1508P - Tumor-specific circulating cell-free DNA (ctDNA) and its clinical value in predicting response to palliative systemic treatment or survival in patients with pancreatic cancer: A systematic review and meta-analysis

Background

We investigate the clinical utility of ctDNA response evaluation criteria and examine the value of ctDNA in predicting disease outcomes in patients with pancreatic ductal adenocarcinoma (PDAC).

Methods

The protocol was registered in PROSPERO (CRD42023438774). PubMed, MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched, and data managed in Covidence. Studies with patients receiving palliative systemic treatment for PDAC, reporting on ctDNA dynamics in relation to treatment response, progression free survival (PFS) or overall survival (OS) were eligible. Studies providing a hazard ratio (HR) based on univariate analysis with corresponding 95% confidence intervals were included in the meta-analysis.

Results

1682 studies were screened for eligibility. CtDNA dynamics were reported in 903 of 2340 patients in 31 included studies. The most used ctDNA methods were Next Generation Sequencing (NGS) and digital droplet PCR, measuring KRAS. Baseline detection rates varied from 26% to 100% with higher scores associated with multiple target NGS. A correlation between ctDNA decrease/clearance and improved clinical outcome or ctDNA increase/persistence and worse clinical outcome was described in 26 studies. Cut-offs for ctDNA dynamics comprised ctDNA detection, concentration, and change as either proportions, ratios, or slopes. Twelve studies descriptively presented ctDNA changes, whereas 19 studies analyzed data with a variety of statistical methods, including only 5 eligible studies for meta-analysis. These show a strong correlation between ctDNA increase, persistence, or emergence with poor PFS, HR 5.9 (1.4-24.5; n=151), and OS, HR 2.2 (1.1-4.3; n=143).

Conclusions

CtDNA response evaluation could become a valuable tool for predicting clinical outcomes in PDAC, but data is heterogeneous and clear definitions of ctDNA response and ctDNA progression are lacking. Ongoing prospective studies must seek to validate well-defined ctDNA response criteria (ctDNA RECIST) and compare ctDNA RECIST with standard image evaluation in randomized trials.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Health Research Foundation of Central Denmark Region, The Danish Cancer Society.

Disclosure

M. Ladekarl: Financial Interests, Institutional, Research Grant, Research grant from Scandion Oncology A/S, Denmark: Scandion Oncology A/S; Financial Interests, Personal, Other, Honoraria for lecture from AstraZeneca, Denmark: AstraZeneca. K.G. Spindler: Financial Interests, Personal, Other, Honoraria for Lecture: Daiichi Sankyo Northern Europe GmbH; Financial Interests, Personal, Other, Honoraria for Teaching: Incyte Biosciences Denmark ApS; Financial Interests, Personal, Other, Honoraria for Lectures, webinars: BMS Norway. All other authors have declared no conflicts of interest.