S Kruger1, V Heinemann1, C Ross2, F Diehl2, D Nagel3, S Ormanns4, S Liebmann4, I Prinz-Bravin5, C B Westphalen1, M Haas1, A Jung4, T Kirchner4, M von Bergwelt-Baildon1, S Boeck1, S Holdenrieder6. 1. Department of Medicine III, University Hospital, LMU, Munich, Germany. 2. Sysmex Inostics, Hamburg, Germany. 3. Institute of Laboratory Medicine, University Hospital, LMU, Munich, Germany. 4. Institute of Pathology, LMU, Munich, Germany. 5. Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany. 6. Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany; Institute of Laboratory Medicine, German Heart Center, Technical University of Munich, Munich, Germany. Electronic address: holdenrieder@dhm.mhn.de.
Abstract
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: The aim of the present study was to explore the potential of repeated mutKRAS ctDNA measurements for response prediction and therapy monitoring in advanced PC patients. 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%). The presence of mutKRAS ctDNA, as well as higher levels of CA 19-9, CEA and CYFRA 21-1 before initiation of the first-line chemotherapy, was 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. A decrease in mutKRAS ctDNA levels during therapy was 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%). 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.
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: The aim of the present study was to explore the potential of repeated mutKRAS ctDNA measurements for response prediction and therapy monitoring in advanced PC patients. 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%). The presence of mutKRAS ctDNA, as well as higher levels of CA 19-9, CEA and CYFRA 21-1 before initiation of the first-line chemotherapy, was 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. A decrease in mutKRAS ctDNA levels during therapy was 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%). 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.
Authors: Marian Liberko; Katarina Kolostova; Arpad Szabo; Robert Gurlich; Martin Oliverius; Renata Soumarova Journal: In Vivo Date: 2021 Jan-Feb Impact factor: 2.155
Authors: Anne Macgregor-Das; Jun Yu; Koji Tamura; Toshiya Abe; Masaya Suenaga; Koji Shindo; Michael Borges; Chiho Koi; Shiro Kohi; Yoshihiko Sadakari; Marco Dal Molin; Jose A Almario; Madeline Ford; Miguel Chuidian; Richard Burkhart; Jin He; Ralph H Hruban; James R Eshleman; Alison P Klein; Christopher L Wolfgang; Marcia I Canto; Michael Goggins Journal: J Mol Diagn Date: 2020-03-20 Impact factor: 5.568