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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

Authors :
Manuel Valladares-Ayerbes
Pilar Garcia-Alfonso
Jorge Muñoz Luengo
Paola Patricia Pimentel Caceres
Oscar Alfredo Castillo Trujillo
Rosario Vidal-Tocino
Marta Llanos
Beatriz Llorente Ayala
Maria Luisa Limon Miron
Antonieta Salud
Luis Cirera Nogueras
Rocio Garcia-Carbonero
Maria Jose Safont
Esther Falco Ferrer
Jorge Aparicio
Maria Angeles Vicente Conesa
Carmen Guillén-Ponce
Paula Garcia-Teijido
Maria Begoña Medina Magan
Isabel Busquier
Mercedes Salgado
Ariadna Lloansí Vila
Source :
Cancers; Volume 14; Issue 24; Pages: 6075
Publication Year :
2022
Publisher :
Multidisciplinary Digital Publishing Institute, 2022.

Abstract

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.

Details

Language :
English
ISSN :
20726694
Database :
OpenAIRE
Journal :
Cancers; Volume 14; Issue 24; Pages: 6075
Accession number :
edsair.doi.dedup.....a6b6d69e18a11de54b71b56e47b6b225
Full Text :
https://doi.org/10.3390/cancers14246075