Evidence map›Paper›PMID 31504112›Full record

ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2019

Relative contribution of clinicopathological variables, genomic markers, transcriptomic subtyping and microenvironment features for outcome prediction in stage II/III colorectal cancer.

R Dienstmann, G Villacampa, A Sveen, M J Mason, D Niedzwiecki, A Nesbakken, V Moreno, R S Warren, R A Lothe, J Guinney

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06314958 (Predicting Recurrence-Free Survival in Stage III and High-Risk Stage II Colorectal Cancer After Curative-Intent Treatment), which is not on this map. Cited by 148 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
148citing papers in PubMed, 1 pooled it
–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.

NCT06314958 recruitingnot on this mapstarted 2023, after this paper: background citation

Predicting Recurrence-Free Survival in Stage III and High-Risk Stage II Colorectal Cancer After Curative-Intent Treatment

TypeobservationalSponsorCity of Hope Medical CenterRan2023 to 2028Enrolled400ConditionsColorectal Cancer, Colorectal Adenocarcinoma, Colorectal Cancer Stage II, Colorectal Cancer Stage IIIArmsCENSURE
3 · Its place in the literature

Who cites it

148 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  3. Loss of ARID1A expression is associated with worse survival and reduced tumor infiltrating lymphocytes in advanced clear cell renal cell carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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88 more citing papers are in PubMed but not listed here.

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

10 authors.

R DienstmannOncology Data Science Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain; Computational Oncology Group, Sage Bionetworks, Seattle, USA. Electronic address: rdienstmann@vhio.net.
G VillacampaOncology Data Science Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
A SveenDepartment of Molecular Oncology, Institute for Cancer Research and K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
M J MasonComputational Oncology Group, Sage Bionetworks, Seattle, USA.
D NiedzwieckiDepartment of Bioinformatics and Biostatistics, Duke University, Durham, USA.
A NesbakkenFaculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Gastrointestinal Surgery, K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo, Norway.
V MorenoUnit of Biomarkers and Susceptibility, Cancer Prevention and Control Program, Catalan Institute of Oncology, Oncobell Program of IDIBELL, CIBERESP, University of Barcelona, Barcelona, Spain.
R S WarrenDepartment of Surgery, The Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, USA.
R A LotheDepartment of Molecular Oncology, Institute for Cancer Research and K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
J GuinneyComputational Oncology Group, Sage Bionetworks, Seattle, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIt remains unknown to what extent consensus molecular subtype (CMS) groups and immune-stromal infiltration patterns improve our ability to predict outcomes over tumor-node-metastasis (TNM) staging and microsatellite instability (MSI) status in early-stage colorectal cancer (CRC). PATIENTS AND

methodsWe carried out a comprehensive retrospective biomarker analysis of prognostic markers in adjuvant chemotherapy-untreated (N = 1656) and treated (N = 980), stage II (N = 1799) and III (N = 837) CRCs. We defined CMS scores and estimated CD8+ cytotoxic lymphocytes (CytoLym) and cancer-associated fibroblasts (CAF) infiltration scores from bulk tumor tissue transcriptomes (CMSclassifier and MCPcounter R packages); constructed a stratified multivariable Cox model for disease-free survival (DFS); and calculated the relative proportion of explained variation by each marker (clinicopathological [ClinPath], genomics [Gen: MSI, BRAF and KRAS mutations], CMS scores [CMS] and microenvironment cells [MicroCells: CytoLym+CAF]).

resultsIn multivariable models, only ClinPath and MicroCells remained significant prognostic factors, with both CytoLym and CAF infiltration scores improving survival prediction beyond other markers. The explained variation for DFS models of ClinPath, MicroCells, Gen markers and CMS4 scores was 77%, 14%, 5.3% and 3.7%, respectively, in stage II; and 55.9%, 35.1%, 4.1% and 0.9%, respectively, in stage III. Patients whose tumors were CytoLym high/CAF low had better DFS than other strata [HR=0.71 (0.6-0.9); P = 0.004]. Microsatellite stable tumors had the strongest signal for improved outcomes with CytoLym high scores (interaction P = 0.04) and the poor prognosis linked to high CAF scores was limited to stage III disease (interaction P = 0.04).

conclusionsOur results confirm that tumor microenvironment infiltration patterns represent potent determinants of the risk for distant dissemination in early-stage CRC. Multivariable models suggest that the prognostic value of MSI and CMS groups is largely explained by CytoLym and CAF infiltration patterns.

Indexed as

Microsatellite InstabilityMutationAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorChemotherapy, AdjuvantColorectal NeoplasmsFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticGenomicsHumansMaleMiddle AgedBiomarkers, TumorCMScolorectal cancerimmunemicrosatellite instabilityprognosisstromal

Identifiers

PMID31504112
PMCPMC6857614

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Registered trials

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.