Monitoring of circulating tumour DNA in advanced pancreatic ductal adenocarcinoma predicts clinical outcome and reveals disease progression earlier than radiological imaging

Author:

Edland Karin Hestnes1,Tjensvoll Kjersti1,Oltedal Satu1,Dalen Ingvild2,Lapin Morten1ORCID,Garresori Herish1,Glenjen Nils3,Gilje Bjørnar1,Nordgård Oddmund14ORCID

Affiliation:

1. Department of Hematology and Oncology Stavanger University Hospital Norway

2. Section of Biostatistics, Department of Research Stavanger University Hospital Norway

3. Department of Oncology Haukeland University Hospital Bergen Norway

4. Department of Chemistry, Bioscience and Environmental Technology, Faculty of Science and Technology University of Stavanger Norway

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a need for better tools to guide treatment selection and follow‐up. The aim of this prospective study was to investigate the prognostic value and treatment monitoring potential of longitudinal circulating tumour DNA (ctDNA) measurements in patients with advanced PDAC undergoing palliative chemotherapy. Using KRAS peptide nucleic acid clamp‐PCR, we measured ctDNA levels in plasma samples obtained at baseline and every 4 weeks during chemotherapy from 81 patients with locally advanced and metastatic PDAC. Cox proportional hazard regression showed that ctDNA detection at baseline was an independent predictor of progression‐free and overall survival. Joint modelling demonstrated that the dynamic ctDNA level was a strong predictor of time to first disease progression. Longitudinal ctDNA measurements during chemotherapy successfully revealed disease progression in 20 (67%) of 30 patients with ctDNA detected at baseline, with a median lead time of 23 days (P = 0.01) over radiological imaging. Here, we confirmed the clinical relevance of ctDNA in advanced PDAC with regard to both the prediction of clinical outcome and disease monitoring during treatment.

Funder

Kreftforeningen

Publisher

Wiley

Subject

Cancer Research,Genetics,Molecular Medicine,General Medicine,Oncology

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