Stephan Kruger1,2, Karoline Schirle3, Michael Haas3, Alexander Crispin4, Jörg Schirra5, Julia Mayerle5, Jan G D'Haese6, Wolfgang G Kunz7, Jens Ricke7, Steffen Ormanns8, Thomas Kirchner8, Sebastian Kobold9, Matthias Ilmer6, Leonie Gebauer3, Christoph B Westphalen3, Michael von Bergwelt-Baildon3, Jens Werner6, Volker Heinemann3, Stefan Boeck3. 1. Department of Medicine III, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany. stephan.kruger@med.uni-muenchen.de. 2. Division of Clinical Pharmacology and Center for Integrated Protein Science Munich (CIPSM), University Hospital, LMU Munich, Munich, Germany. stephan.kruger@med.uni-muenchen.de. 3. Department of Medicine III, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany. 4. Institute of Medical Informatics, Biometry and Epidemiology, LMU Munich, Munich, Germany. 5. Department of Medicine II, University Hospital, LMU Munich, Munich, Germany. 6. Department of General, Visceral, and Transplantation Surgery, University Hospital, LMU Munich, Munich, Germany. 7. Department of Radiology, University Hospital, LMU Munich, Munich, Germany. 8. Institute of Pathology, LMU Munich, Munich, Germany. 9. Division of Clinical Pharmacology and Center for Integrated Protein Science Munich (CIPSM), University Hospital, LMU Munich, Munich, Germany.
Abstract
PURPOSE: A prolonged time to treatment initiation (TTI) correlates with an adverse prognosis in different cancer types including resectable pancreatic cancer (PC). Only limited evidence on the correlation between TTI and prognosis in advanced PC exists. METHODS: Consecutive PC patients (n = 368) who were diagnosed or treated at our high-volume comprehensive cancer center were included in a prospectively maintained database. We retrospectively analyzed time from first imaging showing advanced PC to initiation of palliative first-line chemotherapy. Lead time bias and waiting time paradox were addressed by landmark analysis and correlation of tumor burden with TTI. RESULTS: Two hundred and ninety-seven patients met the pre-specified in- and exclusion criteria of our study. Median TTI was 29 days (range: 1-124 days). Most common reasons for prolonged TTI (> 21 days) were referral from an external treatment center (39%) and a second biopsy (31%). A TTI above the median-, 75th or 90th percentile (43 or 60 days, respectively) had no impact on overall survival. Furthermore, no correlation between levels of carbohydrate antigen 19-9 (CA 19-9) at time of treatment initiation and TTI was observed. CONCLUSION: While a timely work-up of advanced PC patients remains important, delays in treatment initiation due to repeated biopsies, inclusion in a clinical study or transfer to a specialized cancer center appear to be justified in light of the absence of a strong adverse effect of prolonged TTI on prognosis in advanced PC patients.
PURPOSE: A prolonged time to treatment initiation (TTI) correlates with an adverse prognosis in different cancer types including resectable pancreatic cancer (PC). Only limited evidence on the correlation between TTI and prognosis in advanced PC exists. METHODS: Consecutive PCpatients (n = 368) who were diagnosed or treated at our high-volume comprehensive cancer center were included in a prospectively maintained database. We retrospectively analyzed time from first imaging showing advanced PC to initiation of palliative first-line chemotherapy. Lead time bias and waiting time paradox were addressed by landmark analysis and correlation of tumor burden with TTI. RESULTS: Two hundred and ninety-seven patients met the pre-specified in- and exclusion criteria of our study. Median TTI was 29 days (range: 1-124 days). Most common reasons for prolonged TTI (> 21 days) were referral from an external treatment center (39%) and a second biopsy (31%). A TTI above the median-, 75th or 90th percentile (43 or 60 days, respectively) had no impact on overall survival. Furthermore, no correlation between levels of carbohydrate antigen 19-9 (CA 19-9) at time of treatment initiation and TTI was observed. CONCLUSION: While a timely work-up of advanced PCpatients remains important, delays in treatment initiation due to repeated biopsies, inclusion in a clinical study or transfer to a specialized cancer center appear to be justified in light of the absence of a strong adverse effect of prolonged TTI on prognosis in advanced PCpatients.
Entities:
Keywords:
Ductal adenocarcinoma; Lead time bias; Pancreatic cancer; Time to treatment initiation; Treatment delay; Waiting time paradox
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