Dataset Information

The utility of ctDNA in detecting minimal residual disease following curative surgery in colorectal cancer: a systematic review and meta-analysis.

ABSTRACT:

Introduction

Colorectal cancer is the fourth most common cancer in the UK. There remains a need for improved risk stratification following curative resection. Circulating-tumour DNA (ctDNA) has gained particular interest as a cancer biomarker in recent years. We performed a systematic review to assess the utility of ctDNA in identifying minimal residual disease in colorectal cancer.

Methods

Studies were included if ctDNA was measured following curative surgery and long-term outcomes were assessed. Studies were excluded if the manuscript could not be obtained from the British Library or were not available in English.

Results

Thirty-seven studies met the inclusion criteria, involving 3002 patients. Hazard ratios (HRs) for progression-free survival (PFS) were available in 21 studies. A meta-analysis using a random effects model demonstrated poorer PFS associated with ctDNA detection at the first liquid biopsy post-surgery [HR: 6.92 CI: 4.49-10.64 p < 0.00001]. This effect was also seen in subgroup analysis by disease extent, adjuvant chemotherapy and assay type.

Discussion

Here we demonstrate that ctDNA detection post-surgery is associated with a greater propensity to disease relapse and is an independent indicator of poor prognosis. Prior to incorporation into clinical practice, consensus around timing of measurements and assay methodology are critical.

Protocol registration

The protocol for this review is registered on PROSPERO (CRD42021261569).

SUBMITTER: Faulkner LG

PROVIDER: S-EPMC9902552 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

The utility of ctDNA in detecting minimal residual disease following curative surgery in colorectal cancer: a systematic review and meta-analysis.

Faulkner Lucy G LG Howells Lynne M LM Pepper Coral C Shaw Jacqueline A JA Thomas Anne L AL

British journal of cancer 20221108 2

<h4>Introduction</h4>Colorectal cancer is the fourth most common cancer in the UK. There remains a need for improved risk stratification following curative resection. Circulating-tumour DNA (ctDNA) has gained particular interest as a cancer biomarker in recent years. We performed a systematic review to assess the utility of ctDNA in identifying minimal residual disease in colorectal cancer.<h4>Methods</h4>Studies were included if ctDNA was measured following curative surgery and long-term outcom ...[more]

PMID: 36347967

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Project description:BackgroundBreast cancer mortality is principally due to tumor recurrence, which can occur following extended periods of clinical remission that may last decades. While clinical latency has been postulated to reflect the ability of residual tumor cells to persist in a dormant state, this hypothesis remains unproven since little is known about the biology of these cells. Consequently, defining the properties of residual tumor cells is an essential goal with important clinical implications for preventing recurrence and improving cancer outcomes.MethodsTo identify conserved features of residual tumor cells, we modeled minimal residual disease using inducible transgenic mouse models for HER2/neu and Wnt1-driven tumorigenesis that recapitulate cardinal features of human breast cancer progression, as well as human breast cancer cell xenografts subjected to targeted therapy. Fluorescence-activated cell sorting was used to isolate tumor cells from primary tumors, residual lesions following oncogene blockade, and recurrent tumors to analyze gene expression signatures and evaluate tumor-initiating cell properties.ResultsWe demonstrate that residual tumor cells surviving oncogenic pathway inhibition at both local and distant sites exist in a state of cellular dormancy, despite adequate vascularization and the absence of adaptive immunity, and retain the ability to re-enter the cell cycle and give rise to recurrent tumors after extended latency periods. Compared to primary or recurrent tumor cells, dormant residual tumor cells possess unique features that are conserved across mouse models for human breast cancer driven by different oncogenes, and express a gene signature that is strongly associated with recurrence-free survival in breast cancer patients and similar to that of tumor cells in which dormancy is induced by the microenvironment. Although residual tumor cells in both the HER2/neu and Wnt1 models are enriched for phenotypic features associated with tumor-initiating cells, limiting dilution experiments revealed that residual tumor cells are not enriched for cells capable of giving rise to primary tumors, but are enriched for cells capable of giving rise to recurrent tumors, suggesting that tumor-initiating populations underlying primary tumorigenesis may be distinct from those that give rise to recurrence following therapy.ConclusionsResidual cancer cells surviving targeted therapy reside in a well-vascularized, desmoplastic microenvironment at both local and distant sites. These cells exist in a state of cellular dormancy that bears little resemblance to primary or recurrent tumor cells, but shares similarities with cells in which dormancy is induced by microenvironmental cues. Our observations suggest that dormancy may be a conserved response to targeted therapy independent of the oncogenic pathway inhibited or properties of the primary tumor, that the mechanisms underlying dormancy at local and distant sites may be related, and that the dormant state represents a potential therapeutic target for preventing cancer recurrence.

Dataset Information

The utility of ctDNA in detecting minimal residual disease following curative surgery in colorectal cancer: a systematic review and meta-analysis.

Introduction

Methods

Results

Discussion

Protocol registration

Publications

The utility of ctDNA in detecting minimal residual disease following curative surgery in colorectal cancer: a systematic review and meta-analysis.

Similar Datasets

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