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Prognostic factors after imatinib secondary resistance: survival analysis in patients with unresectable and metastatic gastrointestinal stromal tumors

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Abstract

Background

Patients undergoing imatinib therapy for gastrointestinal stromal tumors (GISTs) show drug resistance during treatment in the late stages. The aims of this study were to determine survival after the appearance of imatinib secondary resistance (ISR) and to identify the prognostic factors.

Methods

Eligible were patients with unresectable and metastatic GISTs who were diagnosed with ISR and/or underwent treatment for ISR in our institution between 2001 and 2012. A total of 48 patients were enrolled and overall survival was retrospectively analyzed. The Cox proportional hazards model was used to identify the independent prognostic factors. Median follow-up time was 58 months.

Results

As of the cutoff date, 41 of the 48 patients with ISR had died, of which 39 died of GISTs. The overall 1-, 3-, and 5-year survival rates of the 48 patients were 64.6, 32.8, and 20.4 %, respectively, and median survival time was 22 months. The favorable independent prognostic factors identified were long progression-free survival in first-line imatinib therapy (P = 0.04), small diameter of progressive disease (PD) (P = 0.02), and surgical resection of PD (P = 0.01).

Conclusion

Surgical resection of PD in selected cases could improve prognosis in ISR patients undergoing GIST treatment.

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Abbreviations

BSC:

Best supportive care

CT:

Computed tomography

GIST:

Gastrointestinal stromal tumor

ISR:

Imatinib secondary resistance

IVR:

Interventional radiology

MST:

Median survival time

OS:

Overall survival

PD:

Progressive disease

PDGFRA:

Platelet-derived growth factor receptor alpha

PFS:

Progression-free survival

RECIST:

Response Evaluation Criteria in Solid Tumors

RFA:

Radiofrequency ablation

SD:

Stable disease

TACE:

Transcatheter arterial chemoembolization

TKI:

Tyrosine kinase inhibitor

References

  1. Demetri GD, von Mehren M, Antonescu CR et al (2010) NCCN Task Force report: update on the management of patients with gastrointestinal stromal tumors. J Natl Compr Cancer Netw 8(suppl 2):S1–S41

    CAS  Google Scholar 

  2. The ESMO/European Sarcoma Network Working Group (2014) Gastrointestinal stromal tumours: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 25(suppl 3):iii21–iii26

    Article  Google Scholar 

  3. Nishida T, Hirota S, Yanagisawa A et al (2008) Clinical practice guidelines for gastrointestinal stromal tumor (GIST) in Japan: English version. Int J Clin Oncol 13:416–430

    Article  PubMed  Google Scholar 

  4. Blanke CD, Demetri GD, von Mehren M et al (2008) 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 26:620–625

    Article  CAS  PubMed  Google Scholar 

  5. Kanda T, Ishikawa T, Hirota S et al (2012) Prospective observational study of imatinib therapy in Japanese patients with advanced gastrointestinal stromal tumors: long-term follow-up and second malignancy. Jpn J Clin Oncol 42:578–585

    Article  PubMed  Google Scholar 

  6. Ogata K, Mochiki E, Ojima H et al (2014) A multicenter long-term study of imatinib treatment for Japanese patients with unresectable or recurrent gastrointestinal stromal tumors. J Surg Oncol 110:942–946

    Article  CAS  PubMed  Google Scholar 

  7. Demetri GD, van Oosterom AT, Garrett CR et al (2006) Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 368:1329–1338

    Article  CAS  PubMed  Google Scholar 

  8. Demetri GD, Reichardt P, Kang YK et al (2013) 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 381:295–302

    Article  CAS  PubMed  Google Scholar 

  9. Rutkowski P, Nowecki Z, Nyckowski P (2006) Surgical treatment of patients with initially inoperable and/or metastatic gastrointestinal stromal tumors (GIST) during therapy with imatinib mesylate. J Surg Oncol 93:304–311

    Article  PubMed  Google Scholar 

  10. Raut CP, Posner M, Desai J et al (2006) Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors. J Clin Oncol 24:2325–2331

    Article  CAS  PubMed  Google Scholar 

  11. DeMatteo RP, Maki RG, Singer S et al (2007) Results of tyrosine kinase inhibitor therapy followed by surgical resection for metastatic gastrointestinal stromal tumor. Ann Surg 245:347–352

    Article  PubMed  PubMed Central  Google Scholar 

  12. Kobayashi K, Gupta S, Trent JC et al (2006) Hepatic artery chemoembolization for 110 gastrointestinal stromal tumors: response, survival, and prognostic factors. Cancer 107:2833–2841

    Article  PubMed  Google Scholar 

  13. Takaki H, Litchman T, Covey A et al (2014) Hepatic artery embolization for liver metastasis of gastrointestinal stromal tumor following imatinib and sunitinib therapy. J Gastrointest Cancer 45:494–499

    Article  CAS  PubMed  Google Scholar 

  14. Shankar S, vanSonnenberg E, Desai J et al (2005) Gastrointestinal stromal tumor: new nodule-within-a-mass pattern of recurrence after partial response to imatinib mesylate. Radiology 235:892–898

    Article  PubMed  Google Scholar 

  15. Desai J, Shankar S, Heinrich MC et al (2007) Clonal evolution of resistance to imatinib in patients with metastatic gastrointestinal stromal tumors. Clin Cancer Res 13:5398–5405

    Article  CAS  PubMed  Google Scholar 

  16. Liegl B, Kepten I, Le C et al (2008) Heterogeneity of kinase inhibitor resistance mechanisms in GIST. J Pathol 216:64–74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216

    Article  CAS  PubMed  Google Scholar 

  18. Debiec-Rychter M, Sciot R, Le Cesne A et al (2006) KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer 42:1093–1103

    Article  CAS  PubMed  Google Scholar 

  19. Wakai T, Kanda T, Hirota S et al (2004) Late resistance to imatinib therapy in a metastatic gastrointestinal stromal tumour is associated with a second KIT mutation. Br J Cancer 90:2059–2061

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Heinrich MC, Corless CL, Blanke CD et al (2006) Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. J Clin Oncol 24:4764–4774

    Article  CAS  PubMed  Google Scholar 

  21. Reichardt P, Kang YK, Rutkowski P et al (2015) Clinical outcomes of patients with advanced gastrointestinal stromal tumors: safety and efficacy in a worldwide treatment-use trial of sunitinib. Cancer 121:1405–1413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Mudan SS, Conlon KC, Woodruff JM et al (2000) Salvage surgery for patients with recurrent gastrointestinal sarcoma: prognostic factors to guide patient selection. Cancer 88:66–74

    Article  CAS  PubMed  Google Scholar 

  23. Hasegawa J, Kanda T, Hirota S et al (2007) Surgical interventions for focal progression of advanced gastrointestinal stromal tumors during imatinib therapy. Int J Clin Oncol 12:212–217

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for Promotion of Science (No. 24591934). The authors are grateful to Professor Kohei Akazawa, Niigata University Graduate School of Medical and Dental Sciences, for helpful advice on statistical analysis.

Author information

Authors and Affiliations

  1. Department of Surgery, Sanjo General Hospital, 5-Tsukanome, Sanjo, Niigata, 955-0055, Japan

    Tatsuo Kanda

  2. Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

    Tatsuo Kanda & Toshifumi Wakai

  3. Department of Medical Informatics, Niigata University Medical and Dental Hospital, Niigata, Japan

    Takashi Ishikawa

  4. Department of Digestive and General Surgery, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minami-Uonuma, Niigata, Japan

    Shin-ichi Kosugi

  5. Department of Surgery, Kashiwazaki Medical Center, Kashiwazaki, Niigata, Japan

    Kyo Ueki

  6. Department of Surgery, Nagaoka Red Cross Hospital, Nagaoka, Niigata, Japan

    Tetsuya Naito

  7. Department of Surgical Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan

    Seiichi Hirota

Authors
  1. Tatsuo Kanda
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  2. Takashi Ishikawa
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  3. Shin-ichi Kosugi
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  4. Kyo Ueki
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  5. Tetsuya Naito
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  6. Toshifumi Wakai
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  7. Seiichi Hirota
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Corresponding author

Correspondence to Tatsuo Kanda.

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Conflict of interest

Seiichi Hirota received lecture fees from Novartis. Tatsuo Kanda, Takashi Ishikawa, Shin-ichi Kosugi, Kyo Ueki, Tetsuya Naito, and Toshifumi Wakai have no conflict of interest.

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Kanda, T., Ishikawa, T., Kosugi, Si. et al. Prognostic factors after imatinib secondary resistance: survival analysis in patients with unresectable and metastatic gastrointestinal stromal tumors. Int J Clin Oncol 21, 295–301 (2016). https://doi.org/10.1007/s10147-015-0903-7

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  • DOI: https://doi.org/10.1007/s10147-015-0903-7

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