Predictive factors for long-term survival after surgery for pancreatic ductal adenocarcinoma: Making a case for standardized reporting of the resection margin using certified cancer center data

Weyhe, Dirk; Obonyo, Dennis; Uslar, Verena; Stricker, Ingo; Tannapfel, Andrea

doi:10.1371/journal.pone.0248633

Cited by 16 publications

(13 citation statements)

References 50 publications

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“…As a consequence of the lack of consensus that existed until recently, R1 rates published in the literature may be based on different R1 definitions, which, inevitably, has had an impact on the reported data. Indeed, several recent studies on cancers in the pancreatic head report that the R1 rate increases up to threefold if R1 is based on ≤1 mm clearance instead of 0 mm [ 27 , 28 , 29 , 30 ]. Similarly, for PDAC in the pancreatic body and tail, Hank and colleagues reported an R1 rate of 76.5% with invasion within 1 mm to the margin, and 53.6% with direct margin involvement (0 mm clearance) [ 31 ].…”

Section: Pathology Examination Of the Margin Status—microscopic Exami...mentioning

confidence: 99%

Prognostic Impact of Resection Margin Status on Distal Pancreatectomy for Ductal Adenocarcinoma

Holm

Verbeke

2022

Current Oncology

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Pancreatic cancer is associated with a poor prognosis. While surgical resection is the only treatment option with curative intent, most patients die of locoregional and/or distant recurrence. The prognostic impact of the resection margin status has received much attention. However, the evidence is almost exclusively related to pancreatoduodenectomies, while corresponding data for distal pancreatectomy specimens are limited. The key data, such as the rate of microscopic margin involvement (“R1”), the site of margin involvement, and the impact of R1 on patient outcome, are divergent between studies and do not currently allow any general conclusions. The main reasons for the variability in the published data are the small size of the study cohorts and their heterogeneity, as well as the marked divergence in pathology examination practices. The latter is a consequence of the lack of concrete guidance, both for grossing and microscopic examination. The increasing administration of neoadjuvant chemo(radio)therapy introduces a further factor of uncertainty as the conventional definition of a tumour-free margin (“R0”) based on 1 mm clearance is inadequate for these specimens. This review discusses the published data regarding the prognostic impact of margin status in distal pancreatectomy specimens along with the challenges and uncertainties that are related to the assessment of the margins.

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Section: Pathology Examination Of the Margin Status—microscopic Exami...mentioning

confidence: 99%

Prognostic Impact of Resection Margin Status on Distal Pancreatectomy for Ductal Adenocarcinoma

Holm

Verbeke

2022

Current Oncology

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“…We began variable selection by including chemotherapy and LNR in our model, as they have been found to be the best predictors for long-term survival for pancreatic ductal adenocarcinoma. 36 It should be noted that for our observational data, the association between survival times and chemotherapy should be interpreted with care since treatment with chemotherapy might be subject to channeling bias. Treatment recommendations are usually given through an interdisciplinary tumor board.…”

Section: Analysis Of Overall Survival Of Pancreatic Cancer Patientsmentioning

confidence: 99%

Flexible semiparametric mode regression for time-to-event data

Seipp

Uslar

Weyhe

et al. 2022

Stat Methods Med Res

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The distribution of time-to-event outcomes is usually right-skewed. While for symmetric and moderately skewed data the mean and median are appropriate location measures, the mode is preferable for heavily skewed data as it better represents the center of the distribution. Mode regression has been introduced for uncensored data to model the relationship between covariates and the mode of the outcome. Starting from nonparametric kernel density based mode regression, we examine the use of inverse probability of censoring weights to extend mode regression to handle right-censored data. We add a semiparametric predictor to add further flexibility to the model and we construct a pseudo Akaike’s information criterion to select the bandwidth and smoothing parameters. We use simulations to evaluate the performance of our proposed approach. We demonstrate the benefit of adding mode regression to one’s toolbox for analyzing survival data on a pancreatic cancer data set from a prospectively maintained cancer registry.

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“…Tumor free resection margins generally serve as a long-term prognostic factor [5,6]. A clear definition of resection margin status is therefore essential [7]. According to many centers in Europe, the R classification was adapted to Royal College of Pathologist (RCP) guidelines [8].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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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).

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Predictive factors for long-term survival after surgery for pancreatic ductal adenocarcinoma: Making a case for standardized reporting of the resection margin using certified cancer center data

Cited by 16 publications

References 50 publications

Prognostic Impact of Resection Margin Status on Distal Pancreatectomy for Ductal Adenocarcinoma

Prognostic Impact of Resection Margin Status on Distal Pancreatectomy for Ductal Adenocarcinoma

Flexible semiparametric mode regression for time-to-event data

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

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