Clinical value of consensus molecular subtypes in colorectal cancer: a systematic review and meta-analysis

ten Hoorn, Sanne; de Back, Tim R; Sommeijer, Dirkje W; Vermeulen, Louis

doi:10.1093/jnci/djab106

Cited by 203Colorectal Cancer Treatments and StudiesColorectal Cancer Surgical TreatmentsGenetic factors in colorectal cancer

Clinical value of consensus molecular subtypes in colorectal cancer: a systematic review and meta-analysis

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ten Hoorn, Sanne, de Back, Tim R, Sommeijer, Dirkje W, Vermeulen, Louis·2022·JNCI: Journal of the National Cancer Institute

DOI 10.1093/jnci/djab106PMC PMC9002278

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Abstract

Background: The consensus molecular subtypes (CMSs) of colorectal cancer (CRC) capture tumor heterogeneity at the gene-expression level. Currently, a restricted number of molecular features are used to guide treatment for CRC. We summarize the evidence on the clinical value of the CMSs. Methods: We systematically identified studies in Medline and Embase that evaluated the prognostic and predictive value of CMSs in CRC patients. A random-effect meta-analysis was performed on prognostic data. Predictive data were summarized. Results: In local disease, CMS4 tumors were associated with worse overall survival (OS) compared with CMS1 (hazard ratio [HR] = 3.28, 95% confidence interval = 1.27 to 8.47) and CMS2 cancers (HR = 2.60, 95% confidence interval = 1.93 to 3.50). In metastatic disease, CMS1 consistently had worse survival than CMS2-4 (OS HR range = 0.33-0.55; progression-free survival HR range = 0.53-0.89). Adjuvant chemotherapy in stage II and III CRC was most beneficial for OS in CMS2 and CMS3 (HR range = 0.16-0.45) and not effective in CMS4 tumors. In metastatic CMS4 cancers, an irinotecan-based regimen improved outcome compared with oxaliplatin (HR range = 0.31-0.72). The addition of bevacizumab seemed beneficial in CMS1, and anti-epidermal growth factor receptor therapy improved outcome for KRAS wild-type CMS2 patients. Conclusions: The CMS classification holds clear potential for clinical use in predicting both prognosis and response to systemic therapy, which seems to be independent of the classifier used. Prospective studies are warranted to support implementation of the CMS taxonomy in clinical practice.

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CMS4 colorectal cancer is consistently associated with a dismal outcome, including at early stage.
“CMS4 colorectal cancer is consistently associated with a dismal outcome (1, 26), including at early stage (27).”
From Clinical Challenges of Consensus Molecular Subtype CMS4 Colon Cancer in the Era of Precision Medicine (2024) · cites this paper as [26]
In the metastatic setting, irinotecan-based regimens have superior efficacy compared with those with an oxaliplatin backbone.
“in the metastatic setting, irinotecan-based regimens have superior efficacy compared with those with an oxaliplatin backbone (26).”
From Clinical Challenges of Consensus Molecular Subtype CMS4 Colon Cancer in the Era of Precision Medicine (2024) · cites this paper as [26]
Patients with stage II and III CMS4 colorectal cancer benefit less from adjuvant chemotherapy than other subtypes.
“It is now quite well established that patients with stage II and III CMS4 colorectal cancer benefit less from adjuvant chemotherapy than other subtypes”
From Clinical Challenges of Consensus Molecular Subtype CMS4 Colon Cancer in the Era of Precision Medicine (2024) · cites this paper as [26]
The FOLFIRI + cetuximab combination (for RAS wild-type patients) is superior to the FOLFIRI + bevacizumab combination.
“the FOLFIRI + cetuximab combination (for RAS wild-type patients) is superior to the FOLFIRI + bevacizumab combination (26).”
From Clinical Challenges of Consensus Molecular Subtype CMS4 Colon Cancer in the Era of Precision Medicine (2024) · cites this paper as [26]

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[110]Sirinukunwattana K, Domingo E, Richman SD, et al Image-based consensus molecular subtype (imCMS) classification of colorectal cancer using deep learning. Gut. 2021; 70(3): 544– 554. doi:10.1136/gutjnl-2019-319866. 32690604 PMC7873419 · DOI · Paper page

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Authors: ten Hoorn, S., de Back, T. R., Sommeijer, D. W., & Vermeulen, L.
Affiliations: Amsterdam University Medical Centers (UMC), University of Amsterdam, Lab. for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, Amsterdam, the Netherlands
Flevoziekenhuis (NL)
Amsterdam University Medical Centers (NL)
Corresponding author: Vermeulen, Louis
ORCID: ten Hoorn, Sanne
de Back, Tim R
Sommeijer, Dirkje W
Vermeulen, Louis
Venue: JNCI: Journal of the National Cancer Institute
Publisher: Oxford University Press (OUP)
Published: 2021-06-02
Volume: 114
Issue: 4
Pages: 503-516
ISSN: 0027-8874 (ISSN-L)
1460-2105
DOI: 10.1093/jnci/djab106
PMC: PMC9002278
OpenAlex: W3165521652
Cited by: 203
References: 107
Citations by year: 2026: 44 · 2025: 42 · 2024: 41 · 2023: 47 · 2022: 24 · 2021: 4
FWCI: 3.51
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
creativecommons.org/licenses/by-nc/4.0/ (vor)
Locations: JNCI Journal of the National Cancer Institute (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
Pure Amsterdam UMC (publishedVersion, cc-by)
Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders: Oncode Institute, the Dutch Cancer Society (KWF 10529)
European Research Council (ERG-StG 638193)
ZonMw (Vidi 016.156.308)
Innovatiefonds Zorgverzekeraars (B17-140)
New York Stem Cell Foundation—Robertson Investigator
Topics: Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Keywords: consensus molecular subtypes, colorectal cancer, prognostic value, predictive value, overall survival, progression-free survival, adjuvant chemotherapy, irinotecan, oxaliplatin, bevacizumab, anti-EGFR therapy, KRAS wild-type, metastatic colorectal cancer, stage II and III colorectal cancer, tumor heterogeneity
MeSH terms: Bevacizumab, Oxaliplatin, Humans, Prognosis, Biomarkers, Tumor, Colorectal Neoplasms, Consensus Sequence, Gene Expression Profiling

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Clinical value of consensus molecular subtypes in colorectal cancer: a systematic review and meta-analysis

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