Dataset Information

Clinical Relevance of Viable Circulating Tumor Cells in Patients with Metastatic Colorectal Cancer: The COLOSPOT Prospective Study.

ABSTRACT:

Background

Circulating tumor cells (CTCs) allow the real-time monitoring of tumor course and treatment response. This prospective multicenter study evaluates and compares the early predictive value of CTC enumeration with EPISPOT, a functional assay that detects only viable CTCs, and with the CellSearch^® system in patients with metastatic colorectal cancer (mCRC).

Methods

Treatment-naive patients with mCRC and measurable disease (RECIST criteria 1.1) received FOLFIRI-bevacizumab until progression or unacceptable toxicity. CTCs in peripheral blood were enumerated at D₀, D₁₄, D₂₈, D₄₂, and D₅₆ (EPISPOT assay) and at D₀ and D₂₈ (CellSearch^® system). Progression-free survival (PFS) and overall survival (OS) were assessed with the Kaplan-Meier method and log-rank test.

Results

With the EPISPOT assay, at least 1 viable CTC was detected in 21% (D₀), 15% (D₁₄), 12% (D₂₈), 10% (D₄₂), and 12% (D₅₆) of 155 patients. PFS and OS were shorter in patients who remained positive, with viable CTCs between D₀ and D₂₈ compared with the other patients (PFS = 7.36 vs. 9.43 months, p = 0.0161 and OS = 25.99 vs. 13.83 months, p = 0.0178). The prognostic and predictive values of ≥3 CTCs (CellSearch^® system) were confirmed.

Conclusions

CTC detection at D₂₈ and the D₀-D₂₈ CTC dynamics evaluated with the EPISPOT assay were associated with outcomes and may predict response to treatment.

SUBMITTER: Mazard T

PROVIDER: S-EPMC8231886 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Publications

Clinical Relevance of Viable Circulating Tumor Cells in Patients with Metastatic Colorectal Cancer: The COLOSPOT Prospective Study.

Mazard Thibault T Cayrefourcq Laure L Perriard Françoise F Senellart Hélène H Linot Benjamin B de la Fouchardière Christelle C Terrebonne Eric E François Eric E Obled Stéphane S Guimbaud Rosine R Mineur Laurent L Fonck Marianne M Daurès Jean-Pierre JP Ychou Marc M Assenat Eric E Alix-Panabières Catherine C

Cancers 20210613 12

<h4>Background</h4>Circulating tumor cells (CTCs) allow the real-time monitoring of tumor course and treatment response. This prospective multicenter study evaluates and compares the early predictive value of CTC enumeration with EPISPOT, a functional assay that detects only viable CTCs, and with the CellSearch<sup>®</sup> system in patients with metastatic colorectal cancer (mCRC).<h4>Methods</h4>Treatment-naive patients with mCRC and measurable disease (RECIST criteria 1.1) received FOLFIRI-be ...[more]

PMID: 34199250

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Project description:BackgroundMetastatic breast cancer (mBC) is a heterogeneous disease with varying responses to treatments and clinical outcomes, still requiring the identification of reliable predictive biomarkers. In this context, liquid biopsy has emerged as a powerful tool to assess in real-time the evolving landscape of cancer, which is both orchestrated by the metastatic process and immune-surveillance mechanisms. Thus, we investigated circulating tumor cells (CTCs) coupled with peripheral T-cell immunity to uncover their potential clinical relevance in mBC.MethodsA cohort of 20 mBC patients was evaluated, before and one month after starting therapy, through the following liquid biopsy approaches: CTCs enumerated by a metabolism-based assay, T-cell responses against tumor-associated antigens (TAA) characterized by interferon-γ enzyme-linked immunosorbent spot (ELISpot), and the T-cell receptor (TCR) repertoire investigated by a targeted next-generation sequencing technique. TCR repertoire features were characterized by the Morisita's overlap and the Productive Simpson Clonality indexes, and the TCR richness. Differences between groups were calculated by Fisher's, Mann-Whitney or Kruskal-Wallis test, as appropriate. Prognostic data analysis was estimated by Kaplan-Meier method.ResultsStratifying patients for their prognostic level of 6 CTCs before therapy, TAA specific T-cell responses were detected only in patients with a low CTC level. By analyzing the TCR repertoire, the highest TCR clonality was observed in the case of CTCs under the cut-off and a positive ELISpot response (p=0.03). Whereas, at follow-up, patients showing a good clinical response coupled with a low number of CTCs were characterized by the most elevated TCR clonality (p<0.05). The detection of CTCs≥6 in at least one time-point was associated with a lower TCR clonality (p=0.02). Intriguingly, by combining overall survival analysis with TCR repertoire, we highlighted a potential prognostic role of the TCR clonality measured at follow-up (p=0.03).ConclusionThese data, whether validated in a larger cohort of patients, suggest that the combined analysis of CTCs and circulating anti-tumor T-cell immunity could represent a valuable immune-oncological biomarker for the liquid biopsy field. The clinical application of this promising tool could improve the management of mBC patients, especially in the setting of immunotherapy, a rising approach for BC treatment requiring reliable predictive biomarkers.

Project description:Multiple genomic changes caused by clonal evolution induced by therapeutic pressure and corresponding intratumoral heterogeneity have posed great challenges for personalized therapy against metastatic colorectal cancer (mCRC) in the past decade. Liquid biopsy has emerged as an excellent molecular diagnostic tool for assessing predominant spatial and temporal intratumoral heterogeneity with minimal invasiveness.Previous studies have revealed that genomic alterations in RAS, BRAF, ERBB2, and MET, as well as other cancer-related genes associated with resistance to anti-epidermal growth factor receptor (EGFR) therapy, can be analyzed with high diagnostic accuracy by circulating tumor DNA (ctDNA) analysis. Furthermore, by longitudinally monitoring ctDNAs during anti-EGFR therapy, the emergence of genomic alterations can be detected as acquired resistance mechanisms in specific genes, mainly those associated with the mitogen-activated protein kinase signaling pathway. Analysis of ctDNA can also identify predictive biomarkers to immune checkpoint inhibitors, such as mutations in mismatch repair genes, microsatellite instability-high phenotype, and tumor mutation burden. Some prospective clinical trials evaluating targeted agents for genomic alterations in ctDNA or exploring resistance biomarkers by monitoring of ctDNA are ongoing.To determine the value of ctDNA analysis for decision-making by more accurate molecular marker-based selection of patients and identification of resistance mechanisms to targeted therapies or sensitive biomarkers for immune checkpoint inhibitors, clinical trials must be refined to evaluate the efficacy of study treatment in patients with targetable genomic alterations confirmed by ctDNA analysis, and resistance biomarkers should be explored by monitoring ctDNA in large-scale clinical trials. In the near future, ctDNA analysis will play an important role in precision medicine for mCRC. IMPLICATIONS FOR PRACTICE: Treatment strategies for metastatic colorectal cancer (mCRC) are determined according to the molecular profile, which is confirmed by analyzing tumor tissue. Analysis of circulating tumor DNA (ctDNA) may overcome the limitations of tissue-based analysis by capturing spatial and temporal intratumoral heterogeneity of mCRC. Clinical trials must be refined to test the value of ctDNA analysis in patient selection and identification of biomarkers. This review describes ctDNA analysis, which will have an important role in precision medicine for mCRC.

Dataset Information

Clinical Relevance of Viable Circulating Tumor Cells in Patients with Metastatic Colorectal Cancer: The COLOSPOT Prospective Study.

Background

Methods

Results

Conclusions

Publications

Clinical Relevance of Viable Circulating Tumor Cells in Patients with Metastatic Colorectal Cancer: The COLOSPOT Prospective Study.

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