Cancer-cell-derived cell-free DNA can predict distant metastasis earlier in pancreatic cancer: a prospective cohort study.

Abstract

Background:

Carbohydrate antigen 19-9 (CA19-9) is the only biomarker for monitoring responses during treatments of pancreatic cancer, but its accuracy for disease outcome is controversial. Fluid biopsy is a new method for diagnosis and monitoring treatment response. In this study, we investigate the usefulness of cell-free DNA (cfDNA) in predicting disease progression during the treatment of pancreatic cancer.

Methods:

Biopsy-proved advanced pancreatic cancer patients who received systemic chemotherapy were enrolled after signed informed consent. CA19-9 and cfDNA in blood were measured before and after every two cycles of treatments, and the disease progression was monitored by computed tomography (CT) with 3-month interval.

Results:

In total, 74 patients and 148 blood samples were enrolled in this study. Patients whose average blood cfDNA concentration of >9.71 ng/mL before and after first two courses of chemotherapy would subsequently show new distant metastasis (NDM) on CT scans 3 months later. The accuracy was 94.37% (AUC 0.9705, p < 0.0001) and the progression-free survival (PFS) and overall survival (OS) of patients with cfDNA concentration of >9.71 ng/mL were worse than those patients with cfDNA concentration of <9.71 ng/mL (median PFS: 95 days versus 322 days, p < 0.0001; median OS: 150 days versus 431 days, p < 0.0001). The cfDNA concentration of >9.71 ng/mL is a predictor for PFS, OS, and distant metastasis-free survival by multivariate analysis. Comparison of KRAS G12 variants detected by next-generation sequencing from tumor tissue issue and remnant DNA of cfDNA showed that increased cfDNA was primarily derived from cancer cells.

Conclusion:

The cancer-cell-derived cfDNA levels could be served as a powerful biomarker for prediction of NDM in patients with advanced/metastatic pancreatic cancer.

• Authors: Chien-Jui Huang, Wen-Yen Huang, Chien-Yu Chen, Ying-Jui Chao, Nai-Jung Chiang, Yan-Shen Shan
• Journal: Therapeutic advances in medical oncology (Ther Adv Med Oncol) Vol. 14 Pg. 17588359221106558 ( 2022) ISSN: 1758-8340 [Print] England
• PMID: 35747164 (Publication Type: Journal Article)
• Copyright: © The Author(s), 2022.