1637P - Early retention of KRAS mutations in cfDNA is an ominous sign for pancreatic cancer patients during chemotherapy: A prospective cohort study

Background

Pancreatic ductal adenocarcinoma (PDAC) has a notoriously poor prognosis after treatments without precise biomarkers. The traditional biomarker, carbohydrate antigen 19-9 is not suitable for timely checking treatment responses for all PDAC patients. The usage of low-invasive liquid biopsies, e.g., cell-free DNA (cfDNA) from blood, has shown to improve prognostication for several cancers, but not precisely for PDAC, especially for predictive prognosis by longitudinal sampling. This study aims to address the issue that the dynamic occurrence of oncogenic mutations in cfDNA from serial monitoring could be served as a predictive indicator of disease outcomes in PDAC patients after chemotherapy.

Methods

A total of 65 advanced-staged PDAC patients were enrolled. The plasma cfDNA were subjected to next generation sequencing with a panel of tumor-associated genes and confirmed by digital PCR. Patients were grouped by three risky levels which were designated by the quantities of cfDNA and presence of the oncogenic mutations in cfDNA after treatment (post-cfDNA). Association of different risk factors with progression-free survival (PFS) and overall survival (OS) was assessed in Kaplan-Meier curves and Cox regression analyses.

Results

In the prospective cohort, high-risk patients who had high levels of cfDNA over the threshold showed the worst PFS and OS [HR= 8.83 (3.99-19.51) in PFS, p<0.001; HR=4.25 (2.24-8.06) in OS, p<0.001]. The medium-risk patients, whose cfDNA levels were lower than the threshold but contained KRAS mutants in post-cfDNA, demonstrated moderately worse PFS and OS than low-risk patients without elevated levels and KRAS mutants in post-cfDNA [low risk as reference, HR= 6.08 (2.42-15.27) in PFS, p<0.001; HR=2.64 (1.18-5.91) in OS, p=0.018]. However, patients with TP53 mutants in cfDNA after treatments showed no significance correlations to either PFS (p=0.144) or to OS (p=0.098), respectively.

Conclusions

Early retention of oncogenic KRAS mutants in cfDNA after chemotherapy is an independent factor in predicting worse OS and PFS in PDAC patients. The serial molecular response of oncogenes in post-cfDNA could serve as a leading biomarker in monitoring clinical outcomes in PDAC patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

C-J. Huang.

Funding

National Science and Technology Council.

Disclosure

All authors have declared no conflicts of interest.