Role of surgery combined with kinase inhibition in the management of gastrointestinal stromal tumor (GIST).
BACKGROUND
Surgery is the standard treatment for primary, gastrointestinal stromal tumor (GIST); however, surgical resection often is not curative, particularly in large GIST. Five years after complete removal of their tumor, approximately half of treated patients relapse. Imatinib, an oral tyrosine kinase inhibitor (TKI), is first-line treatment in patients with metastatic or unresectable GIST. It has resulted in durable objective responses or stable disease in 84% of patients and is well tolerated. The efficacy of imatinib in advanced GIST has created interest in a variety of potential multimodal approaches to management that combine surgery with systemic therapy.


RESULTS
Recently, a large, randomized, Phase III, US cooperative group trial that compared adjuvant imatinib, for 1 year after primary complete surgical resection, with placebo in primary GIST, reported a significantly shorter time to relapse for those in the placebo group. This led to the approval of imatinib for this new indication in the US and Europe. Several studies evaluating the efficacy of adjuvant imatinib in patients with primary GIST who are at high risk for postoperative relapse are ongoing; in particular two large European studies are expected to yield preliminary results in the near future. Neoadjuvant therapy with imatinib is also being investigated for its effect on surgical outcomes, with first trial results reported.


CONCLUSIONS
This article provides an update on the rapidly evolving role of surgery, treatment with TKI therapy, and their combination in the management of GIST as well as further reviews pertinent to current clinical research findings.
Hohenberger
Peter
P
Division of Surgical Oncology and Thoracic Surgery, Department of Surgery, Mannheim University Medical Center, University of Heidelberg, Mannheim, Germany. peter.hohenberger@umm.de
Eisenberg
Burton
B
D001549:Benzamides; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D006801:Humans; D000068877:Imatinib Mesylate; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases