%0 Journal Article
%T 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.
%A Valladares-Ayerbes M
%A Garcia-Alfonso P
%A Muñoz Luengo J
%A Pimentel Caceres PP
%A Castillo Trujillo OA
%A Vidal-Tocino R
%A Llanos M
%A Llorente Ayala B
%A Limon Miron ML
%A Salud A
%A Cirera Nogueras L
%A Garcia-Carbonero R
%A Safont MJ
%A Falco Ferrer E
%A Aparicio J
%A Vicente Conesa MA
%A Guillén-Ponce C
%A Garcia-Teijido P
%A Medina Magan MB
%A Busquier I
%A Salgado M
%A Lloansí Vila A
%A  
%J Cancers (Basel)
%V 14
%N 24
%D Dec 2022 9
%M 36551560
%F 6.575
%R 10.3390/cancers14246075
%X 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.