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Management of GIST

Management of GIST. Dr Kwan Ming Wa Tuen Mun Hospital. Contents. Mainly concern about Oncogensis Surgical treatment Targeted therapy. Introduction. GIST the most common Sarcoma of the GI tract derived from the Interstitial cells of Cajal. Oncogenesis of GIST.

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Management of GIST

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  1. Management of GIST Dr Kwan Ming Wa Tuen Mun Hospital

  2. Contents • Mainly concern about • Oncogensis • Surgical treatment • Targeted therapy

  3. Introduction • GIST • the most common Sarcoma of the GI tract • derived from the Interstitial cells of Cajal

  4. Oncogenesis of GIST Mutated KIT receptor become autonomous and cell proliferation become uncontrolled KIT Receptor Gene expression Signal-Transduction ATP ADP Signal Molecule Plasma Membrane Earl W. Sutherland (Nobel Prize – 1971)

  5. Understanding of the oncogenesis is the key to the advances of diagnosis and targeted therapy

  6. Differentiation of GIST from smooth muscle tumour

  7. Targeted therapy (Glivec) Competitive inhibition of Tyrosine Kinase Autonomous KIT Receptor ATP ADP Gene expression Plasma Membrane

  8. Clinical features of GIST • Incidence • Worldwide 10-20/ million • Tuen Mun ~13 cases/ year • Median age at 60 • Sex ratio 1:1

  9. Location of GIST

  10. Presentation • GI Bleeding • the most common presenting symptom • Mass effect • when tumour is large enough • Small GIST • Usually found incidentally

  11. Symptoms related to gastric GIST in TuenMun

  12. Preoperative biopsyNot advocated • GIST is highly vascular and friable • Risk of bleeding • Risk tumour rupture • Risk tumour dissemination and early recurrence

  13. Imaging for diagnosis and staging • CT scan, endoscopy and EUS are commonly used to diagnose GIST • A well circumscribed, vascular mass associated with stomach/ intestine • Staging primary GIST • CT scan and CXR is sufficient • metastasis is usually confined to peritoneum and the liver • For complicated disease, PET-CT • Recurrent disease/ extraperitoneal metastasis

  14. Surgery • The primary treatment for resectable GIST • The goal is complete resection of the mass without disruption of the pseudocapsule

  15. GIST generally displace rather than infiltrating the surrounding structure • Achieving negative margin is usually possible

  16. Dissection of lymph node does notprolong survival or delay recurrence • Connolly EM, Br J Surg 2003 • Sammiian L, Am Surg 2004

  17. Type of operation for gastric GIST in Tuen Mun

  18. Outcome of gastric GIST resection in TMH

  19. Outcome after complete resection • 5yr survival (overall) : 48-65% • Poor outcome is associated with • Big tumour size (>5cm) • High mitotic figure (>5/50HPF)

  20. Example of excising a big GIST

  21. 1 year later..

  22. Conventional adjuvant therapy • Chemotherapy: refractory • Radiotherapy: limited use

  23. Targeted therapy • Evidence of benefit in • Treatment of advanced GIST • As adjuvant to primary tumour resection

  24. Advanced GIST treated with Glivec

  25. 10 years or until death Placebo x 1 year F O L L O W Primary GIST (≥ 3 cm) Glivec 400mg (or 800mg) x 2 years Complete Gross Resection Recurrence Glivec 400mg x 1 year ACOSOG Z9001: A randomized, double blind study of adjuvant Glivec versus placebo following resection of primary GIST Design:

  26. ACOSOG Trial Prematurely Stopped Due to Superior Rates of Recurrence Free Survival (RFS) with Glivec • Data monitoring committee evaluated data on >600 pts with complete resection of primary GIST • At 1 year follow-up, 97% of patients on Glivec arm were free of recurrence compared with 83% of patients on placebo arm • Approximately 65% less likely to experience recurrence within two years • All patients will be unblinded, and patients in the placebo arm will be offered 1 year of Glivec Available at: http://www.cancer.gov/newscenter/pressreleases/GISTtrial

  27. Treatment model Normal Pre-Cancer Cancer Metastatic Cancer prevention Treatment Stage Primary +/- Adjuvant systemic therapy 1st Line 2rd Line

  28. Thankyou

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