Dataset Information

Prognostic value of circulating tumour DNA in metastatic pancreatic cancer patients: post-hoc analyses of two clinical trials.

ABSTRACT:

Objective

The prognostication of metastatic pancreatic adenocarcinoma (mPDAC) patients remains uncertain, mainly based on carbohydrate antigen 19-9 (CA19-9), with limited utility. Circulating tumour DNA (ctDNA) has been suggested as a prognostic factor, but its added value has been poorly explored. The objective was to determine whether ctDNA is an independent factor for the prognostication of mPDAC.

Design

Translational study based on two prospective collections of plasma samples of mPDAC patients naïve for chemotherapy. One used as a test series and the other as validation series coming from two randomised trials (Prodige 35 and Prodige 37). CtDNA was assessed by digital droplet PCR targeting two methylated markers (HOXD8 and POU4F1) according to a newly developed and validated method. Univariate and multivariate analyses were performed according to ctDNA status.

Results

Of 372 plasma samples available, 354 patients were analyzed for survival. In the validation series, 145 of 255 patients were found ctDNA positive (56.8%), Median PFS and OS were 5.3 and 8.2 months in ctDNA-positive and 6.2 and 12.6 months in ctDNA-negative patients, respectively. ctDNA positivity was more often associated with young age, high CA19-9 level and neutrophils lymphocytes ratio. In multivariate analysis including these previous markers, ctDNA was confirmed as an independent prognostic marker for PFS (adjusted hazard ratio (HR) 1.5, CI 95% [1.03-2.18], p = 0.034) and OS (HR 1.62, CI 95% [1.05-2.5], p = 0.029).

Conclusions

In this first ctDNA assessment in a large series of mPDAC derived from clinical trials, ctDNA was detectable in 56.8% of patients and confirmed as an independent prognostic marker.

SUBMITTER: Pietrasz D

PROVIDER: S-EPMC8810868 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

Prognostic value of circulating tumour DNA in metastatic pancreatic cancer patients: post-hoc analyses of two clinical trials.

Pietrasz Daniel D Wang-Renault Shufang S Taieb Julien J Dahan Laetitia L Postel Mathilde M Durand-Labrunie Jerome J Le Malicot Karine K Mulot Claire C Rinaldi Yves Y Phelip Jean-Marc JM Doat Solene S Blons Hélène H de Reynies Aurelien A Bachet Jean-Baptiste JB Taly Valérie V Laurent-Puig Pierre P

British journal of cancer 20211122 3

<h4>Objective</h4>The prognostication of metastatic pancreatic adenocarcinoma (mPDAC) patients remains uncertain, mainly based on carbohydrate antigen 19-9 (CA19-9), with limited utility. Circulating tumour DNA (ctDNA) has been suggested as a prognostic factor, but its added value has been poorly explored. The objective was to determine whether ctDNA is an independent factor for the prognostication of mPDAC.<h4>Design</h4>Translational study based on two prospective collections of plasma samples ...[more]

PMID: 34811505

Similar Datasets

Project description:BackgroundThe potential of circulating tumour DNA (ctDNA) as a reliable biomarker for relapse/metastasis early detection and prognosis in esophageal squamous cell carcinoma (ESCC) after radiotherapy/chemoradiotherapy (RT/CRT) initiation requires comprehensive investigation.MethodsTreatment-naive locally advanced ESCC patients with available baseline plasma samples were prospectively enrolled from November 2018 to January 2020. RT/CRT was delivered with a simultaneous integrated boost of radiation dose. Serial plasma samples were collected at baseline (T0 ), week 4 of RT/CRT (T1 ), 1-3 (T2 ) and 3-6 months post-RT/CRT (T3 ). ctDNA was analysed using next-generation sequencing of 474 cancer-relevant genes.ResultsA total of 128 plasma samples from 40 eligible patients were analysed (median age: 64 [range: 40-78], 88% males, 95% stage III/IV), and the median follow-up time was 20.6 months (range: 12.2-33.3). During the post-RT/CRT surveillance including 36 patients, radiological progression was observed in 16 patients, and 69% (11/16) had detectable post-RT/CRT ctDNA prior to radiological progression, with a median lead time of 4.4 months compared with radiological imaging. ctDNA positivity at T1 (hazard ratio, HR: 3.60, 95% confidence interval, CI: 1.30-10.01) or T2 (HR: 5.45, 95% CI: 1.72-17.26) indicated inferior progression-free survival (PFS). ctDNA clearance between T0 -T1 (HR: 0.31, 95% CI: 0.08-1.13) or T0 -T2 (HR: 0.11; 95% CI: 0.02-0.61) was associated with relatively favourable PFS. Similar results were obtained when focusing on patients without esophagectomy after RT/CRT. Notably, detectable ctDNA at T1 was a potential indicator of high local recurrence risks (HR: 4.43, 95% CI: 1.31-15.04).ConclusionsctDNA was identified as a robust biomarker for early detection of disease progression and post-RT/CRT prognosis stratification in ESCC. Detectable ctDNA at week 4 of RT/CRT might indicate higher local recurrence risks, implying the potential clinical utility of ctDNA tests in guiding post-RT/CRT treatments for locoregional control in ESCC.

Dataset Information

Prognostic value of circulating tumour DNA in metastatic pancreatic cancer patients: post-hoc analyses of two clinical trials.

Objective

Design

Results

Conclusions

Publications

Prognostic value of circulating tumour DNA in metastatic pancreatic cancer patients: post-hoc analyses of two clinical trials.

Similar Datasets

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