Skip to main content

Advertisement

SpringerLink
Log in

The Role of Surgical Resection Following Imatinib Treatment in Patients with Recurrent or Metastatic Gastrointestinal Stromal Tumors: Results of Propensity Score Analyses

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Although benefits of surgical resection of residual gastrointestinal stromal tumors (GISTs) after imatinib therapy have been suggested, those benefits over imatinib alone have not been proven. We compared the clinical outcomes of surgical resection of residual lesions after imatinib treatment (S group) with imatinib treatment alone (NS group) in patients with recurrent or metastatic GISTs.

Methods

A total of 134 patients (42 in the S group, 92 in the NS group) with recurrent or metastatic GIST who had stable disease for more than 6 months after responding to imatinib were included.

Results

There were no statistically significant differences in the baseline characteristics of the S and NS groups except for age and number of peritoneal metastases. The median follow-up period was 58.9 months. Progression-free survival (PFS) and overall survival (OS) were significantly longer in the S group compared with the NS group (median PFS: 87.7 vs. 42.8 months, p = 0.001; median OS: not reached vs. 88.8 months, p = 0.001). Multivariate analysis revealed that S group, female sex, KIT exon 11 mutations, and low initial tumor burden were associated with longer PFS, and S group and low initial tumor burden were associated with a longer OS. Even after applying inverse probability of treatment weighting adjustment, the S group demonstrated significantly better outcomes in terms of PFS (HR 2.326; 95 % confidence interval [CI] 1.034–5.236; p = 0.0412) and OS (HR 5.464; 95 % CI 1.460–20.408; p = 0.0117).

Conclusion

Surgical resection of residual lesions after disease control with imatinib is likely to be beneficial to patients with recurrent or metastatic GISTs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. 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):472−80.

    Article  CAS  PubMed  Google Scholar 

  2. Blanke CD, Rankin C, Demetri GD, et al. Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol. 2008;26(4):626−32.

    Article  CAS  PubMed  Google Scholar 

  3. 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):1052−6.

    Article  CAS  PubMed  Google Scholar 

  4. Blanke CD, Demetri GD, von Mehren M, et al. Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT. J Clin Oncol. 2008;26(4):620−5.

    Article  CAS  PubMed  Google Scholar 

  5. Verweij J, Casali PG, Zalcberg J, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet. 2004;364(9440):1127−34.

    Article  CAS  PubMed  Google Scholar 

  6. von Mehren M, Heinrich MC, Joensuu H, Blanke CD, Wehrle E, Demetri GD. Follow-up results after 9 years (yrs) of the ongoing, phase II B2222 trial of imatinib mesylate (IM) in patients (pts) with metastatic or unresectable kit + gastrointestinal stromal tumors (GIST) [abstract no. 10016]. J Clin Oncol. 2011;29(Suppl):10016.

  7. Wardelmann E, Merkelbach-Bruse S, Pauls K, et al. Polyclonal evolution of multiple secondary KIT mutations in gastrointestinal stromal tumors under treatment with imatinib mesylate. Clin Cancer Res. 2006;12(6):1743−9.

    Article  CAS  PubMed  Google Scholar 

  8. 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):4342−9.

    Article  CAS  PubMed  Google Scholar 

  9. 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):689−95.

    Article  CAS  PubMed  Google Scholar 

  10. Bauer S, Rutkowski P, Hohenberger P, et al. Long-term follow-up of patients with GIST undergoing metastasectomy in the era of imatinib: analysis of prognostic factors (EORTC-STBSG Collaborative Study). Eur J Surg Oncol. 2014;40(4):412−9.

    Article  CAS  PubMed  Google Scholar 

  11. Rutkowski P, Gronchi A, Hohenberger P, et al. Neoadjuvant imatinib in locally advanced gastrointestinal stromal tumors (GIST): the EORTC STBSG experience. Ann Surg Oncol 2013;20(9):2937−43.

    Article  PubMed  Google Scholar 

  12. Mussi C, Ronellenfitsch U, Jakob J, et al. Post-imatinib surgery in advanced/metastatic GIST: is it worthwhile in all patients? Ann Oncol. 2010;21(2):403−8.

    Article  CAS  PubMed  Google Scholar 

  13. Sym SJ, Ryu MH, Lee JL, et al. Surgical intervention following imatinib treatment in patients with advanced gastrointestinal stromal tumors (GISTs). J Surg Oncol. 2008;98(1):27−33.

    Article  PubMed  Google Scholar 

  14. Raut CP, Posner M, Desai J, et al. Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors. J Clin Oncol. 2006;24(15):2325−31.

    Article  CAS  PubMed  Google Scholar 

  15. National Comprehensive Cancer Network. National Comprehensive Cancer Network clinical practice guidelines in oncology, soft tissue sarcoma. 2012.

  16. Kang YK, Kang HJ, Kim KM, et al. Clinical practice guideline for accurate diagnosis and effective treatment of gastrointestinal stromal tumor in Korea. Cancer Res Treat. 2012;44(2):85−96.

    Article  PubMed Central  PubMed  Google Scholar 

  17. European Sarcoma Network Working Group. Gastrointestinal stromal tumors: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(Suppl 7):49−55.

  18. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228−47.

    Article  CAS  PubMed  Google Scholar 

  19. Kim TW, Lee H, Kang YK, et al. Prognostic significance of c-kit mutation in localized gastrointestinal stromal tumors. Clin Cancer Res. 2004;10(9):3076−81.

    Article  CAS  PubMed  Google Scholar 

  20. Green S, Weiss GR. Southwest Oncology Group standard response criteria, endpoint definitions and toxicity criteria. Invest New Drugs. 1992;10(4):239−53.

    Article  CAS  PubMed  Google Scholar 

  21. Robins JM, Hernan MA, Brumback B. Marginal structural models and causal inference in epidemiology. Epidemiology. 2000;11(5):550−60.

    Article  CAS  PubMed  Google Scholar 

  22. Curtis LH, Hammill BG, Eisenstein EL, Kramer JM, Anstrom KJ. Using inverse probability-weighted estimators in comparative effectiveness analyses with observational databases. Med Care. 2007;45(10 Suppl 2):S103−7.

    Article  PubMed  Google Scholar 

  23. de la Fuente SG, Deneve JL, Parsons CM, Zager JS, Conley AP, Gonzalez RJ. A comparison between patients with gastrointestinal stromal tumours diagnosed with isolated liver metastases and liver metastases plus sarcomatosis. HPB. 2013;15(9):655−60.

    Article  PubMed Central  PubMed  Google Scholar 

  24. DeMatteo RP, Maki RG, Singer S, Gonen M, Brennan MF, Antonescu CR. Results of tyrosine kinase inhibitor therapy followed by surgical resection for metastatic gastrointestinal stromal tumor. Ann Surg. 2007;245(3):347−52.

    Article  PubMed Central  PubMed  Google Scholar 

  25. Andtbacka RH, Ng CS, Scaife CL, et al. Surgical resection of gastrointestinal stromal tumors after treatment with imatinib. Ann Surg Oncol. 2007;14(1):14−24.

    Article  PubMed  Google Scholar 

Download references

Disclosure

None declared.

Author information

Authors and Affiliations

  1. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Seong Joon Park MD, Min-Hee Ryu MD, PhD, Baek-Yeol Ryoo MD, PhD, Byeong Seok Sohn MD, PhD, Hwa Jung Kim MD, PhD & Yoon-Koo Kang MD, PhD

  2. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Young Soo Park MD, PhD

  3. Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Chan Wook Kim MD, PhD, Ki-Hun Kim MD, PhD, Chang Sik Yu MD, PhD, Jeong Hwan Yook MD, PhD & Byung Sik Kim MD, PhD

Authors
  1. Seong Joon Park MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Min-Hee Ryu MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Baek-Yeol Ryoo MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Young Soo Park MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Byeong Seok Sohn MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hwa Jung Kim MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chan Wook Kim MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ki-Hun Kim MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Chang Sik Yu MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jeong Hwan Yook MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Byung Sik Kim MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yoon-Koo Kang MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yoon-Koo Kang MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Park, S.J., Ryu, MH., Ryoo, BY. et al. The Role of Surgical Resection Following Imatinib Treatment in Patients with Recurrent or Metastatic Gastrointestinal Stromal Tumors: Results of Propensity Score Analyses. Ann Surg Oncol 21, 4211–4217 (2014). https://doi.org/10.1245/s10434-014-3866-4

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-014-3866-4

Keywords

Search

Navigation