Dataset Information

The impact of resection margin distance on survival and recurrence in pancreatic ductal adenocarcinoma in a retrospective cohort analysis.

ABSTRACT:

Background

The prognostic effect of resection margin status following pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) remains controversial, even with the implementation of standardized pathological assessment. We therefore investigated the impact of resection margin (RM) status and RM distance in curative resected PDAC on overall survival (OS), disease-free survival (DFS) and recurrence.

Method

108 patients were retrieved from a prospectively maintained database of a certified pancreatic cancer center. Distribution and relationships between circumferential resection margin (CRM) involvement (CRM≤1mm; CRM>1mm; CRM≥2mm) and their prognostic impact on OS and DFS were assessed using Kaplan-Meier statistics and the Log-Rank test. Multivariate logistic regression was used explain the development of a recurrence 12 months after surgery.

Results

63 out of 108 patients had medial RM and 32 posterior RM involvement. There was no significant difference in OS and DFS between CRM≤1mm and CRM>1mm resections. Clearance at the medial margin of ≥2mm had an impact on OS and DFS, (RM≥2mm vs. RM<2mm: median OS 29.8 vs 16.8 months, median DFS 19.6 vs. 10.3 months). Multivariate analysis demonstrated that age, medial RM ≥2mm, lymph node status and chemotherapy were prognostic factors for OS and DFS. Posterior RM had no influence on OS or DFS.

Conclusion

Not all RM seem to have the same impact on OS and DFS, and a clearance of 1mm for definition of a negative RM (i.e. CRM>1mm) seems not sufficient. Future studies should include more patients to stratify for potential confounders we could not account for.

Trial registration

This study was registered with the German Clinical Trials Registry (reference number DRKS0017425).

SUBMITTER: Obonyo D

PROVIDER: S-EPMC9937496 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The impact of resection margin distance on survival and recurrence in pancreatic ductal adenocarcinoma in a retrospective cohort analysis.

Obonyo Dennis D Uslar Verena Nicole VN Münding Johanna J Weyhe Dirk D Tannapfel Andrea A

PloS one 20230217 2

<h4>Background</h4>The prognostic effect of resection margin status following pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) remains controversial, even with the implementation of standardized pathological assessment. We therefore investigated the impact of resection margin (RM) status and RM distance in curative resected PDAC on overall survival (OS), disease-free survival (DFS) and recurrence.<h4>Method</h4>108 patients were retrieved from a prospectively maintained database ...[more]

PMID: 36800357

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Project description:BackgroundDistinguishing postoperative fibrosis from isolated local recurrence (ILR) after resection of pancreatic ductal adenocarcinoma (PDAC) is challenging. A prognostic model that helps to identify patients at risk of ILR can assist clinicians when evaluating patients' postoperative imaging. This nationwide study aimed to develop a clinically applicable prognostic model for ILR after PDAC resection.Patients and methodsAn observational cohort study was performed, including all patients who underwent PDAC resection in the Netherlands (2014-2019; NCT04605237). On the basis of recurrence location (ILR, systemic, or both), multivariable cause-specific Cox-proportional hazard analysis was conducted to identify predictors for ILR and presented as hazard ratios (HRs) with 95% confidence intervals (CIs). A predictive model was developed using Akaike's Information Criterion, and bootstrapped discrimination and calibration indices were assessed.ResultsAmong 1194/1693 patients (71%) with recurrence, 252 patients (21%) developed ILR. Independent predictors for ILR were resectability status (borderline versus resectable, HR 1.42; 95% CI 1.03-1.96; P = 0.03, and locally advanced versus resectable, HR 1.11; 95% CI 0.68-1.82; P = 0.66), tumor location (head versus body/tail, HR 1.50; 95% CI 1.00-2.25; P = 0.05), vascular resection (HR 1.86; 95% CI 1.41-2.45; P < 0.001), perineural invasion (HR 1.47; 95% CI 1.01-2.13; P = 0.02), number of positive lymph nodes (HR 1.04; 95% CI 1.01-1.08; P = 0.02), and resection margin status (R1 < 1 mm versus R0 ≥ 1 mm, HR 1.64; 95% CI 1.25-2.14; P < 0.001). Moderate performance (concordance index 0.66) with adequate calibration (slope 0.99) was achieved.ConclusionsThis nationwide study identified factors predictive of ILR after PDAC resection. Our prognostic model, available through www.pancreascalculator.com , can be utilized to identify patients with a higher a priori risk of developing ILR, providing important information in patient evaluation and prognostication.

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

The impact of resection margin distance on survival and recurrence in pancreatic ductal adenocarcinoma in a retrospective cohort analysis.

Background

Method

Results

Conclusion

Trial registration

Publications

The impact of resection margin distance on survival and recurrence in pancreatic ductal adenocarcinoma in a retrospective cohort analysis.

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