Clinical significance of surgical intervention for imatinib-resistant gastrointestinal stromal tumors in the era of multiple tyrosine kinase inhibitors



Imatinib is the standard treatment for unresectable and metastatic GIST. In the late stages, patients undergoing imatinib show drug resistance. Surgical intervention has been occasionally performed for resistant lesions. However, the clinical significance of such intervention remains unclear.


Between 2006 and 2015, 37 patients were diagnosed with imatinib-resistant GISTs. We performed surgical intervention only for localized resistant lesions. We retrospectively investigated the background characteristics, data on surgical intervention and subsequent treatment, progression-free survival (PFS), and overall survival (OS).


Eighteen patients diagnosed with localized resistance received surgical intervention (S-group) and 19 patients diagnosed with generalized resistance were received other TKIs (M-group). In S-group, no serious complications occurred, and all patients restarted imatinib after resection. The median PFS was 14.5 months. Five patients underwent surgical intervention multiple times followed by the continuation of imatinib, and the median duration of imatinib continuation was 22.2 months. Second-line TKIs were administered to 93% of the patients and the dose-intensity and outcome were similar in both groups. The median OS was 47.2 months after surgery.


Surgical intervention could be performed safely and therefore could be followed by the continuation of TKI therapy. Surgical intervention based on the appropriate criteria of resistance might thus be useful for imatinib-resistant GISTs.

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  1. 1.

    Nishida T, Blay JY, Hirota S, Kitagawa Y, Kang YK. The standard diagnosis, treatment, and follow-up of gastrointestinal stromal tumors based on guidelines. Gastric Cancer. 2016;19:3–14.

    CAS  Article  Google Scholar 

  2. 2.

    Yoshikawa K, Shimada M, Kurita N, Sato H, Iwata T, Morimoto S, et al. The efficacy of PET-CT for predicting the malignant potential of gastrointestinal stromal tumors. Surg Today. 2013;43:1162–7.

    CAS  Article  Google Scholar 

  3. 3.

    Takahashi T, Serada S, Ako M, Fujimoto M, Miyazaki Y, Nakatsuka R, et al. New findings of kinase switching in gastrointestinal stromal tumor under imatinib using phosphoproteomic analysis. Int J Cancer. 2013;133:2737–43.

    CAS  PubMed  Google Scholar 

  4. 4.

    Nishida T, Doi T, Naito Y. Tyrosine kinase inhibitors in the treatment of unresectable or metastatic gastrointestinal stromal tumors. Expert Opin Pharmacother. 2014;15:1979–89.

    CAS  Article  Google Scholar 

  5. 5.

    Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006;368:1329–38.

    CAS  Article  Google Scholar 

  6. 6.

    Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, et al. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381:295–302.

    CAS  Article  Google Scholar 

  7. 7.

    Nishida T, Hirota S, Yanagisawa A, Sugino Y, Minami M, Yamamura Y, et al. GIST Guideline Subcommittee: clinical practice guidelines for gastrointestinal stromal tumor (GIST) in Japan: english version. Int J Clin Oncol. 2008;13:416–30.

    Article  Google Scholar 

  8. 8.

    ESMO/European Sarcoma Network Working Group. Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(Suppl 3):iii21–6.

    Google Scholar 

  9. 9.

    Ford SJ, Gronchi A. Indications for surgery in advanced/metastatic GIST. Eur J Cancer. 2016;63:154–67.

    Article  Google Scholar 

  10. 10.

    Demetri GD, von Mehren M, Antonescu CR, DeMatteo RP, Ganjoo KN, Maki RG, et al. NCCN Task Force report: update on the management of patients with gastrointestinal stromal tumors. J Natl Compr Canc Netw. 2010;8:S1-41.

    CAS  Article  Google Scholar 

  11. 11.

    Raut CP, Posner M, Desai J, Morgan JA, George S, Zahrieh D, et al. Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors. J Clin Oncol. 2006;24:2325–31.

    CAS  Article  Google Scholar 

  12. 12.

    Gao X, Xue A, Fang Y, Shu P, Ling J, Qin J, et al. Role of surgery in patients with focally progressive gastrointestinal stromal tumors resistant to imatinib. Sci Rep. 2016;6:22840.

    CAS  Article  Google Scholar 

  13. 13.

    Hasegawa J, Kanda T, Hirota S, Fukuda M, Nishitani A, Takahashi T, et al. Surgical interventions for focal progression of advanced gastrointestinal stromal tumors during imatinib therapy. Int J Clin Oncol. 2007;12:212–7.

    Article  Google Scholar 

  14. 14.

    Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–13.

    Article  Google Scholar 

  15. 15.

    Katayama H, Kurokawa Y, Nakamura K, Ito H, Kanemitsu Y, Masuda N, et al. Extended Clavien-Dindo classification of surgical complications: Japan Clinical Oncology Group postoperative complications criteria. Surg Today. 2016;46:668–85.

    Article  Google Scholar 

  16. 16.

    Yeh CN, Chen TW, Tseng JH, Liu YY, Wang SY, Tsai CY, et al. Surgical management in metastatic gastrointestinal stromal tumor (GIST) patients after imatinib mesylate treatment. J Surg Oncol. 2010;102:599–603.

    Article  Google Scholar 

  17. 17.

    Mussi C, Ronellenfitsch U, Jakob J, Tamborini E, Reichardt P, Casali PG, et al. Post-imatinib surgery in advanced/metastatic GIST: is it worthwhile in all patients? Ann Oncol. 2010;21:403–8.

    CAS  Article  Google Scholar 

  18. 18.

    Nishida T, Takahashi T, Miyazaki Y. Gastrointestinal stromal tumor: a bridge between bench and bedside. Gastric Cancer. 2009;12(4):175–88.

    Article  Google Scholar 

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Correspondence to Tsuyoshi Takahashi.

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Wada, N., Takahashi, T., Kurokawa, Y. et al. Clinical significance of surgical intervention for imatinib-resistant gastrointestinal stromal tumors in the era of multiple tyrosine kinase inhibitors. Surg Today (2021).

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  • Gastrointestinal stromal tumor
  • Imatinib-resistance
  • Surgical intervention