Dataset Information

Tumor-Agnostic Circulating Tumor DNA Testing for Monitoring Muscle-Invasive Bladder Cancer.

ABSTRACT: Circulating tumor DNA (ctDNA) has recently emerged as a real-time prognostic and predictive biomarker for monitoring cancer patients. Here, we aimed to ascertain whether tumor-agnostic ctDNA testing would be a feasible strategy to monitor disease progression and therapeutic response in muscle-invasive bladder cancer (MIBC) patients after radical cystectomy (RC). Forty-two MIBC patients who underwent RC were prospectively included. Blood samples from these patients were collected at different follow-up time points. Two specific mutations (TERT c.1-124C>T and ATM c.1236-2A>T) were analyzed in the patients' plasma samples by droplet digital PCR to determine their ctDNA status. During a median follow-up of 21 months, 24% of patients progressed in a median of six months. ctDNA status was identified as a prognostic biomarker of tumor progression before RC and 4 and 12 months later (HR 6.774, HR 3.673, and HR 30.865, respectively; p < 0.05). Lastly, dynamic changes in ctDNA status between baseline and four months later were significantly associated with patient outcomes (p = 0.045). In conclusion, longitudinal ctDNA analysis using a tumor-agnostic approach is a potential tool for monitoring MIBC patients after RC. The implementation of this testing in a clinical setting could improve disease management and patients' outcomes.

SUBMITTER: Carrasco R

PROVIDER: S-EPMC10706140 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Tumor-Agnostic Circulating Tumor DNA Testing for Monitoring Muscle-Invasive Bladder Cancer.

Carrasco Raquel R Ingelmo-Torres Mercedes M Trullas Ramón R Roldán Fiorella L FL Rodríguez-Carunchio Leonardo L Juez Lourdes L Sureda Joan J Alcaraz Antonio A Mengual Lourdes L Izquierdo Laura L

International journal of molecular sciences 20231121 23

Circulating tumor DNA (ctDNA) has recently emerged as a real-time prognostic and predictive biomarker for monitoring cancer patients. Here, we aimed to ascertain whether tumor-agnostic ctDNA testing would be a feasible strategy to monitor disease progression and therapeutic response in muscle-invasive bladder cancer (MIBC) patients after radical cystectomy (RC). Forty-two MIBC patients who underwent RC were prospectively included. Blood samples from these patients were collected at different fol ...[more]

PMID: 38068899

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Project description:BackgroundAt present, there is no effective prognostic indicator for muscle invasive bladder cancer (MIBC). A liquid biopsy method, plasma circulating tumor DNA (ctDNA) detection, was evaluated for use in predicting the prognosis of different cancers. This study aims to assess the prognostic value of ctDNA state for muscle-invasive bladder cancer patients.MethodsWe comprehensively searched three public databases (PubMed, EMBASE, and the Cochrane Library) in December 2023 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Studies investigating ctDNA and prognostic outcome indicators in patients with MIBC were included in our analysis. The hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted to evaluate the association between ctDNA and the prognosis in patients with MIBC.ResultsEleven studies and 1,170 patients diagnosed with muscle-invasive bladder cancer, comprising a total of four retrospective cohort studies and eight prospective cohort studies, included in our meta-analysis, one of which had two different cohorts. The analysis revealed that a positive ctDNA state was associated with poor overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS) in patients with MIBC (HR = 4.51, 95% CI: 2.64-7.69, P < 0.001; HR = 4.50, 95% CI: 2.77-7.30, P < 0.001; HR = 6.56, 95% CI: 4.18-10.30, P < 0.001), with significant prognostic effects both pre- and post-treatment. In addition, longitudinal ctDNA analysis proved to be effective in the monitoring of patients with MIBC receiving different treatments (HR = 0.24, 95% CI: 0.14-0.41, P < 0.001).ConclusionsA positive ctDNA state was associated with poor OS, PFS, and RFS in patients with MIBC pre- and post-treatment. Meanwhile, clearance of ctDNA was associated with improved RFS in patients with MIBC. These findings suggest that the ctDNA state is a predictive and prognostic indicator for patients with MIBC, which can be used to monitor recurrence and guide treatment. Thus, ctDNA level detection shows potential for the treatment and prognosis of patients with MIBC.

Project description:BackgroundLiquid biopsy has been proposed to be a promising noninvasive tool to obtain information on tumor progression. Through a clinical observation of a case series of 6 consecutive patients, we aim to determine the value of circulating tumor DNA (ctDNA) for monitoring the tumor burden during the treatment of colorectal cancer (CRC).Materials and methodsWe used capture sequencing of 545 genes to identify somatic alternations in primary tumor tissues of the six CRC patients who underwent radical surgery and in 23 plasma samples collected at serial time points. We compared the mutation patterns and variant allele frequencies (VAFs) between the matched tissue and the plasma samples and evaluated the potential advantage of using ctDNA as a better tumor load indicator to detect disease relapse over carcinoembryonic antigen (CEA), cancer antigen (CA) 19-9 and imaging studies.ResultsWe identified low-frequency mutations with a mean VAF of 0.88% (corresponding to a mean tumor burden of 0.20ng/mL) in the preoperative plasmas of four patients with locally advanced CRC and a subset of mutations shared by their primary tumors. The tumor loads appeared a sudden decrease upon surgery or other adjuvant treatments and then generally maintained at low levels (0.092ng/mL) until disease recurred. ctDNA increased by 13-fold when disease relapsed in one patient while the CEA and CA 19-9 levels remained normal. In this patient, all six somatic mutations identified in the preoperative plasma were detected in the recrudescent plasma again, with five mutations showing allele fraction increase.ConclusionsWe described a multi-time-point profile of ctDNA of CRC patients during the course of comprehensive treatment and observed a correlation of ctDNA level with the clinically evaluated tumor progression. This demonstrated a new strategy by analyzing the heterogeneous ctDNA to evaluate and monitor the tumor burden in the treatment and follow-up of CRC patients, with potentially better potency than conventional biomarkers.

Dataset Information

Tumor-Agnostic Circulating Tumor DNA Testing for Monitoring Muscle-Invasive Bladder Cancer.

Publications

Tumor-Agnostic Circulating Tumor DNA Testing for Monitoring Muscle-Invasive Bladder Cancer.

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