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
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 chemothera...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
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MDPI AG
2020-12-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/10/1/87 |
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| author | Vincenzo Formica 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 Mario Roselli |
| author_facet | Vincenzo Formica 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 Mario Roselli |
| author_sort | Vincenzo Formica |
| collection | DOAJ |
| description | 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, <i>p</i> 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, <i>p</i> = 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, <i>p</i> = 0.008. At a multivariate cox regression analysis for PFS, PL mutations were independent prognostic factor superior to T analysis (HR 0.13, <i>p</i> = 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. |
| first_indexed | 2024-03-10T13:42:23Z |
| format | Article |
| id | doaj.art-3014c6b97089419dbb733e4b897c7b58 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T13:42:23Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-3014c6b97089419dbb733e4b897c7b582023-11-21T02:54:20ZengMDPI AGJournal of Clinical Medicine2077-03832020-12-011018710.3390/jcm10010087Clinical Utility of Plasma KRAS, NRAS and BRAF Mutational Analysis with Real Time PCR in Metastatic Colorectal Cancer Patients—The Importance of Tissue/Plasma Discordant CasesVincenzo Formica0Jessica Lucchetti1Elena Doldo2Silvia Riondino3Cristina Morelli4Renato Argirò5Nicola Renzi6Daniele Nitti7Antonella Nardecchia8Emanuela Dell’Aquila9Patrizia Ferroni10Fiorella Guadagni11Giampiero Palmieri12Augusto Orlandi13Mario Roselli14Medical Oncology Unit, Department of Systems Medicine, Tor Vergata University Hospital, Viale Oxford 81, 00133 Rome, ItalyMedical Oncology Unit, Department of Systems Medicine, Tor Vergata University Hospital, Viale Oxford 81, 00133 Rome, ItalyAnatomic Pathology, Department of Biomedicine and Prevention, Tor Vergata University Hospital, Viale Oxford 81, 00133 Rome, ItalyMedical Oncology Unit, Department of Systems Medicine, Tor Vergata University Hospital, Viale Oxford 81, 00133 Rome, ItalyMedical Oncology Unit, Department of Systems Medicine, Tor Vergata University Hospital, Viale Oxford 81, 00133 Rome, ItalyInterventional Radiology Unit, Department of Diagnostic Imaging and Interventional Radiology, Tor Vergata University Hospital, Viale Oxford 81, 00133 Rome, ItalyMedical Oncology Unit, Department of Systems Medicine, Tor Vergata University Hospital, Viale Oxford 81, 00133 Rome, ItalyMedical Oncology Unit, Department of Systems Medicine, Tor Vergata University Hospital, Viale Oxford 81, 00133 Rome, ItalyMedical Oncology Unit, Department of Systems Medicine, Tor Vergata University Hospital, Viale Oxford 81, 00133 Rome, ItalyMedical Oncology Department, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128 Rome, ItalyBioBIM (InterInstitutional Multidisciplinary Biobank), IRCCS San Raffaele Pisana, Via di Val Cannuta 247, 00166 Rome, ItalyBioBIM (InterInstitutional Multidisciplinary Biobank), IRCCS San Raffaele Pisana, Via di Val Cannuta 247, 00166 Rome, ItalyAnatomic Pathology, Department of Biomedicine and Prevention, Tor Vergata University Hospital, Viale Oxford 81, 00133 Rome, ItalyAnatomic Pathology, Department of Biomedicine and Prevention, Tor Vergata University Hospital, Viale Oxford 81, 00133 Rome, ItalyMedical Oncology Unit, Department of Systems Medicine, Tor Vergata University Hospital, Viale Oxford 81, 00133 Rome, ItalyBackground: 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, <i>p</i> 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, <i>p</i> = 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, <i>p</i> = 0.008. At a multivariate cox regression analysis for PFS, PL mutations were independent prognostic factor superior to T analysis (HR 0.13, <i>p</i> = 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.https://www.mdpi.com/2077-0383/10/1/87metastatic colorectal cancerctDNAliquid biopsy |
| spellingShingle | Vincenzo Formica 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 Mario Roselli 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 metastatic colorectal cancer ctDNA liquid biopsy |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | metastatic colorectal cancer ctDNA liquid biopsy |
| url | https://www.mdpi.com/2077-0383/10/1/87 |
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