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Margin distance as an independent predictor of survival after R0 resection for pancreatic adenocarcinoma.

321 Background: Microscopic tumor at the surgical margin is a predictor of recurrence and poor survival for pancreatic ductal adenocarcinoma (PDA). However, the impact of distance between the surgical margin and microscopic tumor on survival remains controversial. We hypothesized that margin distance (MD) would correlate with disease free survival (DFS) and overall survival (OS) in R0 resected PDA.


METHODS
Retrospective analysis of 191 resections for PDA. Margin distance was measured (0-1, 1-2, 2-4, 4-10, and > 10 mm) and categorized by location. Parameters including age, gender, BMI, TNM, AJCC stage, lymph node (LN) ratio, vascular and perineural invasion, vein resection, and adjuvant therapy were analyzed. Primary endpoints were DFS and disease specific OS. Univariate analysis was used to estimate factors associated with outcomes. The log rank test was applied to selected group comparisons.


RESULTS
149 (78%) R0 outcomes were analyzed. 118 (79%) patients received adjuvant chemotherapy, 31 of whom also received XRT. Univariate analysis demonstrated reduced DFS (HR = 1.65, 95% CI = 1.13 - 2.48, p = .009) and OS (HR = 1.52 95% CI =.98 - 2.35, p = .059) among patients with margins ≤ 2mm compared to margins > 2mm. In addition LN status, LN ratio, tumor size, AJCC stage, vascular invasion, perineural invasion and adjuvant chemotherapy were found to influence OS on univariate analysis. Adjuvant XRT had no measurable effect on DFS or OS. Following adjustment for covariates in a multivariate model, margin distance >2mm did not correlate with DFS (HR = 1.14, 95%CI = .73 - 1.78, p = .57) or OS (HR = 1.13 95% CI = .69 - 1.85, p = .63), whereas adjuvant chemotherapy and presence of vascular invasion significantly affected OS (P=0.0006 and P=0.008 respectively). The retroperitoneal margin was the margin most commonly in close proximity to tumor (43% of Whipple), although there was no correlation between the closest margin and DFS (p=0.94) or OS (p=0.94).


CONCLUSIONS
Margin distance is not an independent predictor of DFS or OS after R0 resection for PDA. Irrespective of margin distance, adjuvant chemotherapy, but not XRT, was associated with improved OS.