Les sarcomes cutanés sont des tumeurs malignes issues du tissu conjonctif commun ou spécialisé et du tissu nerveux. Ils peuvent prendre leur origine dans le derme ou dans les tissus cutanés profonds sus- et sousaponévrotiques. Il s'agit de tumeurs qui nécessitent une prise en charge dans des centres spécialisés car elles posent des problèmes difficiles de diagnostic anatomopathologique, d'évaluation pronostique et de stratégie thérapeutique, du fait de leur rareté, de leur diversité histologique et de leur hétérogénéité évolutive.
9550 Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue sarcoma of intermediate malignant potential. Treatment relies on a wide local excision with negative margin with frequent need of reconstructive surgery. A translocation between chromosomes 17 and 22 that places PDGFB under the control of the collagen 1A1 promoter is present in > 90% of the cases leading to an up regulation of PDGFB expression and activation of the tyrosinase kinase PDGFRβ. Anecdotal reports and a report on 8 patients suggest that Imatinib mesylate (IM) has a clinical interest in DFSP. The primary aim of this phase II multicentric study is to define the percentage of clinical responders (RECIST) to a preoperative 2 months 600mg IM daily before wide local excision. The secondary goals are to determine tolerance, imaging (ultrasound and MRI), pathological responses and to analyse PDGFRβ phosphorylation status and tumour cell apoptosis in sequential tissues specimen. Fifteen adults suffering from primary or recurrent DFSP have been included since July 2004. All tumors had a diameter ≥2cm. A flexible design with interim analysis after recruitment of 6 patients was used. 18 to 28 patients had to be enrolled to detect a 30% response rate with power 80%, using a one-sided test against 5%, at the 2.5% level. Three men and 3 women, median age 48.4 years [23; 72.5] have been evaluated. Tumour characteristics are as follows : primary (n=4), recurrence (n=2) all involved trunk, median size 5.75cm [2.5–12]. Tolerance was good apart from grade 1 facial oedema (n=6) grade 2 maculopapular rash (n=1), grade 1 asthenia (n=1), grade 1 pyrosis (n=2). Translocation t(17;22) was detected in all tumours. A partial response was achieved in 3 of 6 patients. The median relative decrease of tumor in the PR and non responder patients was of 21.9% [−3.3; 72.0]. Histological analysis revealed a global decrease of cellularity often accompanied with a CD34 loss of expression, a fibrosis and mild peripheral lymphoid infiltrates. No evidence of apoptosis on tissue specimen after surgery was observed using TUNEL. These encouraging interim results weresubmitted to an independent committee who allowed to continue the trial and to include a total of 24 patients in order to reduce the confidence interval of response rate. [Table: see text]
