KRAS and BRAF Mutations in Stage II and III Colon Cancer: A Systematic Review and Meta-Analysis

JNCI Journal of the National Cancer Institute, Journal Year: 2021, Volume and Issue: 114(4), P. 517 - 527

Published: Sept. 17, 2021

KRAS and BRAF mutations are well-established predictive prognostic factors in metastatic colorectal cancer; however, their impact the adjuvant setting has not yet been established.We performed a meta-analysis of phase III trials patients with stage II colon cancer available data on or both disease-free survival (DFS) overall (OS). Trials were subgrouped based whether adjustment for microsatellite instability (MSI) was subgroup effect analyzed through meta-regression. To increase precision estimates, joint DFS-OS (so-called "multivariate") performed. All statistical tests 2-sided.Nine selected (QUASAR 2, PETACC-8, N0147, CALGB-89803, NSABP-C07, NSABP-C08, PETACC-3, QUASAR, MOSAIC) including total 10 893 patients. In primary meta-analysis, mutation associated poor DFS (pooled hazard ratio [HR] = 1.36, 95% confidence interval [CI] 1.15 to 1.61, P < .001) OS HR 1.27, CI 1.03 1.55, .03) also 1.33, 1.00 1.78, .05) 1.49, 1.31 1.70, .001). The outcome enhanced MSI-adjusted 1.43, 1.79, .001; pooled 1.71, 1.59, 1.22 2.07, 1.67, 1.37 2.04, interaction between MSI statistically significant (Pinteraction .02). This even more pronounced multivariate meta-analysis.Both significantly OS, being by adjustment. Effective treatment microsatellite-stable KRAS-mutated represents an unmet clinical need, exploring use recently inhibitors this would be highly desirable.

Language: Английский

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Liquid biopsy in colorectal cancer: Onward and upward

Critical Reviews in Oncology/Hematology, Journal Year: 2023, Volume and Issue: 194, P. 104242 - 104242

Published: Dec. 20, 2023

Language: Английский

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Management of Colorectal Cancer with Synchronous Liver Metastases: An Inception Cohort Study (CoSMIC)

Annals of Surgical Oncology, Journal Year: 2021, Volume and Issue: 29(3), P. 1939 - 1951

Published: Oct. 30, 2021

Language: Английский

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Rapid Multiplex Strip Test for the Detection of Circulating Tumor DNA Mutations for Liquid Biopsy Applications

Biosensors, Journal Year: 2022, Volume and Issue: 12(2), P. 97 - 97

Published: Feb. 4, 2022

In the era of personalized medicine, molecular profiling patient tumors has become standard practice, especially for patients with advanced disease. Activating point mutations KRAS proto-oncogene are clinically relevant many types cancer, including colorectal cancer (CRC). While several approaches have been developed tumor genotyping, liquid biopsy gaining much attention in clinical setting. Analysis circulating DNA genetic alterations challenging, and methodologies both advantages disadvantages developed. We here a gold nanoparticle-based rapid strip test that applied first time multiplex detection (ctDNA) CRC patients. The method involved ctDNA isolation, PCR-amplification gene, primer extension (PEXT) reaction, test. optimized efficiency specificity synthetic targets, cell lines, tissue samples, blood-derived from cancer. proposed achieved easy (normal allele three major single-point mutations) blood samples high repeatability. This represents minimally invasive, rapid, low-cost, promising diagnostic tool

Language: Английский

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Circulating tumor DNA for diagnosis, prognosis and treatment of gastrointestinal malignancies

World Journal of Clinical Oncology, Journal Year: 2022, Volume and Issue: 13(6), P. 473 - 484

Published: June 17, 2022

Minimally invasive detection of circulating tumor DNA (ctDNA) in peripheral blood or other body fluids patients with gastrointestinal malignancies via liquid biopsy has emerged as a promising biomarker. This is urgently needed, conventional imaging and plasma protein-derived biomarkers lack sensitivity specificity prognosis, early relapse treatment monitoring. review summarizes the potential role diagnosis, prognosis monitoring malignancies, including upper gastrointestinal, liver, bile duct, pancreatic colorectal cancer. CtDNA can now be part clinical routine promising, highly sensitive specific biomarker broad range applicability. Liquid-biopsy based postoperative prediction could lead to improved survival by intensification adjuvant identified at risk recurrence. Moreover, ctDNA allows antineoplastic success, identification potentially developed resistance therapeutic targets during course treatment. It may also assist change chemotherapy metastatic prior findings relapse. Nevertheless, utility dependent on tumor's entity burden.

Language: Английский

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The dynamics of circulating tumour DNA (ctDNA) during treatment reflects tumour response in advanced melanoma patients

Experimental Dermatology, Journal Year: 2023, Volume and Issue: 32(10), P. 1785 - 1793

Published: Aug. 2, 2023

Despite the introduction of targeted (BRAFi/MEKi) and immune checkpoint inhibitors (ICIs) has significantly reduced recurrence rate improved overall survival (OS) patients with Stage III IV melanoma, only a percentage will benefit durable disease control. The aim this study was to examine whether levels circulating tumour DNA (ctDNA) in plasma advanced melanoma undergoing BRAFi/MEKi or ICIs vary according patients' outcomes (i.e. progression-free (PFS) OS) progression. Plasma samples III-IV were collected at baseline (treatment initiation) thereafter every 3 months. Circulating BRAFV600E/K NRASQ61R/K mutations analysed through droplet digital PCR (ddPCR, Bio-Rad) total 177 from 48 (19 III, 29 IV). Baseline ctDNA concentration associated OS (HR = 1.003, 95% CI 1.000-1.006, p 0.043) PFS 1.004, 1.000-1.007, 0.029) independent clinical-prognostic confounders. For each unit increase ∆ctDNA (concentration difference between last follow-up baseline) there 24% increased risk progression, irrespective treatment type stage diagnosis (OR 1.24, 1.03-1.49, 0.020, AUC 0.93). Patients reduction level had longer 0.14; 0.05-0.44, 0.001) 0.08; 0.03-0.27, < 0.0001) compared ctDNA, including adjustment for confounding factors. Our findings suggest that variation over time during reflects clinical outcome response therapy might be helpful monitoring.

Language: Английский

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Evolution of RAS Mutations in Cell-Free DNA of Patients with Tissue RAS Wild-Type Metastatic Colorectal Cancer Receiving First-Line Treatment: The PERSEIDA Study

Cancers, Journal Year: 2022, Volume and Issue: 14(24), P. 6075 - 6075

Published: Dec. 9, 2022

The serial analysis of cell-free DNA (cfDNA) enables minimally invasive monitoring tumor evolution, providing continuous genetic information. PERSEIDA was an observational, prospective study assessing the cfDNA RAS (KRAS/NRAS) mutational status evolution in first-line, metastatic CRC, wild-type (according to baseline tissue biopsy) patients. Plasma samples were collected before first-line treatment, after 20 ± 2 weeks, and at disease progression. One hundred nineteen patients included (102 received panitumumab chemotherapy as treatment-panitumumab subpopulation). Fifteen (12.6%) presented mutations (n = 14 [13.7%], subpopulation) (mutant allele fraction ≥0.02 for all results). No emergent (cfDNA not present baseline) weeks. At progression, 11 9; (RAS conversion rate: 19.0% [11/58]; 17.7% [9/51], In contrast, three (5.2%) presenting significant associations observed between overall response rate or progression-free survival total subpopulation. Although, with left-sided tumors, a significantly longer compared those any time. Continuous evaluation may provide valuable insights on molecular dynamics that can help clinical practice.

Language: Английский

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Liquid biopsy as a tool for KRAS/NRAS/BRAF baseline testing in metastatic colorectal cancer

Clinics and Research in Hepatology and Gastroenterology, Journal Year: 2024, Volume and Issue: 48(8), P. 102417 - 102417

Published: July 14, 2024

Language: Английский

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Tumor irradiation may facilitate the detection of tumor-specific mutations in plasma

World Journal of Clinical Oncology, Journal Year: 2021, Volume and Issue: 12(12), P. 1215 - 1226

Published: Dec. 20, 2021

The mutation-based analysis of circulating tumor DNA (ctDNA) is a promising diagnostic tool for clinical oncology. However, it has low success rate because many cancer patients do not have detectable ctDNA in the bloodstream.To evaluate whether preoperative irradiation results transient increase plasma concentration due to induction apoptosis radiation-exposed cells.This study focused on with locally advanced rectal cancer, part their standard treatment plan. Nine subjects, whose tumors contained KRAS, NRAS or BRAF mutations, donated serial blood samples 1 h prior first fraction (at baseline), immediately after (time 0), and 1, 3, 6, 12, 24, 36, 48, 72 96 fraction. amount mutated gene copies was measured by droplet digital PCR.Five out nine were mutation-negative test at baseline; two these subjects demonstrated an emergence bloodstream within follow-up period. There 4 patients, who had start experiment; three them showed evident treatment-induced content RAS/RAF alleles.Local may facilitate detection tumor-specific bloodstream. These data justify further assessment feasibility irradiation-assisted liquid biopsy.

Language: Английский

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Liquid biopsy: Novel perspectives on the importance and spectrum of PIK3CA, PTEN and RET mutations in solid tumors

Molecular and Clinical Oncology, Journal Year: 2021, Volume and Issue: 16(1)

Published: Nov. 3, 2021

Many people die from lung and breast cancer. Consequently, both physicians researchers strive to provide reliable monitoring for disease, diagnosis prognosis as well resistance prediction. In the present study, a comprehensive liquid biopsy panel was performed on 474 patients examine importance spectrum of recurrent somatic cancer mutations. Most visited clinic with advanced resistant The underwent panel. Patients were divided into four groups based type follows: Lung (n=379, 79.9%), (n=72, 15.2%), gastrointestinal (n=11, 2.3%) other (n=12, 2.5%). Tier I-II-III classified variants included in study. mean age 60 years, range 20-86 years. There notably more male (n=272, 57.4%) than female (n=202, 42.6%). most commonly mutated genes TP53, EGFR, PIK3CA, RET, PTEN, MET, ATM KRAS. common mutations 'PIK3CA, c.3140A>G, p.His1047Arg', 'RET, c.2324delinsGAC, p.Glu775Glyfs*6', 'TP53, c.217G>C, p.Val73Leu', 'EGFR, c.2155G>A, p.Gly719Ser', c.1624G>A, p.Glu542Lys', 'PTEN, c.397G>A, p.Val133Ile' c.2235_2249del, p.Glu746_Ala750del'. PTEN RET showed higher incidence compared groups. To best our knowledge, study is first concentrate context adenocarcinoma evaluate genetic variability effect treatment. results that solid tumors, particularly cancer, may benefit sequencing assess clinical characteristics prognosis. Discoveries regarding gene structure mechanisms inform clinically meaningful therapeutic approaches serve an essential role improving individual risk prediction, therapy

Language: Английский

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