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Implications of the Pattern of Disease Recurrence on Survival Following Pancreatectomy for Pancreatic Ductal Adenocarcinoma.

ABSTRACT: BACKGROUND:After radical resection of pancreatic ductal adenocarcinoma (PDAC), approximately 80% of patients will develop disease recurrence. It remains unclear to what extent the location of recurrence carries prognostic significance. Additionally, stratifying the pattern of recurrence may lead to a deeper understanding of the heterogeneous biological behavior of PDAC. OBJECTIVE:The aim of this study was to characterize the relationship of recurrence patterns with survival in patients with resected PDAC. METHODS:This single-center cohort study included patients undergoing pancreatectomy at the Johns Hopkins Hospital between 2000 and 2013. Exclusion criteria were neoadjuvant therapy and incomplete follow-up. Sites of first recurrence were stratified into five groups and survival outcomes were estimated using Kaplan-Meier curves. The association of specific recurrence locations with overall survival (OS) was analyzed using Cox proportional-hazards models with and without landmark analysis. RESULTS:Accurate follow-up data were available for 877 patients, 662 (75.5%) of whom had documented recurrence at last follow-up. Patients with multiple-site (n?=?227, 4.7 months) or liver-only recurrence (n?=?166, 7.2 months) had significantly worse median survival after recurrence when compared with lung- (n?=?93) or local-only (n?=?158) recurrence (15.4 and 9.7 months, respectively). On multivariable analysis, the unique recurrence patterns had variable predictive values for OS. Landmark analyses, with landmarks set at 12, 18, and 24 months, confirmed these findings. CONCLUSIONS:This study demonstrates that specific patterns of PDAC recurrence result in different survival outcomes. Furthermore, distinct first recurrence locations have unique independent predictive values for OS, which could help with prognostic stratification and decisions regarding treatment after the diagnosis of recurrence.

SUBMITTER: Groot VP

PROVIDER: S-EPMC6220676 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Implications of the Pattern of Disease Recurrence on Survival Following Pancreatectomy for Pancreatic Ductal Adenocarcinoma.

Groot Vincent P VP Gemenetzis Georgios G Blair Alex B AB Ding Ding D Javed Ammar A AA Burkhart Richard A RA Yu Jun J Borel Rinkes Inne H IH Molenaar I Quintus IQ Cameron John L JL Fishman Elliot K EK Hruban Ralph H RH Weiss Matthew J MJ Wolfgang Christopher L CL He Jin J

Annals of surgical oncology 20180614 8

<h4>Background</h4>After radical resection of pancreatic ductal adenocarcinoma (PDAC), approximately 80% of patients will develop disease recurrence. It remains unclear to what extent the location of recurrence carries prognostic significance. Additionally, stratifying the pattern of recurrence may lead to a deeper understanding of the heterogeneous biological behavior of PDAC.<h4>Objective</h4>The aim of this study was to characterize the relationship of recurrence patterns with survival in pat ...[more]

PMID: 29948425

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Project description:Background: Total pancreatectomy (TP) seems to be experiencing a renaissance in recent years. In this study, we aimed to determine the long-term survival of pancreatic ductal adenocarcinoma (PDAC) patients who underwent TP by comparing with pancreaticoduodenectomy (PD), and formulate a nomogram to predict overall survival (OS) for PDAC individuals following TP. Methods: Patients who were diagnosed with PDAC and received PD (n = 5,619) or TP (n = 1,248) between 2004 and 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. OS and cancer-specific survival (CSS) of the PD and TP groups were compared using Kaplan-Meier method and log-rank test. Furthermore, Patients receiving TP were randomly divided into the training and validation cohorts. Univariate and multivariate Cox regression were applied to identify the independent factors affecting OS to construct the nomogram. The performance of the nomogram was measured according to concordance index (C-index), calibration plots, and decision curve analysis (DCA). Results: There were no significant differences in OS and CSS between TP and PD groups. Age, differentiation, AJCC T stage, radiotherapy, chemotherapy, and lymph node ratio (LNR) were identified as independent prognostic indicators to construct the nomogram. The C-indexes were 0.67 and 0.69 in the training and validation cohorts, while 0.59 and 0.60 of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system. The calibration curves showed good uniformity between the nomogram prediction and actual observation. DCA curves indicated the nomogram was preferable to the AJCC staging system in terms of the clinical utility. A new risk stratification system was constructed which could distinguish patients with different survival risks. Conclusions: For PDAC patients following TP, the OS and CSS are similar to those who following PD. We developed a practical nomogram to predict the prognosis of PDAC patients treated with TP, which showed superiority over the conventional AJCC staging system.

Project description:AimTo detect linc00675 expression in pancreatic ductal adenocarcinoma (PDAC), to analyze the relationship between the expression level of linc00675 and the clinical pathological characteristics, to explore the biological functions of linc00675, and to determine whether linc00675 has independent prognostic value in PDAC.MethodsWe studied linc00675 expression among eight histologically confirmed PDAC tissue samples and four chronic pancreatitis tissue samples through microarray screening. RT-qPCR was conducted to further investigate linc00675 expression in PDAC cell lines as well as archived tissues from a large cohort of PDAC patients. The correlations between the level of lnc00675 and clinicopathological characteristics and survival in patients with pancreatic cancer were evaluated using Correlation analysis. Univariate and multivariate analyses were conducted to predict whether lnc00675 expression is an independent prognostic and recurrence factor in patients with pancreatic cancer. After downregulating the expression of linc00675 through siRNA, MTT assay, flow cytometry, transwell assay and Western blot were used to explore the biological function of linc00675 in proliferation, invasion, and cell cycle progression of pancreatic cancer cells. The relative molecular expression levels of epithelial-mesenchymal transition were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot.ResultsThe expression of Linc00675 in PDAC tissue samples was shown to be 672 times that in chronic pancreatitis tissue samples by microarray screening (P = 3.69 × 10(-5)). This finding was confirmed in tumor tissues from 90 patients with PDAC compared with adjacent normal tissue samples by quantitative RT-PCR. We found that linc00675 overexpression positively correlated with lymph node metastasis (P = 0.005), perineural invasion (P = 0.006), and poor survival (P < 0.001). Univariate and multivariate analyses showed that linc00675 expression served as an independent predictor of overall survival (P = 0.009). Additionally, receiver operating characteristic curve analysis showed that high linc00675 might serve as a predictor of tumor progression within 6 mo to a year after surgery. In vitro functional analysis demonstrated that knockdown of linc00675 attenuated pancreatic cancer cell proliferation and invasion as well as induced S phase arrest. Suppression of linc00675 in pancreatic cancer cells resulted can reverse the progress of epithelial-mesenchymal transition.ConclusionLinc00675 may function as an oncogene during PDAC development, and its expression is an independent predictor of unfavorable prognosis in patients with PDAC.

Dataset Information

Implications of the Pattern of Disease Recurrence on Survival Following Pancreatectomy for Pancreatic Ductal Adenocarcinoma.

Publications

Implications of the Pattern of Disease Recurrence on Survival Following Pancreatectomy for Pancreatic Ductal Adenocarcinoma.

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