title: Surgery of residual disease following molecular-targeted therapy with imatinib mesylate in advanced/metastatic GIST.
abstract: OBJECTIVE
  To explore the role of surgery of residual disease following a period of therapy with imatinib mesylate in advanced gastrointestinal stromal tumors (GIST).
  
  
  METHODS
  From January 2001 to June 2005, 159 patients with advanced/metastatic GIST were treated with imatinib mesylate at a single institution. As of June 2002, 38 patients were selected for surgery following a variable period of imatinib therapy. Twenty-seven patients were operated on while they were in response, 8 in progression, 3 for localized disease. Clinical, pathologic, and molecular features were assessed and are reported.
  
  
  RESULTS
  Postsurgery PFS was 96% at 12 months and 69% at 24 months for responding patients, while it was nil at 12 months for progressing ones. Disease-specific survival at 12 months was 100% for responding patients and 60% for progressing ones. In responding cases, secondary progression was mainly related to postsurgical imatinib discontinuation, irrespective of pathologic or molecular variables. In progressing patients, secondary resistance was mainly related to acquired mutations.
  
  
  CONCLUSIONS
  In advanced GIST patients who are responding to imatinib mesylate, the role of surgery is not formally demonstrated at the moment, but this option may well be considered investigational, or suitable for an individualized decision-making in the lack of evidence. In our series, patients progressing on imatinib mesylate did not seem to have any major benefit from surgery, although their number is low.
authors: Department of Surgery, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy. alessandro.gronchi@istitutotumori.mi.it
authors: Alessandro
authors: A
authors: Gronchi
authors: Marco
authors: M
authors: Fiore
authors: Francesca
authors: F
authors: Miselli
authors: Maria Stefania
authors: MS
authors: Lagonigro
authors: Paola
authors: P
authors: Coco
authors: Antonella
authors: A
authors: Messina
authors: Silvana
authors: S
authors: Pilotti
authors: Paolo Giovanni
authors: PG
authors: Casali
mesh_terms: D001549:Benzamides; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000556:secondary / Q000601:surgery; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018365:Neoplasm, Residual; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000627:therapeutic use*; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit