Skip to main content

Advertisement

Log in

Liver resection for metastatic GIST tumor improves survival in the era of tyrosine kinase inhibitors: a systematic review and meta-analysis

  • Systematic Review
  • Published:
Langenbeck's Archives of Surgery Aims and scope Submit manuscript

Abstract

Introduction

Survival for gastrointestinal stromal tumor (GIST) has been increasing over the years after the introduction of tyrosine kinase inhibitors. However, the role of metastasectomy for GIST is still controversial. Patients are currently treated with imatinib or sunitinib in case of imatinib failures as optimal medical therapy for metastatic GIST.

Methods

The Pubmed, EMBASE, and Cochrane Library were systematically searched. Overall survival following liver resection ± tyrosine kinase inhibitor treatment for metastatic GIST was compared to treatment with tyrosine kinase inhibitors alone.

Results

Eleven studies including both randomized control trials and retrospective cohort studies were included in the final analysis with a total of 988 patients. Seven studies encompassed data on 556 patients with isolated liver metastases (219 surgery ± drug groups and 337 drug-only groups) were included. Overall survival was significantly improved in patients undergoing liver resection ± drug therapy in comparison to drug therapy alone. [HR (95%CI) = 2.10 (1.58, 2.79); p<0.00001]. Subgroup analysis showed that patients also had improved progression free survival based on 4 studies. [HR (95%CI) = 1.92 (1.43, 2.56); p<0.00001]. In case of concurrent liver and peritoneal metastases, patients showed improved overall survival with aggressive surgical approaches based on 10 studies. [HR (95%CI) = 1.90 (1.56, 2.31); p<0.00001].

Conclusion

This meta-analysis found that liver resection for patients with metastatic GIST regardless of peritoneal metastases improved progression free and overall survival in conjunction with tyrosine kinase inhibitors as compared with medical therapy alone. Furthermore, liver resections did not have any immediate detrimental impact on survival in the group of patients selected.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

Published data only. N/A.

References

  1. Mazur MT, Clark HB (1983) Gastric stromal tumors. Reappraisal of histogenesis. Am J Surg Pathol 7(6):507–519

    Article  CAS  PubMed  Google Scholar 

  2. Miettinen M, Virolainen M, Maarit SR (1995) Gastrointestinal stromal tumors—value of CD34 antigen in their identification and separation from true leiomyomas and schwannomas. Am J Surg Pathol 19(2):207–216

    Article  CAS  PubMed  Google Scholar 

  3. Hirota S, Isozaki K, Moriyama Y et al (1998) Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Sci 279(5350):577–580

    Article  CAS  Google Scholar 

  4. Kindblom LG, Remotti HE, Aldenborg F et al (1998) Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol 152(5):1259–1269

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Corless CL, Barnett CM, Heinrich MC (2011) Gastrointestinal stromal tumours: origin and molecular oncology. Nat Rev Cancer 11(12):865–878

    Article  CAS  PubMed  Google Scholar 

  6. Nishida T, Hirota S, Taniguchi M et al (1998) Familial gastrointestinal stromal tumours with germline mutation of the KIT gene. Nat Genet 19:323–324

    Article  CAS  PubMed  Google Scholar 

  7. Nakahara M, Isozaki K, Hirota S et al (1998) A novel gain-of-function mutation of c-kit gene in gastrointestinal stromal tumors. Gastroenterol 115(5):1090–1095

    Article  CAS  Google Scholar 

  8. Rubin BP, Singer S, Tsao C et al (2001) KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res 61(22):8118–8121

    CAS  PubMed  Google Scholar 

  9. Heinrich MC, Corless CL, Duensing A et al (2003) PDGFRA activating mutations in gastrointestinal stromal tumors. Sci 299(5607):708–710

    Article  CAS  Google Scholar 

  10. Corless CL (2014) Gastrintestinal stromal tumors: what do we know now? Mod Pathol 27:S1–S16. https://doi.org/10.1038/modpathol.2013.173

    Article  CAS  PubMed  Google Scholar 

  11. Emory TS, Sobin LH, Lukes L et al (1999) Prognosis of gastrointestinal smooth-muscle (stromal) tumors: dependence on anatomic site. Am J Surg Pathol 23(1):82–87

    Article  CAS  PubMed  Google Scholar 

  12. DeMatteo RP, Lewis JJ, Leung D et al (2000) Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg 231(1):51–58

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Joensuu H, Roberts PJ, Sarlomo-Rikala M et al (2001) Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med 344(14):1052–1056

    Article  CAS  PubMed  Google Scholar 

  14. Balachandran VP, Dematteo RP (2013) Targeted therapy for cancer: the gastrointestinal stromal tumor model. Surg Oncol Clin N Am 22(4):805–821

    Article  PubMed  PubMed Central  Google Scholar 

  15. Blay JY, Le Cesne A, Ray-Coquard I et al (2007) Prospective multicentric randomized phase III study of imatinib in patients with advanced gastrointestinal stromal tumors comparing interruption versus continuation of treatment beyond 1 year: the French Sarcoma Group. J Clin Oncol 25(9):1107–1113

    Article  CAS  PubMed  Google Scholar 

  16. Demetri GD, von Mehren M, Blanke CD et al (2002) Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347(7):472–480

    Article  CAS  PubMed  Google Scholar 

  17. Le Cesne A, Ray-Coquard I, Bui BN et al (2010) Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment: an open-label multicentre randomised phase 3 trial. Lancet Oncol 11(10):942–949

    Article  PubMed  Google Scholar 

  18. 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(9544):1329–1338

    Article  CAS  PubMed  Google Scholar 

  19. Gronchi A, Fiore M, Miselli F et al (2007) Surgery of residual disease following molecular-targeted therapy with imatinib mesylate in advanced/metastatic GIST. Ann Surg 245(3):341–346

    Article  PubMed  PubMed Central  Google Scholar 

  20. 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(3):347–352

    Article  PubMed  PubMed Central  Google Scholar 

  21. Higgins JP, Green S (2011) Cochrane handbook for systematic reviews of interventions, vol 4. John Wiley & Sons, England

    Google Scholar 

  22. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2010) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 8:336–341

    Article  PubMed  Google Scholar 

  23. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D et al (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA 283:2008–2012

    Article  CAS  PubMed  Google Scholar 

  24. Ducimetiere F, Lurkin A, Ranchere-Vince D et al (2011) Incidence of sarcoma histotypes and molecular subtypes in a prospective epidemiological study with central pathology review and molecular testing. PLoS One 6(8):e20294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Xia L, Zhang MM, Ji L et al (2010) Resection combined with imatinib therapy for liver metastases of gastrointestinal stromal tumors. Surg Today 40(10):936–942

    Article  CAS  PubMed  Google Scholar 

  26. Du CY, Zhou Y, Song C et al (2014) Is there a role of surgery in patients with recurrent or metastatic gastrointestinal stromal tumours responding to imatinib: a prospective randomised trial in China. Eur J Cancer 50(10):1772–1778

    Article  PubMed  Google Scholar 

  27. Kanda T, Masuzawa T, Hirai T, Ikawa O, Takagane A, Hata Y, Ojima H, Sodeyama H, Mochizuki I, Ishikawa T, Kagimura T, Nishida T (2017) Surgery and imatinib therapy for liver oligometastasis of GIST: a study of Japanese study group on GIST. Jpn J Clin Oncol 47:369–372

    PubMed  Google Scholar 

  28. Shi YN, Li Y, Wang LP et al (2017) Gastrointestinal stromal tumor (GIST) with liver metastases: an 18-year experience from the GIST cooperation group in North China. Med 96(46):e8240

    Article  Google Scholar 

  29. Sato S, Tsujinaka T, Masuzawa T et al (2016) Role of metastasectomy for recurrent/metastatic gastrointestinal stromal tumors based on an analysis of the Kinki Gist Registry. Surg Today 47(1):58–64

    Article  PubMed  Google Scholar 

  30. Qiu HB, Zhou ZG, Feng XY, Liu XC, Guo J, Ma MZ, Chen YB, Sun XW, Zhou ZW (2018) Advanced gastrointestinal stromal tumor patients benefit from palliative surgery after tyrosine kinase inhibitors therapy. Med 97(2):e9097

    Article  Google Scholar 

  31. Xiao B, Peng J, Tang J et al (2018) Liver surgery prolongs the survival of patients with gastrointestinal stromal tumor liver metastasis: a retrospective study from a single center. Cancer Manag Res 10:6121–6127

    Article  PubMed  PubMed Central  Google Scholar 

  32. Chang SC, Liao CH, Wang SY et al (2015) Feasibility and timing of cytoreduction surgery in advanced (metastatic or recurrent) gastrointestinal stromal tumors during the era of Imatinib. Med 94(24):e1014

    Article  CAS  Google Scholar 

  33. Zaydfudim V, Okuno SH, Que FG et al (2012) Role of operative therapy in treatment of metastatic gastrointestinal stromal tumors. J Surg Res 177(2):248–254

    Article  PubMed  Google Scholar 

  34. Sutton TL, Walker BS, Billingsley KG et al (2022) Hepatic metastases in gastrointestinal stromal tumors: oncologic outcomes with curative-intent hepatectomy, resection of treatment-resistant disease, and tyrosine kinase inhibitor therapy alone. HPB 24:986–993

    Article  PubMed  Google Scholar 

  35. Xue A, Gao X, He Y et al (2022) Role of surgery in the management of liver metastases from gastrointestinal stromal tumors. Front Oncol 12:903487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Fletcher CD, Berman JJ, Corless C et al (2002) Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol 33(5):459–465

    Article  PubMed  Google Scholar 

  37. Raut CP, Ashley SW (2008) How I do it: surgical management of gastrointestinal stromal tumors. J Gastrointest Surg 12(9):1592–1599

    Article  PubMed  Google Scholar 

  38. Blanke CD, Eisenberg BL, Heinrich MC (2001) Gastrointestinal stromal tumors. Curr Treat Options in Oncol 2(6):485–491

    Article  CAS  Google Scholar 

  39. Van Glabbeke M, Verweij J, Casali PG, Le Cesne A, Hohenberger P, Ray-Coquard I, Schlemmer M, van Oosterom AT, Goldstein D, Sciot R, Hogendoorn PC, Brown M, Bertulli R, Judson IR (2005) Initial and late resistance to imatinib in advanced gastrointestinal stromal tumors are predicted by different prognostic factors: a European Organisation for Research and Treatment of Cancer-Italian Sarcoma Group-Australasian Gastrointestinal Trials Group study. J Clin Oncol 23(24):5795–5804

    Article  PubMed  Google Scholar 

  40. Bonvalot S, Eldweny H, Pechoux CL et al (2006) Impact of surgery on advanced gastrointestinal stromal tumors (GIST) in the imatinib era. Ann Surg Oncol 13(12):1596–1603

    Article  CAS  PubMed  Google Scholar 

  41. 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(15):2325–2331

    Article  CAS  PubMed  Google Scholar 

  42. Rutkowski P, Nowecki Z, Nyckowski P et al (2006) Surgical treatment of patients with initially inoperable and/or metastatic gastrointestinal stromal tumors (GIST) during therapy with imatinib mesylate. J Surg Oncol 93(4):304–311

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  44. Von Mehren M, Joensuu H (2018) Gastrointestinal stromal tumors. J Clin Oncol 36(2):136–143

    Article  Google Scholar 

  45. Antonescu CR (2008) Targeted therapy of cancer: new roles for pathologists in identifying GISTs and other sarcomas. Mod Pathol 21(Suppl 2):S31–S36

    Article  CAS  PubMed  Google Scholar 

  46. Gold JS, Dematteo RP (2006) Combined surgical and molecular therapy: the gastrointestinal stromal tumor model. Ann Surg 244(2):176–184

    Article  PubMed  PubMed Central  Google Scholar 

  47. Verweij J (2012) Adjuvant treatment of gastrointestinal stromal tumor: the proof, the pro, and the practice. Am Soc Clin Oncol Educ Book 32:659–662

    Article  Google Scholar 

  48. Bümming P, Andersson J, Meis-Kindblom JM, Klingenstierna H, Engström K, Stierner U, Wängberg B, Jansson S, Ahlman H, Kindblom LG, Nilsson B (2003) Neoadjuvant, adjuvant and palliative treatment of gastrointestinal stromal tumours (GIST) with imatinib: a centre-based study of 17 patients. Br J Cancer 89(3):460–464

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

AR and XD did the data analysis and the systematic review. AR, SM, MD, BZ, KG, KM, and KG did the literature search and review. AR, SM, KA, MK, SM, and XD did the manuscript preparation and writing. AR, MD, BZ, KG, KM, KG, and XD did the design and concept for the project.

Corresponding author

Correspondence to Xiang Da Dong.

Ethics declarations

Consent for publication

Systemic review of published data. N/A

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

ESM 1

(DOCX 36 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rahimi-Ardabily, A., Murdande, S., Dong, M. et al. Liver resection for metastatic GIST tumor improves survival in the era of tyrosine kinase inhibitors: a systematic review and meta-analysis. Langenbecks Arch Surg 408, 373 (2023). https://doi.org/10.1007/s00423-023-03052-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00423-023-03052-7

Keywords

Navigation