Dataset Information

Recurrence Patterns for Pancreatic Ductal Adenocarcinoma after Upfront Resection Versus Resection Following Neoadjuvant Therapy: A Comprehensive Meta-Analysis.

ABSTRACT: BACKGROUND:Neoadjuvant therapy (NAT) represents a paradigm shift in the management of patients with pancreatic ductal adenocarcinoma (PDAC) with perceived benefits including a higher R0 rate. However, it is unclear whether NAT affects the sites and patterns of recurrence after surgery. This review seeks to compare sites and patterns of recurrence after resection between patients undergoing upfront surgery (US) or after NAT. METHODS:The EMBASE, SCOPUS, PubMed, and Cochrane library databases were systematically searched to identify eligible studies that compare recurrence patterns between patients who had NAT (followed by resection) with those that had US. The primary outcome included site-specific recurrence. RESULTS:26 articles were identified including 4986 patients who underwent resection. Borderline resectable pancreatic cancer (BRPC, 47% 1074/2264) was the most common, followed by resectable pancreatic cancer (RPC 42%, 949/2264). The weighted overall recurrence rates were lower among the NAT group, 63.4% vs. 74% (US) (OR 0.67 (CI 0.52-0.87), p = 0.006). The overall weighted locoregional recurrence rate was lower amongst patients who received NAT when compared to US (12% vs 27% OR 0.39 (CI 0.22-0.70), p = 0.004). In BRPC, locoregional recurrence rates improved with NAT (NAT 25.8% US 37.7% OR 0.62 (CI 0.44-0.87), p = 0.007). NAT was associated with a lower weighted liver recurrence rate (NAT 19.4% US 30.1% OR 0.55 (CI 0.34-0.89), p = 0.023). Lung and peritoneal recurrence rates did not differ between NAT and US cohorts (p = 0.705 and p = 0.549 respectively). NAT was associated with a significantly longer weighted mean time to first recurrence 18.8 months compared to US (15.7 months) (OR 0.18 (CI 0.05-0.32), p = 0.015). CONCLUSION:NAT was associated with lower overall recurrence rate and improved locoregional disease control particularly for those with BRPC. Although the burden of liver metastases was less, there was no overall effect upon distant metastatic disease.

SUBMITTER: Ratnayake B

PROVIDER: S-EPMC7408905 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Recurrence Patterns for Pancreatic Ductal Adenocarcinoma after Upfront Resection Versus Resection Following Neoadjuvant Therapy: A Comprehensive Meta-Analysis.

Ratnayake Bathiya B Savastyuk Alina Y AY Nayar Manu M Wilson Colin H CH Windsor John A JA Roberts Keith K French Jeremy J JJ Pandanaboyana Sanjay S

Journal of clinical medicine 20200706 7

<h4>Background</h4>Neoadjuvant therapy (NAT) represents a paradigm shift in the management of patients with pancreatic ductal adenocarcinoma (PDAC) with perceived benefits including a higher R0 rate. However, it is unclear whether NAT affects the sites and patterns of recurrence after surgery. This review seeks to compare sites and patterns of recurrence after resection between patients undergoing upfront surgery (US) or after NAT.<h4>Methods</h4>The EMBASE, SCOPUS, PubMed, and Cochrane library ...[more]

PMID: 32640720

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Project description:Pancreatic ductal adenocarcinoma (PDAC) is a disease with a very unfavorable prognosis. Surgical resection represents the only potentially curative treatment option, but recurrence after complete resection is almost certain. In an exploratory attempt we here aimed at identifying preoperative plasma protein biomarkers with the potential to predict early recurrence after resection of PDAC. Peripheral blood samples from 14 PDAC patients divided into three groups according to their time to tumor recurrence after curatively intended resection (early: < 6 months, medium: 6-12 months, late: > 12 months) underwent targeted proteome analysis. Proteins most strongly discriminating early and late recurrence were then examined in a number of established PDAC cell lines and their culture supernatants. Finally, PDAC organoid lines from primary tumors of patients with early and late recurrence were analyzed for confirmation and validation of results. In total, 23 proteins showed differential abundance in perioperative plasma from PDAC patients with early recurrence when compared to patients with late recurrence. Following confirmation of expression on a transcriptional and translational level in PDAC cell lines we further focused on three upregulated (MAEA, NT5E, AZU1) and two downregulated proteins (ATP6AP2, MICA). Increased expression of NT5E was confirmed in a subset of PDAC organoid cultures from tumors with early recurrence. MICA expression was heterogeneous and ATP6AP2 levels were very similar in both organoids from early and late recurrent tumors. Most strikingly, we observed high MAEA expression in all tested PDAC (n = 7) compared to a non-cancer ductal organoid line. MAEA also demonstrated potential to discriminate early recurrence from late recurrence PDAC organoids. Our study suggests that identification of plasma protein biomarkers released by tumor cells may be feasible and of value to predict the clinical course of patients. Prediction of recurrence dynamics would help to stratify up-front resectable PDAC patients for neoadjuvant chemotherapy approaches in an individualized fashion. Here, MAEA and NT5E were the most promising candidates for further evaluation.

Project description:BackgroundThe high recurrence rate after radical resection of pancreatic ductal adenocarcinoma (PDAC) leads to its poor prognosis. We aimed to develop a model to preoperatively predict the risk of recurrence based on computed tomography (CT) radiomics and multiple clinical parameters.MethodsDatasets were retrospectively collected and analysed of 220 PDAC patients who underwent contrast-enhanced computed tomography (CE-CT) and received radical resection at 3 institutions in China between 2013 and 2017, with 153 from one institution as a training set, the remaining 67 as a validation set. For each patient, CT radiomics features were extracted from intratumoral and peritumoral regions to establish intratumoral, peritumoral and combined radiomics models using artificial neural network (ANN) algorithm. By incorporating clinical factors, radiomics-clinical nomograms were finally built by multivariable logistic regression analysis to predict 1- and 2-year recurrence risk.FindingsThe developed radiomics model integrating intratumoral and peritumoral radiomics features was superior to the conventionally constructed model merely using intratumoral radiomics features. Further, radiomics-clinical nomograms outperformed other models in predicting 1-year recurrence with an area under the receiver operating characteristic curve (AUROC) of 0.916 (95%CI, 0.860-0.955) in the training set and 0.764 (95%CI, 0.644-0.859) in the validation set, and 2-year recurrence with an AUROC of 0.872 (95%CI: 0.809-0.921) in the training set and 0.773 (95%CI, 0.654-0.866) in the validation set.InterpretationThis study has developed and externally validated a radiomics-clinical nomogram integrating intra- and peritumoral CT radiomics signature as well as clinical factors to predict the recurrence risk of PDAC after radical resection, which will facilitate optimized and individualized treatment strategies.FundingThis work was supported by the National Key R&D Program of China [grant number: 2018YFE0114800], the General Program of National Natural Science Foundation of China [grant number: 81772562, 2017; 81871351, 2018], the Fundamental Research Funds for the Central Universities [grant number: 2021FZZX005-08], and Zhejiang Provincial Key Projects of Technology Research [grant number: WKJ-ZJ-2033].

Dataset Information

Recurrence Patterns for Pancreatic Ductal Adenocarcinoma after Upfront Resection Versus Resection Following Neoadjuvant Therapy: A Comprehensive Meta-Analysis.

Publications

Recurrence Patterns for Pancreatic Ductal Adenocarcinoma after Upfront Resection Versus Resection Following Neoadjuvant Therapy: A Comprehensive Meta-Analysis.

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