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CTOS 14th Annual Meeting London, 13-15 November 2008 ALTERNATIVE CLINICAL APPROACH

CTOS 14th Annual Meeting London, 13-15 November 2008 ALTERNATIVE CLINICAL APPROACH IN AGGRESSIVE FIBROMATOSIS: WAIT & SEE FRONTLINE POLICY. A MULTI-INSTITUTIONAL RETROSPECTIVE REVIEW. Marco Fiore and Sylvie Bonvalot.  -Catenin. Primary AF 5-yrs DFS 81% 10-yrs DFS 76%.

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CTOS 14th Annual Meeting London, 13-15 November 2008 ALTERNATIVE CLINICAL APPROACH

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  1. CTOS 14th Annual Meeting London, 13-15 November 2008 ALTERNATIVE CLINICAL APPROACH IN AGGRESSIVE FIBROMATOSIS: WAIT & SEE FRONTLINE POLICY. A MULTI-INSTITUTIONAL RETROSPECTIVE REVIEW. Marco Fiore and Sylvie Bonvalot

  2. -Catenin

  3. Primary AF 5-yrs DFS 81% 10-yrs DFS 76%

  4. Background

  5. Objective

  6. Evaluate the PFS of AF primarily observed (no surgery, no radiation, no medical treatments) on a large series of patients coming from two major referral institutions Correlate PFS with known clinical prognostic factors

  7. Patients and Methods

  8. Aggressive Fibromatosis1995-2008 N° pts. NO SURGERY 142 Primary 74 52.1% Recurrent 68 47.9% Female 99 69.7% Male 43 30.3% Age 15-25 yrs 35 24.6% 26-45 yrs 75 52.8% >45 yrs 32 22.5% Gardner Yes 6 4.2% No / NA 136 95.8% Recent Pregnancy Yes 23 23.2% No 44 44.4% NA 32 32.3%

  9. na >100 <50 50 -100 Distribution by Site and Size Intrabdominal Abdominal Wall H&N Thoracic Wall Extremity Trunk

  10. 73% 43% Treatment at Referral

  11. Treatment at Referral

  12. Which definition of PD ? • IGR: increase in size of 25% of the target lesion in comparison with baseline. • INT: any increase in size at MRI, and/or worsening of symptoms in comparison with baseline.

  13. Results

  14. Progression-free Survival (Median follow-up 32.5 mos)

  15. PFS – Primary AF Any Tx W&S

  16. PFS – Recurrent AF Any Tx W&S

  17. Trunk > > Abd. Wall Extremity > > 100 mm < 50 mm Cox Model (Hazard Ratio)

  18. Discussion

  19. W&S: size increase at PD ratio months

  20. W&S: size decrease at spontaneous regression ratio months

  21. W&S: local control after PD 6 / 19 pts Median TTP 5.3 mos Median size 105 mm Local relapse none 10 / 19 pts Median TTP 11.1 mos Median size 66 mm Local relapse 2 / 10

  22. … and what about RT?

  23. Soft tissue necrosis; Fracture; Edema; Fibrosis; Neuropathy; Limb shortening; Second malignancy Local control, 5yrs = 75% Surgery + RT vs RT alone, p = 0.21

  24. ♀♂ Site W&S / Tx Primary / Recurrent Size Age

  25. … Next step?? Molecular Prognosticators Primary disease, W&S

  26. Conclusion

  27. 50.0% Avoid any treatment 63.0% Avoid Surgery

  28. It would be useful to identify upfront those who will progress… (molecular analysis??) • Even in the absence of clinical prognosticators, Wait & See approach revealed to be a good tool to tailor the best treatment strategy

  29. … marco.fiore@istitutotumori.mi.it

  30. Distribution by site Site Extremities / Girdles 65 45.8% Abdominal wall 33 23.2% Thoracic wall 13 9.2% Trunk 9 6.3% H&N 7 4.9% Intrabdominal / Pelvic 15 10.6% Size < 50 mm 54 38.0% 51-100 mm 55 38.7% > 100 mm 21 14.8% NA 12 8.5% Monofocal 124 87.3% Multifocal 18 12.7%

  31. AF - Treatment at referral N° pts. NO SURGERY 142 100.0% Wait & See 83 58.5% Any Medical Tx 59 41.5% Chemotherapy 2847.4% Hormonal (anti-E) 2033.9% NSAIDs 23.4% Imatinib 11.7% ILP 35.1% Multiple 58.8%

  32. Primary AF: W&S approach All Primary 74 39 52.7% 35 47.3% 58 78.4% 16 21.6% 10 13.5% 49 66.2% 15 20.3% N° pts. W&S 54 IGR 34 63.0% INT 20 37.0% Female 44 81.5% Male 10 18.5% Age 15-25 yrs 4 7.4% 26-45 yrs 38 70.4% >45 yrs 12 22.2%

  33. Primary AF: W&S approach All Primary 74 20 27.0% 28 37.8% 9 10.8% 4 5.4% 3 4.1% 10 13.5% 70 94.6% 4 5.4% N° pts. W&S 54 Site Extr. / Girdles 12 22.2% Abdominal wall 28 51.9% Thoracic wall 7 13.0% Trunk 1 1.9% H&N 1 1.9% Intrabd. / Pelvic 5 9.1% Monofocal 51 94.4% Multifocal 3 5.6%

  34. Primary AF: W&S approach All Primary 74 32 43.2% 28 37.8% 10 13.5% 4 5.4% 3 4.1% 71 95.9% 17 23.0% 31 41.9% 26 35.1% N° pts. W&S 54 Size < 50 mm 29 53.7% 51-100 mm 21 38.9% > 100 mm 2 3.7% NA 2 3.7% Gardner Yes 3 5.5% No / NA 51 94.5% Pregnancy Yes 16 29.6% No 27 50.0% NA 11 20.4%

  35. Cox Model

  36. W&S: treatment at PD

  37. W&S: local control after surgery at PD N° pts. SURGERY after PD 6 / 19 IGR 5 INT 1 Median tumor size at PD (mm) 105 Median TTP 5.3 (range 1.3 – 46.9) Local relapse none Median FU after PD 12.3 (range 0.8 - 34.8)

  38. W&S: local control after Tx at PD N° pts. Medical Tx after PD 10 / 19 IGR 7 INT 3 Median tumor size at PD (mm) 66 Median TTP 11.1 (range 4.3 – 27.8) Further PD 2 / 10 Median FU after initial PD 7.9 (range 0.0 - 74.4)

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