title: Adjuvant Therapy in Pancreas Cancer: Does It Influence Patterns of Recurrence?
abstract: BACKGROUND
  Level 1 data demonstrate that adjuvant chemotherapy (ACT) improves survival after surgical resection of pancreatic ductal adenocarcinoma (PDAC), (adjuvant gemcitabine, CONKO-001 study; adjuvant 5-FU, ESPAC3 study). The role of adjuvant chemoradiation therapy (ACRT) remains controversial. What is less clear is whether adjuvant therapy influences patterns of recurrence. The purpose of this study was to perform the first multicenter study analyzing patterns of recurrence after adjuvant therapy for PDAC.
  
  
  METHODS
  Patients undergoing resection for PDAC from 8 medical centers over a 10-year period were analyzed. Demographics, tumor characteristics, operative treatment, type of adjuvant therapy, recurrence pattern, and survival were reviewed. Using Cox-proportional hazards multivariate (MV) regression, the impact of ACT and ACRT on overall survival (OS), local recurrence (LR), and distant recurrence (DR) was investigated.
  
  
  RESULTS
  There were 1,130 patients who were divided into those having surgery alone (n = 392), ACT (n = 291), or ACRT (n = 447). Median follow-up was 18 months. Compared with patients undergoing surgery alone, ACT, but not ACRT, demonstrated a significant OS advantage on MV analysis. Patients receiving ACT had significantly fewer recurrences (LR and DR); those receiving ACRT had significantly less LR but not DR. On subset MV analysis, ACT and ACRT resulted in less LR in patients with lymph node (LN) positive and margin negative disease. No improvements in LR, DR, or OS were seen in margin positive patients with either ACT or ACRT.
  
  
  CONCLUSIONS
  This is the first analysis demonstrating differences in recurrence patterns in PDAC patients based on type of adjuvant therapy. Adjuvant chemotherapy provided an OS advantage likely related to its effect on reducing both LR and DR. Adjuvant chemoradiation therapy appears to decrease LR, but not DR, and therefore has less impact on OS. Future investigations and treatment protocols should consider additional ACT rather than ACRT in the treatment of PDAC.
authors.affiliation: Department of Surgery, Vanderbilt University, Nashville, TN. Electronic address: alexander.parikh@vanderbilt.edu.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Parikh
authors.affiliation: Department of Surgery, Vanderbilt University, Nashville, TN.
authors.forename: Amelia
authors.initials: A
authors.lastname: Maiga
authors.affiliation: Department of Surgery, Northwestern University, Chicago, IL.
authors.forename: David
authors.initials: D
authors.lastname: Bentrem
authors.affiliation: Department of Surgery, Emory University, Atlanta, GA.
authors.forename: Malcolm H
authors.initials: MH
authors.lastname: Squires
authors.affiliation: Department of Surgery, Emory University, Atlanta, GA.
authors.forename: David A
authors.initials: DA
authors.lastname: Kooby
authors.affiliation: Department of Surgery, Emory University, Atlanta, GA.
authors.forename: Shishir K
authors.initials: SK
authors.lastname: Maithel
authors.affiliation: Department of Surgery, University of Wisconsin, Madison, WI.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Weber
authors.affiliation: Department of Surgery, University of Wisconsin, Madison, WI.
authors.forename: Clifford S
authors.initials: CS
authors.lastname: Cho
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Matthew
authors.initials: M
authors.lastname: Katz
authors.affiliation: Department of Surgery, University of Louisville, Louisville, KY.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Martin
authors.affiliation: Department of Surgery, University of Louisville, Louisville, KY.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Scoggins
authors.affiliation: Department of Surgery, University of Cincinnati, Cincinnati, OH.
authors.forename: Jeff
authors.initials: J
authors.lastname: Sutton
authors.affiliation: Department of Surgery, University of Cincinnati, Cincinnati, OH.
authors.forename: Syed A
authors.initials: SA
authors.lastname: Ahmad
authors.affiliation: Department of Surgery, University of Cincinnati, Cincinnati, OH.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Abbott
authors.affiliation: Department of Surgery, University of North Carolina, Chapel Hill, NC.
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Carr
authors.affiliation: Department of Surgery, University of North Carolina, Chapel Hill, NC.
authors.forename: Hong Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Surgery, University of Miami, Miami, FL.
authors.forename: Danny
authors.initials: D
authors.lastname: Yakoub
authors.affiliation: Department of Surgery, Vanderbilt University, Nashville, TN.
authors.forename: Kamran
authors.initials: K
authors.lastname: Idrees
authors.affiliation: Department of Surgery, University of Miami, Miami, FL.
authors.forename: Nipun
authors.initials: N
authors.lastname: Merchant
mesh_terms: D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059186:Chemoradiotherapy, Adjuvant; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000453:epidemiology*; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016577:Pancreaticoduodenectomy; D016016:Proportional Hazards Models; D012189:Retrospective Studies