학술논문
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.
Document Type
Article
Author
Valladares-Ayerbes, Manuel; Garcia-Alfonso, Pilar; Muñoz Luengo, Jorge; Pimentel Caceres, Paola Patricia; Castillo Trujillo, Oscar Alfredo; Vidal-Tocino, Rosario; Llanos, Marta; Llorente Ayala, Beatriz; Limon Miron, Maria Luisa; Salud, Antonieta; Cirera Nogueras, Luis; Garcia-Carbonero, Rocio; Safont, Maria Jose; Falco Ferrer, Esther; Aparicio, Jorge; Vicente Conesa, Maria Angeles; Guillén-Ponce, Carmen; Garcia-Teijido, Paula; Medina Magan, Maria Begoña; Busquier, Isabel
Source
Subject
*DNA
*GENETIC mutation
*CONFIDENCE intervals
*ONCOGENES
*METASTASIS
*REGRESSION analysis
*MANN Whitney U Test
*COLORECTAL cancer
*T-test (Statistics)
*DESCRIPTIVE statistics
*KAPLAN-Meier estimator
*CHI-squared test
*DATA analysis software
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Language
ISSN
2072-6694
Abstract
Simple Summary: Cell-free DNA RAS mutation is being increasingly monitored in metastatic colorectal cancer (mCRC) for disease molecular characterization and selecting eligible patients for anti-EGFR initiation and rechallenge. Here, we monitored a homogeneous mCRC RAS wild-type (as per baseline solid biopsy) population starting first-line treatment using a BEAMing technique at three different mutant allele fraction (MAF) sensitivity cut-offs and we characterized the role of each MAF threshold and its correlation with clinical variables. The serial analysis of cell-free DNA (cfDNA) enables minimally invasive monitoring of 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, RAS wild-type (according to baseline tumor tissue biopsy) patients. Plasma samples were collected before first-line treatment, after 20 ± 2 weeks, and at disease progression. One hundred and nineteen patients were included (102 received panitumumab and chemotherapy as first-line treatment—panitumumab subpopulation). Fifteen (12.6%) patients presented baseline cfDNA RAS mutations (n = 14 [13.7%], panitumumab subpopulation) (mutant allele fraction ≥0.02 for all results). No patients presented emergent mutations (cfDNA RAS mutations not present at baseline) at 20 weeks. At disease progression, 11 patients (n = 9; panitumumab subpopulation) presented emergent mutations (RAS conversion rate: 19.0% [11/58]; 17.7% [9/51], panitumumab subpopulation). In contrast, three (5.2%) patients presenting baseline cfDNA RAS mutations were RAS wild-type at disease progression. No significant associations were observed between overall response rate or progression-free survival and cfDNA RAS mutational status in the total panitumumab subpopulation. Although, in patients with left-sided tumors, a significantly longer progression-free survival was observed in cfDNA RAS wild-type patients compared to those presenting cfDNA RAS mutations at any time. Continuous evaluation of RAS mutations may provide valuable insights on tumor molecular dynamics that can help clinical practice. [ABSTRACT FROM AUTHOR]