Clinicopathological factors associated with tumour-specific mutation detection in plasma of patients with RAS-mutated or BRAF-mutated metastatic colorectal cancer.
Biomarkers, Tumor
/ genetics
Circulating Tumor DNA
/ genetics
Colorectal Neoplasms
/ blood
Female
GTP Phosphohydrolases
/ genetics
Gene Frequency
Humans
Logistic Models
Lung Neoplasms
/ blood
Male
Membrane Proteins
/ genetics
Mutation
Prognosis
Proto-Oncogene Proteins B-raf
/ genetics
Proto-Oncogene Proteins p21(ras)
/ genetics
Survival Analysis
blood biomarkers
carbohydrate antigen 19-9
carcinoembryonic antigen
colorectal cancer
tumour-specific circulating cell-free DNA
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
15 09 2021
15 09 2021
Historique:
revised:
09
04
2021
received:
02
12
2020
accepted:
20
04
2021
pubmed:
8
5
2021
medline:
14
9
2021
entrez:
7
5
2021
Statut:
ppublish
Résumé
Detection of tumour-specific circulating cell-free DNA in plasma (ctDNA) fails in a significant number of cases depending on the clinical context. The primary aim was to investigate clinicopathological factors associated with detection of ctDNA in patients with RAS-/BRAF-mutated metastatic colorectal cancer (mCRC) prior to first-line therapy. A secondary aim was to evaluate the prognostic impact of ctDNA compared to other biomarkers. Patients were included from the NORDIC-VII study (N = 253). ctDNA was sampled prior to treatment and analysed for hotspot tissue mutations (KRAS, NRAS, and BRAF) using droplet digital PCR. Multivariable regression models were constructed to predict the probability of mutation detection and survival. Increasing radiological size of target lesions by increments of 1 cm (odds ratio [OR] = 1.18; 95% confidence interval [CI] 1.09-1.27; P < .001), intact primary tumour (OR = 3.17; 95% CI 1.22-8.22; P = .018) and more than one metastatic site (OR = 3.08; 95% CI 1.32-7.19; P = .009) were associated with mutation detection in plasma. Metastatic involvement of the lung was associated with non-detection (OR = 0.26; 95% CI 0.12-0.58; P = .001). Preanalytical and analytical factors modulated detection. High allele frequencies of ctDNA indicated poor prognosis independently of CEA and CA19-9 (hazard ratio [HR] = 2.38; 95% CI 1.74-3.26; P < .001; N = 206). Clinicopathological characteristics should be carefully considered when evaluating ctDNA results from mCRC patients, especially when confronted with a plasma negative result. ctDNA may prove to be a clinically useful marker in the evaluation of mCRC treatment.
Substances chimiques
Biomarkers, Tumor
0
Circulating Tumor DNA
0
KRAS protein, human
0
Membrane Proteins
0
BRAF protein, human
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
GTP Phosphohydrolases
EC 3.6.1.-
NRAS protein, human
EC 3.6.1.-
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Clinical Trial, Phase III
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1385-1397Informations de copyright
© 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
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