11th International Symposium on Circulating Nucleic Acids in Plasma and Serum (CNAPS)

Repeated mutKRAS ctDNA measurements in patients with advanced pancreatic cancer: Prognostic value, kinetics, response prediction and therapy monitoring in comparison to protein-based tumor markers

Stefan Holdenrieder 5,6 Stephan Kruger 1 Volker Heinemann 1 Carina Ross 2 Frank Diehl 2 Dorothea Nagel 3 Steffen Ormanns 4 Sibylle Liebmann 4 Ina Prinz-Bravin 5 C Benedikt Westphalen 1 Michael Haas 1 Andreas Jung 4 Thomas Kirchner 4 Michael von Bergwelt-Baildon 1 Stefan Boeck 1
1Department of Internal Medicine III, University Hospital Munich, Germany
2Hamburg, Sysmex-Inostics, Germany
3Department of Laboratory Medicine, University Hospital Munich, Germany
4Department of Pathology, University Hospital Munich, Germany
5Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Germany
6Institute of Laboratory Medicine, German Heart Centre, Technical University Munich, Germany

Background: The presence of mutated KRAS (mutKRAS ctDNA) in plasma samples has been consistently shown to be a negative prognostic indicator in pancreatic cancer (PC). Only small pilot studies have evaluated the value of serial mutKRAS ctDNA-measurements in PC.

Patients and methods: We used the BEAMing technology to determine levels of mutKRAS ctDNA, CA 19-9, CEA and CYFRA 21-1 in 284 plasma samples of 54 patients with advanced PC receiving gemcitabine-based chemotherapy. Absolute levels and kinetics of mutKRAS ctDNA, CA-19-9, CEA and CYFRA 21-1 were correlated to radiological response, progression free- and overall survival.

Results: mutKRAS ctDNA was present in a majority of advanced PC patients (n=36/54, 67%) and indicated tissue KRAS mutation status with a high sensitivity (75%) and specificity (100%). Presence of mutKRAS ctDNA, as well as higher levels of CA 19-9, CEA and CYFRA 21-1 prior to initiation of first-line chemotherapy were significantly correlated to an adverse overall survival. During therapy, changes in mutKRAS ctDNA levels were more rapid and pronounced than changes in protein-based tumor markers. Early and complete decreases of mutKRAS ctDNA were an early indicator of response to therapy, while there was no significant correlation between kinetics of CA 19-9, CEA or CYFRA 21-1 and response to chemotherapy during the first four weeks of treatment. Repeated mutKRAS ctDNA measurements during follow-up appeared to be superior to protein-based tumor markers in detecting progressive disease (sensitivity: 83%, specificity: 100%). As in progressive patients, mutKRAS ctDNA often re-increased after a temporary decrease, appropriate time points for monitoring have to be chosen.

Conclusion: mutKRAS ctDNA kinetics appear to be a powerful and highly specific tool in early response prediction and therapy monitoring of advanced PC patients receiving chemotherapy. (Ann Oncol 2018; 29: 2348-2355)









Powered by Eventact EMS