Prospective Evaluation of Circulating Tumor DNA using Next Generation Sequencing as a Biomarker during Neoadjuvant Chemotherapy in Localized Pancreatic Cancer

Annals of Surgery Manuscript
Authors Dhavan Shah, Amy Wells, Madison Cox, Kevin Dawravoo, John Abad, Arlene D’Souza, Grace Suh, Robert Bayer, Sohail Chaudhry, Qiang Zhang, Massimo Cristofanilli, David Bentrem, and Akhil Chawla


In this prospective study, we aim to characterize the prognostic value of circulating tumor DNA (ctDNA) by next-generation-sequencing (NGS) in patients undergoing neoadjuvant chemotherapy (NAC) for pancreatic ductal adenocarcinoma (PDAC).

Summary Background Data

Circulating tumor DNA is a promising blood-based biomarker that is prognostic in several malignancies. Detection of ctDNA by NGS may provide insights regarding the mutational profiles in PDAC to help guide clinical decisions for patients in a potentially curative setting. However, the utility of ctDNA as a biomarker in localized PDAC remains unclear.


Patients with localized PDAC were enrolled in a prospective study at Northwestern Medicine between October 2020 and October 2022. Blood samples were collected to perform targeted tumor agnostic NGS utilizing the Tempus x|F 105 gene panel at three timepoints: pre-therapy (at diagnosis), post-NAC, and after local therapy, including surgery. The relationship between ctDNA detection and CA19-9, and the prognostic significance of ctDNA detection were analyzed.


56 patients were included in the analysis. ctDNA was detectable in 48% at diagnosis, 33% post-NAC, and 41% after local therapy. After completion of NAC, patients with detectable ctDNA had higher CA19-9 levels versus those without (78.4 vs. 30.0, P=0.02). The presence of baseline ctDNA was associated with a CA19-9 response; those without ctDNA had a significant CA19-9 response following NAC (109.0 U/mL vs. 31.5 U/mL; P=0.01), while those with ctDNA present at diagnosis did not (198.1 U/mL vs. 113.8 U/mL; P=0.77). In patients treated with NAC, the presence of KRAS ctDNA at diagnosis was associated with and independently predicted worse progression-free-survival.


This report demonstrates the prognostic value of ctDNA analysis with NGS in localized PDAC. NGS ctDNA is a biomarker of treatment response to NAC. KRAS ctDNA at diagnosis independently predicts worse survival in patients treated with NAC.