Surgical outcomes of patients with gastrointestinal stromal tumors in the era of targeted drug therapy

J Gastrointest Surg. 2008 Nov;12(11):2023-31. doi: 10.1007/s11605-008-0561-4. Epub 2008 Jun 11.

Abstract

Background: The discovery of the c-KIT mutation and the advent of targeted drug therapy with imatinib mesylate have revolutionized the management of gastrointestinal stromal tumors (GISTs). The outcome of patients with surgically treated GISTs treated in the era of targeted drug therapy was assessed and factors associated with adverse outcomes determined.

Materials and methods: Patients with GISTs requiring surgery at a tertiary care center from 2002 to 2007 were reviewed and prognostic factors determined.

Results: Forty patients were surgically treated for GISTs. The median age at presentation was 59 years. The stomach (55%) was the main site of primary disease. The median tumor size was 7 cm. Eleven (28%) patients had metastatic disease at presentation. Surgery was undertaken in all patients with curative intent. Multi-organ resection was required in 10 (25%) patients. Imatinib mesylate was administered postoperatively in 68% of cases. Median follow-up was 24 months. There was a 40% recurrence rate with 63% undergoing repeat surgical resection. The peritoneum and liver were the main sites of recurrent disease. The 5-year disease-specific survival and disease-free survival (DFS) were 65% and 35%, respectively. High mitotic rate (P = 0.017) and tumor size greater than 10 cm (P = 0.009) were the only prognostically significant adverse factors of DFS on multivariate analysis, independent of imatinib mesylate treatment.

Conclusion: Aggressive surgical treatment and follow-up of GISTs, combined with targeted drug therapy, leads to long-term DFS survival. Tumor recurrence is independently associated with a high tumor mitotic rate and size greater than 10 cm, despite the use of adjuvant targeted drug therapy.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Benzamides
  • Chemotherapy, Adjuvant
  • Cohort Studies
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Delivery Systems
  • Female
  • Follow-Up Studies
  • Gastrointestinal Stromal Tumors / drug therapy*
  • Gastrointestinal Stromal Tumors / mortality
  • Gastrointestinal Stromal Tumors / pathology
  • Gastrointestinal Stromal Tumors / surgery*
  • Humans
  • Imatinib Mesylate
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Piperazines / administration & dosage*
  • Probability
  • Proportional Hazards Models
  • Proto-Oncogene Proteins c-kit / drug effects*
  • Proto-Oncogene Proteins c-kit / genetics
  • Pyrimidines / administration & dosage*
  • Retrospective Studies
  • Risk Assessment
  • Statistics, Nonparametric
  • Survival Analysis
  • Treatment Outcome

Substances

  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Proto-Oncogene Proteins c-kit