(S017) Pattern of Failure, Margin Status and Adjuvant Therapy in Pancreatic Cancer: Impact on Survival

The prognostic significance of margin clearance and its correlation with patterns of failure in pancreatic ductal adenocarcinoma(PDA) remains a point of controversy. We performed an archival analysis of all surgical resection margins(SRM) to determine the effect on locoregional recurrence and survival and the clinical significance of adjuvant radiotherapy. Three pathologists reviewed archival surgical specimens of 105 patients with resected stage 1-3 PDA and recategorized each margin as pancreatic, anterior, bile-duct, and posterior margins(PM) (posterior-surface, uncinate and vascular-groove) with the following measurements: tumor at ink/transected, <0.5mm, 0.5-1mm, >1-2mm or >2mm from the inked surface. Recurrence patterns were defined as local, distant, or local plus distant(LD). The significance of margins, recurrence and clinical variables was assessed on disease-free survival(DFS) and overall survival(OS) using multivariate cox proportional hazards modeling. The pancreatic, anterior and bile duct SRMs were not significant (p>0.05) predictors of DFS and OS. However, increasing PM clearance up to 2mm was a significant predictor of DFS(p=0.01) and OS (p=0.01). Dichotomizing the PM at 2mm revealed it to be an independent predictor of DFS(HR;0.46,95%CI,0.22-0.96,p=0.03) and OS(HR;0.31,95% CI,0.14-0.74;p=0.008) on multivariate analysis (MVA) (mDFS:13.9[≤2mm]vs27.3[>2mm] months,mOS:23.2[≤2mm]vs60[>2mm] months). A margin status of >2mm, was a significant predictor of OS in patients who received adjuvant chemotherapy(ACT;HR;0.31,95%CI,0.11-0.89,p=0.03), yet this difference was not significant in patients receiving adjuvant chemoradiotherapy(CRT;p=0.19). On MVA, margin clearance of at least 2mm was significantly predictive of OS and DFS in patients with local recurrence (OS:HR;0.15,95%CI,0.028–0.849,p=0.031 DFS:HR;0.19,95%CI,0.06-0.647,p=0.007), but not predictive in patients with LD and distant failure(p>0.05). The PM is the most clinically important SRM and achieving a margin of 2 mm has a significant impact on clinical outcomes. The addition of radiotherapy to ACT mitigates the negative prognostic significance of a PM<2 mm. Local control is a key clinical variable correlated with margin status and is implicated in long term survival.