1. Multimodality Treatment of Mesenteric Desmoid Tumors Monica M. Bertagnolli, Jeffrey A. Morgan, Christopher D.M. Fletcher, Chandrajit P. Raut, Palma Dileo, Ritu R. Gill, George D. Demetri and Suzanne George Brigham and Women’s Hospital Dana-Farber Cancer Institute Harvard Medical School CTOS Annual Meeting London November 13, 2008

2. Desmoid tumors Clonal proliferation of fibroblasts with an abundant collagen matrix Occur in 10-20% of patients with Familial Polyposis mesentery 50% abdominal wall/trunk 48% extremities 2% multifocal 40% Sporadic tumors are rare (600-1200 per year in the US) extremity 60% abdominal wall/trunk 35% mesentery 5%

3. Mesenteric Desmoid tumors Wide range of clinical behavior Life threatening due to impact on small bowel and mesenteric blood supply Surgery can be complex due to location Radiation may be difficult due to toxicity associated with this anatomic site

4. CT Characteristics Localized Infiltrative

5. Methods Single institution retrospective review Consecutive series of patients with desmoid tumors of the intestinal mesentery, 2001-2005 Patients were seen by both surgical and medical oncology Reviewed treatment course and outcome

6. Methods Tumor Characteristics at presentation to DFCI/BWH – Resectable vs Unresectable all grossly visible tumor could be removed without sacrificing small bowel function – Progressing vs Stable – Infiltrative vs Localized

7. Treatment Strategy ResectableUnresectable Stable Progressing

8. Treatment Strategy ResectableUnresectable StableSurgery Progressing

9. Treatment Strategy ResectableUnresectable StableSurgery ProgressingSurgery

10. Treatment Strategy ResectableUnresectable StableSurgeryObservation ProgressingSurgery

11. Treatment Strategy ResectableUnresectable StableSurgeryObservation ProgressingSurgeryChemotherapy* *1 st line liposomal doxorubicin; 2 nd line vinorelbine

12. Results: Patient Characteristics 52 pts –21 FAP (age 20-50, median 31) –31 sporadic (age 24-67, median 41) Prior NSAID, tamoxifen or both60% Prior imatinib12% Prior cytotoxic chemotherapy 8% Median Followup50 months

13. Results: Disease Characteristics (n=52) Localized disease 16 (31%) Infiltrative disease 36 (69%) Progressive disease40 (78%) Stable disease12 (23%) Resectable36 (69%) Unresectable16 (31%)

14. Summary

18. Results: Extent of Surgery Localized (n=15) Infiltrative (n=28) Single segment of small bowel resected 9 (60%)9 (32%) Multiple segments of small bowel resected 1 (7%)15 (53%) Positive Margins3 (20%)28 (100%) Significant postop complications 16% of pts – anastomotic leak, abcess, EC fistula, postop bleed All patients retained adequate small bowel function, no chronic TPN, no surgery associated deaths.

19. Results: Chemotherapy NPR/SD*PD Liposomal doxorubicin1091 Vinorelbine431 Total1412 (94%)2 (6%) * by RECIST

20. Impact of liposomal doxorubicin in mesenteric desmoid tumor

21. Summary Multidisciplinary assessment and treatment planning is effective in patients with mesenteric desmoid tumors Tumor characteristics matter No apparent detrimental effect of surgery with regard to disease control in carefully chosen patients Chemotherapy can be effective in disease control Observation is a reasonable approach in patients with non-progressing, asymptomatic disease

22. Limitations Short followup Relatively small number of patients Variable natural history Mesenteric location only - unknown application to desmoids of other body sites

23. Thank you

24. Summary

25. Mesenteric desmoid tumors Localized vs diffuse disease Incidentally discovered during 12-22% of surgeries for FAP (Clark BrJSurg 1999, Hartley DC&R 2004) 2 nd leading cause of disease-related mortality in patients with FAP –13% of FAP patients with desmoids in a series of 88 patients died within 5 years of diagnosis (Clark Br J Surg 1999)