Abstract

BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with high metastatic potential. Clinical observations suggest that there is disease heterogeneity among patients with different sites of distant metastases, yielding distinct clinical outcomes. Herein, we investigate the impact of clinical and pathological parameters on recurrence patterns and compare survival outcomes for patients with a first site of recurrence in the liver versus lung from PDAC following original curative surgical resection.MethodsUsing the Memorial Sloan Kettering Cancer Center ICD billing codes and tumor registry database over a 10 years period (January 2004–December 2014), we identified PDAC patients who underwent resection and subsequently presented with either liver or lung recurrence. Time from relapse to death (TRD) was calculated from date of recurrence to date of death. Using the Kaplan-Meier method, TRD was estimated and compared by recurrence site using log-rank test.ResultsThe median overall follow-up was 37.3 months among survivors in the entire cohort. Median TRD in this cohort was 10.7 months (95%CI: 8.9–14.6 months). Patients with first site of lung recurrence had a more favorable outcome compared to patients who recurred with liver metastasis as the first site of recurrence (median TRD of 15 versus 9 months respectively, P = 0.02). Moderate to poorly or poor differentiation was associated more often with liver than lung recurrence (40% vs 21% respectively, P = 0.047). A trend to increased lymph node metastasis in the lung recurrence cohort was observed.ConclusionPDAC patients who recur with a first site of lung metastasis have an improved clinical outcome compared to patients with first site of liver recurrence. Our data suggests there may be epidemiologic and pathologic determinants related to patterns of recurrence in PDAC.

Highlights

  • Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with high metastatic potential

  • In the study reported we focus on patterns of liver and lung recurrence of PDAC and examine the impact of first site of recurrence on disease behavior and post-relapse survival outcomes

  • Our data suggests that there may be an association between the use of alcohol and the first site of recurrence in PDAC, with lung metastasis compared to liver metastasis as first site of recurrence (P = 0.011)

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Summary

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with high metastatic potential. The pre-metastatic niche formation in the host organ may influence the molecular and clinical behavior of cancer cells [6], indicating that there may be multiple elements that lead to the distinct course of the disease. PDAC-derived exosomes that are received by Kupffer cells have been shown to create a pre-metastatic niche formation in the liver by recruiting bone marrow-derived macrophages [9]. These data indicate that there are inter-site signaling networks between tumor cells and the future host organ to condition the pre-metastatic niche, thereby suggesting that metastasis is an organ-specific, programmed process rather than a random event

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