Liquid Biopsy For Molecular Characterization And Monitoring In Patients With Metastatic Colorectal Cancer.

Abstract The use of liquid biopsy in the clinical management of colorectal cancer (CRC) patients is not yet a routine clinical practice, although it could give important information for tumor baseline characterization and for monitoring during treatment. In this retrospective exploratory study, we examined plasma-circulating tumor DNA (ctDNA) in a series of 27 metastatic CRC patients receiving chemotherapy plus bevacizumab as firstline treatment, both at baseline and at progression. All patients were characterized for RAS and BRAF status on tumor tissue before the start of treatment: 70% of patients were RAS-mutated(16 KRAS, 3 NRAS),15% were BRAF mutated and 15% were RAS/BRAF wild-type. Detection of ctDNA mutations were performed using Oncomine™Colon cfDNA Assay on Ion GeneStudio™ S5 System (Thermofisher). All mutations observed in the tissue were identified also in the baseline ctDNA, excluding one BRAF mutated case that was not detected in the ctDNA. Additional mutations on TP53, APC, PIK3CA, FBXW7 were detected respectively in 11, 12, 3 and 2 cases. TP53 mutations were identified also in 3 RAS/BRAF wild-type cases. Baseline RAS/BRAF variant allele frequency (VAF) lower than 10% was found associated with longer progression free survival (PFS) (log-rank p-value=0.027) (Table 1). At progression, 80% of patients carried the same mutations identified at baseline, and 7 cases carried additional mutations of TP53. Predominantly mutations has a lower VAF at progression with respect to baseline, however RAS/BRAF VAF at progression was found not associated with PFS. In conclusion, we report a concordance-rate >96% between ctDNA and tissue demonstrating the high sensibility of liquid biopsy for detection of mutations in metastatic CRC. Thus, ctDNA could be useful for monitoring of minimal residual disease and tumor heterogeneity during therapeutic treatment. These data, if confirmed in a larger cohort, might support the use of liquid biopsy in the clinical management of CRC patients. Table 1.Relationships between RAS/BRAF mutation VAF and progression free survival during treatmentTimeConditionN. of casesMedian PFS (range), daysχ2p-valueBaselineVAF<10%11504 (244-843)4,8960,0269VAF>10%11373 (41-719)ProgressionVAF<10%14414 (110-763)0,32390,5693VAF>10%8412 (41-843) Citation Format: Milena Urbini, Giorgia Marisi, Alessandro Passardi, Chiara Molinari, Matteo Canale, Laura Matteucci, Gianluca Tedaldi, Giovanni Martinelli, Giovanni L. Frassineti, Ulivi Paola. Liquid biopsy for molecular characterization and monitoring in patients with metastatic colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 541.