Adjuvant FOLFOX +/− cetuximab in fullRAS andBRAF wildtype stage III colon cancer patients

Taı̈eb, Julien; Balogoun, Ralyath; Malicot, Karine Le; Tabernero, Josep; Mini, Enrico; Folprecht, Gunnar; Laethem, Jean Luc Van; Émile, Jean-François; Mulot, Claire; Fratté, S.; Levaché, Charles-Briac; Saban-Roche, Léa; Thaler, Josef; Petersen, Lone; Bridgewater, John; Perkins, Géraldine; Lepage, Côme; Cutsem, Éric Van; Zaanan, Aziz; Laurent‐Puig, Pierre

doi:10.1093/annonc/mdw687

Cited by 42 publications

(22 citation statements)

References 25 publications

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“…All 2559 patients were originally included between 22 December 2005 and 5 November 2009. Microsatellite stable (MSS) status, K-RAS, N-RAS and BRAF mutational statuses were determined as previously described 25 28. Enrolled patients had signed an informed consent for translational research.…”

Section: Methodsmentioning

confidence: 99%

Artificial intelligence-guided tissue analysis combined with immune infiltrate assessment predicts stage III colon cancer outcomes in PETACC08 study

Reichling

Taieb

Dérangère

et al. 2019

Gut

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ObjectiveDiagnostic tests, such as Immunoscore, predict prognosis in patients with colon cancer. However, additional prognostic markers could be detected on pathological slides using artificial intelligence tools.DesignWe have developed a software to detect colon tumour, healthy mucosa, stroma and immune cells on CD3 and CD8 stained slides. The lymphocyte density and surface area were quantified automatically in the tumour core (TC) and invasive margin (IM). Using a LASSO algorithm, DGMate (DiGital tuMor pArameTErs), we detected digital parameters within the tumour cells related to patient outcomes.ResultsWithin the dataset of 1018 patients, we observed that a poorer relapse-free survival (RFS) was associated with high IM stromal area (HR 5.65; 95% CI 2.34 to 13.67; p<0.0001) and high DGMate (HR 2.72; 95% CI 1.92 to 3.85; p<0.001). Higher CD3+ TC, CD3+ IM and CD8+ TC densities were significantly associated with a longer RFS. Analysis of variance showed that CD3+ TC yielded a similar prognostic value to the classical CD3/CD8 Immunoscore (p=0.44). A combination of the IM stromal area, DGMate and CD3, designated ‘DGMuneS’, outperformed Immunoscore when used in estimating patients’ prognosis (C-index=0.601 vs 0.578, p=0.04) and was independently associated with patient outcomes following Cox multivariate analysis. A predictive nomogram based on DGMuneS and clinical variables identified a group of patients with less than 10% relapse risk and another group with a 50% relapse risk.ConclusionThese findings suggest that artificial intelligence can potentially improve patient care by assisting pathologists in better defining stage III colon cancer patients’ prognosis.

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Section: Methodsmentioning

confidence: 99%

Artificial intelligence-guided tissue analysis combined with immune infiltrate assessment predicts stage III colon cancer outcomes in PETACC08 study

Reichling

Taieb

Dérangère

et al. 2019

Gut

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“…Interestingly, the benefit of having a codon 13 mutation is restricted to cancers from the right side colon [29]. Moreover, CRC patients with codon 146 mutations appear to exhibit improved overall survival relative to patients with other mutations, while patients with codon 61 mutations exhibit poor overall and progression-free survival [31, 32]. Whether this difference in survival is a direct function of KRAS allele status, or whether it reflects a genotype-independent ( i.e.…”

Section: Epidemiology Of Kras Allelesmentioning

confidence: 99%

KRAS Alleles: The Devil Is in the Detail

2017

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KRAS is the most frequently mutated oncogene in cancer and KRAS mutation is commonly associated with poor prognosis and resistance to therapy. Since the KRAS oncoprotein is, as yet, not directly druggable, efforts to target KRAS mutant cancers focus on identifying vulnerabilities in downstream signaling pathway or in stress-response pathways that are permissive for strong oncogenic signaling. One aspect of KRAS biology that is not well appreciated is the potential biological differences between the many distinct KRAS activating mutations. This review draws upon insights from both clinical and experimental studies to explore similarities and differences among KRAS alleles. Historical and emerging evidence supports the notion that the specific biology related to each allele might be exploitable for allele-specific therapy.

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“…[27][28][29] And prevous study reported the relationship of F. nucleatum with immune response to CRC by different MSI status, 30 which suggesting that F. nucleatum abundance correlated with MSI status and regulates antitumor immune response in CRC. Moreover, KRAS mutation also is an important molecular feature for chemotherapy resistance in CRC, 31 and F. nucleatum was abundant in colorectal cancer tissues also will cause chemoresistance. 32 Therefore, our result further con rmed this correlation which imply F. nucleatum is another underlying biomarker for response of immunotherapy and chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological and prognostic significance of Fusobacterium nucleatum infection in colorectal cancer: a meta-analysis

Huangfu

Zhang

Zhang³

et al. 2020

Preprint

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Background: Accumulating evidences about the association between Fusobacterium nucleatum (F. nucleatum) and colorectal cancer (CRC) has been reported in various studies. However, the definite relationship between abundance of F. nucleatum with clinical characteristics and prognosis of CRC is still controversial. Methods: PubMed, Embase and Web of Science were searched for relevant articles up to April 7, 2020. Outcomes of interest included clinical characteristics, molecular characteristic and survival analysis. HR (OR), odds ratios (OR) and 95% confidence interval (CI) were calculated to explore the prognostic value and relationship of clinical characteristics of Fusobacterium nucleatum in CRC.Results: A total of 3626 patients with CRC from 13 eligible studies were included. High abundance of F. nucleatum was associated with worse prognosis on overall survival (OS) (HR= 1.40, P < 0.0001), disease-free survival (DFS) (HR = 1.71, P = 0.0002) and cancer-specific survival (OR= 1.93, P <0.0001). In addition, F. nucleatum abundance was related with T (T3-T4) stage(OR = 2.20, P < 0.00001), M (M1) stage (OR = 2.11, P = 0.005), poor tumor differentation(OR = 1.83, P =0.02), microsatellite instability (MSI) -high (OR = 2.53, P = 0.0003) and KRAS mutation (OR =1.27, P=0.05).Conclusion: The present evidences revealed that high abundance of F. nucleatum is inclined to indicate worse prognosis and is associated with tumor growth, distant Impact: This study highlights the risk factor of F. nucleatum for worse prognosis of CRC.

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Adjuvant FOLFOX +/− cetuximab in fullRAS andBRAF wildtype stage III colon cancer patients

Abstract: This is an ancillary study of the PETACC8 trial: EUDRACT 2005-003463-23.

Cited by 42 publications

References 25 publications

Artificial intelligence-guided tissue analysis combined with immune infiltrate assessment predicts stage III colon cancer outcomes in PETACC08 study

Artificial intelligence-guided tissue analysis combined with immune infiltrate assessment predicts stage III colon cancer outcomes in PETACC08 study

KRAS Alleles: The Devil Is in the Detail

Clinicopathological and prognostic significance of Fusobacterium nucleatum infection in colorectal cancer: a meta-analysis

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