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The Surgeon’s Role in the Management of Gastrointestinal Stromal Tumors (GIST)

The Surgeon’s Role in the Management of Gastrointestinal Stromal Tumors (GIST). 2011 Phoenix Surgical Symposium John M. Kane III, MD Chief-Melanoma/Sarcoma Roswell Park Cancer Institute. GIST Overview. soft tissue sarcoma share characteristics with interstitial cells of Cajal (ICC)

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The Surgeon’s Role in the Management of Gastrointestinal Stromal Tumors (GIST)

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  1. The Surgeon’s Role in the Management of Gastrointestinal Stromal Tumors (GIST) 2011 Phoenix Surgical Symposium John M. Kane III, MD Chief-Melanoma/Sarcoma Roswell Park Cancer Institute

  2. GIST Overview • soft tissue sarcoma • share characteristics with interstitial cells of Cajal (ICC) • pacemaker cells of the gut • neural and myogenous features • expression of KIT (CD117) in ~95% of cases Sircar et al. Am J Surg Pathol. 1999;23:377. Wang et al. Arch Pathol Lab Med. 2000;124:1471.

  3. GIST Overview • association with other neoplasms • up to 27% of patients will have a 2nd or 3rd cancer • Carney’s triad: GIST, extra-adrenal paraganglioma, pulmonary chondroma • association with neurofibromatosis

  4. Colon Other (rectum, esophagus, mesentery, retroperitoneum, omentum) 10% 15% 25% Small intestine 50% Stomach GIST Location • GIST may occur anywhere along the GI tract, intra-abdominally, and even the retroperitoneum Emory et al. Am J Surg Pathol. 1999;23:82.

  5. GIST Metastatic Risk • malignant potential • size • anatomic location • mitotic rate • metastatic sites • common: liver, peritoneum (sarcomatosis) • less common: lungs, bone, pleura, soft tissue • nodal metastases are rare (2-16%)

  6. GIST Presentation • nonspecific symptoms • GI/intra-abdominal bleeding • urgent laparotomy • obstruction less common • small intestine • incidental on imaging or endoscopy • endophytic, exophytic, or “dumbbell”

  7. GIST Work-up • diagnosis • staging • evaluate the extent of the tumor • CT, endoscopy, EUS • assess for metastases • CT, PET • determine tumor resectability

  8. GIST Biopsy • limited role for preoperative biopsy for a potentially resectable GIST • clearly unresectable/neoadjuvant therapy • high likelihood of lymphoma or other pathology • enrollment in a clinical trial • significant risk for tumor seeding or hemorrhage • endoscopic biopsy, if possible • 2nd choice- image guided transabdominalneedle biopsy

  9. GIST Treatment • Surgical Therapy • Primary Tumor • Recurrent/Metastatic Disease

  10. GIST Surgical Points • complete resection of tumor with pseudocapsule • >80% complete resection rate • fragility of tumor risks rupture • bleeding • peritoneal dissemination • careful examination for metastases • peritoneal surfaces, liver • synchronous disease in up to 15% • occasionally invade surrounding organs (<40%)

  11. GIST Surgical Margins • complete resection of disease is the goal • excision with 1-2 cm margins • no benefit to radical surgery • lymphadenectomy rarely indicated • management of microscopic positive margins • re-resection not indicated • consultation with a multidisciplinary team recommended • role for adjuvant imatinibmesylate (Gleevec) therapy being evaluated

  12. GIST: Minimally Invasive Approach • GIST is murally based, so endoscopic removal is NOT possible • except for a readily accessableGIST that would require minimal dissection/manipulation, laparoscopic resection is discouraged • greater curvature/anterior stomach • jejunum/ileum • preserve pseudocapsule/no spillage • Endocatch bag

  13. GIST Resection and Survival • poor outcome if unresectable/metastatic disease or incomplete resection • before imatinibmesylate, median survival of <1 year • “downstaging” with neoadjuvantimatinibmesylate DeMatteo et al. Ann Surg. 2000;231:51.

  14. Locally Advanced GIST and Neoadjuvant Therapy • based upon high response rates of metastatic disease to imatinibmesylate • attempt to shrink the tumor to minimize the potential morbidity of surgical resection • imatinibmesylate 400 mg/day • may take up to several months to achieve maximal treatment response DeMatteo et al. Ann Surg. 2000;231:51.

  15. Locally Advanced GIST and Neoadjuvant Therapy DeMatteo et al. Ann Surg. 2000;231:51.

  16. Locally Advanced GIST and Neoadjuvant Therapy DeMatteo et al. Ann Surg. 2000;231:51.

  17. Neoadjuvant Trial (RTOG S-0132):Study Design R E S E C T I O N Continue imatinib mesylate (600 mg/d for 2 years) SD/PR Neoadjuvantimatinib mesylate (600 mg/d for 8 weeks) Resectable primary or metastaticGIST FollowforPFS R E S E C T I O N PD Off study At: http://www.rtog.org/members/protocols/S0132/S0132.pdf.

  18. Results of RTOG S-0132 • limited response to neoadjuvant therapy • primary (30 pts) • 7% PR, 83% SD, no PD • recurrent/mets (22 pts) • 4.5% PR, 91% SD, 4.5% PD Eisenberg et al., J SurgOncol. 2009

  19. Recurrence-Free Survival Following Surgical Treatment of Primary GIST • recurrence-free survival is predicted by tumor size and mitotic index 1.0 1.0 3 mitoses/30 HPF <5 cm 0.75 0.75 >3 to 15 mitoses/30 HPF 5-10 cm Recurrence-free survival Recurrence-freesurvival 0.50 0.50 >10 cm 0.25 0.25 >15 mitoses/30 HPF P=0.03 P=0.0001 0 0 0 20 40 60 80 0 20 40 60 80 Months Months Singer et al. J Clin Oncol. 2002;20:3898. Reprinted with permission from the American Society of Clinical Oncology.

  20. Risk for GIST Recurrence and Death http://www.mskcc.org/mskcc/html/98103.cfm Miettinen and Lasota, Seminars in Diagnostic Pathology 2006

  21. GIST Recurrence After Surgery • recurrence/metastasis is not uncommon • majority of high-risk patients have recurrence following surgery • median time to recurrence is 7-24 months • only 10% of patients may remain disease-free after extended follow-up • no consistent benefit from radiation or traditional cytotoxic chemotherapy • role of adjuvant imatinibmesylate is still evolving DeMatteo et al. Hum Pathol. 2002;33:466. Buemming et al. Proc Am Soc Clin Oncol. 2003;22:818. Abstract 3289. Ng et al. Cancer. 1992;69:1334.

  22. Phase III Trial (ACOSOG Z9001): Study Design Placebo (for 1 year) Recurrence Imatinib mesylate (400 mg/d) Follow for OS Resection of primary GIST Imatinib mesylate (400 mg/d for 1 year) Recurrence At: http://www.acosog.org/studies/synopses/Z9001_Synopsis.pdf.

  23. Results of ACOSOG Z9001 Dematteo et al., Lancet. 2009

  24. GIST Treatment • Surgical Therapy • Primary Tumor • Recurrent/Metastatic Disease

  25. GIST Surgery for Recurrent or Metastatic Tumors • potential role for surgical resection of isolated disease • surgery for liver metastases (33%) • 5 year overall survival 30% • consider radiofrequency ablation (RFA) or hepatic artery embolization for unresectable tumors • resection of recurrence/peritoneal disease (50%) • concept of “stabilization” with imatinibmesylate • 83% will have some response

  26. Metastatic Disease Surgical Algorithm • symptomatic tumor • obstruction/bleeding • resectable after maximal response • limited refractory disease

  27. GIST Summary I • most common sarcoma of the GI tract • pathologic characteristics of GIST well defined • diagnosis remains challenging in some cases • clinical presentation is variable • often asymptomatic • common, nonspecific symptoms can result in underdiagnosis or misdiagnosis • all GIST have malignant potential • risk is based upon size, mitotic index, and anatomic location

  28. GIST Summary II • surgery main potentially curative treatment • goal is negative margins • some role for resection of isolated recurrence or metastases • no significant benefit to radiation or traditional cytotoxic chemotherapy • increasing role of imatinibmesylate in multimodality therapy

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