Aggressive extra-abdominal fibromatosis: can aggressive management be avoided in a subgroup of patients ? S. Bonvalot *, H. Eldweny *, V Haddad A. Le Cesne, G. Missenard *, P. Terrier D. Vanel, O. Oberlin, J.Y Blay C. Le Péchoux * Department of surgery, Gustave Roussy, Villejuif, France CTOS, VENEZIA, 2006

RATIONALE  Contrast between: -high rate of repeated recurrences -ever-decreasing possibilities of conservative surgery -But, low rate of reported amputations  Should the surgeon stop to operate when there is no further possibility of conservation?  Or, should we propose “ non surgical ” policy at the beginning of patient’s history instead of considering it at the end (by necessity) ?

Recurrent fibromatosis after surgery No 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 growth factors is ambiguous on potential microscopic residual disease and surgery could act as a tumor enhancer in aggressive fibromatosis  Presently, all clinical and evolutive forms are called the same way Objective of this retrospective study:  Impact of surgery as first line treatment

PATIENTS  June January 2005  112 patients with full data were considered  Sex ratio: 39 men/73 females  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 – 300 mm).  Median follow up: 80 months

Therapeutic strategies for primary lesions two groups : 1.surgical strategies with or without adjuvant treatment 2.non surgical strategies with systemic treatment or “wait and see” policy

Comparison of the 2 groups Surgery was performed more frequently before 1992 and for abdominal/chest wall or limbs

Surgical strategies for primaries  89 patients (79.5%)  60 patients (67%) had macroscopically complete surgery (R0 = 17, R1 = 43) (R0 = 17, R1 = 43)  Adjuvant treatments 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 affecting the distal limb developed an angiosarcoma 11 years later 1 patient treated with radiotherapy (50 Gy) for fibromatosis affecting the distal limb developed an angiosarcoma 11 years later

Non surgical strategies for primaries  23 patients (20.5%) had no surgery  12 patients had 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 “wait and see” policy

Evolution after medical treatment only  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 treated with hormonal therapy - 1 patient who received anti-inflammatory agents was treated with hormonal therapy - 2 patients had isolated limb perfusion with TNF and melphalan (ILP) (1 operated secondarily) - 2 patients had isolated limb perfusion with TNF and melphalan (ILP) (1 operated secondarily)

September 2006 September 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” policy  3/11 patients progressed: they received medical treatment (hormonal therapy followed by imatinib)  Secondarily, 2/3 patients with thoracic wall fibromatosis had to be operated because of continuous progression under medical treatment.

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

Non prognostic factors   Gender, age, tumor size   Date of primary treatment (before or after 1992)   Surgical/non surgical strategy

Primary tumor, EFS: 35 months 1rst recurrence, EFS: 40 months 2 nd recurrence, EFS: 50 months 3rd recurrence, EFS: 55 months Event free survival according to presentation

prognostic factors Univariate analysis Multivariate analysis 3 years EFS HRp P Tumor location Abdom/chest wall (n=46) Limb (n=33) Head and neck (n=16) Back (n=15) 64% 29% 43% 47% Quality of surgery/no surgery No surgery (n=23) R0 (n=<17) R1/R2/R? (n=72) 68% 65% 39%

Event-free survival according to the quality of surgery R0 No surgery R1,R2,R?

CONCLUSIONS  3 years EFS seems to be the same after non surgical treatment or R0 surgery, and progressive/recurrent patients could have the same biological characteristics  R1 surgery is deleterious (natural supply of growth factors on residual disease?)  Surgery could be avoided in 70% patients, and “wait and see” policy or systemic treatments should be considered before embarking on radical local treatment  In the future, biological factors could help to foresee the sub- group of patients at higher risk in order to adapt the treatment