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.
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Funding
Stephan Kruger is supported by the “Else Kröner-Forschungskolleg: Cancer Immunotherapy”.
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Writing of the manuscript and conception of the study: SK and SB. Assistance in writing the manuscript: SebK. Data analysis: SK, KS and AC. Analysis of tumor material (to confirm diagnosis of PC): SO, TK. Inclusion of patients: SK, MH, JS, JM, JGDH, WGK, JR, MI, LG, CBW, MvB, JW, VH, SB.
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The study was approved by the local ethics committee of Ludwig-Maximilians-University of Munich (approval number 134-15). The study was performed in accordance with the Declaration of Helsinki.
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432_2019_3061_MOESM1_ESM.eps
Suppl. Figure 1 Progression-free survival (PFS) according to time to treatment initiation (TTI). Data on PFS was available for 268 patients. Patients were divided into groups according to different cutoffs for TTI (median TTI, 75th and 90th percentile). After 29, 43 and 60 days one, three and four patients in the whole cohort had died, respectively, and were excluded by landmark analysis. Progression-free survival was calculated from the date of first imaging showing advanced pancreatic cancer. The log-rank test was used to test for a survival difference between groups. (EPS 112 kb)
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Kruger, S., Schirle, K., Haas, M. et al. Prolonged time to treatment initiation in advanced pancreatic cancer patients has no major effect on treatment outcome: a retrospective cohort study controlled for lead time bias and waiting time paradox. J Cancer Res Clin Oncol 146, 391–399 (2020). https://doi.org/10.1007/s00432-019-03061-4
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DOI: https://doi.org/10.1007/s00432-019-03061-4