Plasmatic KRAS Kinetics for the Prediction of Treatment Response and Progression in Patients With KRAS-mutant Lung Adenocarcinoma

• Published in: Archivos de bronconeumología (English ed.) 2021-05, Vol.57 (5), p.323-329
• Main Authors: Taus, Álvaro, Camacho, Laura, Rocha, Pedro, Hernández, Ainhoa, Longarón, Raquel, Clavé, Sergi, Fernández-Ibarrondo, Lierni, Salido, Marta, Hardy-Werbin, Max, Fernández-Rodríguez, Concepción, Albanell, Joan, Bellosillo, Beatriz, Arriola, Edurne
• Format: Article
• Language: English
• Subjects: Adenocarcinoma de pulmón; ADN tumoral circulante; Biopsia líquida; Circulating tumor DNA; Clonal dynamics; Dinámica clonal; KRAS; Liquid biopsy; Lung adenocarcinoma
• ISSN: 0300-2896; 1579-2129
• DOI: 10.1016/j.arbres.2020.01.023

[Display omitted] KRAS is the most common driver mutation in lung cancer. ctDNA-based assessment offers advantages over tumor as a minimally invasive method able to capture tumor heterogeneity. Monitoring KRAS mutational load in ctDNA may be useful in the management of the patients. Consecutive patients diagnosed with KRAS mutant lung adenocarcinoma in the tumor biopsy were included in this study. Plasma samples were obtained at different time points during the course of the disease. KRAS mutations in plasma were quantified using digital PCR and correlated with mutations in tumor and with radiological response and progression. Two hundred and forty-five plasma samples from 56 patients were analyzed. The rate of detection of KRAS mutations in plasma in our previously characterized KRAS-mutant cases was 82% overall, reaching 96% in cases with more than 1 metastatic location. The dynamics of KRAS mutational load predicted response in 93% and progression in 63% of cases, 33 and 50 days respectively in advance of radiological evaluation. Progression-free survival for patients in whom ctDNA was not detectable in plasma after treatment initiation was significantly longer than for those in whom ctDNA remained detectable (7.7 versus 3.2 months; HR: 0.44, p=0.004). The detection of KRAS mutations in ctDNA showed a good correlation with that in tumor biopsy and, in most cases, predicted tumor response and progression to chemotherapy in advance of radiographic evaluation. The liquid biopsies for ctDNA-based molecular analyses are a reliable tool for KRAS testing in clinical practice. La mutación en KRAS es la mutación iniciadora más común en el cáncer de pulmón. La valoración basada en el ctDNA ofrece ventajas frente a la tumoral, al ser un método mínimamente invasivo capaz de capturar la heterogeneidad del tumor. La monitorización de la carga de KRAS mutado en el ctDNA puede ser útil en el manejo de los pacientes. En este estudio se incluyó, mediante selección consecutiva, a pacientes diagnosticados con adenocarcinoma de pulmón con mutación en KRAS en la biopsia tumoral. Se obtuvieron muestras de plasma en diferentes momentos durante el curso de la enfermedad. Las mutaciones de KRAS en plasma se cuantificaron mediante PCR digital y se correlacionaron con las mutaciones en el tumor y con la respuesta radiológica y la progresión. Se analizaron 245 muestras de plasma de 56 pacientes. La tasa de detección de mutaciones KRAS en plasma en aquellos casos previamente definid