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Surgical Management of Advanced GIST Following KIT-Directed Therapy

Surgical Management of Advanced GIST Following KIT-Directed Therapy. Chandrajit P. Raut, Jayesh Desai, Jeffrey A. Morgan, Suzanne George, Matthew Posner, David Zahrieh, Christopher D. M. Fletcher, George D. Demetri, and Monica M. Bertagnolli Brigham and Women’s Hospital

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Surgical Management of Advanced GIST Following KIT-Directed Therapy

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  1. Surgical Management of Advanced GIST Following KIT-Directed Therapy Chandrajit P. Raut, Jayesh Desai, Jeffrey A. Morgan, Suzanne George, Matthew Posner, David Zahrieh, Christopher D. M. Fletcher, George D. Demetri, and Monica M. Bertagnolli Brigham and Women’s Hospital Dana-Farber Cancer Institute Harvard Medical School November 20, 2005

  2. Gastrointestinal Stromal Tumor (GIST): Therapy in Advanced Disease • Imatinib therapy results in disease regression or stabilization in approximately 80% of patients with advanced GIST • Sunitinib may achieve significant anti-tumor responses in imatinib-resistant tumors • However, response to KIT-directed therapy is not maintained indefinitely, resulting in disease progression

  3. GIST: Therapy in Advanced Disease • Once drug resistance occurs, disease progression may be: • Limited • Drug responsiveness or growth stability in most metastatic tumor deposits • Progressive growth in isolated lesions • Generalized • Progressive growth in most tumor deposits • Traditional role of surgery in advanced disease: palliation

  4. Progression-Free Survival Overall Survival 25-mo PFS: 50-56% 12-mo OS: 85-86% 24-mo OS: 69-74% Survival in Advanced GISTVerweij et al. (2004), Lancet 364:1127 • 964 pts with advanced GIST • Randomized to imatinib 400 qd vs. bid • Median f/u 760 days

  5. Should Advanced GIST Be Managed More Aggressively? • Treatment with imatinib has altered the natural course of the disease • However, drug resistance may limit long-term efficacy • Re-evaluation of the role of surgery in advanced GIST

  6. Study Objective • Determine if resection or debulking of stable or progressive advanced GIST after treatment with KIT-directed therapy impacted survival?

  7. Patient Cohort • March, 2002 – November, 2004 • 69 consecutive patients with advanced, biopsy-proven GIST • Diagnosis confirmed by review of tumor pathology • Multidisciplinary team approach: • Treatment with KIT-directed therapy • Surgery

  8. Patient Characteristics

  9. Preoperative Therapy

  10. Patient Cohort: Extent of Disease • Stable disease • Initially unresectable primary or metastatic disease who demonstrated maximal response to drug • No tumor progression prior to surgery for a median of 211 days (range 62-1196 days) • All sites were resectable • Limited disease progression • Metastatic disease with limited progression on drug • All progressing sites were resectable • Generalized disease progression • Metastatic disease with generalized progression on drug • All progressing sites were not resectable • 43% were emergent procedures • Remaining patients had excellent performance status

  11. Indications for Surgery

  12. Extent of Surgical Resection Additional localized peritoneal stripping / omentectomy – 43/69 (62%)

  13. Postoperative Therapy

  14. Surgical Outcome • Results of operation were recorded as: • No evidence of disease (NED) No grossly visible residual disease • Minimal residual disease Visible tumor nodule(s) < 1 cm • Bulky residual disease Visible tumor nodule(s) ≥ 1 cm

  15. Surgical Outcome According to Disease Presentation • Disease presentation prior to surgery strongly correlated with surgical result (p<0.0001)

  16. Progression-Free Survival Median follow-up 14.6 mo

  17. Overall Survival Median follow-up 14.6 mo

  18. Stable Disease • 21/23 (91%) pts with stable disease prior to surgery were treated with imatinib preoperatively • Outcomes: • 5/21 (24%) recurred PFS recalculated from the time imatinib commenced (median follow-up 25 mo) 12-mo PFS 100% 24-mo PFS 88% ± 8% 36-mo PFS 59% ± 15% • 2/21 (9.5%) died

  19. Conclusions • Patients with stable disease on KIT-directed therapy have prolonged PFS/OS after resection • Patients with limited disease progression may benefit from debulking procedures • Benefits of surgery in patients with generalized disease progression are limited

  20. Future Directions • Prospective clinical trial in patients with stable advanced GIST randomized to KIT-directed therapy alone vs. surgery plus KIT-directed therapy Arm 1: KIT-directed therapy plus surgery Consent Patients with stable metastatic gastrointestinal stromal tumor Registration and randomization Follow Arm 2: KIT-directed therapy

  21. Medical Oncology Karen Albritton, MD George Demetri, MD Suzanne George, MD Jeffrey Morgan, MD Rhaea Photopoulos, NP Kathleen Polson, NP Surgical Oncology Monica Bertagnolli, MD Chandrajit Raut, MD Radiation Oncology Elizabeth Baldini, MD Philip Devlin, MD Karen Marcus, MD Orthopedic Oncology John Ready, MD Pathology Christopher Fletcher, MD Jonathan Fletcher, MD Dana-Farber / Brigham and Women’s Cancer Center:Sarcoma Center

  22. Surgical Complications

  23. Surgical Complications • Overall complication rate 33% • Complication rate, generalized progression pts 50% • Complication rate, emergency surgery 40%

  24. Postoperative Therapy

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