Trial reportGastroenterology2014
CpG island methylator phenotype is associated with response to adjuvant irinotecan-based therapy for stage III colon cancer.
Trial report in Gastroenterology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 5 of them syntheses that pooled it.
What it found
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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.
Who cites it
78 citing papers in PubMed, 5 syntheses or guidelines pooled it, 131 citations in OpenAlex.
- Meta-Analysis of the Prognostic and Predictive Role of the CpG Island Methylator Phenotype in Colorectal Cancer.Disease markers · 2022Pooled it
- Distant Metastasis in Colorectal Cancer Patients-Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review.International journal of molecular sciences · 2020Pooled it
- Global differences in the prevalence of the CpG island methylator phenotype of colorectal cancer.BMC cancer · 2019Pooled it
- Epigenetic Biomarkers in Colorectal Cancer Patients Receiving Adjuvant or Neoadjuvant Therapy: A Systematic Review of Epidemiological Studies.International journal of molecular sciences · 2019Pooled it
- Different definitions of CpG island methylator phenotype and outcomes of colorectal cancer: a systematic review.Clinical epigenetics · 2016Pooled it
- Evaluating the utility ofEpigenetics · 2024Trial
- Evaluation of CpG Island Methylator Phenotype as a Biomarker in Colorectal Cancer Treated With Adjuvant Oxaliplatin.Clinical colorectal cancer · 2016Trial
- MALMPS: A Machine Learning-Based Metabolic Gene Prognostic Signature for Stratifying Clinical Outcomes and Molecular Heterogeneity in Stage II/III Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Insight into the role of DNA methylation in prognosis and treatment response prediction of gastrointestinal cancers.Epigenomics · 2025Review
- Tumor aggression-defense index-a novel indicator to predicts recurrence and survival in stage II-III colorectal cancer.Journal of translational medicine · 2025Article
- Unveiling tumor senescence-driven prognostic heterogeneity via MALISS in stage II/III colorectal cancer.Frontiers in immunology · 2025Article
- Phenotype driven data augmentation methods for transcriptomic data.Bioinformatics advances · 2025Article
- Review
- The CpG Island Methylator Phenotype Status in Synchronous and Solitary Primary Colorectal Cancers: Prognosis and Effective Therapeutic Drug Prediction.International journal of molecular sciences · 2024Review
- The Tumor Suppressor SOCS1 Diminishes Tolerance to Oxidative Stress in Hepatocellular Carcinoma.Cancers · 2024Article
- Article
- SOCS1 expression in cancer cells: potential roles in promoting antitumor immunity.Frontiers in immunology · 2024Article
- A Multi-Omics Overview of Colorectal Cancer to Address Mechanisms of Disease, Metastasis, Patient Disparities and Outcomes.Cancers · 2023Review
- DNA methylation profile in CpG-depleted regions uncovers a high-risk subtype of early-stage colorectal cancer.Journal of the National Cancer Institute · 2023Article
- Identification of a ferroptosis-related gene signature predicting recurrence in stage II/III colorectal cancer based on machine learning algorithms.Frontiers in pharmacology · 2023Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 13 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsThe CpG island methylator phenotype (CIMP), defined by a high frequency of aberrantly methylated genes, is a characteristic of a subclass of colon tumors with distinct clinical and molecular features. Cohort studies have produced conflicting results on responses of CIMP-positive tumors to chemotherapy. We assessed the association between tumor CIMP status and survival of patients receiving adjuvant fluorouracil and leucovorin alone or with irinotecan (IFL).
methodsWe analyzed data from patients with stage III colon adenocarcinoma randomly assigned to groups given fluorouracil and leucovorin or IFL after surgery, from April 1999 through April 2001. The primary end point of the trial was overall survival and the secondary end point was disease-free survival. DNA isolated from available tumor samples (n = 615) was used to determine CIMP status based on methylation patterns at the CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1 loci. The effects of CIMP on survival were modeled using Kaplan-Meier and Cox proportional hazards; interactions with treatment and BRAF, KRAS, and mismatch repair (MMR) status were also investigated.
resultsOf the tumor samples characterized for CIMP status, 145 were CIMP positive (23%). Patients with CIMP-positive tumors had shorter overall survival times than patients with CIMP-negative tumors (hazard ratio = 1.36; 95% confidence interval: 1.01-1.84). Treatment with IFL showed a trend toward increased overall survival for patients with CIMP-positive tumors, compared with treatment with fluorouracil and leucovorin (hazard ratio = 0.62; 95% CI: 0.37-1.05; P = .07), but not for patients with CIMP-negative tumors (hazard ratio = 1.38; 95% CI: 1.00-1.89; P = .049). In a 3-way interaction analysis, patients with CIMP-positive, MMR-intact tumors benefited most from the addition of irinotecan to fluorouracil and leucovorin therapy (for the interaction, P = .01). CIMP was more strongly associated with response to IFL than MMR status. Results for disease-free survival times were comparable among all analyses.
conclusionsPatients with stage III, CIMP-positive, MMR-intact colon tumors have longer survival times when irinotecan is added to combination therapy with fluorouracil and leucovorin.
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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.