title: Analysis of prognostic factors impacting oncologic outcomes after neoadjuvant tyrosine kinase inhibitor therapy for gastrointestinal stromal tumors.
abstract: BACKGROUND
  Management of gastrointestinal stromal tumors (GISTs) has been transformed with tyrosine kinase inhibitors (TKIs). While data on optimal duration of adjuvant imatinib remains elusive, guidelines for administration of neoadjuvant TKIs remain unknown.
  
  
  METHODS
  Under an institutional review board-approved protocol, patients at our institution with a diagnosis of GIST treated with neoadjuvant TKIs and surgical resection were identified. Clinical and pathologic characteristics were obtained from medical records.
  
  
  RESULTS
  Ninety-three patients underwent surgical resection after neoadjuvant TKI therapy; 41 had primary and 52 had recurrent/metastatic GIST. Median follow-up was 2.4 years. Median duration of neoadjuvant therapy was 315 (range 3-1,611) days for primary and 537 (range 4-3,257) days for recurrent/metastatic GIST (p = 0.001). Two-year, recurrence-free survival (RFS) was 85 and 44 % for primary and recurrent/metastatic disease, respectively, whereas 2-year overall survival (OS) was 97 % for primary and 73 % for recurrent/metastatic GIST. For primary GIST, duration of neoadjuvant therapy >365 days (p = 0.02) was associated with higher risk of recurrence on univariate analysis, whereas none of the clinicopathologic factors impacted OS. For recurrent/metastatic disease, disease progression was associated with a shorter OS (p = 0.001), but no factors were found to impact RFS. Lastly, when examining all patients, KIT mutations (p = 0.03) and multivisceral resection (p = 0.011) predicted shorter RFS.
  
  
  CONCLUSIONS
  Neoadjuvant TKIs can be effectively used for the treatment of primary and recurrent/metastatic GIST. While duration of neoadjuvant therapy, KIT mutation status, and the need for multivisceral resection can help to predict higher risk for recurrence, progression on neoadjuvant TKIs can aid in selection of patients with recurrent/metastatic disease for surgical resection.
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Bednarski
authors.forename: Dejka M
authors.initials: DM
authors.lastname: Araujo
authors.forename: Min
authors.initials: M
authors.lastname: Yi
authors.forename: Keila E
authors.initials: KE
authors.lastname: Torres
authors.forename: Alexander
authors.initials: A
authors.lastname: Lazar
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Trent
authors.forename: Janice N
authors.initials: JN
authors.lastname: Cormier
authors.forename: Peter W T
authors.initials: PW
authors.lastname: Pisters
authors.forename: Dina Chelouche
authors.initials: DC
authors.lastname: Lev
authors.forename: Raphael E
authors.initials: RE
authors.lastname: Pollock
authors.forename: Barry W
authors.initials: BW
authors.lastname: Feig
authors.forename: Kelly K
authors.initials: KK
authors.lastname: Hunt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D015996:Survival Rate
chemical_list: D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases