Aggressive Aggressive extra-abdominal fibromatosisextra-abdominal fibromatosis: : can aggressive management be avoided can aggressive management be avoided

in a subgroup of patients ?in a subgroup of patients ?

S. BonvalotS. Bonvalot**, H. Eldweny, H. Eldweny**, V Haddad , V Haddad

A. Le Cesne, G. MissenardA. Le Cesne, G. Missenard**, P. Terrier , P. Terrier D. Vanel, O. Oberlin, J.Y Blay D. Vanel, O. Oberlin, J.Y Blay

C. Le PéchouxC. Le Péchoux* Department of surgery, Gustave Roussy, * Department of surgery, Gustave Roussy,

Villejuif, FranceVillejuif, France CTOS, VENEZIA, 2006

RATIONALERATIONALE

Contrast between:Contrast between:- high rate of repeated recurrences high rate of repeated recurrences - ever-decreasing possibilities of conservative surgeryever-decreasing possibilities of conservative surgery- But, low rate of reported amputationsBut, low rate of reported amputations

Should the surgeon stop to operate when there is Should the surgeon stop to operate when there is no further possibility of conservation?no further possibility of conservation?

Or, should we propose “ non surgical ” policy at the Or, should we propose “ non surgical ” policy at the beginning of patient’s history instead of beginning of patient’s history instead of considering it at the end (by necessity) ?considering it at the end (by necessity) ?

Recurrent fibromatosis after surgeryNo change 5 years later

Primary fibromatosis (surgical biopsy)No change 6 years later

Exemples of « wait and see » policy

Implication of surgery with its natural supply of Implication of surgery with its natural supply of growth factors is ambiguous on potential growth factors is ambiguous on potential microscopic residual disease and surgery could microscopic residual disease and surgery could act as a act as a tumortumor enhancer in aggressive enhancer in aggressive fibromatosisfibromatosis

Presently, all clinical and evolutive forms are Presently, all clinical and evolutive forms are called the same waycalled the same way

Objective of this retrospective study:Objective of this retrospective study: Impact of surgery as first line treatmentImpact of surgery as first line treatment

PATIENTSPATIENTS

June 1988 - January 2005June 1988 - January 2005 112 patients112 patients with full data were considered with full data were considered Sex ratio: 39 men/73 femalesSex ratio: 39 men/73 females Median age 30 years (range: 3 months-67 years) Median age 30 years (range: 3 months-67 years)

- 25 (22%) were younger than 15 years old - 25 (22%) were younger than 15 years old

- 87 (78 %) were older or 15 years old- 87 (78 %) were older or 15 years old Median size of primary was 60 mm (range: 10 –Median size of primary was 60 mm (range: 10 –

300 mm). 300 mm). Median follow up: 80 monthsMedian follow up: 80 months

Therapeutic strategies for Therapeutic strategies for primary primary lesionslesions

two groups : two groups :

1.1. surgical strategies with or without adjuvant surgical strategies with or without adjuvant treatmenttreatment

2.2. non surgical strategies with systemic non surgical strategies with systemic treatment or “wait and see” policytreatment or “wait and see” policy

Comparison of the 2 groupsComparison of the 2 groups Treatment of primary tumor Initial characteristic Surgery

(n=89) No surgery

(n=23) p

Sex 0.62 Male (n=39) 32 (36%) 7 (30%) Female (n=73) 57 (64%) 16 (70%) Age (year) at diagnosis* 30 (0-65) 30 (0-67) 0.99 Size (mm)* 60 (10-300) 68 (20-130) 0.75 Tumor location 0.03 Abdominal/chest wall (n=46) 38 (43%) 8 (36%) Limb (n=33) 31 (35%) 2 (9%) Head and neck (n=16) 10 (11%) 6 (27%) Back (n=15) 9 (10%) 6 (27%) Date of initial treatment 0.01 <1992 (n=26) 25 (28%) 1 (4%) 1992 (n=86) 64 (72%) 22 (96%)

Surgery was performed more frequently before 1992 and for abdominal/chest wall or limbs

Surgical strategies for primariesSurgical strategies for primaries

89 patients89 patients (79.5%) (79.5%) 60 patients (67%) had macroscopically complete surgery 60 patients (67%) had macroscopically complete surgery (R0 = 17, R1 = 43)(R0 = 17, R1 = 43) Adjuvant treatmentsAdjuvant treatments n = 22 (25%) n = 22 (25%) - 9 (10%): (hormonotherapy, anti-inflammatory agents) - 9 (10%): (hormonotherapy, anti-inflammatory agents) - 13 (15%) radiotherapy (mean 50 Gy, range 45-60)- 13 (15%) radiotherapy (mean 50 Gy, range 45-60)

1 patient treated with radiotherapy (50 Gy) for fibromatosis 1 patient treated with radiotherapy (50 Gy) for fibromatosis affecting the distal limb developed an angiosarcoma 11 affecting the distal limb developed an angiosarcoma 11 years lateryears later

Non surgical strategies for primariesNon surgical strategies for primaries

23 patients23 patients (20.5%) had no surgery (20.5%) had no surgery

12 patients had 12 patients had medical treatment:medical treatment: - anti-inflammatory agents (n=1) - anti-inflammatory agents (n=1) - hormonal therapy (n=7)- hormonal therapy (n=7) - systemic chemotherapy (n=1) - systemic chemotherapy (n=1) - imatinib (n=3)- imatinib (n=3)

11 patients had 11 patients had “wait and see” policy“wait and see” policy

Evolution after medical treatment onlyEvolution after medical treatment only

6/12 patients progressed: 6/12 patients progressed: - 3/12 were operated with R0 surgery - 3/12 were operated with R0 surgery - 1 patient who received anti-inflammatory agents was - 1 patient who received anti-inflammatory agents was

treated with hormonal therapy treated with hormonal therapy - 2 patients had isolated limb perfusion with TNF and - 2 patients had isolated limb perfusion with TNF and

melphalan (ILP) (1 operated secondarily)melphalan (ILP) (1 operated secondarily)

September 2006

September 2004

20 years old Female Fibromatosis of the thigh (CT biopsy)

September 2004: • 20% increase after medical treatment•ILP (TNF and Melphalan)

September 2006: stable disease

Evolution after “wait and see” policyEvolution after “wait and see” policy

3/11 patients progressed: they received medical 3/11 patients progressed: they received medical treatment (hormonal therapy followed by imatinib)treatment (hormonal therapy followed by imatinib)

Secondarily, 2/3 patients with thoracic wall Secondarily, 2/3 patients with thoracic wall fibromatosis had to be operated because of fibromatosis had to be operated because of continuous progression under medical treatment.continuous progression under medical treatment.

Aggressive fibromatosis of the chest wall arising near a breast prosthesis J Clin Oncol. 2003

Non prognostic factorsNon prognostic factors

Gender, age, tumor size Date of primary treatment (before or after

1992) Surgical/non surgical strategy

2022273137495876112

0%

20%

40%

60%

80%

100%

0 1 2 3 4 5 6 7 8

Years

PF

S r

ate

At risk

1a

35 25 21 13 9 8 7 7 5

0%

20%

40%

60%

80%

100%

0 1 2 3 4 5 6 7 8

Years

PF

S r

ate

At risk

1c

66 49 34 23 19 13 12 12 11

0%

20%

40%

60%

80%

100%

0 1 2 3 4 5 6 7 8

1b

PF

S r

ate

At risk

124458111214

0%

20%

40%

60%

80%

100%

0 1 2 3 4 5 6 7 8

Years

PF

S r

ate

At risk

1d

Primary tumor, EFS: 35 months

1rst recurrence, EFS: 40 months

2nd recurrence, EFS: 50 months

3rd recurrence, EFS: 55 months

Event free survival according to presentation

prognostic factorsprognostic factorsUnivariate

analysis

Multivariate

analysis

3 years EFS

HR p HR P

Tumor location

Abdom/chest wall (n=46)

Limb (n=33)

Head and neck (n=16)

Back (n=15)

64%

29%

43%

47%

1

2.86

2

1.67

0.005

1

2.45

2.21

1.63

0.04

Quality of surgery/no surgery

No surgery (n=23)

R0 (n=<17)

R1/R2/R? (n=72)

68%

65%

39%

1

0.97

2.23

0.01

1

1.16

2.07

0.09

6678101112131799121518263245725788912141823

0%

20%

40%

60%

80%

100%

0 1 2 3 4 5 6 7 8

Years

PF

S r

ate

R0R1,R2,R?No surgery

At risk

Event-free survival according to the quality of surgery

R0No surgery

R1,R2,R?

CONCLUSIONSCONCLUSIONS

3 years EFS seems to be the same after non surgical 3 years EFS seems to be the same after non surgical treatment or R0 surgery, and progressive/recurrent patients treatment or R0 surgery, and progressive/recurrent patients could have the same biological characteristicscould have the same biological characteristics

R1 surgery is deleterious (R1 surgery is deleterious (natural supply of growth factors natural supply of growth factors on residual disease?)on residual disease?)

Surgery could be avoided in 70% patients, and “wait and Surgery could be avoided in 70% patients, and “wait and see” policy or systemic treatments should be considered see” policy or systemic treatments should be considered before embarking on radical local treatment before embarking on radical local treatment

In the future, biological factors could help to foresee the sub-In the future, biological factors could help to foresee the sub-group of patients at higher risk in order to adapt the group of patients at higher risk in order to adapt the treatmenttreatment