Skip to main content Accessibility help
  • Print publication year: 2015
  • Online publication date: November 2015

18 - Management of gastrointestinal stromal tumours



Gastrointestinal stromal tumours (GISTs) are rare mesenchymal tumours that can occur anywhere in the gastrointestinal tract, although most commonly in the stomach or small intestine. GISTs have been difficult to diagnose in the past, which, along with their rarity, means their true incidence is hard to determine and probably underestimated. Until relatively recently, there were very few treatment options for patients with GIST and the prognosis for patients with advanced disease was extremely poor. However, this has changed markedly over the past decade with increases in understanding of molecular pathology. These developments have made diagnosis more accurate and have led to effective treatments with molecular-targeted therapies. As research continues, it is likely that more therapies will become available for this condition.

GISTs probably originate from the interstitial cells of Cajal (ICC) – pacemaker cells that control gut motility. The tumours are diagnosed by a combination of morphological features and immunohistochemistry staining. Oncogenesis appears to be related to dysregulation of the proto-oncogenes KIT or PDGFRA, which encode growth factor receptor tyrosine kinases. Most tumours harbour an activating mutation in KIT or less commonly PDGFRA.

Types of tumour

There are a number of gastrointestinal mesenchymal (non-epithelial) tumours which include smooth muscle tumours, schwannomas and intra-abdominal fibromatosis. GIST is the most common of the gastrointestinal soft tissue tumours.

Incidence and epidemiology

The annual incidence in the UK is between 10 and 20 per million; it is difficult to obtain an accurate count because of the cancer's rarity and because of previous difficulty in diagnosis. There are 600–1200 new cases reported per year in England and 30–60 new cases per year in Wales.

GISTs have become more reliably diagnosable since KIT expression has become detectable by immunohistochemistry, which may have changed the perceived incidence. GIST is rare before age 40; the median age at diagnosis is 60–65 years. It is rarely seen in patients < 20 years and in these cases is usually associated with a syndrome. Most studies show an equal gender distribution of the disease.

GISTs represent 1% or fewer of all primary tumours of the GI tract and 5% of soft tissue sarcomas (Duffaud and Blay, 2003).

Benjamin, R. S., Ranking, C., Fletcher, C., et al. (2003). Phase III dose-randomized study of imatinib mesylate (STI571) for GIST: intergroup S0033 early results. Proc. Am. Soc. Clin. Oncol., Abstr. 3271.
Blanke, C. D., Demetri, G. D., 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 tumours expressing KIT.J. Clin. Oncol., 26, 620–625.
Bümming, P., Andersson, J., Meis-Kindblom, J. M., et al. (2003). Neoadjuvant, adjuvant and palliative treatment of gastrointestinal stromal tumours (GIST) with imatinib: a centre-based study of 17 patients. Br. J. Cancer, 89, 460–464.
Casali, P. G., Cesne, A. L., Velasco, A. P., et al. (2013). Imatinib failure-free survival (IFS) in patients with localized gastrointestinal stromal tumours (GIST) treated with adjuvant imatinib (IM): the EORTC/AGITG/FSG/GEIS/ISG randomized controlled phase 3 trial. J. Clin. Oncol. 31 (suppl; abstract 10500).
Corless, C. L., Fletcher, J. A. and Heinrich, M. C. (2004). Biology of gastrointestinal stromal tumors. J. Clin. Oncol., 22, 3813–3825.
DeMatteo, R. P., Ballman, K. V., Antonescu, C. R., et al. (2009). Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumor: a randomised, double blind, placebo-controlled trial. Lancet, 373, 1097–1010.
Demetri, G. D., von Mehren, M., Blanke, C. D., et al. (2002). Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N. Engl. J. Med., 347, 472–480.
Demetri, G. D., van Oosterom, A. T., Garrett, C. R., 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.
Demetri, G. D., Reichardt, P., Kang, Y. K., 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.
Duffaud, F. and Blay, J.-Y. (2003). Gastrointestinal stromal tumors: biology and treatment. Oncology, 65, 187–97.
Eisenberg, B. L. and Judson, I. (2004). Surgery and imatinib in the management of GIST: emerging approaches to adjuvant and neoadjuvant therapy. Ann. Surg. Oncol., 11, 465–475.
Eisenberg, B. L., Harris, J., Blanke, C. D., et al. (2009). 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., 99, 42–47.
Fletcher, C. D., Berman, J. J., Corless, C., et al. (2002). Diagnosis of gastrointestinal stromal tumours. A consensus approach. Hum. Pathol., 33, 459–465.
Gastrointestinal Stromal Tumour Meta-Analysis Group (MetaGIST). (2010). Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumours: a meta-analysis of 1,640 patients.J. Clin. Oncol., 28, 1247–1253.
Heinrich, M. C., Corless, C. L., Demitri, G. D., et al. (2003). Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J. Clin. Oncol., 21, 4342–4349.
Joensuu, H., Eriksson, M., Sundby Hall., K., et al. (2012a). One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. J. Am. Med. Assoc., 307, 1265–1272.
Joensuu, H., Vehtari, A., Riihimaki, J., et al. (2012b). Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts. Lancet Oncol., 13, 265–274.
Joensuu, H., Hohenberger, P. and Corless, C. L. (2013). Gastrointestinal stromal tumour. Lancet, 382, 973–983.
Knowlton, C. A., Brady, L. W. and Heintzelman, R. C. (2011). Radiotherapy in the treatment of gastrointestinal stromal tumor. Rare Tumors, 3, e35.
Meza, J. M. and Wong, S. L. (2011). Surgical options in advanced/metastatic gastrointestinal stromal tumours. Curr. Probl. Cancer, 35, 283–293.
Miettinen, M. and Lasota, J. (2006). Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin. Diagn. Pathol., 23, 70–83.
NICE. (2004). Technology Appraisal 86. Imatinib for the Treatment of Unresectable and/or Metastatic Gastrointestinal Stromal Tumours. London: NICE.
NICE. (2006). Guidance on Cancer Services. Improving Outcomes for People with Sarcoma. The Manual. London: NICE.
NICE. (2009). Sunitinib for the Treatment of Gastrointestinal Stromal Tumours. NICE Technology Appraisal Guidance 179. London: NICE.
NICE. (2014). Imatinib for the Adjuvant Treatment of Gastrointestinal Stromal Tumours (review of NICE technology appraisal guidance 196). NICE Technology Appraisal Guidance 326.London: NICE.
Novelli, M., Rossi, S., Rodriguez-Justo, M., et al. (2010). DOG1 and CD117 are the antibodies of choice in the diagnosis of gastrointestinal stromal tumors. Histopathology, 57, 259–270.
Silberman, S. and Joensuu, H. (2002). Overview of issues related to Imatinib therapy of advanced gastrointestinal stromal tumors: a discussion amongst experts. Eur. J. Cancer, 38(Suppl. 5), S66–69.
Stroobants, S., Goeminne, J., Seegers, M., et al. (2003). 18FDG-Positron Emission Tomography for the early prediction of response in advanced soft tissue sarcoma treated with imatinib mesylate. Eur. J. Cancer, 39, 2012–2020.
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).
van Oosterom, A. T., Judson, I., Verweij, J., et al. (2001). Safety and efficacy of Imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet, 358, 1421–1423.
van Oosterom, A. T., Judson, I., Verweij, J., et al. (2002). Update of phase I study of imatinib (STI571) in advanced soft tissue sarcomas and gastrointestinal stromal tumors: a report of the EORTC Soft Tissue and Bone Sarcoma Group. Eur. J. Cancer, 38 (Suppl. 5), S83–87.
Verweij, J., Casali, P. G., Zalcberg, J., et al. (2003a). Early efficacy comparison of two doses of Imatinib for the treatment of advanced gastrointestinal stromal tumors (GIST): interim results of a randomised phase III trial from the EORTC-STBSG, ISG and AGITG.Proc. Am. Soc. Clin. Oncol., Abstr. 3272.
Verweij, J., van Oosterom, A., Blay, J. Y., etal. (2003b). Imatinib mesylate (STI-571 Glivec, Gleevec) is an active agent for gastrointestinal stromal tumours but does not yield responses in other soft tissue sarcomas that are unselected for molecular target: results form an EORTC Soft Tissue and Bone Sarcoma Group phase II study. Eur. J. Cancer, 39, 2006–2011.
Verweij, J., Casali, P. G., Zalcberg, J., et al. (2004). Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomized trial. Lancet, 364, 1127–1134.
Von Mehren, M., Blanke, C., Joensuu, H., et al. (2002). High incidence of durable responses induced by Imatinib mesylate (Gleevec) in patients with resectable and metastatic gastrointestinal stromal tumors (GISTs). Proc. Am. Soc. Clin. Oncol., Abstr. 1608.
Zalcberg, J., Verweij, J., Casali, P. G., et al. (2004). Outcome of patients with advanced gastro-intestinal stromal tumours (GIST) crossing over to a daily imatinib dose of 800 mg (HD) after progression on 400 mg – an international, intergroup study of the EORTC, ISG and AGITG.Proc. Am. Soc. Clin. Oncol., Abstr. 9004.