title: Impact of Chemotherapy and External-Beam Radiation Therapy on Outcomes among Patients with Resected Gallbladder Cancer: A Multi-institutional Analysis.
abstract: Use of adjuvant chemotherapy (CTx) and chemoradiation therapy (cXRT) for the treatment of gallbladder cancer (GBC) remains varied. We sought to define the utilization and effect of adjuvant therapy for patients with GBC.
  
  
  
  Using a multi-institutional national database, 291 patients with GBC who underwent curative-intent resection between 2000 and 2015 were included. Patients with metastasis or an R2 margin were excluded.
  
  
  
  Median patient age was 66.6 years. Most patients had a T2 (46.2 %) or T3 (38.6 %) lesion, and 37.8 % of patients had lymph node (LN) metastasis. A total of 186 (63.9 %) patients underwent surgery alone, 61 (21.0 %) received CTx, and 44 (15.1 %) patients received cXRT. On multivariable analysis, factors associated with worse overall survival (OS) included T3/T4 stage [hazard ratio (HR) 1.82], LN-metastasis (HR 1.84), lymphovascular invasion (HR 2.02), perineural invasion (HR 1.42), and R1 surgical margin status (HR 2.06); all P < 0.05). In contrast, receipt of CTx/cXRT was associated with improved OS (CTx, HR 0.38; cXRT, HR 0.26; P < 0.001) compared with surgery alone. Similar results were observed for disease-free survival (DFS) (CTx, HR 0.61; cXRT, HR 0.43; P < 0.05). Of note, only patients with high-risk features, such as AJCC T3/T4 stage (HR 0.41), LN metastasis (HR 0.45), and R1 disease (HR 0.21) (all P < 0.05) derived an OS benefit from CTx/cXRT.
  
  
  
  Adjuvant CTx/cXRT was utilized in 36 % of patients undergoing curative-intent resection for GBC. After adjusted analyses, CTx/cXRT were independently associated with improved long-term outcomes, but the benefit was isolated to only patients with high-risk characteristics.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Yuhree
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Division of Surgical Oncology, Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Neda
authors.initials: N
authors.lastname: Amini
authors.affiliation: Division of Surgical Oncology, Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Wilson
authors.affiliation: Division of Surgical Oncology, Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Georgios A
authors.initials: GA
authors.lastname: Margonis
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: Cecilia G
authors.initials: CG
authors.lastname: Ethun
authors.affiliation: Department of Surgery, Stanford University Medical Center, Stanford, CA, USA.
authors.forename: George
authors.initials: G
authors.lastname: Poultsides
authors.affiliation: Department of Surgery, Stanford University Medical Center, Stanford, CA, USA.
authors.forename: Thuy
authors.initials: T
authors.lastname: Tran
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Kamran
authors.initials: K
authors.lastname: Idrees
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Chelsea A
authors.initials: CA
authors.lastname: Isom
authors.affiliation: Department of Surgery, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Fields
authors.affiliation: Department of Surgery, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Bradley
authors.initials: B
authors.lastname: Krasnick
authors.affiliation: Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Weber
authors.affiliation: Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Salem
authors.affiliation: Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, KY, USA.
authors.forename: Robert C G
authors.initials: RC
authors.lastname: Martin
authors.affiliation: Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, KY, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Scoggins
authors.affiliation: Department of Surgery, Wake Forest University, Winston-Salem, NC, USA.
authors.forename: Perry
authors.initials: P
authors.lastname: Shen
authors.affiliation: Department of Surgery, Wake Forest University, Winston-Salem, NC, USA.
authors.forename: Harveshp D
authors.initials: HD
authors.lastname: Mogal
authors.affiliation: Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
authors.forename: Carl
authors.initials: C
authors.lastname: Schmidt
authors.affiliation: Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
authors.forename: Eliza
authors.initials: E
authors.lastname: Beal
authors.affiliation: Department of Surgery, New York University, New York, NY, USA.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Hatzaras
authors.affiliation: Department of Surgery, New York University, New York, NY, USA.
authors.forename: Rivfka
authors.initials: R
authors.lastname: Shenoy
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Cardona
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: Shishir K
authors.initials: SK
authors.lastname: Maithel
authors.affiliation: Division of Surgical Oncology, Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA. tpawlik1@jhmi.edu.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Pawlik
mesh_terms: D000368:Aged; D059186:Chemoradiotherapy, Adjuvant; D005260:Female; D005706:Gallbladder Neoplasms / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D009367:Neoplasm Staging; D016896:Treatment Outcome