Effect of platelet inhibition with perioperative aspirin on survival in patients undergoing curative resection for pancreatic cancer: a propensity score matched analysis

E Pretzsch,M K Angele,R C Miksch,M Ilmer,H Nieß,J G D’Haese,M Guba,M Albertsmeier,B Renz,J Werner,T Schiergens

doi:10.1186/s12893-021-01083-9

Abstract

BackgroundThe importance of platelets in the pathogenesis of metastasis formation is increasingly recognized. Although evidence from epidemiologic studies suggests positive effects of aspirin on metastasis formation, there is little clinical data on the perioperative use of this drug in pancreatic cancer patients.MethodsFrom all patients who received curative intent surgery for pancreatic cancer between 2014 and 2016 at our institution, we identified 18 patients that took aspirin at time of admission and continued to throughout the inpatient period. Using propensity score matching, we selected a control group of 64 patients without aspirin intake from our database and assessed the effect of aspirin medication on overall, disease-free, and hematogenous metastasis-free survival intervals as endpoints.ResultsAspirin intake proved to be independently associated with improved mean overall survival (OS) (46.5 vs. 24.6 months, *p = 0.006), median disease-free survival (DFS) (26 vs. 10.5 months, *p = 0.001) and mean hematogenous metastasis-free survival (HMFS) (41.9 vs. 16.3 months, *p = 0.005). Three-year survival rates were 61.1% in patients with aspirin intake vs. 26.3% in patients without aspirin intake. Multivariate cox regression showed significant independent association of aspirin with all three survival endpoints with hazard ratios of 0.36 (95% CI 0.15–0.86) for OS (*p = 0.021), 0.32 (95% CI 0.16–0.63) for DFS (**p = 0.001), and 0.36 (95% CI 0.16–0.77) for HMFS (*p = 0.009).ConclusionsPatients in our retrospective, propensity-score matched study showed significantly better overall survival when taking aspirin while undergoing curative surgery for pancreatic cancer. This was mainly due to a prolonged metastasis-free interval following surgery.

Highlights

The importance of platelets in the pathogenesis of metastasis formation is increasingly recognized
Since we wanted to focus our analysis on the metastases that might be favored by the perioperative period, we excluded patients who developed metastases within the first 6 weeks after resection, as these must have presumably already existed at the time of surgery
As defined per study protocol and confirmed by histology, all patients suffered from ductal adenocarcinoma of the pancreas

Summary

Introduction

The importance of platelets in the pathogenesis of metastasis formation is increasingly recognized. Evidence from epidemiologic studies suggests positive effects of aspirin on metastasis formation, there is little clinical data on the perioperative use of this drug in pancreatic cancer patients. The “invasion-metastasis cascade” that a localized primary tumor undergoes in order to form metastases, is highly dependent on interactions with healthy cells and components from the surrounding tumor microenvironment [1]. It is highly inefficient concerning the very small proportion of circulating tumor cells (CTCs) that will successfully form overt metastases in distant organs. The importance of platelets in facilitating metastasis is undisputed [7]

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Conclusion