Abstract 5779
Background
The presence of mutated KRAS circulating tumor DNA (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.
Methods
We used 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 first-line 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 (74%) and specificity (100%). Presence of mutKRAS ctDNA, as well as higher levels of CA 19-9, CEA and CYFRA 21-1 at treatment initiation 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. Kinetics 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 indicated progressive disease with high sensitivity (84%) and specificity (100%).
Conclusions
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.
Clinical trial identification
Legal entity responsible for the study
Stephan Kruger, Stefan Holdenrieder, Stefan Boeck.
Funding
Sysmex Inostics.
Editorial Acknowledgement
Disclosure
C. Ross, F. Diehl: Employee: Sysmex Inostics. All other authors have declared no conflicts of interest.
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