Sarcomi del Retroperitoneo

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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
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Background
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Objective
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• 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

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Patients and Methods
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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
• gt45 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

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Distribution by Site and Size
Intrabdominal
Abdominal Wall
HN
Thoracic Wall
Extremity
Trunk
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Treatment at Referral
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Treatment at Referral
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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.

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Results
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Progression-free Survival (Median follow-up 32.5
mos)
Treatment group 5-yrs PFS () Logrank P-value Hazard ratio (95 CL) Hazard ratio (95 CL) Hazard ratio (95 CL) Hazard ratio (95 CL)
Overall series WS 49.9 0.3196 0.760 0.441 - 1.310
Overall series Any Tx 58.6 0.3196 0.760 0.441 - 1.310
Primary AF WS 47.0 0.7018 0.853 0.377 - 1.933
Primary AF Any Tx 53.6 0.7018 0.853 0.377 - 1.933
Recurrent AF WS 54.0 0.4832 0.754 0.341 - 1.666
Recurrent AF Any Tx 61.1 0.4832 0.754 0.341 - 1.666
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PFS Primary AF
Any Tx
WS
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PFS Recurrent AF
Any Tx
WS
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Cox Model (Hazard Ratio)
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Discussion
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WS size increase at PD
ratio
months
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WS size decrease at spontaneous regression
ratio
months
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WS 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
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and what about RT?
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Soft tissue necrosis Fracture Edema
Fibrosis Neuropathy Limb shortening Second
malignancy
Local control, 5yrs 75 Surgery RT vs RT
alone, p 0.21
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Site
WS / Tx
Primary / Recurrent
Size
Age
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Next step??
Molecular Prognosticators
Primary disease, WS
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Conclusion
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50.0 Avoid any treatment
63.0 Avoid Surgery
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• 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

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marco.fiore_at_istitutotumori.mi.it
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Distribution by site

• Site Extremities / Girdles 65 45.8
• Abdominal wall 33 23.2
• Thoracic wall 13 9.2
• Trunk 9 6.3
• HN 7 4.9
• Intrabdominal / Pelvic 15 10.6
• Size lt 50 mm 54 38.0
• 51-100 mm 55 38.7
• gt 100 mm 21 14.8
• NA 12 8.5
• Monofocal 124 87.3
• Multifocal 18 12.7

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AF - Treatment at referral

• N pts. NO SURGERY 142 100.0
• Wait See 83 58.5
• Any Medical Tx 59 41.5
• Chemotherapy 28 47.4
• Hormonal (anti-E) 20 33.9
• NSAIDs 2 3.4
• Imatinib 1 1.7
• ILP 3 5.1
• Multiple 5 8.8

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Primary AF WS approach
All Primary

• N pts. WS 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
• gt45 yrs 12 22.2

74 39 52.7 35 47.3 58 78.4 16 21.6 10 13.5
49 66.2 15 20.3
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Primary AF WS approach
All Primary

• N pts. WS 54
• Site Extr. / Girdles 12 22.2
• Abdominal wall 28 51.9
• Thoracic wall 7 13.0
• Trunk 1 1.9
• HN 1 1.9
• Intrabd. / Pelvic 5 9.1
• Monofocal 51 94.4
• Multifocal 3 5.6

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
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Primary AF WS approach
All Primary

• N pts. WS 54
• Size lt 50 mm 29 53.7
• 51-100 mm 21 38.9
• gt 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

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
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Cox Model
Variable Walds P-value Hazard Ratio 95 HR C.L. 95 HR C.L.
Any Tx vs WS 0.3992 0.744 0.374 1.479
Male vs Female 0.1737 1.536 0.828 2.848
26-45 yrs vs lt25 yrs 0.7907 0.909 0.448 1.842
gt45 yrs vs lt25 yrs 0.5603 0.793 0.364 1.730
Recurrent vs Primary 0.6199 0.860 0.473 1.562
Trunk vs Extremity 0.0593 2.091 0.972 4.502
HN vs Extremity 0.9973 0.997 0.223 4.456
Abdom wall vs Extremity 0.3047 1.616 0.646 4.042
Intrabdominal vs Extremity 0.5045 0.692 0.235 2.040
51-100 mm vs lt50 mm 0.8286 0.931 0.488 1.777
gt100 mm vs lt50 mm 0.0676 2.101 0.948 4.658
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WS treatment at PD
Surgery (first line) Surgery (first line) Surgery (first line) Surgery (first line) 3 / 19 16
1 ? Limb 100 ?
2 ? Abd wall 100 ? 120 ? 100 ? 120 ?
Surgery (second line) Surgery (second line) Surgery (second line) Surgery (second line) 3 / 19 16
1 ? Thor wall 150 ? After Hormonal CT After Hormonal CT
2 ? Abd wall 110 ? 100 ? After Hormonal After Hormonal
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Hormonal therapy Hormonal therapy Hormonal therapy Hormonal therapy 10 / 19 53
8 ? / 2 ? median 70 ? median 70 ?
Imatinib 1 / 19 5
1 ? Abd wall 65 ?
Chemotherapy Chemotherapy Chemotherapy Chemotherapy 2 / 19 11
1 ? Limb 1 ? HN
W S ( again ) W S ( again ) 3 / 19 16
1 ? Limb 90 ? 100 ? 90 ? 100 ? 90 ? 100 ?
2 ? Abd wall 50 ? 60 ? 34 ? 38 ? ( pregnant ) 50 ? 60 ? 34 ? 38 ? ( pregnant ) 50 ? 60 ? 34 ? 38 ? ( pregnant )
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WS 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)
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WS 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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PFS WS in Primary AF
Limbs
Abd wall
Other
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