INTRODUCTION: The poor overall survival associated with pancreatic ductal adenocarcinoma (PDAC) despite complete resection suggests that occult metastatic disease is present in most at the time of surgery. Resection margin involvement (R1) following resection is an established poor prognostic factor. However, the definition of an R1 resection varies and the impact of margin clearance on outcome has not been examined in detail. METHODS: In a cohort of 217 consecutive patients who underwent pancreaticoduodenectomy for PDAC with curative intent at a single institution between 1996 and 2011, the prognostic significance of the proximity of margin clearance was investigated. Microscopic margin clearance was stratified by 0.5 mm increments from tumor present at the margin to >2.0 mm. Groups were dichotomized into clear and involved groups according to the different R1 definitions. Multivariate survival analysis was used to establish independent prognostic factors. RESULTS: For the 38 patients (17.5 %) where the tumor was >1.5 mm from the closest involved margin, there was a significantly prolonged overall median survival (63.1 months; 95 % confidence interval, 32.5-93.8) compared to R1 resections (16.9 months; 95 % confidence interval, 14.5-19.4; P < 0.0001, log-rank test). This cutoff represented the optimum distance for predicting long-term survival. As margin clearance increased, R1 status became a more powerful independent predictor of outcome; however, margin clearance did not relate to site of tumor recurrence. CONCLUSION: These data demonstrate that margin clearance by at least 1.5 mm identifies a subgroup of patients which may potentially achieve long-term survival. This study further confirms the need to achieve standardization across pancreatic specimen reporting. Stratification of patients into future clinical trials based upon the degree of margin clearance may identify those patients likely to benefit from adjuvant therapy.
INTRODUCTION: The poor overall survival associated with pancreatic ductal adenocarcinoma (PDAC) despite complete resection suggests that occult metastatic disease is present in most at the time of surgery. Resection margin involvement (R1) following resection is an established poor prognostic factor. However, the definition of an R1 resection varies and the impact of margin clearance on outcome has not been examined in detail. METHODS: In a cohort of 217 consecutive patients who underwent pancreaticoduodenectomy for PDAC with curative intent at a single institution between 1996 and 2011, the prognostic significance of the proximity of margin clearance was investigated. Microscopic margin clearance was stratified by 0.5 mm increments from tumor present at the margin to >2.0 mm. Groups were dichotomized into clear and involved groups according to the different R1 definitions. Multivariate survival analysis was used to establish independent prognostic factors. RESULTS: For the 38 patients (17.5 %) where the tumor was >1.5 mm from the closest involved margin, there was a significantly prolonged overall median survival (63.1 months; 95 % confidence interval, 32.5-93.8) compared to R1 resections (16.9 months; 95 % confidence interval, 14.5-19.4; P < 0.0001, log-rank test). This cutoff represented the optimum distance for predicting long-term survival. As margin clearance increased, R1 status became a more powerful independent predictor of outcome; however, margin clearance did not relate to site of tumor recurrence. CONCLUSION: These data demonstrate that margin clearance by at least 1.5 mm identifies a subgroup of patients which may potentially achieve long-term survival. This study further confirms the need to achieve standardization across pancreatic specimen reporting. Stratification of patients into future clinical trials based upon the degree of margin clearance may identify those patients likely to benefit from adjuvant therapy.
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Authors: Lee M Ocuin; Jennifer L Miller-Ocuin; Mazen S Zenati; John A Vargo; Aatur D Singhi; Steven A Burton; Nathan Bahary; Melissa E Hogg; Herbert J Zeh; Amer H Zureikat Journal: J Gastrointest Oncol Date: 2017-08