title: Hepatic resection for metastatic gastrointestinal stromal tumors in the tyrosine kinase inhibitor era.
abstract: BACKGROUND
  Before the advent of tyrosine kinase inhibitors (TKIs), surgical resection was the primary treatment for hepatic gastrointestinal stromal tumor (GIST) metastases. Although TKIs have improved survival in the metastatic setting, outcomes after multimodal therapy comprised of hepatectomy and TKIs for GIST are unknown. The objective of this study was to determine whether combination therapy for hepatic GIST metastases is associated with improved overall survival compared with reported outcomes from surgery or TKI therapy alone.
  
  
  METHODS
  Demographics, clinicopathologic tumor characteristics, treatments, and outcomes of patients who underwent hepatic resection at 3 high-volume centers from 1995 to 2010 were reviewed.
  
  
  RESULTS
  In total, 39 patients underwent hepatectomy for metastatic GISTs, and 27 patients received postoperative TKI therapy. At a median follow-up of 39.7 months, 23 patients (59%) experienced recurrence at a median of 18 months. The 1-year, 2-year, and 3-year overall survival rates were 96.7%, 76.8%, and 67.9%, respectively. Median survival was not reached at 5 years. The rates of severe complication and mortality were 10.2% (4 patients) and 2.5% (1 patient), respectively. When controlling for confounders, postoperative TKI therapy was associated with improved survival (hazard ratio, 0.04; 95% confidence interval, 0.01-0.50; P = .006), and extrahepatic disease was associated with worse survival (hazard ratio, 9.51; 95% confidence interval, 1.63-55.7; P = .012).
  
  
  CONCLUSIONS
  Overall survival after combination therapy exceeded previous reports for the treatment of metastatic GIST with hepatic resection or TKI therapy alone and was significantly enhanced by postoperative TKI therapy. The results from this study support findings that combination therapy for GIST liver metastases comprised of surgical resection and TKI therapy is more effective than surgery or TKI therapy alone.
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, NC 27110, USA. ryan.turley@duke.edu
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Turley
authors.forename: Peter D
authors.initials: PD
authors.lastname: Peng
authors.forename: Srinevas K
authors.initials: SK
authors.lastname: Reddy
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Barbas
authors.forename: David A
authors.initials: DA
authors.lastname: Geller
authors.forename: J Wallis
authors.initials: JW
authors.lastname: Marsh
authors.forename: Allan
authors.initials: A
authors.lastname: Tsung
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Pawlik
authors.forename: Bryan M
authors.initials: BM
authors.lastname: Clary
mesh_terms: D000368:Aged; D003131:Combined Modality Therapy; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000473:pathology*; D046152:Gastrointestinal Stromal Tumors / Q000473:pathology*; D006498:Hepatectomy / Q000379:methods*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000556:secondary* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors
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