Baseline and Kinetic Circulating Tumor Cell Counts Are Prognostic Factors in a Prospective Study of Metastatic Colorectal Cancer.

Virgílio Souza E Silva,Celso Abdon Lopes De Mello,Emne Ali Abdallah,Rachel Riechelmann,Milena Shizue Tariki,Ludmilla Thomé Domingos Chinen,Angelo Borsarelli Carvalho De Brito,Alexcia Camila Braun,Vinicius Fernando Calsavara

doi:10.3390/diagnostics11030502

Virgílio Souza E Silva, Celso Abdon Lopes De Mello + Show 7 more

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https://doi.org/10.3390/diagnostics11030502

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Journal: Diagnostics	Publication Date: Mar 12, 2021
Citations: 8	License type: CC BY 4.0

Affiliation: AC Camargo Hospital

Abstract

The discovery of predictive biomarkers in metastatic colorectal cancer (mCRC) is essential to improve clinical outcomes. Recent data suggest a potential role of circulating tumor cells (CTCs) as prognostic indicators. We conducted a follow-on analysis from a prospective study of consecutive patients with mCRC. CTC analysis was conducted at two timepoints: baseline (CTC1; before starting chemotherapy), and two months after starting treatment (CTC2). CTC isolation/quantification were completed by ISET® (Rarecells, France). CTC expressions of drug resistance-associated proteins were evaluated. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan–Meier method. Seventy-five patients were enrolled from May 2012 to May 2014. A CTC1 cut-off of >1.5 CTCs/mL was associated with an inferior median OS compared to lower values. A difference of CTC2−CTC1 > 5.5 CTCs/mL was associated with a reduced median PFS. By multivariate analysis, CTC1 > 1.5 CTCs/mL was an independent prognostic factor for worse OS. Multi-drug resistance protein-1 (MRP-1) expression was associated with poor median OS. CTC baseline counts, kinetics, and MRP-1 expression were predictive of clinical outcomes. Larger studies are warranted to explore the potential clinical benefit of treating mCRC patients with targeted therapeutic regimens guided by CTC findings.

Highlights

Colorectal cancer (CRC) is one of the most common gastrointestinal tumors, constituting the second most common cancer diagnosed in women and third most common in men, and accounting for approximately 10% of all incident cancers and cancer-related deaths worldwide [1]
With part of the cohort included, we previously demonstrated the importance of kinetic evaluations of circulating tumor cells (CTCs) [26] and assessments of CTC expressions of thymidylate synthase (TYMS) and multidrug resistance protein-1 (MRP-1) as potential predictive biomarkers in metastatic colorectal cancer (mCRC) patients [29,31]
Seventy-five consecutive mCRC patients were enrolled from May 2012 to May 2014

Summary

Introduction

Colorectal cancer (CRC) is one of the most common gastrointestinal tumors, constituting the second most common cancer diagnosed in women and third most common in men, and accounting for approximately 10% of all incident cancers and cancer-related deaths worldwide [1]. 12 months, to current therapies that result in an average OS that is reaching three years. These improvements have been driven primarily by the availability of new active agents that include cytotoxic drugs such as oxaliplatin and irinotecan, and monoclonal antibodies 4.0/). That inhibit angiogenesis and proliferation pathways by targeting vascular endothelial growth factor and the epidermal growth factor receptor, respectively [5,6,7,8,9] Despite these advances, the heterogeneity of mCRC impedes efforts by the oncologist to design targeted treatment strategies and to optimize personalized therapy. In the era of precision medicine, the liquid biopsy has become an important decision-support tool for the oncologist in the design of treatment strategies [13,14,15,16,17]

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