Evidence map›Paper›PMID 33631043›Full record

ArticleThe oncologist2021

Mismatch Repair (MMR) Gene Alteration and BRAF V600E Mutation Are Potential Predictive Biomarkers of Immune Checkpoint Inhibitors in MMR-Deficient Colorectal Cancer.

Ibrahim Halil Sahin, Subir Goyal, Yoanna Pumpalova, Mohamad B Sonbol, Satya Das, Sigurdis Haraldsdottir, Daniel Ahn, Kristen K Ciombor, Zhengjia Chen, Amber Draper and 5 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The oncologist, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 2 pooled it
5.6field-weighted citation impact, top 3% 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

25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 47 citations in OpenAlex.

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  15. Clinical research progress on BRAF V600E-mutant advanced colorectal cancer.Journal of cancer research and clinical oncology · 2023
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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

15 authors at 6 institutions in 1 country.

Ibrahim Halil SahinH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.ORCID 0000-0003-2758-3077
Subir GoyalEmory University School of Medicine, Winship Cancer Institute, Atlanta, Georgia, USA.
Yoanna PumpalovaStanford University Cancer Institute, Stanford, California, USA.
Mohamad B SonbolMayo Clinic, Rochester, Minnesota, USA.
Satya DasVanderbilt University Ingram Cancer Center, Nashville, Tennessee, USA.
Sigurdis HaraldsdottirDana-Farber Cancer Institute, Boston, Massachusetts, USA.
Daniel AhnMayo Clinic, Rochester, Minnesota, USA.
Kristen K CiomborVanderbilt University Ingram Cancer Center, Nashville, Tennessee, USA.
Zhengjia ChenEmory University School of Medicine, Winship Cancer Institute, Atlanta, Georgia, USA.
Amber DraperEmory University School of Medicine, Winship Cancer Institute, Atlanta, Georgia, USA.
Jordan BerlinVanderbilt University Ingram Cancer Center, Nashville, Tennessee, USA.
Tanios Bekaii-SaabMayo Clinic, Rochester, Minnesota, USA.
Gregory B LesinskiEmory University School of Medicine, Winship Cancer Institute, Atlanta, Georgia, USA.
Bassel F El-RayesEmory University School of Medicine, Winship Cancer Institute, Atlanta, Georgia, USA.
Christina WuEmory University School of Medicine, Winship Cancer Institute, Atlanta, Georgia, USA.
Emory University · USMayo Clinic · USVanderbilt University · USDana-Farber Cancer Institute · USMoffitt Cancer Center · USStanford University · US

Funding

Winship Cancer Institute Cancer Center Support GrantP30CA138292 · NCI · EMORY UNIVERSITY · PI Suresh S Ramalingam · 2009 to 2026
$47.5M
Vanderbilt Clinical Oncology Research Career Development ProgramK12CA090625 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Debra L. Friedman, Paula Jill Hurley · 2001 to 2026
$16.9M
NCI NIH HHS K12 CA090625NCI NIH HHS P30 CA138292
6 · The paper itself

Abstract

backgroundImmune checkpoint inhibitor (ICI) therapy is highly effective in metastatic mismatch repair-deficient (MMR-D) colorectal cancer (CRC). In this study, we evaluated molecular and clinical predictors of ICI response in MMR-D CRC. MATERIALS AND

methodsPatient databases at four cancer institutions were queried. The Fisher exact test was performed to test the association of clinical and molecular markers. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and compared by the log-rank test. Twelve- and 24-month PFS rates were compared by the Z test.

resultsA total of 60 patients with CRC with MMR-D/microsatellite instability-high who previously received ICIs were identified. Patients with liver metastasis had a lower overall response rate as compared with other sites of metastasis (36.4% vs. 68.7%; p = .081). Patients with MLH1/PMS2 loss had worse 1-year and 2-year PFS rates compared with patients with MSH2/MSH6 loss (84.2% vs. 57.8% and 78.2% vs. 54.2%, respectively; p < .001). There were improved 1-year and 2-year PFS rates in patients with wild-type BRAF when compared with patients with BRAF V600E mutation (73.3% vs. 40%, and 73.3% vs. 26.7%; respectively; p < .001). Patients aged >65 had significantly worse PFS rates as compared with patients aged ≤65 (p < .001).

conclusionBRAF V600E mutation, MLH1 and/or PMS2 loss, as well as age >65 years and liver metastasis, may be predictive of duration of ICI response in patients with MMR-D CRC. Larger cohorts are needed to confirm our findings. IMPLICATIONS FOR PRACTICE: The results of this study reveal clinically important biomarkers that potentially predict immune checkpoint inhibitor response in patients with mismatch repair-deficient colorectal cancer.

Indexed as

Colonic NeoplasmsColorectal NeoplasmsAgedBiomarkersBiomarkers, TumorDNA Mismatch RepairHumansImmune Checkpoint InhibitorsMicrosatellite InstabilityMutationMutL Protein Homolog 1Proto-Oncogene Proteins B-rafBiomarkersBiomarkers, TumorBRAF protein, humanImmune Checkpoint InhibitorsMutL Protein Homolog 1Proto-Oncogene Proteins B-rafBRAFColorectal cancerImmune checkpoint inhibitorsLiver metastasisMicrosatellite instability highMismatch repair-deficientMLH1MSH2MSH6PMS2

Identifiers

PMID33631043
PMCPMC8342606
OpenAlexW3133400147

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.