.

methodsWe performed a Cochrane Review to examine studies using different techniques to measure MGMT and predict survival in glioblastoma patients treated with temozolomide. Eligible longitudinal studies included (i) adults with glioblastoma treated with temozolomide with or without radiotherapy, or surgery; (ii) where MGMT status was determined in tumor tissue, and assessed by 1 or more technique; and (iii) where overall survival was an outcome parameter, with sufficient information to estimate hazard ratios (HRs). Two or more methods were compared in 32 independent cohorts with 3474 patients.

resultsMethylation-specific PCR (MSP) and pyrosequencing (PSQ) techniques were more prognostic than immunohistochemistry for MGMT protein, and PSQ is a slightly better predictor than MSP.

conclusionsWe cannot draw strong conclusions about use of frozen tissue vs formalin-fixed paraffin-embedded in MSP and PSQ. Also, our meta-analysis does not provide strong evidence about the best CpG sites or threshold. MSP has been studied mainly for CpG sites 76-80 and 84-87 and PSQ at CpG sites ranging from 72 to 95. A cutoff threshold of 9% for CpG sites 74-78 performed better than higher thresholds of 28% or 29% in 2 of the 3 good-quality studies. About 190 studies were identified presenting HRs from survival analysis in patients in which MGMT methylation was measured by 1 technique only.

Indexed as

Brain NeoplasmsGlioblastomaGliomaAntineoplastic Agents, AlkylatingDNA MethylationDNA Modification MethylasesDNA Repair EnzymesHumansMethylationPromoter Regions, GeneticTemozolomideTumor Suppressor ProteinsAntineoplastic Agents, AlkylatingDNA Modification MethylasesDNA Repair EnzymesMGMT protein, humanTemozolomideTumor Suppressor Proteinsglioblastomameta-analysisMGMT promoter methylationprognostic biomarkertemozolomide

Identifiers

PMID34467991
PMCPMC8408882
OpenAlexW3158989562

What OpenQuestion holds

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LicenceCC BY-NC
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.