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Gastrointestinal Stromal Tumours

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Surgical Oncology Manual

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Abstract

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. These tumours result from activating mutations in the KIT (CD117) proto-oncogene or platelet-derived growth factor receptor alpha gene (PDGFRAa). They can arise in any location throughout the gastrointestinal tract but are found primarily in the stomach (60 %) and small intestine (30 %). Surgical resection is the cornerstone of management for localized, non-metastatic GISTs and remains the only curative primary treatment. Despite undergoing complete resection, however, at least 50 % of patients develop tumour recurrence within 18–24 months with an associated 5-year overall survival rate of ~50 %. The development of the tyrosine kinase inhibitor Imatinib mesylate has led to improvements in recurrence-free survival and overall survival in select patients following surgical resection.

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References

  1. Connolly E, Gaffney E, Reynolds J. Gastrointestinal stromal tumors. Br J Surg. 2003;90:1178–86.

    Article  CAS  PubMed  Google Scholar 

  2. Blackstein ME, Blay JY, Corless C, et al. Gastrointestinal stromal tumours: consensus statement on diagnosis and treatment. Can J Gastroenterol. 2006;20:157–63.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Kitamura Y, Hirota S, Nishida T. Gastrointestinal stromal tumors (GIST): a model for molecule based diagnosis and treatment of solid tumors. Cancer Sci. 2003;94:315–20.

    Article  CAS  PubMed  Google Scholar 

  4. Hirota S, Isozaki K, Moriyama Y, et al. Gain of function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998;279:577–80.

    Article  CAS  PubMed  Google Scholar 

  5. Heinrich MC, Corless CL, Duensing A, et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 2003;299:708–10.

    Article  CAS  PubMed  Google Scholar 

  6. Blay JY, von Mehren M, Blackstein ME. Perspective on updated treatment guidelines for patients with gastrointestinal stromal tumors. Cancer. 2010;116:5126–37.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Miettinen M, Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol. 2006;23:70–83.

    Article  PubMed  Google Scholar 

  8. Miettinen M, Sarlomo-Rikala M, Lasota J. Gastrointestinal stromal tumours. Ann Chir Gynaecol. 1998;87:278–81.

    CAS  PubMed  Google Scholar 

  9. Hasegawa T, Matsuno Y, Shimoda T, Hirohashi S. Gastrointestinal stromal tumor: Consistent CD117 immunostaining for diagnosis, and prognostic classification based on tumor size and MIB-1 grade. Hum Pathol. 2002;44:669–76.

    Article  Google Scholar 

  10. Kindblom LG, Remotti HE, Aldenborg F, et al. Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol. 1998;152:1259–69.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Tran T, Davila JA, El Serag HB. The epidemiology of malignant gastrointestinal stromal tumors: an analysis of 1458 cases from 1992 to 2000. Am J Gastroenterol. 2005;100:162–8.

    Article  PubMed  Google Scholar 

  12. Nilsson B, Bumming P, Meis-Kindblom JM, et al. Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the pre-imatinib mesylate era – a population-based study in western Sweden. Cancer. 2005;103(4):821–9.

    Article  PubMed  Google Scholar 

  13. Woodall C, Brock G, Fan J, et al. An evaluation of 2537 gastrointestinal stromal tumors for a proposed clinical staging system. Arch Surg. 2009;144(7):670–8.

    Article  PubMed  Google Scholar 

  14. vonMehren M, Randal RL, et al. National Comprehensive Cancer Network (NCCN) Clinical practice guidelines in oncology: soft tissue sarcoma. Version 2.2014.

    Google Scholar 

  15. DeMatteo RP, Lewis JJ, et al. Two hundred gastrointestinal stromal tumours: recurrence patterns and prognostic factors for survival. Ann Surg. 2000;231:51–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Ng EH, Pollock RE, Munsell MF, et al. Prognostic factors influencing survival in gastrointestinal leiomyosarcomas. Implications for surgical management and staging. Ann Surg. 1992;215:68–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. DeMatteo RP, Ballman KV, Antonescu CR, et al. Adjuvant imatinib mesylate after resection of localized, primary gastrointestinal stromal tumour: a randomized, double blind, placebo-controlled trial. Lancet. 2009;373:1097–104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gold JS, DeMatteo RP. Combined surgical and molecular therapy: the gastrointestinal stromal tumor model. Ann Surg. 2006;244:176–84.

    Article  PubMed  PubMed Central  Google Scholar 

  19. DeMatteo RP, Antonescu CR, Chadaram V, et al. Adjuvant imatinib mesylate in patients with primary high risk gastrointestinal stromal tumor (GIST) following complete resection: Safety results from the U.S. Intergroup Phase II trial ACOSOG Z9000. 2005 ASCO Annual Meeting Proceedings. J Clin Oncol. 2005;23:16S (abstr 9009).

    Google Scholar 

  20. Nilsson B, Sjölund K, Kindblom LG, et al. Adjuvant imatinib treatment improves recurrence-free survival in patients with high-risk gastrointestinal stromal tumours (GIST). Br J Cancer. 2007;96(11):1656–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Joensuu H, Eriksson M, Hatrmann J, et al. Twelve versus 36 months of adjuvant imatinib (IM) as treatment of operable GIST with a high risk of recurrence: Final results of a randomized trial (SSGXVIII/AIO) J Clin Oncol. 2001;29(Suppl) Abstr LBA1.

    Google Scholar 

  22. Casali PG, Blay JY. Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21(Suppl):v98–102.

    Article  PubMed  Google Scholar 

  23. Choi H, Charnsangavej C, de Castro FS, et al. CT evaluation of the response of gastrointestinal stromal tumors after imatinib mesylate treatment: a quantitative analysis correlated with FDG PET findings. Am J Roentgenol. 2004;183:1619–28.

    Article  Google Scholar 

  24. Choi H. Response evaluation of gastrointestinal stromal tumours. Oncologist. 2008;13 Suppl 2:4–7.

    Article  PubMed  Google Scholar 

  25. Fletcher CD, Berman JJ, Corless C, et al. Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol. 2002;33(5):459–65.

    Article  PubMed  Google Scholar 

  26. Joensuu H. Risk stratification of patients diagnosed with gastrointestinal stromal tumor. Hum Pathol. 2008;39:1411–9.

    Article  PubMed  Google Scholar 

  27. Gold JS, Gonen M, Gutierrez A, et al. Development and validation of a prognostic nomogram for recurrence-free survival after complete surgical resection of localized primary gastrointestinal stromal tumour: a retrospective analysis. Lancet Oncol. 2009;10:1045–52.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Joensuu H, Vehtari A, Riihimaki J, et al. Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts. Lancet Oncol. 2012;13:265–74.

    Article  PubMed  Google Scholar 

  29. Lasota J, Miettinen M. Clinical significance of oncogenic KIT and PDGFRA mutations in gastrointestinal stromal tumours. Histopathology. 2008;53:245–66.

    Article  CAS  PubMed  Google Scholar 

  30. Mussi C, Ronelllenfitsch U, Jakob J, et al. Post-imatinib surgery in advanced/metastatic GIST: is it worthwhile in all patients? Ann Oncol. 2010;21:403–8.

    Article  CAS  PubMed  Google Scholar 

  31. 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 

  32. Bednarski BK, Araujo DM, Yi M, et al. Analysis of prognostic factors impacting oncologic outcomes after neoadjuvant tyrosine kinase inhibitor therapy for gastrointestinal stromal tumors. Ann Surg Oncol. 2014;21(8):2499–505.

    Article  PubMed  PubMed Central  Google Scholar 

  33. 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 

  34. Crosby JA, Catton CN, Davis A, et al. Malignant gastrointestinal stromal tumors of the small intestine: a review of 50 cases from a prospective database. Ann Surg Oncol. 2001;8:50–9.

    Article  CAS  PubMed  Google Scholar 

  35. Demetri GD, van Oosteron AT, Garrett CR, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomized control trial. Lancet. 2006;368:1329–38.

    Article  CAS  PubMed  Google Scholar 

  36. Bauer S, Hartmann JT, Lang H, et al. Imatinib may enable complete resection in previously unresectable or metastatic GIST. Proc Am Soc Clin Oncol. 2004;23:819 (Abstr 9023).

    Google Scholar 

  37. Eisenberg BL, Harris J, Blanke CD, et al. Phase II trial of neoadjuvant/adjuvant Imatinib mesylate (IM) for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumor (GIST): early results of RTOG 0132/ACRIN 6665. J Surg Oncol. 2009;99:42–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. McAuliffe JC, Hunt KK, Lazar AJ, et al. A randomized, phase II study of preoperative plus postoperative imatinib in GIST: evidence of rapid radiographic response and temporal induction of tumor cell apoptosis. Ann Surg Oncol. 2009;16:910–9.

    Article  PubMed  Google Scholar 

  39. Sjölund K, Andersson A, Nilsson E, et al. Downsizing treatment with tyrosine kinase inhibitors in patients with advanced gastrointestinal stromal tumors improves resectability. World J Surg. 2010;34(9):2090–7.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Blesius A, Cassier PA, Bertucci F, et al. Neoadjuvant imatinib in patients with locally advanced non-metastatic GIST in the prospective BFR14 trial. BMC Cancer. 2011;11:72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  42. Van Oosterom AT, Judson I, Verweij J, et al. Safety and efficacy of imatinib (ST1571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet. 2001;358:121–1423.

    Article  Google Scholar 

  43. Demetri GD, vonMehren M, von Mehren M, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. NEJM. 2002;347:472–80.

    Article  CAS  PubMed  Google Scholar 

  44. Heinrich MC, Corless CL, Demetri GD, et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol. 2003;21:4342–9.

    Article  CAS  PubMed  Google Scholar 

  45. Verweij J, Casali PG, Zalcberg J, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomized trial. Lancet. 2004;364:1127–34.

    Article  CAS  PubMed  Google Scholar 

  46. George S, Wang Q, Heinrich MC, et al. Efficacy and safety of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of Imatinib and sunitinib: a multicenter phase II trial. J Clin Oncol. 2012;30(19):2401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Fellow, General Surgical Oncology, University of Toronto, Toronto, ON, Canada

    Jennifer Racz M.D., M.B.A., F.R.C.S.C.

  2. Department of Medicine, University of Toronto, Toronto, ON, Canada

    Martin Blackstein MD,PhD,FRCPC,FACP

  3. Department of Surgery, University of Toronto, Toronto, ON, Canada

    Fayez A. Quereshy M.D., M.B.A., F.R.C.S.C.

Authors
  1. Jennifer Racz M.D., M.B.A., F.R.C.S.C.
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  2. Martin Blackstein MD,PhD,FRCPC,FACP
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  3. Fayez A. Quereshy M.D., M.B.A., F.R.C.S.C.
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Corresponding author

Correspondence to Jennifer Racz M.D., M.B.A., F.R.C.S.C. .

Editor information

Editors and Affiliations

  1. Department of Surgery, University of Toronto, Toronto, Ontario, Canada

    Frances C. Wright

  2. Department of Surgery, University of Toronto, Toronto, Ontario, Canada

    Jaime Escallon

  3. Department of Surgical Oncology, National Cancer Institute, Panama City, Panama

    Moises Cukier

  4. General Surgical Oncology, University of Toronto, 1X5, Ontario, Canada

    Melanie E. Tsang

  5. General Surgical Oncology, University of Toronto, Toronto, Ontario, Canada

    Usmaan Hameed

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© 2016 University of Toronto General Surgery Oncology Program

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Racz, J., Blackstein, M., Quereshy, F.A. (2016). Gastrointestinal Stromal Tumours. In: Wright, F., Escallon, J., Cukier, M., Tsang, M., Hameed, U. (eds) Surgical Oncology Manual. Springer, Cham. https://doi.org/10.1007/978-3-319-26276-5_11

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  • DOI: https://doi.org/10.1007/978-3-319-26276-5_11

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-26274-1

  • Online ISBN: 978-3-319-26276-5

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