Annals of Surgical Oncology

, Volume 14, Issue 1, pp 134–142 | Cite as

Outcome of Metastatic GIST in the Era before Tyrosine Kinase Inhibitors

  • Jason S. Gold
  • Sanne M. van der Zwan
  • Mithat Gönen
  • Robert G. Maki
  • Samuel Singer
  • Murray F. Brennan
  • Cristina R. Antonescu
  • Ronald P. DeMatteo



Treatment of metastatic GIST with imatinib mesylate results in a 2-year survival of approximately 72%. The outcome of patients with metastatic GIST not treated with tyrosine kinase inhibitors is not well defined.


One hundred nineteen patients with metastatic GIST diagnosed prior to July 1, 1998 (approximately 2 years prior to the use of imatinib for GIST) were identified from an institutional database of patients with pathologically confirmed GIST. Mutational analysis was performed in cases with available tissue. The log rank test and Cox regression models were used to assess prognostic factors.


Median survival was 19 months with a 41% 2-year survival and a 25% 5-year survival. Resection of metastatic GIST was performed in 81 patients (68%), while 50 (42%) received conventional chemotherapy. Twelve patients (10%) were eventually started on imatinib. Primary tumor size <10 cm, <5 mitoses/50 HPF in the primary tumor, epithelioid morphology, longer disease-free interval, and surgical resection were independent predictors of improved survival on multivariate analysis. Mutational status did not predict outcome. In patients who underwent resection, the 2 year survival was 53%, and negative microscopic margins also independently predicted improved survival.


Treatment with imatinib appears to improve 2-year survival of metastatic GIST by approximately 20% when compared to surgery alone. The combination of imatinib and surgery for the treatment of metastatic GIST therefore warrants investigation.


Gastrointestinal stromal tumor GIST Imatinib mesylate Gleevec Surgery 



Supported in part by: PO1 CA 47179 (MFB), ACS MRSG CCE-106841 (CRA), and CA94503 and CA102613 (RPD).


  1. 1.
    Nilsson B, Bumming P, Meis-Kindblom JM, et al. Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era–a population-based study in western Sweden. Cancer 2005; 103(4):821–9PubMedCrossRefGoogle Scholar
  2. 2.
    Segal NH, Pavlidis P, Antonescu CR, et al. Classification and subtype prediction of adult soft tissue sarcoma by functional genomics. Am J Pathol 2003; 163(2):691–700PubMedGoogle Scholar
  3. 3.
    DeMatteo RP, Lewis JJ, Leung D, et al. Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg 2000; 231(1):51–8PubMedCrossRefGoogle Scholar
  4. 4.
    Crosby JA, Catton CN, Davis A, et al. Malignant Gastrointestinal Stromal Tumors of the Small Intestine: A Review of 50 Cases from a Prospective Database. Ann Surg Oncol 2001; 8(1):50–59PubMedCrossRefGoogle Scholar
  5. 5.
    Pierie J-PEN, Choudry U, Muzikansky A, et al. The Effect of Surgery and Grade on Outcome of Gastrointestinal Stromal Tumors. Arch Surg 2001; 136(4):383–389PubMedCrossRefGoogle Scholar
  6. 6.
    Fujimoto Y, Nakanishi Y, Yoshimura K, Shimoda T. Clinicopathologic study of primary malignant gastrointestinal stromal tumor of the stomach, with special reference to prognostic factors: analysis of results in 140 surgically resected patients. Gastric Cancer 2003; 6(1):39–48PubMedCrossRefGoogle Scholar
  7. 7.
    Langer C, Gunawan B, Schuler P, et al. Prognostic factors influencing surgical management and outcome of gastrointestinal stromal tumours. Br J Surg 2003; 90(3):332–9PubMedCrossRefGoogle Scholar
  8. 8.
    Joensuu H, Roberts PJ, Sarlomo-Rikala M, et al. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med 2001; 344(14):1052–6PubMedCrossRefGoogle Scholar
  9. 9.
    van Oosterom AT, Judson I, Verweij J, et al. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet 2001; 358(9291):1421–3PubMedCrossRefGoogle Scholar
  10. 10.
    van Oosterom AT, Judson IR, Verweij J, et al. Update of phase I study of imatinib (STI571) in advanced soft tissue sarcomas and gastrointestinal stromal tumors: a report of the EORTC Soft Tissue and Bone Sarcoma Group. European Journal of Cancer 2002; 38(Supplement 5):S83-S87PubMedCrossRefGoogle Scholar
  11. 11.
    Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002; 347(7):472–80PubMedCrossRefGoogle Scholar
  12. 12.
    Benjamin RS, Rankin C, Fletcher C, et al. Phase III dose-randomized study of imatinib mesylate (STI571) for GIST: Intergroup S0033 early results. Proc Am Soc Clin Oncol 2003; 22:814 (abstract 3271)Google Scholar
  13. 13.
    Blanke C, Joensuu H, Demetri G, et al. Long-term follow up of advanced gastrointestinal stromal tumor (GIST) patients treated with imatinib mesylate. 2004 Gastrointestinal Cancers Symposium. San Francisco, California, 2004 (abstract 2).Google Scholar
  14. 14.
    Verweij PJ, Casali PG, Zalcberg PJ, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. The Lancet 2004; 364(9440):1127–1134CrossRefGoogle Scholar
  15. 15.
    Dematteo RP, Heinrich MC, El-Rifai WeM, Demetri G. Clinical management of gastrointestinal stromal tumors: Before and after STI-571. Human Pathology 2002; 33(5):466–477PubMedCrossRefGoogle Scholar
  16. 16.
    Mudan SS, Conlon KC, Woodruff JM, et al. Salvage surgery for patients with recurrent gastrointestinal sarcoma: prognostic factors to guide patient selection. Cancer 2000; 88(1):66–74PubMedCrossRefGoogle Scholar
  17. 17.
    DeMatteo RP, Shah A, Fong Y, et al. Results of hepatic resection for sarcoma metastatic to liver. Ann Surg 2001; 234(4):540–7PubMedCrossRefGoogle Scholar
  18. 18.
    Antonescu CR, Viale A, Sarran L, et al. Gene Expression in Gastrointestinal Stromal Tumors Is Distinguished by KIT Genotype and Anatomic Site. Clin Cancer Res 2004; 10(10):3282–3290PubMedCrossRefGoogle Scholar
  19. 19.
    Antonescu CR, Besmer P, Guo T, et al. Acquired Resistance to Imatinib in Gastrointestinal Stromal Tumor Occurs Through Secondary Gene Mutation. Clin Cancer Res 2005; 11(11):4182–4190PubMedCrossRefGoogle Scholar
  20. 20.
    Kaplan EL, Meier P. Nonparametric estimation form incomplete observations. J Am Stat Assoc 1958; 53:457–62CrossRefGoogle Scholar
  21. 21.
    Blanke CD, Joensuu H, Demetri GD, et al. Outcome of advanced gastrointestinal stromal tumor (GIST) patients treated with imatinib mesylate: Four-year follow-up of a phase II randomized trial. Gastrointestinal Cancers Symposium. San Francisco, California, 2006 (abstract 7)Google Scholar
  22. 22.
    Maki RG, Fletcher JA, Heinrich MC, et al. Results from a continuation trial of SU11248 in patients (pts) with imatinib (IM)-resistant gastrointestinal stromal tumor (GIST). J Clin Oncol 2005; 23(16S):9011Google Scholar
  23. 23.
    Demetri G, van Oosterom AT, Garrett C, et al. Improved survival and sustained clinical benefit with SU11248 (SU) in pts with GIST after failure of imatinib mesylate (IM) therapy in a phase III trial. Gastrointestinal Cancers Symposium. San Francisco, California, 2006 (abstract 8)Google Scholar
  24. 24.
    Taniguchi M, Nishida T, Hirota S, et al. Effect of c-kit Mutation on Prognosis of Gastrointestinal Stromal Tumors. Cancer Res 1999; 59(17):4297–4300PubMedGoogle Scholar
  25. 25.
    Nishida T, Nakamura J, Taniguchi M, et al. Clinicopathological features of gastric stromal tumors. J Exp Clin Cancer Res 2000; 19(4):417–25PubMedGoogle Scholar
  26. 26.
    Singer S, Rubin BP, Lux ML, et al. Prognostic Value of KIT Mutation Type, Mitotic Activity, and Histologic Subtype in Gastrointestinal Stromal Tumors. J Clin Oncol 2002; 20(18):3898–3905PubMedCrossRefGoogle Scholar
  27. 27.
    Kim TW, Lee H, Kang Y-K, et al. Prognostic Significance of c-kit Mutation in Localized Gastrointestinal Stromal Tumors. Clin Cancer Res 2004; 10(9):3076–3081PubMedCrossRefGoogle Scholar
  28. 28.
    Lasota J, Dansonka-Mieszkowska A, Sobin LH, Miettinen M. A great majority of GISTs with PDGFRA mutations represent gastric tumors of low or no malignant potential. Lab Invest 2004; 84(7):874–83PubMedCrossRefGoogle Scholar
  29. 29.
    Iesalnieks I, Rummele P, Dietmaier W, et al. Factors associated with disease progression in patients with gastrointestinal stromal tumors in the pre-imatinib era. Am J Clin Pathol 2005; 124(5):740–8PubMedCrossRefGoogle Scholar
  30. 30.
    Koay MH, Goh YW, Iacopetta B, et al. Gastrointestinal stromal tumours (GISTs): a clinicopathological and molecular study of 66 cases. Pathology 2005; 37(1):22–31PubMedCrossRefGoogle Scholar
  31. 31.
    Liu XH, Bai CG, Xie Q, et al. Prognostic value of KIT mutation in gastrointestinal stromal tumors. World J Gastroenterol 2005; 11(25):3948–52PubMedGoogle Scholar
  32. 32.
    Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. Am J Surg Pathol 2005; 29(1):52–68PubMedCrossRefGoogle Scholar
  33. 33.
    Heinrich MC, Corless CL, Demetri GD, et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 2003; 21(23):4342–9PubMedCrossRefGoogle Scholar
  34. 34.
    Heinrich MC, Shoemaker JS, Corless CL, et al. Correlation of target kinase genotype with clinical activity of imatinib mesylate (IM) in patients with metastatic GI stromal tumors (GISTs) expressing KIT (KIT+). J Clin Oncol 2005; 23(16S):7Google Scholar
  35. 35.
    Debiec-Rychter M, Dumez H, Judson I, et al. Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal tumours entered on phase I and II studies of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer 2004; 40(5):689–95PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2006

Authors and Affiliations

  • Jason S. Gold
    • 1
  • Sanne M. van der Zwan
    • 1
  • Mithat Gönen
    • 1
  • Robert G. Maki
    • 1
  • Samuel Singer
    • 1
  • Murray F. Brennan
    • 1
  • Cristina R. Antonescu
    • 1
  • Ronald P. DeMatteo
    • 1
    • 2
  1. 1.Departments of Surgery (JSG, SMV, SS, MFB, RPD), Epidemiology and Biostatistics (MG), Medicine (RGM), and Pathology (CRA)Memorial Sloan-Kettering Cancer CenterNew YorkUSA
  2. 2.Department of SurgeryMemorial Sloan-Kettering Cancer CenterNew YorkUSA

Personalised recommendations