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Resection Combined with TKI Therapy for Resectable Liver Metastases of Gastrointestinal Stromal Tumours: Results from Three National Centres in China

  • Original Article
  • Published:
Journal of Gastrointestinal Surgery

Abstract

Objective

To investigate the differences in the efficacy of hepatic resection combined with tyrosine kinase inhibitor (TKI) therapy versus TKI therapy alone and the timing of the TKI therapy and hepatic resection for resectable liver metastases from gastrointestinal stromal tumours (GISTs).

Methods

This was a retrospective review of 43 patients confirmed to have resectable liver metastases from GISTs who received TKI treatment alone or the therapy model of hepatic resection combined with TKIs and were admitted to one of 3 institutions between January 2006 and December 2017.

Results

For all liver metastases patients, the 1-, 3- and 5-year survival rates were 97.67%, 88.98% and 66.46%, respectively. The median overall survival (OS) was 85 months. Patients who underwent hepatic resection combined with TKI therapy had a significantly better OS and a trend towards improved progression-free survival (PFS) than patients who received TKIs alone (P = 0.001, mOS 102 months versus 51 months; P = 0.077, mPFS 42 months versus 30 months). Hepatic resection combined with TKI therapy was the only prognostic factor for long-term survival in the multivariate analysis (HR = 0.198, 95% CI 0.048–0.813, P = 0.025). Compared with patients who underwent hepatic resection combined with postoperative TKIs only, patients who underwent hepatic resection combined with perioperative TKIs had a significantly better PFS (P = 0.032, mPFS 29 months versus 19 months) but did not have a significantly better OS (P = 0.662, mOS 92 months versus 102 months). Resection combined with perioperative TKI therapy was the only prognostic factor for PFS in the multivariate analysis (HR = 0.295, 95% CI 0.101–0.862, P = 0.026).

Conclusions

For patients with resectable liver metastases, hepatic resection combined with TKI therapy was more beneficial in terms of improving prognosis than TKIs alone. In terms of the timing of TKI therapy and hepatic resection, resection combined with perioperative TKIs may prolong PFS more than resection combined with postoperative TKIs only.

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Abbreviations

GISTs:

Gastrointestinal stromal tumours

TKIs:

Tyrosine kinase inhibitors

RECIST:

Response Evaluation Criteria in Solid Tumours

OS:

Overall survival

PFS:

Progression-free survival

IQR:

Interquartile range

CR:

Complete response

PR:

Partial response

SD:

Stable disease

PD:

Progressive disease

References

  1. Raut CP, Morgan JA, Ashley SW. Current issues in gastrointestinal stromal tumors: incidence, molecular biology, and contemporary treatment of localized and advanced disease. Current opinion in gastroenterology. 2007;23(2):149–58. https://doi.org/10.1097/MOG.0b013e32802086d0.

    Article  PubMed  Google Scholar 

  2. DeMatteo RP, Lewis JJ, Leung D, Mudan SS, Woodruff JM, Brennan MF. Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Annals of surgery. 2000;231(1):51–8.

    Article  CAS  Google Scholar 

  3. Unalp HR, Derici H, Kamer E, Bozdag AD, Tarcan E, Onal MA. Gastrointestinal stromal tumours: outcomes of surgical management and analysis of prognostic variables. Canadian journal of surgery Journal canadien de chirurgie. 2009;52(1):31–8.

    PubMed  PubMed Central  Google Scholar 

  4. Woodall CE, 3rd, Brock GN, Fan J, Byam JA, Scoggins CR, McMasters KM, Martin RC, 2nd. An evaluation of 2537 gastrointestinal stromal tumors for a proposed clinical staging system. Archives of surgery (Chicago, Ill : 1960). 2009;144(7):670–8. https://doi.org/10.1001/archsurg.2009.108.

    Article  Google Scholar 

  5. Zhang L, Smyrk TC, Young WF, Jr., Stratakis CA, Carney JA. Gastric stromal tumors in Carney triad are different clinically, pathologically, and behaviorally from sporadic gastric gastrointestinal stromal tumors: findings in 104 cases. The American journal of surgical pathology. 2010;34(1):53–64. https://doi.org/10.1097/PAS.0b013e3181c20f4f.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Joensuu H. Gastrointestinal stromal tumor (GIST). Annals of oncology : official journal of the European Society for Medical Oncology. 2006;17 Suppl 10:x280–6. https://doi.org/10.1093/annonc/mdl274.

    Article  Google Scholar 

  7. Chaudhry UI, DeMatteo RP. Advances in the surgical management of gastrointestinal stromal tumor. Advances in surgery. 2011;45:197–209.

    Article  Google Scholar 

  8. Park SJ, Ryu MH, Ryoo BY, Park YS, Sohn BS, Kim HJ, Kim CW, Kim KH, Yu CS, Yook JH, Kim BS, Kang YK. The role of surgical resection following imatinib treatment in patients with recurrent or metastatic gastrointestinal stromal tumors: results of propensity score analyses. Annals of surgical oncology. 2014;21(13):4211–7. https://doi.org/10.1245/s10434-014-3866-4.

    Article  PubMed  Google Scholar 

  9. Chen LL, Trent JC, Wu EF, Fuller GN, Ramdas L, Zhang W, Raymond AK, Prieto VG, Oyedeji CO, Hunt KK, Pollock RE, Feig BW, Hayes KJ, Choi H, Macapinlac HA, Hittelman W, Velasco MA, Patel S, Burgess MA, Benjamin RS, Frazier ML. A missense mutation in KIT kinase domain 1 correlates with imatinib resistance in gastrointestinal stromal tumors. Cancer research. 2004;64(17):5913–9. https://doi.org/10.1158/0008-5472.can-04-0085.

    Article  CAS  PubMed  Google Scholar 

  10. Antonescu CR, Besmer P, Guo T, Arkun K, Hom G, Koryotowski B, Leversha MA, Jeffrey PD, Desantis D, Singer S, Brennan MF, Maki RG, DeMatteo RP. Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clinical cancer research : an official journal of the American Association for Cancer Research. 2005;11(11):4182–90. https://doi.org/10.1158/1078-0432.ccr-04-2245.

    Article  CAS  Google Scholar 

  11. Xia L, Zhang MM, Ji L, Li X, Wu XT. Resection combined with imatinib therapy for liver metastases of gastrointestinal stromal tumors. Surgery today. 2010;40(10):936–42. https://doi.org/10.1007/s00595-009-4171-x.

    Article  CAS  PubMed  Google Scholar 

  12. Turley RS, Peng PD, Reddy SK, Barbas AS, Geller DA, Marsh JW, Tsung A, Pawlik TM, Clary BM. Hepatic resection for metastatic gastrointestinal stromal tumors in the tyrosine kinase inhibitor era. Cancer. 2012;118(14):3571–8. https://doi.org/10.1002/cncr.26650.

    Article  PubMed  Google Scholar 

  13. Bauer S, Rutkowski P, Hohenberger P, Miceli R, Fumagalli E, Siedlecki JA, Nguyen BP, Kerst M, Fiore M, Nyckowski P, Hoiczyk M, Cats A, Casali PG, Treckmann J, van Coevorden F, Gronchi A. Long-term follow-up of patients with GIST undergoing metastasectomy in the era of imatinib -- analysis of prognostic factors (EORTC-STBSG collaborative study). European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2014;40(4):412–9. https://doi.org/10.1016/j.ejso.2013.12.020.

    Article  CAS  Google Scholar 

  14. Vassos N, Agaimy A, Hohenberger W, Croner RS. Management of liver metastases of gastrointestinal stromal tumors (GIST). Annals of hepatology. 2015;14(4):531–9.

    Article  CAS  Google Scholar 

  15. Seesing MF, Tielen R, van Hillegersberg R, van Coevorden F, de Jong KP, Nagtegaal ID, Verhoef C, de Wilt JH. Resection of liver metastases in patients with gastrointestinal stromal tumors in the imatinib era: A nationwide retrospective study. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2016;42(9):1407–13. https://doi.org/10.1016/j.ejso.2016.02.257. Seesing MF and Tielen R shared co-first authorship.

    Article  CAS  Google Scholar 

  16. Shi YN, Li Y, Wang LP, Wang ZH, Liang XB, Liang H, Zhang L, Li B, Fan LQ, Zhao Q, Ma ZX, Zhao XF, Zhang ZD, Liu Y, Tan BB, Wang D, Wang LL, Hao YJ, Jia N. Gastrointestinal stromal tumor (GIST) with liver metastases: An 18-year experience from the GIST cooperation group in North China. Medicine. 2017;96(46):e8240. https://doi.org/10.1097/md.0000000000008240. Shi YN, Li Y and Wang LP shared co-first authorship.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Blackstein ME, Blay JY, Corless C, Driman DK, Riddell R, Soulieres D, Swallow CJ, Verma S. Gastrointestinal stromal tumours: consensus statement on diagnosis and treatment. Canadian journal of gastroenterology = Journal canadien de gastroenterologie. 2006;20(3):157–63.

    Article  Google Scholar 

  18. B Section of Gastrointestinal Surgery CMA, B Section of Colorectal & Anal Surgery, Chinese Medical Association, A CoCCoCA-C, CCoS Chinese Society of Colon & Rectal Surgeons, Chinese Medical Doctors Association, CIEaPAfMaHC Committee of Colorectal Liver Metastases Treatment. Guideline for the diagnosis and comprehensive treatment of colorectal cancer with liver metastases (2016 edition). Chin J Dig Surg. 2016:15(8):755–67.

    Google Scholar 

  19. Steeghs N, Nortier JW, Gelderblom H. Small molecule tyrosine kinase inhibitors in the treatment of solid tumors: an update of recent developments. Annals of surgical oncology. 2007;14(2):942–53. https://doi.org/10.1245/s10434-006-9227-1.

    Article  PubMed  Google Scholar 

  20. Pantel K, Alix-Panabieres C, Riethdorf S. Cancer micrometastases. Nature reviews Clinical oncology. 2009;6(6):339–51. https://doi.org/10.1038/nrclinonc.2009.44.

    Article  CAS  PubMed  Google Scholar 

  21. Fujitani K. Overview of adjuvant and neoadjuvant therapy for resectable gastric cancer in the East. Dig Surg. 2013;30(2):119–29. https://doi.org/10.1159/000350877.

    Article  CAS  PubMed  Google Scholar 

  22. Suh SW, Choi YS. Predictors of Micrometastases in Patients with Barcelona Clinic Liver Cancer Classification B Hepatocellular Carcinoma. Yonsei medical journal. 2017;58(4):737–42. https://doi.org/10.3349/ymj.2017.58.4.737.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Demetri GD, Baker LH, Beech D, Benjamin R, Casper ES, Conrad EU, 3rd, DeLaney TF, Ettinger DS, Heslin MJ, Hutchinson RJ, Kiel K, Kraybill WG, Letson GD, Neff J, O'Donnell RJ, Paz IB, Pollock RE, Randall RL, Schupak KD, Tyler DS, von Mehren M, Wayne J. Soft tissue sarcoma clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network : JNCCN. 2005;3(2):158–94.

    PubMed  Google Scholar 

  24. Blanke CD, Rankin C, Demetri GD, Ryan CW, von Mehren M, Benjamin RS, Raymond AK, Bramwell VH, Baker LH, Maki RG, Tanaka M, Hecht JR, Heinrich MC, Fletcher CD, Crowley JJ, Borden EC. 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. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2008;26(4):626–32. https://doi.org/10.1200/jco.2007.13.4452.

    Article  CAS  Google Scholar 

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Acknowledgements

Special thanks should go to Dr. Xingjin Wu for critically reading the manuscript and providing her valuable comments.

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Author notes

  1. Cong Li contributed equally to this work.

Authors and Affiliations

  1. Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

    Qichen Chen, Hong Zhao, Jianxiong Wu, Jianjun Zhao, Xinyu Bi, Zhiyu Li, Zhen Huang, Yefan Zhang, Jianqiang Cai & Jianguo Zhou

  2. Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China

    Cong Li

  3. The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Han Yang

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  1. Qichen Chen
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Contributions

All authors have made substantial contributions to the conception of the work or the acquisition, analysis or interpretation of the data for this work, drafted or revised the paper and provided final approval of the version to be published. All authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Jianqiang Cai or Jianguo Zhou.

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This study was approved by the Institutional Review Board of the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Sun Yat-sen University Cancer Center and the First Affiliated Hospital of Zhengzhou University. All patients provided written informed consent.

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Chen, Q., Li, C., Yang, H. et al. Resection Combined with TKI Therapy for Resectable Liver Metastases of Gastrointestinal Stromal Tumours: Results from Three National Centres in China. J Gastrointest Surg 24, 1330–1341 (2020). https://doi.org/10.1007/s11605-019-04278-x

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