title: Early Recurrence and Omission of Adjuvant Therapy after Pancreaticoduodenectomy Argue against a Surgery-First Approach.
abstract: Sequencing therapy for patients with periampullary malignancy is controversial. Clinical trial data report high rates of adjuvant therapy completion, though contemporary, real-world rates remain incomplete. We sought to identify patients who failed to receive adjuvant therapy and those at risk for early recurrence (ER) who might benefit most from neoadjuvant therapy (NT).
  
  
  
  We retrospectively reviewed medical records of 201 patients who underwent pancreaticoduodenectomy for periampullary malignancies between 1999 and 2015; patients receiving NT were excluded. Univariate and multivariate analyses were performed to identify predictors of failure to receive adjuvant therapy and ER (within 6 months) as the primary end points.
  
  
  
  The median age at the time of surgery was 65.5 years (interquartile range 57-74 years). The majority of tumors were pancreatic ductal adenocarcinoma (76.6 %), and 71.6 % of patients received adjuvant therapy after resection. Univariate predictors of failure to undergo adjuvant therapy were advanced age, age-adjusted Charlson comorbidity index, operative transfusion, reoperation, length of stay, and 30- to 90-day readmissions (all p < 0.05). Advanced age, specifically among patients >70 years, persisted as a significant preoperative predictor on multivariate analysis (p < 0.01). Patients who failed to receive adjuvant therapy and/or developed ER had significantly worse overall survival rates compared to all other patients (27.8 vs. 9.7 months; p < 0.01).
  
  
  
  Approximately one-third of surgery-first patients undergoing pancreaticoduodenectomy at our institution did not receive adjuvant therapy and/or demonstrated ER. This substantial subset of patients may particularly benefit from NT, ensuring completion of multimodal therapy and/or avoiding futile surgical intervention.
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Brent T
authors.initials: BT
authors.lastname: Xia
authors.affiliation: College of Medicine, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Habib
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Vikrom K
authors.initials: VK
authors.lastname: Dhar
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Nick C
authors.initials: NC
authors.lastname: Levinsky
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Young
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Hanseman
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Sutton
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Wilson
authors.affiliation: Department of Medicine, Division of Gastroenterology, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Milton
authors.initials: M
authors.lastname: Smith
authors.affiliation: Department of Radiology, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Kyuran Ann
authors.initials: KA
authors.lastname: Choe
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Sussman
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Syed A
authors.initials: SA
authors.lastname: Ahmad
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Wisconsin, Madison, WI, USA. abbott@surgery.wisc.edu.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Abbott
mesh_terms: D000367:Age Factors; D000368:Aged; D014670:Ampulla of Vater; D021441:Carcinoma, Pancreatic Ductal / Q000556:secondary / Q000628:therapy*; D003131:Combined Modality Therapy / Q000706:statistics & numerical data*; D003138:Common Bile Duct Neoplasms / Q000473:pathology / Q000628:therapy*; D004379:Duodenal Neoplasms / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging*; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D016577:Pancreaticoduodenectomy; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors