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Defining and Predicting Early Recurrence in 957 Patients With Resected Pancreatic Ductal Adenocarcinoma.

ABSTRACT: OBJECTIVES:To establish an evidence-based cut-off to differentiate between early and late recurrence and to compare clinicopathologic risk factors between the two groups. SUMMARY BACKGROUND DATA:A clear definition of "early recurrence" after pancreatic ductal adenocarcinoma resection is currently lacking. METHODS:Patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma between 2000 and 2013 were included. Exclusion criteria were neoadjuvant therapy and incomplete follow-up. A minimum P-value approach was used to evaluate the optimal cut-off value of recurrence-free survival to divide the patients into early and late recurrence cohorts based on subsequent prognosis. Potential risk factors for early recurrence were assessed with logistic regression models. RESULTS:Of 957 included patients, 204 (21.3%) were recurrence-free at last follow-up. The optimal length of recurrence-free survival to distinguish between early (n = 388, 51.5%) and late recurrence (n = 365, 48.5%) was 12 months (P < 0.001). Patients with early recurrence had 1-, and 2-year post-recurrence survival rates of 20 and 6% compared with 45 and 22% for the late recurrence group (both P < 0.001). Preoperative risk factors for early recurrence included a Charlson age-comorbidity index ?4 (OR 1.65), tumor size > 3.0?cm on computed tomography (OR 1.53) and CA 19-9 > 210?U/mL (OR 2.30). Postoperative risk factors consisted of poor tumor differentiation grade (OR 1.66), microscopic lymphovascular invasion (OR 1.70), a lymph node ratio > 0.2 (OR 2.49), and CA 19-9 > 37?U/mL (OR 3.38). Adjuvant chemotherapy (OR 0.28) and chemoradiotherapy (OR 0.29) were associated with a reduced likelihood of early recurrence. CONCLUSION:A recurrence-free interval of 12 months is the optimal threshold for differentiating between early and late recurrence, based on subsequent prognosis.

SUBMITTER: Groot VP

PROVIDER: S-EPMC6191366 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Defining and Predicting Early Recurrence in 957 Patients With Resected Pancreatic Ductal Adenocarcinoma.

Groot Vincent P VP Gemenetzis Georgios G Blair Alex B AB Rivero-Soto Roberto J RJ Yu Jun J Javed Ammar A AA Burkhart Richard A RA Rinkes Inne H M Borel IHMB Molenaar I Quintus IQ Cameron John L JL Weiss Matthew J MJ Wolfgang Christopher L CL He Jin J

Annals of surgery 20190601 6

<h4>Objectives</h4>To establish an evidence-based cut-off to differentiate between early and late recurrence and to compare clinicopathologic risk factors between the two groups.<h4>Summary background data</h4>A clear definition of "early recurrence" after pancreatic ductal adenocarcinoma resection is currently lacking.<h4>Methods</h4>Patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma between 2000 and 2013 were included. Exclusion criteria were neoadjuvant therapy and incomp ...[more]

PMID: 31082915

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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.

Dataset Information

Defining and Predicting Early Recurrence in 957 Patients With Resected Pancreatic Ductal Adenocarcinoma.

Publications

Defining and Predicting Early Recurrence in 957 Patients With Resected Pancreatic Ductal Adenocarcinoma.

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