Minimal residual disease in gastroesophageal adenocarcinoma: the search for the invisible

Tarazona, Noelia; Gimeno-Valiente, Francisco

doi:10.1016/j.esmoop.2022.100547

Cited by 3 publications

(5 citation statements)

References 25 publications

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“…The detection of ctDNA after nCRT seems to be hampered by lower shedding and possibly more background biological noise as we observed higher cfDNA concentrations in non-baseline samples. To accurately predict CR pre-surgery, ultra-sensitive techniques may be necessary or other methods of detection including sequencing for tumor methylation signatures [28][29][30][31]. Personalized tumor-informed assays could also help to boost sensitivity by providing high reliability and a reduction in the amount of targets that need to be sequenced [26].…”

Section: Discussionmentioning

confidence: 99%

Genome‐wide and panel‐based cell‐free DNA characterization of patients with resectable esophageal adenocarcinoma

van den Ende,

van der Pol,

Creemers

et al. 2023

The Journal of Pathology

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Circulating tumor DNA (ctDNA) holds promise in resectable esophageal adenocarcinoma (EAC) to predict patient outcome but is not yet sensitive enough to be clinically applicable. Our aim was to combine ctDNA mutation data with shallow whole‐genome sequencing (sWGS)‐derived copy number tumor fraction estimates (ichorCNA) to improve pathological response and survival prediction in EAC. In total, 111 stage II/III EAC patients with baseline (n = 111), post‐neoadjuvant chemoradiotherapy (nCRT) (n = 68), and pre‐surgery (n = 92) plasma samples were used for ctDNA characterization. sWGS (<5× coverage) was performed on all time‐point samples, and copy number aberrations were estimated using ichorCNA. Baseline and pre‐surgery samples were sequenced using a custom amplicon panel for mutation detection. Detection of baseline ctDNA was successful in 44.3% of patients by amplicon sequencing and 10.5% by ichorCNA. Combining both, ctDNA could be detected in 50.5% of patients. Baseline ctDNA positivity was related to higher T stage (cT3, 4) (p = 0.017). There was no relationship between pathological response and baseline ctDNA positivity. However, baseline ctDNA metrics (variant allele frequency > 1% or ichorCNA > 3%) were associated with a high risk of disease progression [HR = 2.23 (95% CI 1.22–4.07), p = 0.007]. The non‐clearance of a baseline variant or ichorCNA > 3% in pre‐surgery samples was related to early progression [HR = 4.58 (95% CI 2.22–9.46), p < 0.001]. Multi‐signal analysis improves detection of ctDNA and can be used for prognostication of resectable EAC patients. Future studies should explore the potential of multi‐modality sequencing for risk stratification and treatment adaptation based on ctDNA results. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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Section: Discussionmentioning

confidence: 99%

Genome‐wide and panel‐based cell‐free DNA characterization of patients with resectable esophageal adenocarcinoma

van den Ende,

van der Pol,

Creemers

et al. 2023

The Journal of Pathology

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“…To date, no comparative data are available on these two assays in terms of MRD detection sensitivity, but ongoing prospective trials will provide more information in this regard. 54 , 55 …”

Section: Discussionmentioning

confidence: 99%

Sequencing paired tumor DNA and white blood cells improves circulating tumor DNA tracking and detects pathogenic germline variants in localized colon cancer

Gimeno-Valiente,

Martín-Arana,

Tébar-Martínez

et al. 2023

ESMO Open

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“…Since the advent of blood-based circulating tumor DNA (ctDNA), different efforts have been made in order to evaluate its use in GC [43]. Currently, there are two approaches for MRD assessment: a tumor-informed one that starts from the genomic sequencing of the primary tumor and a tumor-agnostic one that is uninformed by the mutations in the primary tumor [44]. Although more expensive than tumor-naïve tests, tumor-informed approaches are preferable as far as they are able to determine MRD with both high sensitivity and specificity, with the possible identification of tumor-specific variants with a very low variant allele frequency of 0.01%.…”

Section: Minimal Residual Diseasementioning

confidence: 99%

“…Differently, tumor-agnostic tests are less sensitive and able to detect tumor-specific variants for a VAF between 0.1 and 1%. On the whole, sequencing of multiple tumor regions increases the sensitivity of the test and the possibility to detect ctDNA variants [44]. However, the discrepancy between the primary tissue and ctDNA profile may be caused by cancer heterogeneity.…”

Section: Minimal Residual Diseasementioning

confidence: 99%

“…Moreover, MRD cannot be immediately detected in plasma after surgery, and the evaluation of serial timepoints of plasma after resection allowed the identification of ctDNA variants with a progressive increase in VAF in relapsed patients. Usually, ctDNA detection typically precedes radiological relapse by a median time of 3-8 months [44].…”

Section: Minimal Residual Diseasementioning

confidence: 99%

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Circulating Tumor DNA in Gastric Adenocarcinoma: Future Clinical Applications and Perspectives

Grizzi,

Salati,

Bonomi

et al. 2023

IJMS

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Gastric cancer (GC) is still one of the most aggressive cancers with a few targetable alterations and a dismal prognosis. A liquid biopsy allows for identifying and analyzing the DNA released from tumor cells into the bloodstream. Compared to tissue-based biopsy, liquid biopsy is less invasive, requires fewer samples, and can be repeated over time in order to longitudinally monitor tumor burden and molecular changes. Circulating tumor DNA (ctDNA) has been recognized to have a prognostic role in all the disease stages of GC. The aim of this article is to review the current and future applications of ctDNA in gastric adenocarcinoma, in particular, with respect to early diagnosis, the detection of minimal residual disease (MRD) following curative surgery, and in the advanced disease setting for treatment decision choice and therapeutic monitoring. Although liquid biopsies have shown potentiality, pre-analytical and analytical steps must be standardized and validated to ensure the reproducibility and standardization of the procedures and data analysis methods. Further research is needed to allow the use of liquid biopsy in everyday clinical practice.

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Minimal residual disease in gastroesophageal adenocarcinoma: the search for the invisible

Cited by 3 publications

References 25 publications

Genome‐wide and panel‐based cell‐free DNA characterization of patients with resectable esophageal adenocarcinoma

Genome‐wide and panel‐based cell‐free DNA characterization of patients with resectable esophageal adenocarcinoma

Sequencing paired tumor DNA and white blood cells improves circulating tumor DNA tracking and detects pathogenic germline variants in localized colon cancer

Circulating Tumor DNA in Gastric Adenocarcinoma: Future Clinical Applications and Perspectives

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