Journal Article

Ultra-sensitive CTC-based liquid biopsy for pancreatic cancer enabled by large blood volume analysis

Sudarsanam, Monica, Franken, André, Stoecklein, Nikolas H., Fehm, Tanja, Böhme, Petra, Rox, Jutta M., Häberle, Lena, Fischer, Johannes C., Rahbari, Nuh N., Hackert, Thilo, Cieslik, Stefan A., Topp, Stefan A., Knoefel, Wolfram T., Bork, Ulrich, van Dalum, Guus, Weitz, Jürgen, Niederacher, Dieter, Neubauer, Hans, Driemel, Christiane, Esposito, Irene, Guglielmi, Rosa, Coumans, Frank A.W., Birgin, Emrullah, Fluegen, Georg, Neves, Rui P.L., Göring, Wolfgang

2023

Overview

The limited sensitivity of circulating tumor cell (CTC) detection in pancreatic adenocarcinoma (PDAC) stems from their extremely low concentration in the whole circulating blood, necessitating enhanced detection methodologies. This study sought to amplify assay-sensitivity by employing diagnostic leukapheresis (DLA) to screen large blood volumes. Sixty patients were subjected to DLA, with a median processed blood volume of ~ 2.8 L and approximately 5% of the resulting DLA-product analyzed using CellSearch (CS). Notably, DLA significantly increased CS-CTC detection to 44% in M0-patients and 74% in M1-patients, yielding a 60-fold increase in CS-CTC enumeration. DLA also provided sufficient CS-CTCs for genomic profiling, thereby delivering additional genomic information compared to tissue biopsy samples. DLA CS-CTCs exhibited a pronounced negative prognostic impact on overall survival (OS), evidenced by a reduction in OS from 28.6 to 8.5 months (univariate: p = 0.002; multivariable: p = 0.043). Additionally, a marked enhancement in sensitivity was achieved (by around 3-4-times) compared to peripheral blood (PB) samples, with positive predictive values for OS being preserved at around 90%. Prognostic relevance of CS-CTCs in PDAC was further validated in PB-samples from 228 PDAC patients, consolidating the established association between CTC-presence and reduced OS (8.5 vs. 19.0 months, p < 0.001). In conclusion, DLA-derived CS-CTCs may serve as a viable tool for identifying high-risk PDAC-patients and aiding the optimization of multimodal treatment strategies. Moreover, DLA enables comprehensive diagnostic profiling by providing ample CTC material, reinforcing its utility as a reliable liquid-biopsy approach. This high-volume liquid-biopsy strategy presents a potential pathway for enhancing clinical management in this malignancy.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adenocarcinoma / Adenocarcinoma - diagnosis / Biomarkers / Biomarkers, Tumor / Biomedical and Life Sciences / Biomedicine / Biopsy / Blood / Blood Volume / Breast cancer / Cancer Research / Circulating tumor cells / Correspondence / CTCs / Enumeration / Genomics / High-blood volume analysis / Humans / Leukapheresis / Liquid biopsy / Liquid Biopsy - methods / Liquid Biopsy at the Frontier of Early Detection / Malignancy / Metastasis / Mutation / Neoplastic Cells, Circulating - pathology / Oncology / Pancreatic cancer / Pancreatic ductal adenocarcinoma / Pancreatic Neoplasms / Pancreatic Neoplasms - diagnosis / Patients / PDAC / Peripheral blood / Prognosis and Cancer Treatments / Prostate / Surgery