Early Gastrointestinal Stromal Tumour Resection and Adjuvant Therapy with Imatinib
Early Gastrointestinal Stromal Tumour Resection and Adjuvant Therapy with Imatinib
European Oncological Disease 2006 Issue ll
Published: October 2008
Published: October 2008
Gastrointestinal stromal tumour (GIST) is the most frequent form of gastrointestinal (GI) sarcoma, a lifethreatening disease highly resistant to traditional treatment with chemotherapy and radiation. Currently, it is believed to originate from an intestinal pacemaker cell called the interstitial cell of Cajal.1 Over the past five years GIST has attracted widespread interest because the principal genetic mutation, which gives rise to the condition, has been identified to be the ‘gain-of-function’ mutation in the KIT (mast/stem cell growth factor receptor) proto-oncogene or, to a lesser extent the platelet-derived growth factor receptor-? (PDGFR?) gene. Mutation results in the constitutive activation of the protein tyrosine kinase, KIT, an essential first stage of GIST oncogenesis. In a landmark development in cancer treatment a specific inhibitor of KIT was identified, imatinib mesylate, which has revolutionised the treatment of patients with metastatic disease and is currently being tested as an adjuvant therapy after resection of primary GIST.
Epidemiology of GIST
The mean age at the time of first diagnosis is 63 years,2 with most patients between 40 and 80 years old.3 Men show slightly higher prevalence than woman, supported by the recent US study of 1,458 cases, with 54% and 46% incidence rate respectively.2 The stomach is the most common location for 51% of tumours in Caucasian studies, followed by 36% in the small intestine, 7% in the colon, 5% in the rectum and 1% in the oesophagus.3 More recent Chinese studies estimate an increased presence in the stomach with 72.3% compared with 17% in the small intestine, 4.3% in oesophagus, 4.3% in the omentum and 2.1% in the colon.4 On rare occasions, GIST develops outside of the GI tract in the mesentert, omentum or retroperitoneum. Because of prior diagnostic inconsistencies the precise incidence is unknown. A recent study, using immunohistochemical markers that distinguish GISTs from intestinal leiomyosarcomas of the GI tract, found an incidence of approximately 14.5 cases per million in Sweden, which suggests an annual US incidence of 5,000,5 excluding tumours <1cm discovered incidentally.
Patient Presentation of GIST
GISTs represent a spectrum of tumours and exhibit highly variable behaviour that makes predicting clinical behaviour difficult. Although conclusive studies are absent, the consensus amongst pathologists is that tumour size, mitotic activity and tumour site influence the malignant potential of a GIST. There is a broad range of patient presentation in GIST. Small GISTs (<2cm) are asymptomatic and are often only discovered incidentally during routine investigation for other medical conditions through endoscopy, surgery or abdominal examination. Patients with larger tumours are more likely to present with symptoms (dependent on tumour origin) ranging from haematemesis to anorexia in the case of oesophageal GIST and gastric GIST, respectively. Large tumours may remain undetected and rupture, causing haemorrhage into the GI tract or peritoneum or, on discovery, are likely to have already metastasised to the liver.
References:
1. Kindblom LG, et al., “Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal”, Am J Pathol (1998);152: pp. 1259–1269.
2. Tran T, Davila JA, El-Serag HB, “The epidemiology of malignant gastrointestinal stromal tumors: an analysis of 1,458 cases from 1992 to 2000”, Am J Gastroenterol (2005);100(1): pp. 162–168.
3. DeMatteo RP, et al., “Two hundred gastrointestinal stromal tumours: recurrence patterns and prognostic factors for survival”, Ann Surg (2000);231: pp. 51–58.
4. Chan KH, et al., “Gastrointestinal stromal tumors in a cohort of Chinese patients in Hong Kong”, World J Gastroenteral (2006);12(14): pp. 2223–2228.
5. Nilsson B, et al., “Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era-a population-based study in western Sweden”, Cancer (2005);103(4):821–829.
6. Roberts PJ, Eisenberg B, “Clinical presentation of gastrointestinal stromal tumors and treatment of operable disease”, Eur J Cancer (2002);38(9);Suppl 5: pp. S37–8.
7. Lehnert T, “Gastrointestinal sarcoma (GIST)-a review of surgical management”, Ann Chir Gynecol (1998); 87: pp. 297–305.
8. Joensuu H, et al., “Management of malignant gastrointestinal stromal tumors.”, Lancet Oncol (2002);3: pp. 655-664.
9. Ng EM, et al., “Prognostic factors influencing survival in gastrointestinal Leimyosarcomas. Implications for surgical management and staging”, Ann Surg (1992);215(1): pp. 68–77.
10. Hirota S, et al., “Gain-of-Functions Mutations of c-kit in Human Gastrointestinal Stromal Tumors”, Science (1998);279(5350): pp. 577–580.
11. Rubin BP, et al., “KIT activation is a ubiquitous feature of gastrointestinal stromal tumors”, Cancer Res (2001);61: pp. 8118–21.
12. Singer S, et al., “Prognostic value of KIT mutation type, mitotic activity, and histologic subtype in gastrointestinal stromal tumors”, J Clin Oncol (2002);20: pp. 3898–3905.
13. Druker BJ, et al., “Efficacy and safety of a specific inhibitor of the BCR-ABLt yrosine kinase in chronic myeloid leukemia”, N Engl J Med (2001);344: pp. 1031–1037.
14. Druker BJ, et al., “Activity of a specific inhibitor of the BCR-ABLt yrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome”, N Engl J Med (2001);344: pp. 1038–1042.
15. Joensuu H, et al., “Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor”, New Eng J Med (2001);244(14): pp. 1052–1056.
16. Demetri GD, et al., “Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors”, N Engl J Med (2002);347: pp. 472–480.
17. Hohenberger P, et al., “Tumor resection following imatinib pretreatment in GI stromal tumors”, Proc Am Soc Clin Oncol (2003);22: p. 818.
18. Heinrich MC, et al., “Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor”, Blood (2000);96: pp. 925–932.
2. Tran T, Davila JA, El-Serag HB, “The epidemiology of malignant gastrointestinal stromal tumors: an analysis of 1,458 cases from 1992 to 2000”, Am J Gastroenterol (2005);100(1): pp. 162–168.
3. DeMatteo RP, et al., “Two hundred gastrointestinal stromal tumours: recurrence patterns and prognostic factors for survival”, Ann Surg (2000);231: pp. 51–58.
4. Chan KH, et al., “Gastrointestinal stromal tumors in a cohort of Chinese patients in Hong Kong”, World J Gastroenteral (2006);12(14): pp. 2223–2228.
5. Nilsson B, et al., “Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era-a population-based study in western Sweden”, Cancer (2005);103(4):821–829.
6. Roberts PJ, Eisenberg B, “Clinical presentation of gastrointestinal stromal tumors and treatment of operable disease”, Eur J Cancer (2002);38(9);Suppl 5: pp. S37–8.
7. Lehnert T, “Gastrointestinal sarcoma (GIST)-a review of surgical management”, Ann Chir Gynecol (1998); 87: pp. 297–305.
8. Joensuu H, et al., “Management of malignant gastrointestinal stromal tumors.”, Lancet Oncol (2002);3: pp. 655-664.
9. Ng EM, et al., “Prognostic factors influencing survival in gastrointestinal Leimyosarcomas. Implications for surgical management and staging”, Ann Surg (1992);215(1): pp. 68–77.
10. Hirota S, et al., “Gain-of-Functions Mutations of c-kit in Human Gastrointestinal Stromal Tumors”, Science (1998);279(5350): pp. 577–580.
11. Rubin BP, et al., “KIT activation is a ubiquitous feature of gastrointestinal stromal tumors”, Cancer Res (2001);61: pp. 8118–21.
12. Singer S, et al., “Prognostic value of KIT mutation type, mitotic activity, and histologic subtype in gastrointestinal stromal tumors”, J Clin Oncol (2002);20: pp. 3898–3905.
13. Druker BJ, et al., “Efficacy and safety of a specific inhibitor of the BCR-ABLt yrosine kinase in chronic myeloid leukemia”, N Engl J Med (2001);344: pp. 1031–1037.
14. Druker BJ, et al., “Activity of a specific inhibitor of the BCR-ABLt yrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome”, N Engl J Med (2001);344: pp. 1038–1042.
15. Joensuu H, et al., “Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor”, New Eng J Med (2001);244(14): pp. 1052–1056.
16. Demetri GD, et al., “Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors”, N Engl J Med (2002);347: pp. 472–480.
17. Hohenberger P, et al., “Tumor resection following imatinib pretreatment in GI stromal tumors”, Proc Am Soc Clin Oncol (2003);22: p. 818.
18. Heinrich MC, et al., “Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor”, Blood (2000);96: pp. 925–932.
