Surgery of residual disease following molecular-targeted therapy with imatinib mesylate in advanced/metastatic GIST.
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.
Gronchi
Alessandro
A
Department of Surgery, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy. alessandro.gronchi@istitutotumori.mi.it
Fiore
Marco
M
Miselli
Francesca
F
Lagonigro
Maria Stefania
MS
Coco
Paola
P
Messina
Antonella
A
Pilotti
Silvana
S
Casali
Paolo Giovanni
PG
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
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit