MANAGEMENT OF GIST involving medical and surgical.pptx

Gastro Intestinal Stromal Tumor

1. MANAGEMENT OF GIST

2. GIST – clinical features generally detected when they become symptomatic. Non specific symptoms , Vague abdominal pain& fullness early satiety , malaise,fatigue . Symptoms due to obstruction or bleeding haemetemisis or malena dysphagia obstructive jaundice(duodenal tumor) features of small bowel obstruction constipation( colo rectal)

3. smaller gists (<4cms) incidentally on radiological studies , endoscopy or laparotomy surgery f some other pathology Mass per abdomen in case of advanced disease involving liver or peritoneum.

4. Differential diagnosis Lymphoma Metastatic melanoma Schwannoma Leiomyoma , leiomyosarcoma immunohistochemistry helps in differentiating gists from these lesions.it stains for cd117 antigen , part of kit receptor. cd117 expression is characteristic of most gist

5. gist - diagnosis investigtions usg abdomen and pelvis for mass abdomen upper gi endoscopy/colonoscopy/barium series contrast ct of abdomen and pelvis mri of abdomen and pelvis for metastases and peri rectal gist fdg -pet is done in case of ambiguity on CT , MONITOR RESPONSE TO MEDICAL THERAPY AND ALSO TO DETECT emergence of drug- resistant clones.

6. ct image of gastric gist

7. mri image of gist

8. gist-diagnosis endoscopy, fnac/biopsy endoscopically primary gist appears as submucosal lesion, with or without ulceration eus not routinelyrequired guided fnac may be attempted.

9. endoscopic image of gist

10. gist diagnosis immunohistochemistry to detect cd117. pcr analysis for kit mutions for diagnosis/prognosis. routine biopsy is not necessary for suspected gistthat is resectable. biopsy is appropriate for neo adjuvant therapy metastatic disease differential diagnosis being lymphoma.

11. gist - tnm staging

12. gist - ajcc staging 7th edit ion

13. gist - treatment surgery is the defnitive therapy for patients with primary ,resectable, localised gists gist >2cms, symptomatic tumors, and all gists of non gastric origin should be considered for surgical resection and adjuvant medical treatment. principle is to achieve negative microscopic margin ( R0) resection. en bloc resection of adjacent invoved ordgans, such as colon,spleen or liver for locally advanced gists. in these cases tumor rescetion is preceeded by imatinib therapy for tumor shrinkage and to minimise the extent of resection adjuvant treatment with imatinib has improved recurrence free survival 400mg po/day for 3 years.

14. gist treatment wedge or segmental resection of the involved stomach or bowel is feasible. large gastric tumors require total/ subtotal gastrectomy subcentimeter gastric gists may be followed up by endoscopy risks and benefits of surgery versus observation should be discussed with the patient for gists 1-2cm regardless of open or laproscopic resection gists are approached in a similar fashion. non gastric gists of any size should be resected because of aggressive behaviour.

15. gist - treatment rarely pancreaticoduodenectomy or apr may be done depending on location of tumor. endoscopic resection is not recommended , as gists involve muscularis propria , therefore endoscopic resection risks leaving deep postive margin and due to depth ofv the lesion may result in gastric perforation. laproscopic resection of primary gists is safe and feasible particularly in small gastric gists with no differences in margin postivity , recurrence free survival or overall survival when compared to oprn resection.

16. gist - treatment unresectable/metastatic gist: targeted therapy with tyrosine kinase inhibitors( tki) imatinib mesylate 400mg po/day 4oomg twice daily in progressive disease sunitinib malate 50mg po/day for 4 weeks +2weeks of drug free interval as second line treatment. regorafenib 160mg po/day for 21 days when advanced gists no longer respond to imatinib or sunitinib.

17. gist - treatment cytoreductive surgery palliative surgery may benefit in select cases responding to target therapy. surgery may reduce the burden of clonal variability in the tumor population and may prevent the formation of drug resistant clones. also has role in decresing symptoms and developement of complications like perforation and bleeding. also concluded that patients with stable disease or limited progression are more beneficial from debulking surgeries particularly if r1 or r0 resection completed. the patients should be treated with imatinib for atleast 6months prior to consideration of surgery.

18. gist - treatment therapy for imatinib resistance primary resistance is defined as evidence of clinical progression during first 6 months of imatinib therapy. it is most common with mutations involving kit exon 9, d842v mutation in pdgfra exon 18. eventually most patients develope secondary resistance most commomnly due to secondary mutations in exon 13, 14 and 17. resistance is managed by increasing imatinib dose to 800 mg/day or switching to second or third line drugs.

19. gist - treatment sunitinib and regorafenib are considered as secon and third line drugs, both of them targets kit, pdgfra, and vegf1,2,3. these are considered in pts who have progressed or intolerant of imatinib. nilotinib is a second generatiion tki originally designed for cml. trials are currently ongoing to investigate efficacy and safety of nilotinib versus imatinib as first line treatment for advanced gists. additional tki under investigatiion are dasatinib, vatalanib, crenolanib. crenolanib has been found to 135 fold more potent than imatinib against pdgfra d842v mutation gist.

20. scheme of management of gist

21. gist - prognosis despite a macroscopically complete resection, 50 % recurrences are noted at a median of 24 months. overall 5 year survival rates are 30-60%. localized primary gists, median survival of 5 years. metastatic or recurrent disease the median survival is 10-20 months.

22. gist - prognostic factors tumor size: smaller the size better prognosis. mitotic index : low mitotic rate < 5 per hpf have better prognosis. site of origin: gastric gists have better prognosis. stage : localized primary have better prognosis. r0 or r1 resection has better prognosis than r2. mutational status: kit exon 11 mutation has better prognosis.

23. gist - follow up nccn panel recommends localised gists: history, physical examination and cect abdomen & pelvis every 3-6months for first 3-5 yrs then anually. endoscopic surveillance for gastric gists without high risk features at 6-12months interval. metastatic/gross residual gist: history and physical examination and abdominal/pelvic ct every 3-6 months.

24. gist - conclusions gists are most common mesenchymal neoplasms of gi tract(80%) 95% of gists stain positively for kit ( cd 117) over 85% of gists have activating kit mutations every gist carries risk of malignancy from very low to every high occurs in stomach more commonly surgery is the principle & only potentially curative treatment for gist the treatment of localized gist is r0 resection + adjuvant imatinib targeted therapy using tki form the mainstay of treatment for advanced gists.

25. gist - conclusions tki therapy has shown improved prognosis of localized & advanced gists. cytoreductive surgery may be considered in subset of patients with advanced disease. recurrences are common needing lifelong follow up. future studies will focus on integration of surgery with targeted therapy and the develpoement of new agents for drug resistant gists.

26. thank you