Is there a role for surgery in patients with "unresectable" cKIT+ gastrointestinal stromal tumors treated with imatinib mesylate?

BACKGROUND: Imatinib mesylate (Gleevec) is being studied as adjuvant chemotherapy for the treatment of cKIT+ gastrointestinal stromal tumors (GISTs). Early reports using Gleevec for the treatment of unresectable GISTs have shown 50% to 60% partial response rates based on radiographic evaluation alone. No study has yet correlated radiographic response with pathologic findings. This retrospective review of patients with cKIT+ GISTs who received Gleevec prior to surgical resection examines the pathologic response to therapy and the feasibility of surgical resection after treatment.
METHODS: Patients with cKIT+ GISTs were identified from the institutional sarcoma database. Patients were included if they had pathologic confirmation of cKIT mutation and therapy with Gleevec. The pretreatment and preoperative radiographs, surgeons' operative notes, and pathology reports were reviewed for documentation of the extent of disease.
RESULTS: Between January 2001 and Octorber 2002, 126 patients with unresectable cKIT + GISTs treated with Gleevec were identified. Of these 126 patients, 17 have subsequently undergone surgical resection after a median of 10 months (range 2 to 16) of treatment with Gleevec. Based on computed tomographic (CT) scanning, 1 (6%) patient had evidence of a complete tumor response, 12 (70%) patients had a partial response, 3 (24%) patients had stable disease, and 1 (6%) patient had progressive disease. Posttreatment/preoperative CT imaging documented an overall response rate of 76%. The pathologic review of the operative specimens showed that 2 (12%) patients had a complete response to therapy, 11 (65%) had a partial response to therapy, 3 (18%) patients had no evidence of treatment effect on the excised tumor, 1 patient had progressive disease. Sixteen patients (94%) underwent complete surgical resection of disease, including 3 patients with no pathologic evidence of response to therapy. One patient had progression of disease and was unresectable at surgical exploration.
CONCLUSIONS: This series is the first to present pathologic data after the treatment of cKIT+ GISTs with Gleevec. In this series, the majority of responses were limited to partial responses, indicating that surgical resection remains a vital component of the treatment plan for patients with cKIT+ GISTs. This series is consistent with previous reports indicating that complete responses are extremely rare in response to treatment with Gleevec. Patients with advanced disease may benefit from a course of neoadjuvant therapy with Gleevec followed by resection, even when there is evidence of multifocal disease. A prospective evaluation of neoadjuvant Gleevec therapy for advanced cKIT+ GISTs is warranted.