Konstantin Schlick1, Steiner Markus1, Florian Huemer1, Lukas Ratzinger1, Nadja Zaborsky1, Hufnagl Clemens2, Daniel Neureiter3, Bettina Neumayer3, Alinger-Scharinger Beate3, Steiner Florian4, Varga Martin5, Michael Grundbichler1, Lukas Weiss1, Thomas Melchardt1, Richard Greil1, Alexander Egle6. 1. 3rd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Paracelsus Medical University, Salzburg, Austria; Salzburg Cancer Research Institute (SCRI), Salzburg, Austria; Laboratory for Immunological and Molecular Cancer Research (LIMCR), Salzburg, Austria; Center for Clinical Cancer and Immunology Trials (CCCIT), Salzburg, Austria. 2. Department for Neuroinvention, Christian-Doppler-Klinik Universitätsklinik für Neurologie Paracelsus Medical University, Salzburg, Austria. 3. Department of Pathology, Paracelsus Medical University Salzburg, Salzburg, Austria. 4. Department of Radiology, Paracelsus Medical University Salzburg, Salzburg, Austria. 5. Department of Surgery, Paracelsus Medical University Salzburg, Salzburg, Austria. 6. 3rd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Paracelsus Medical University, Salzburg, Austria; Salzburg Cancer Research Institute (SCRI), Salzburg, Austria; Laboratory for Immunological and Molecular Cancer Research (LIMCR), Salzburg, Austria; Center for Clinical Cancer and Immunology Trials (CCCIT), Salzburg, Austria. Electronic address: K.Schlick@salk.at.
Abstract
BACKGROUND: Pancreatic carcinoma carries a devastating prognosis and is the 4th leading cause for cancer related death in the US and most European countries. Apart from imaging and CA 19-9, pancreatic carcinoma is still lacking reliable markers to assess tumor dynamics and to monitor treatment response over time. The aim of this study was to evaluate the feasibility of cell free tumor-DNA (cft-DNA), respectively KRAS mutation in peripheral blood, detection as a prognostic and predictive value for chemotherapy monitoring. METHODS: Serial plasma samples from 42 patients with KRAS mutated pancreatic cancer were prospectively collected and the ctKRAS Mutation Assay (Idylla™, Biocartis, Mechelen, Belgium) of cft-DNA was performed on 29 patients that did not receive curative surgery and went on to palliative chemotherapy. To monitor cft-DNA KRAS mutation levels during treatment quantitative assessment of cft-DNA was performed at baseline and during follow up at predetermined times. RESULTS: All 29 patients included in our analyses had a detected KRAS mutation in the tumor biopsy. In almost half (48.2%) of patients a KRAS mutation could also be detected in peripheral plasma. Patients with detectable KRAS mutations before treatment start in plasma had a significantly worse survival (16.8 months vs not reached, p < 0.031 and HR 3.303). Looking for a dynamic assessment of tumor response, we found a statistically significant association between the KRAS mutant ratio from first staging CT scan to basal levels with tumor response or progress (p = 0.014). CONCLUSION: Performing KRAS testing from peripheral blood for patients, who have no elevated tumor markers, might be a novel option for treatment monitoring complementing routine imaging techniques.
BACKGROUND: Pancreatic carcinoma carries a devastating prognosis and is the 4th leading cause for cancer related death in the US and most European countries. Apart from imaging and CA 19-9, pancreatic carcinoma is still lacking reliable markers to assess tumor dynamics and to monitor treatment response over time. The aim of this study was to evaluate the feasibility of cell free tumor-DNA (cft-DNA), respectively KRAS mutation in peripheral blood, detection as a prognostic and predictive value for chemotherapy monitoring. METHODS: Serial plasma samples from 42 patients with KRAS mutated pancreatic cancer were prospectively collected and the ctKRAS Mutation Assay (Idylla™, Biocartis, Mechelen, Belgium) of cft-DNA was performed on 29 patients that did not receive curative surgery and went on to palliative chemotherapy. To monitor cft-DNA KRAS mutation levels during treatment quantitative assessment of cft-DNA was performed at baseline and during follow up at predetermined times. RESULTS: All 29 patients included in our analyses had a detected KRAS mutation in the tumor biopsy. In almost half (48.2%) of patients a KRAS mutation could also be detected in peripheral plasma. Patients with detectable KRAS mutations before treatment start in plasma had a significantly worse survival (16.8 months vs not reached, p < 0.031 and HR 3.303). Looking for a dynamic assessment of tumor response, we found a statistically significant association between the KRAS mutant ratio from first staging CT scan to basal levels with tumor response or progress (p = 0.014). CONCLUSION: Performing KRAS testing from peripheral blood for patients, who have no elevated tumor markers, might be a novel option for treatment monitoring complementing routine imaging techniques.
Authors: Patrick Kirchweger; Alexander Kupferthaler; Jonathan Burghofer; Gerald Webersinke; Emina Jukic; Simon Schwendinger; Helwig Wundsam; Matthias Biebl; Andreas Petzer; Holger Rumpold Journal: Front Oncol Date: 2022-08-30 Impact factor: 5.738