1506P - ctDNA testing based on deep NGS predicts treatment efficacy and prognosis in advanced pancreatic cancer patients

Background

Pancreatic ductal adenocarcinoma (PDAC) is a rapidly progressing cancer with poor prognosis. This study explores the utility of deep next-generation sequencing (NGS) of ctDNA for managing locally advanced or metastatic PDAC.

Methods

Peripheral blood samples were collected from newly diagnosed PDAC patients before starting systemic therapy (B1) and at initial disease evaluation (B2). Plasma-free DNA was extracted and sequenced using targeted NGS at over 30,000× depth. We gathered clinical-pathological data, treatment details, response evaluations, and survival information, including progression-free survival (PFS).

Results

From February to December 2023, 80 patients were recruited, split between 34 with locally advanced and 46 with metastatic PDAC. In the locally advanced group, ctDNA-positive patients at B1 more frequently had elevated CA19-9 levels compared to ctDNA-negative patients (100% vs. 61.5%, p = 0.005). As of January 1, 2024, Kaplan‒Meier analysis, showed that in the locally advanced group, decreased ctDNA levels (B2-B1) and a negative ctDNA status at B2 were linked to better PFS (NR vs. 103 days, P = 0.0047; NR vs. 149 days, p = 0.0008). Similarly, the metastatic group showed improved PFS with decreased ctDNA (NR vs 153 days, p = 0.066; 56 vs 125 days, p = 0.000011). For those shifting from positive to negative ctDNA status, longer PFS was noted (NR vs. 136 days,p = 0.0062) in the locally advanced cohort. ROC curve analysis indicated ctDNA at B2 as the most effective PFS predictor in the locally advanced group (AUC = 0.864) and showed good predictive value for ctDNA and CA19-9 in the metastatic group (AUC = 0.808; 0.812), with enhanced accuracy when combined (AUC = 0.909). Univariate Cox regression identified ctDNA changes and ctDNA status at B2 as potential PFS predictors in both cohorts. Multivariate analysis confirmed ctDNA status at B2 as an independent prognostic factor in the locally advanced group, with ctDNA changes similarly significant in the metastatic group.

Conclusions

NGS ctDNA serve as critical prognostic markers. Ongoing expansion of the sample size and extended follow-up are aimed at further validating the clinical significance of NGS ctDNA testing.

Clinical trial identification

NCT05802420, NCT05802394.

Editorial acknowledgement

Legal entity responsible for the study

T. You.

Funding

National High level Hospital Clinical Research Funding 2022-PUMCH-D-001.

Disclosure

All authors have declared no conflicts of interest.