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- Title
Early assessment of KRAS mutation in cfDNA correlates with risk of progression and death in advanced non-small-cell lung cancer.
- Authors
Zulato, Elisabetta; Attili, Ilaria; Pavan, Alberto; Nardo, Giorgia; Del Bianco, Paola; Boscolo Bragadin, Andrea; Verza, Martina; Pasqualini, Lorenza; Pasello, Giulia; Fassan, Matteo; Calabrese, Fiorella; Guarneri, Valentina; Amadori, Alberto; Conte, PierFranco; Indraccolo, Stefano; Bonanno, Laura
- Abstract
<bold>Background: </bold>Liquid biopsy has the potential to monitor biological effects of treatment. KRAS represents the most commonly mutated oncogene in Caucasian non-small-cell lung cancer (NSCLC). The aim of this study was to explore association of dynamic plasma KRAS genotyping with outcome in advanced NSCLC patients.<bold>Methods: </bold>Advanced NSCLC patients were prospectively enrolled. Plasma samples were collected at baseline (T1), after 3 or 4 weeks, according to treatment schedule (T2) and at first radiological restaging (T3). Patients carrying KRAS mutation in tissue were analysed in plasma with droplet digital PCR. Semi-quantitative index of fractional abundance of mutated allele (MAFA) was used.<bold>Results: </bold>KRAS-mutated cohort included 58 patients, and overall 73 treatments (N = 39 chemotherapy and N = 34 immune checkpoint inhibitors) were followed with longitudinal liquid biopsy. Sensitivity of KRAS detection in plasma at baseline was 48.3% (95% confidence interval (CI): 35.0-61.8). KRAS mutation at T2 was associated with increased probability of experiencing progressive disease as best radiological response (adjusted odds ratio: 7.3; 95% CI: 2.1-25.0, p = 0.0016). Increased MAFA (T1-T2) predicted shorter progression-free survival (adjusted hazard ratio (HR): 2.1; 95% CI: 1.2-3.8, p = 0.0142) and overall survival (adjusted HR: 3.2; 95% CI: 1.2-8.4, p = 0.0168).<bold>Conclusions: </bold>Longitudinal analysis of plasma KRAS mutations correlated with outcome: its early assessment during treatment has great potentialities for monitoring treatment outcome in NSCLC patients.
- Subjects
PROTEINS; LUNG cancer; DISEASE progression; RESEARCH; GENETIC mutation; RESEARCH methodology; EVALUATION research; MEDICAL cooperation; TUMOR classification; COMPARATIVE studies; LONGITUDINAL method
- Publication
British Journal of Cancer, 2020, Vol 123, Issue 1, p81
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/s41416-020-0833-7