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Article

Clinical Utility of Plasma KRAS, NRAS and BRAF Mutational Analysis with Real Time PCR in Metastatic Colorectal Cancer Patients—The Importance of Tissue/Plasma Discordant Cases

1
Medical Oncology Unit, Department of Systems Medicine, Tor Vergata University Hospital, Viale Oxford 81, 00133 Rome, Italy
2
Anatomic Pathology, Department of Biomedicine and Prevention, Tor Vergata University Hospital, Viale Oxford 81, 00133 Rome, Italy
3
Interventional Radiology Unit, Department of Diagnostic Imaging and Interventional Radiology, Tor Vergata University Hospital, Viale Oxford 81, 00133 Rome, Italy
4
Medical Oncology Department, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128 Rome, Italy
5
BioBIM (InterInstitutional Multidisciplinary Biobank), IRCCS San Raffaele Pisana, Via di Val Cannuta 247, 00166 Rome, Italy
6
Department of Human Sciences & Quality of Life Promotion, San Raffaele Roma Open University, Via di Val Cannuta 247, 00166 Rome, Italy
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2021, 10(1), 87; https://doi.org/10.3390/jcm10010087
Received: 26 November 2020 / Revised: 22 December 2020 / Accepted: 25 December 2020 / Published: 29 December 2020
Background: Tumor tissue (T) mutational analysis represents the standard for metastatic colorectal cancer (mCRC); however, circulating tumor DNA (ctDNA) detected by liquid biopsy in plasma (PL) can better represent tumor heterogeneity. Methods: mCRC patients undergoing standard first-line chemotherapy with known T-KRAS/NRAS/BRAF status were enrolled in the present prospective study. PL mutations were assessed within 2 weeks before chemotherapy start with real time PCR and correlated with T status and Progression free survival (PFS). Clinical and biochemical variables including also total number of tumor lesions (TNL) and the sum of maximum diameter (SMD) of all lesions were assessed as potential predictors of T/PL discordance. RESULTS: Among 45 enrolled patients, all BRAF mutations were concordant between T and PL and there were 20% of patients RAS discordant: 9% wild type in T and mutated in PL and 11% mutated in T and wild type in PL. T mutations were significantly associated to median PFS (mPFS of 4.5, 8.3 and 22.9 months for T-BRAF mutated, T-RAS mutated, and T-wild type patients, respectively, p for trend 0.00014). PL mutations further refined prognosis: RAS wild type in T and mutated in PL had significantly shorter PFS than concordant RAS wild type in T and PL: mPFS 9.6 vs. 23.3 months, respectively, p = 0.02. Patients RAS mutated in T and wild type in PL had longer PFS than concordant RAS mutated in T and PL: 24.4 vs. 7.8 months, respectively, p = 0.008. At a multivariate cox regression analysis for PFS, PL mutations were independent prognostic factor superior to T analysis (HR 0.13, p = 0.0008). At multivariate logistic regression analysis TNL and SMD were significant predictors of discordant cases. Conclusions: PL mutational analysis allows a better prognostication than T analysis alone and could help in mCRC treatment management. View Full-Text
Keywords: metastatic colorectal cancer; ctDNA; liquid biopsy metastatic colorectal cancer; ctDNA; liquid biopsy
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MDPI and ACS Style

Formica, V.; Lucchetti, J.; Doldo, E.; Riondino, S.; Morelli, C.; Argirò, R.; Renzi, N.; Nitti, D.; Nardecchia, A.; Dell’Aquila, E.; Ferroni, P.; Guadagni, F.; Palmieri, G.; Orlandi, A.; Roselli, M. Clinical Utility of Plasma KRAS, NRAS and BRAF Mutational Analysis with Real Time PCR in Metastatic Colorectal Cancer Patients—The Importance of Tissue/Plasma Discordant Cases. J. Clin. Med. 2021, 10, 87. https://doi.org/10.3390/jcm10010087

AMA Style

Formica V, Lucchetti J, Doldo E, Riondino S, Morelli C, Argirò R, Renzi N, Nitti D, Nardecchia A, Dell’Aquila E, Ferroni P, Guadagni F, Palmieri G, Orlandi A, Roselli M. Clinical Utility of Plasma KRAS, NRAS and BRAF Mutational Analysis with Real Time PCR in Metastatic Colorectal Cancer Patients—The Importance of Tissue/Plasma Discordant Cases. Journal of Clinical Medicine. 2021; 10(1):87. https://doi.org/10.3390/jcm10010087

Chicago/Turabian Style

Formica, Vincenzo, Jessica Lucchetti, Elena Doldo, Silvia Riondino, Cristina Morelli, Renato Argirò, Nicola Renzi, Daniele Nitti, Antonella Nardecchia, Emanuela Dell’Aquila, Patrizia Ferroni, Fiorella Guadagni, Giampiero Palmieri, Augusto Orlandi, and Mario Roselli. 2021. "Clinical Utility of Plasma KRAS, NRAS and BRAF Mutational Analysis with Real Time PCR in Metastatic Colorectal Cancer Patients—The Importance of Tissue/Plasma Discordant Cases" Journal of Clinical Medicine 10, no. 1: 87. https://doi.org/10.3390/jcm10010087

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