Plasma Dynamics of RAS/RAF Mutations in Patients With Metastatic Colorectal Cancer Receiving Chemotherapy and Anti-EGFR Treatment

Caroline Brenner Thomsen*, Rikke Fredslund Andersen, Jan Lindebjerg, Torben Frøstrup Hansen, Lars Henrik Jensen, Anders Jakobsen

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Background: RAS and RAF mutations in colorectal cancer (CRC) hold value in precision medicine. Liquid biopsy is an alternative to tumor tissue biopsy, and circulating tumor DNA (ctDNA) has been intensively investigated, but the clinical relevance of RAS and RAF mutations in plasma is yet to be determined. This study aimed to investigate the clinical aspects of RAS/RAF mutations during combination treatment. Patients and Methods: Patients with RAS/RAF tumor wild-type metastatic CRC treated with combination chemotherapy and an EGFR inhibitor were included. Blood samples were collected at baseline and every treatment cycle and analyzed for 31 RAS, RAF, and EGFR mutations until progressive disease or censoring using droplet digital PCR. Results: Forty-six patients were prospectively enrolled onto the study. At baseline, 7% had detectable RAS/RAF mutations in ctDNA. During the treatment course, the fraction of patients with mutated ctDNA increased to 22%. The emergence of mutations did not correlate with response or risk of progression while receiving treatment (P = 1.0). Conclusion: Emergence of plasma RAS/RAF mutations was not correlated with the effect of combination chemotherapy and EGFR inhibition in patients with RAS/RAF wild-type metastatic CRC. This study aimed to investigate the clinical aspects of RAS/RAF mutations during chemotherapy and anti-EGFR treatment in tumor wild-type patients. Blood samples were collected from 46 patients at every treatment cycle until progressive disease or censoring. Emergence of mutations was not correlated with treatment effect.

OriginalsprogEngelsk
TidsskriftClinical Colorectal Cancer
Vol/bind18
Udgave nummer1
Sider (fra-til)28-33.e3
ISSN1533-0028
DOI
StatusUdgivet - 2019

Fingeraftryk

Colorectal Neoplasms
Mutation
Neoplasms
DNA
Precision Medicine
Polymerase Chain Reaction

Citer dette

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title = "Plasma Dynamics of RAS/RAF Mutations in Patients With Metastatic Colorectal Cancer Receiving Chemotherapy and Anti-EGFR Treatment",
abstract = "Background: RAS and RAF mutations in colorectal cancer (CRC) hold value in precision medicine. Liquid biopsy is an alternative to tumor tissue biopsy, and circulating tumor DNA (ctDNA) has been intensively investigated, but the clinical relevance of RAS and RAF mutations in plasma is yet to be determined. This study aimed to investigate the clinical aspects of RAS/RAF mutations during combination treatment. Patients and Methods: Patients with RAS/RAF tumor wild-type metastatic CRC treated with combination chemotherapy and an EGFR inhibitor were included. Blood samples were collected at baseline and every treatment cycle and analyzed for 31 RAS, RAF, and EGFR mutations until progressive disease or censoring using droplet digital PCR. Results: Forty-six patients were prospectively enrolled onto the study. At baseline, 7{\%} had detectable RAS/RAF mutations in ctDNA. During the treatment course, the fraction of patients with mutated ctDNA increased to 22{\%}. The emergence of mutations did not correlate with response or risk of progression while receiving treatment (P = 1.0). Conclusion: Emergence of plasma RAS/RAF mutations was not correlated with the effect of combination chemotherapy and EGFR inhibition in patients with RAS/RAF wild-type metastatic CRC. This study aimed to investigate the clinical aspects of RAS/RAF mutations during chemotherapy and anti-EGFR treatment in tumor wild-type patients. Blood samples were collected from 46 patients at every treatment cycle until progressive disease or censoring. Emergence of mutations was not correlated with treatment effect.",
keywords = "Biomarkers, ctDNA, Liquid biopsy, Precision medicine, Targeted therapy",
author = "Thomsen, {Caroline Brenner} and Andersen, {Rikke Fredslund} and Jan Lindebjerg and Hansen, {Torben Fr{\o}strup} and Jensen, {Lars Henrik} and Anders Jakobsen",
year = "2019",
doi = "10.1016/j.clcc.2018.10.004",
language = "English",
volume = "18",
pages = "28--33.e3",
journal = "Clinical Colorectal Cancer",
issn = "1533-0028",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Plasma Dynamics of RAS/RAF Mutations in Patients With Metastatic Colorectal Cancer Receiving Chemotherapy and Anti-EGFR Treatment

AU - Thomsen, Caroline Brenner

AU - Andersen, Rikke Fredslund

AU - Lindebjerg, Jan

AU - Hansen, Torben Frøstrup

AU - Jensen, Lars Henrik

AU - Jakobsen, Anders

PY - 2019

Y1 - 2019

N2 - Background: RAS and RAF mutations in colorectal cancer (CRC) hold value in precision medicine. Liquid biopsy is an alternative to tumor tissue biopsy, and circulating tumor DNA (ctDNA) has been intensively investigated, but the clinical relevance of RAS and RAF mutations in plasma is yet to be determined. This study aimed to investigate the clinical aspects of RAS/RAF mutations during combination treatment. Patients and Methods: Patients with RAS/RAF tumor wild-type metastatic CRC treated with combination chemotherapy and an EGFR inhibitor were included. Blood samples were collected at baseline and every treatment cycle and analyzed for 31 RAS, RAF, and EGFR mutations until progressive disease or censoring using droplet digital PCR. Results: Forty-six patients were prospectively enrolled onto the study. At baseline, 7% had detectable RAS/RAF mutations in ctDNA. During the treatment course, the fraction of patients with mutated ctDNA increased to 22%. The emergence of mutations did not correlate with response or risk of progression while receiving treatment (P = 1.0). Conclusion: Emergence of plasma RAS/RAF mutations was not correlated with the effect of combination chemotherapy and EGFR inhibition in patients with RAS/RAF wild-type metastatic CRC. This study aimed to investigate the clinical aspects of RAS/RAF mutations during chemotherapy and anti-EGFR treatment in tumor wild-type patients. Blood samples were collected from 46 patients at every treatment cycle until progressive disease or censoring. Emergence of mutations was not correlated with treatment effect.

AB - Background: RAS and RAF mutations in colorectal cancer (CRC) hold value in precision medicine. Liquid biopsy is an alternative to tumor tissue biopsy, and circulating tumor DNA (ctDNA) has been intensively investigated, but the clinical relevance of RAS and RAF mutations in plasma is yet to be determined. This study aimed to investigate the clinical aspects of RAS/RAF mutations during combination treatment. Patients and Methods: Patients with RAS/RAF tumor wild-type metastatic CRC treated with combination chemotherapy and an EGFR inhibitor were included. Blood samples were collected at baseline and every treatment cycle and analyzed for 31 RAS, RAF, and EGFR mutations until progressive disease or censoring using droplet digital PCR. Results: Forty-six patients were prospectively enrolled onto the study. At baseline, 7% had detectable RAS/RAF mutations in ctDNA. During the treatment course, the fraction of patients with mutated ctDNA increased to 22%. The emergence of mutations did not correlate with response or risk of progression while receiving treatment (P = 1.0). Conclusion: Emergence of plasma RAS/RAF mutations was not correlated with the effect of combination chemotherapy and EGFR inhibition in patients with RAS/RAF wild-type metastatic CRC. This study aimed to investigate the clinical aspects of RAS/RAF mutations during chemotherapy and anti-EGFR treatment in tumor wild-type patients. Blood samples were collected from 46 patients at every treatment cycle until progressive disease or censoring. Emergence of mutations was not correlated with treatment effect.

KW - Biomarkers

KW - ctDNA

KW - Liquid biopsy

KW - Precision medicine

KW - Targeted therapy

U2 - 10.1016/j.clcc.2018.10.004

DO - 10.1016/j.clcc.2018.10.004

M3 - Journal article

VL - 18

SP - 28-33.e3

JO - Clinical Colorectal Cancer

JF - Clinical Colorectal Cancer

SN - 1533-0028

IS - 1

ER -