Current Management of Gastrointestinal Stromal Tumor (GIST)

1. Current Management of Gastrointestinal Stromal Tumor (GIST) Joint Hospital Surgical Grand Round Dr. Tony Cheung PYNEH

2. Gastrointestinal Stromal Tumor • Neoplasm of interstitial Cajal cells • 3000-6000 cases/ year in the US • Equal prevalence in male and female

4. Landmark discovery • 1998 • Majority of GIST have oncogenic gain-of-function mutations of the KIT receptor tyrosine kinase Hirota S et al. Science 1998;279:577–580. • 2001 • Imatinib (Gleevec) • KIT tyrosine kinase inhibitor (TKI) Joensuu et al. N Engl J Med 2001;1052:1052–1056.

5. OGD CXR EUS CT PET

6. Investigations • CXR • OGD • EUS • look for size, irregular borders, echogenic foci, cystic spaces Gastrointest Endosc 2003;57: 469–474. Med Clin North Am 2005;89:139–158, viii. • Contrast CT • for size and anatomical location • determine features of GIST – well vascularized, necrotic centre, heterogeneous appearance • PET • identify metastatic disease • monitor response to medical tx

7. Risk Stratification of GIST Miettinen et al. Am J Surg Pathol 2005;29:52–68.

8. Management • Primary GIST • Advanced / Metastatic GIST

9. Localized GIST • Goal of operation • Complete macroscopic resection with an intact pseudocapsule • Negative microscopic margin (R0 resection) • If tumor rupture  associated with high risk of intraabdominal dissemination of tumor cells and recurrence • However, no additional benefit of wide resection of gastric GIST to obtain generous negative resection margin

10. Laparotomy OR Laparoscopy

11. Laparotomy • R0 resection options • Wedge resection, segmental resection • Extensive resection • En bloc contiguous visceral resection • Method of choice for all non-gastric GISTs

12. Laparoscopy • < 5cm tumor for stomach GIST • Laparoscopic wedge resections of stomach GIST Otani et al. Surgery 2006;139(4):484–492. • No series on long term outcome with laparoscopy for non-stomach GIST

13. adapted from Otani et al. Surgery 2006;139(4):484–492.

14. But… • 5-year overall survival despite negative resection margin  42-52% Crosby et al. Ann Surg Oncol 2001;8(1):50–59. Neoadjuvant or adjuvant use of tyrosine kinase inhibitors

16. Advanced / Metastatic GIST • Imatinib alone • Imatinib + Cytoreductive surgery

17. Nature of GIST • Metastatic spread • peritoneal cavity • liver • uncommonly regional lymph nodes • Large GISTs tend to displace rather than invade adjacent organs Miettinen et al. Am J Surg Pathol 2005;29:52–68.

18. Imatinib alone • Outcome • Response • Primary resistance • Secondary resistance

19. Treatment response of Imatinib for Advanced unresectable GIST

20. Time response to Imatinib Verweij et al. Lancet 2004;364(9440):1127–1134.

21. Overall survival using Imatinib Verweij et al. Lancet 2004;364(9440):1127–1134.

22. Response • Overall disease control in 70-85% of patient • Median progression-free survival is 20-24 months • Overall survival time following imatinib therapy > 36 months

23. Do not achieve stable disease Progress within 6 months of initial objective response Develop one or more sites of disease progression after 6 months of measurable benefit Primary resistance / Secondary resistance

24. Imatinib then surgery • Recommended timing: • when maximal response to TKI observed • after at least 6 months of TKI treatment • Optimal time interval from start of TKI to surgery is unclear • Minimal tumor shrinkage noted after 9 months of imatinib DeMatteo et al. Ann Surg 2007;245(3):347–352.

25. Resection rates during surgery for advanced GIST after TKI therapy High rate of R0/ R1 after TKI therapy

26. Surgical candidates • ongoing response • limited disease progression • evolving necrosis or impending emergency • Non surgical candidates • generalized progression

27. Surveillance • Surveillance CT thorax/ abdomen/ pelvis q3-6months for 1st 5 years, then annually • PET not routinely needed Chandrajit et al. J Gastrointest Surg (2008) 12:1592–1599

28. NCCN guideline Feb 2008

29. Thank you!