Molecular characterization of a large unselected cohort of metastatic colorectal cancers in relation to primary tumor location, rare metastatic sites and prognosis

Nunes, Luís; Aasebø, Kristine; Mathot, Lucy; Ljungström, Viktor; Edqvist, Per Henrik; Sundström, Magnus; Dragomir, Anca; Pfeiffer, Per; Ameur, Adam; Pontén, Fredrik; Mezheyeuski, Artur; Sørbye, Halfdan; Sjöblom, Tobias; Glimelius, Bengt

doi:10.1080/0284186x.2019.1711169

Cited by 26 publications

(49 citation statements)

References 39 publications

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“…These two associations could be explained by the fact that only KRAS wild-type specimens were screened for BRAF. These results coincide with the association between BRAF (but no KRAS) mutational status and the proximal colon in Chinese, Australian, and Swedish populations [8,10,40].…”

Section: Traditional Statistical Associationssupporting

confidence: 83%

“…The only study in an African population, conducted in Morocco, registered a KRAS mutation frequency of 23.9% [37]. Studies performed in Asian populations report KRAS mutation prevalence varying from 37.9% (Japan) to 52.7% (China), whereas NRAS and BRAF mutations prevalence are closer with China reporting 3.4% and 4.5% while Japan referring 4.2% and 5.4%, respectively [8,38], nevertheless, population-based studies report up to 20% of CRC patients with BRAF mutations [39,40]. This difference could be due since every specimen was screened for KRAS, but only those that were KRAS wild type were screened for BRAF since KRAS and BRAF mutations are generally mutually exclusive.…”

Section: Plos Onementioning

confidence: 99%

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KRAS, NRAS, and BRAF mutation prevalence, clinicopathological association, and their application in a predictive model in Mexican patients with metastatic colorectal cancer: A retrospective cohort study

Sánchez-Ibarra¹,

Jiang

Gallegos-Gonzalez³

et al. 2020

PLoS ONE

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Mutations in KRAS, NRAS, and BRAF (RAS/BRAF) genes are the main predictive biomarkers for the response to anti-EGFR monoclonal antibodies (MAbs) targeted therapy in metastatic colorectal cancer (mCRC). This retrospective study aimed to report the mutational status prevalence of these genes, explore their possible associations with clinicopathological features, and build and validate a predictive model. To achieve these objectives, 500 mCRC Mexican patients were screened for clinically relevant mutations in RAS/BRAF genes. Fifty-two percent of these specimens harbored clinically relevant mutations in at least one screened gene. Among these, 86% had a mutation in KRAS, 7% in NRAS, 6% in BRAF, and 2% in both NRAS and BRAF. Only tumor location in the proximal colon exhibited a significant correlation with KRAS and BRAF mutational status (p-value = 0.0414 and 0.0065, respectively). Further t-SNE analyses were made to 191 specimens to reveal patterns among patients with clinical parameters and KRAS mutational status. Then, directed by the results from classical statistical tests and t-SNE analysis, neural network models utilized entity embeddings to learn patterns and build predictive models using a minimal number of trainable parameters. This study could be the first step in the prediction for RAS/ BRAF mutational status from tumoral features and could lead the way to a more detailed and more diverse dataset that could benefit from machine learning methods.

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Section: Traditional Statistical Associationssupporting

confidence: 83%

Section: Plos Onementioning

confidence: 99%

KRAS, NRAS, and BRAF mutation prevalence, clinicopathological association, and their application in a predictive model in Mexican patients with metastatic colorectal cancer: A retrospective cohort study

Sánchez-Ibarra¹,

Jiang

Gallegos-Gonzalez³

et al. 2020

PLoS ONE

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“…Vishal et al have suggested that CEA, CA-199, and the primary tumor location are independent predictors for patients with CRC [34,35]. Serum levels of CEA and CA-199 are recommended to be evaluated clinically, which plays a vital role in disease monitoring, e cacy evaluation [36].…”

Section: Discussionmentioning

confidence: 99%

The Decreased Platelet-to-Lymphocyte Ratio Could Predict a Good Prognosis in Patients with Oligometastatic Colorectal Cancer: A Single-Center Cohort Retrospective Study

Huang

Cui

et al. 2021

Preprint

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Background Inflammation markers have an important effect on tumor proliferation, invasion, and metastasis. Oligometastatic disease (OMD) is an intermediate state between widespread metastases and locally confined disease, where curative strategies may be effective for some patients. We aimed to explore the predictive value of inflammatory markers in patients with oligometastatic colorectal cancer (OMCC) and build a nomogram to predict the prognosis of these patients.Methods 209 patients with OMCC were retrospectively collected in this study. The Kaplan-Meier survival curves and Cox regression analysis were used to estimate overall survival (OS) and progression-free survival (PFS). A Multivariate Cox analysis model was utilized to establish the nomogram. The concordance index (C-index), calibration curve, and receiver operating characteristics (ROC) were established to verify the validity and accuracy of the prediction model.Results According to the multivariate analysis, decreased platelet-to-lymphocyte ratio (PLR) might independently improve OS in patients with OMCC (HR = 2.396, 95%CI: 1.391- 4.126, P = 0.002). Metastases of extra-regional lymph nodes indicated poor OS (HR = 2.472, 95%CI: 1.247-4.903, P = 0.010). While the patients with early N stage had better OS (HR = 4.602, 95%CI: 2.055-10.305, P = 0.001) and PFS (HR = 2.100, 95%CI: 1.364-3.231, P = 0.007). Primary tumor resection (HR = 0.367, 95%CI: 0.148-0.908, P = 0.030) and lower fibrinogen (HR = 2.254, 95%CI: 1.246-4.078, P = 0.007) could significantly prolong the OS in patients with OMCC. PLR, metastases of extra-regional lymph nodes, N stage, primary tumor resection, and fibrinogen were used to make up the nomogram. The C-index and area under the curve (AUC) of the ROC in nomogram were 0.721 and 0.772 respectively for OS, showed good consistency between predictive probability of OS and actual survival.Conclusions Decreased PLR could predict a good prognosis in patients with OMCC. The nomogram including inflammatory factors and clinicopathological markers was credible and accurate to predict survivals in patients with OMCC.

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“…However, the anti-VEGF agent bevacizumab may be used independent of RAS mutation status or primary tumour sidedness [9]. BRAF V600E mutations, found in about 5-12% of all mCRC cases included in clinical trials but in about 20% in unselected populationbased patient materials [10,11], also require consideration when selecting treatment regimens and in the evaluation of the prognosis; BRAF V600E-mutation generally means rapid progression and poor survival with less and/or shorter response to chemotherapy. Several tyrosine kinase inhibitors such as vemurafenib, dabrafenib, and encorafenib bind specifically to the ATP-binding domain of BRAF V600E [12].…”

Section: Recent Advances In Mcrc Treatmentmentioning

confidence: 99%

“…In mCRC, MSI-H tumours are quite rare, affecting ~4% of the trial population [28,29]. However, again, incidence of these tumours is higher (7-8%) in the background population [11,28]. Notably, atezolizumab with/without cobimetinib recently failed to achieve superior efficacy outcomes relative to regorafenib in the third-line treatment of patients with predominantly microsatellite-stable mCRC within a phase 3 randomised trial [30].…”

Section: Recent Advances In Mcrc Treatmentmentioning

confidence: 99%

Metastatic colorectal cancer: Advances in the folate-fluoropyrimidine chemotherapy backbone

Glimelius

Stintzing

Marshall

et al. 2021

Cancer Treatment Reviews

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Molecular characterization of a large unselected cohort of metastatic colorectal cancers in relation to primary tumor location, rare metastatic sites and prognosis

Abstract: Glimelius (2020) Molecular characterization of a large unselected cohort of metastatic colorectal cancers in relation to primary tumor location, rare metastatic sites and prognosis,

Cited by 26 publications

References 39 publications

KRAS, NRAS, and BRAF mutation prevalence, clinicopathological association, and their application in a predictive model in Mexican patients with metastatic colorectal cancer: A retrospective cohort study

KRAS, NRAS, and BRAF mutation prevalence, clinicopathological association, and their application in a predictive model in Mexican patients with metastatic colorectal cancer: A retrospective cohort study

The Decreased Platelet-to-Lymphocyte Ratio Could Predict a Good Prognosis in Patients with Oligometastatic Colorectal Cancer: A Single-Center Cohort Retrospective Study

Metastatic colorectal cancer: Advances in the folate-fluoropyrimidine chemotherapy backbone

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