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Background While the anti-PDGFRA antibody olaratumab failed to confirm an impact on survival in unselected advanced soft tissue sarcoma (STS) patients, the level of expression and the prognosis of platelet-derived growth factor (PDGF) receptors and ligands in STS remain unclear. Patients and methods We analyzed PDGF ligands and receptors' expression levels in a series of 255 patients with different histologies of STS [gastrointestinal stromal tumor (GIST), myxoid liposarcoma (MLPS), sarcoma with complex genomics, synovial sarcoma (SyS)] with Agilent single-color micro-arrays. We explored expression levels as prognostic values in univariate and multivariate analysis using R software (version 3.4.2). Results Complex patterns of correlation of expression between ligands and receptors were observed for each histotype. PDGFA levels were highest in SyS and lowest in MLPS (P < 4 × 10−9), PDGFB and C levels were lower in GIST (P < 2 × 10−15 and P < 3 × 10−9) while PDGFD expression was similar across histological subtypes. PDGF receptor (PDGFR) A expression was lowest in MLPS (P < 0.002), whereas PDGFRB and L expressions were lowest in GIST and SyS (P < 0.0004). Interestingly, high PDGFA expression levels were associated with higher risk of metastasis (P = 0.006), whereas PDGFD levels above average were associated with a reduced risk of metastasis (P = 0.01) in univariate and multivariate analysis. Conclusions The expression of PDGF ligands and receptors varies across sarcoma histological subtypes. PDGFA and D expression levels independently and inversely correlate with the risk of metastatic relapse., Highlights • The expression of PDGF ligands and receptors substantially varies across sarcoma histological subtypes. • PDGFA and D expression levels independently and inversely correlate with the risk of metastatic relapse. • The differential expression of ligands might be used as biomarker of efficacy for PDGFRα antibodies in STS.

International audience; Soft tissue sarcomas are a group of rare and aggressive connective tissue neoplasms for which curative therapeutic opportunities are limited in advanced phase. Clinical trials assessing immunotherapy in these tumors have so far reported limited efficacy. The objective of this study is to provide a description of the immunologic landscape of sarcomas to guide the next clinical trials of immunotherapy in these diseases. The gene expression profile of 93 immune checkpoint (ICP) and membrane markers (MM) of immune cells was analyzed in a series of 253 soft tissue sarcoma (synovial sarcoma, myxoid liposarcoma, sarcoma with complex genomic and GIST) using Agilent Whole Human Genome Microarrays. The unsupervised hierarchical clustering of gene expression level was found able to properly group patients according to the histological subgroup of sarcoma, indicating that each sarcoma subgroup is associated with a specific immune signature defined by its gene expression pattern. Using the prognostic impact of CIBERSORT signature on metastatic-free survival in each subgroup, specific target could be proposed for each of the four groups: Treg through ICOS and GITR in GIST, M0 macrophages in all four sarcoma subtypes, OX40 in SS, CD40 in GIST and SS. The immune landscape of sarcoma was found to be as heterogeneous as the histotypes and molecular subtypes, but strongly correlated to the histotype. Histotype adapted immunotherapeutic approaches in each sarcoma subtypes must be considered in view of these results, consistently with the already reported specific response of histotypes of ICPs.

Item does not contain fulltext Background: Solitary fibrous tumors (SFT) are rare unusual ubiquitous soft tissue tumors that are presumed to be of fibroblastic differentiation. At present, the challenge is to establish accurate prognostic factors. Patients and methods: A total of 214 consecutive patients with SFT diagnosed in 24 participating cancer centers were entered into the European database (www.conticabase.org) to perform univariate and multivariate analysis for overall survival (OS), local recurrence incidence (LRI) and metastatic recurrence incidence (MRI) by taking competing risks into account. A prognostic model was constructed for LRI and MRI. Internal and external validations of the prognostic models were carried out. An individual risk calculator was carried out to quantify the risk of both local and metastatic recurrence. Results: We restricted our analysis to 162 patients with local disease. Twenty patients (12.3%) were deceased at the time of analysis and the median OS was not reached. The LRI rates at 10 and 20 years were 19.2% and 38.6%, respectively. The MRI rates at 10 and 20 years were 31.4% and 49.8%, respectively. Multivariate analysis retained age and mitotic count tended to significance for predicting OS. The factors influencing LRI were viscera localization, radiotherapy and age. Mitotic count, tumor localization other than limb and age had independent values for MRI. Three prognostic groups for OS were defined based on the number of unfavorable prognostic factors and calculations were carried out to predict the risk of local and metastatic recurrence for individual patients. Conclusion: LRI and MRI rates increased between 10 and 20 years so relapses were delayed, suggesting that long-term monitoring is useful. This study also shows that different prognostic SFT sub-groups could benefit from different therapeutic strategies and that use of a survival calculator could become standard practice in SFTs to individualize treatment based on the clinical situation.

Les sarcomes sont des cancers rares et heterogenes, dont la prise en charge est complexe et non optimale pour la majorite des patients. Les trois elements cles de la prise en charge sont l’obtention d’un diagnostic avere, la discussion pluridisciplinaire du dossier en reunion de concertation pluridisciplinaire specialisee et la chirurgie effectuee dans une equipe entrainee. Afin d’ameliorer significativement la prise en charge des patients, trois reseaux nationaux anatomopathologiques et cliniques dedies aux sarcomes/GIST/tumeurs desmoides et constitues de centres experts regionaux ont ete structures en 2010 avec le soutien de l’Institut national du cancer et de la direction generale de l’Offre de soins: les reseaux RRePS, NetSarc et ResOs. Une base de donnees partagee a ete mise en oeuvre avec pour objectif de collecter differents indicateurs de qualite de prise en charge et de suivre leur evolution a l’echelle nationale. Apres cinq annees d’activite, les trois reseaux couvrent entre 73 et 91 % des 4 000 nouveaux patients annuels attendus. Cette organisation en reseaux de soins apporte de nombreux benefices pour les patients: elle permet de faciliter l’acces aux expertises anatomopathologiques et cliniques ainsi qu’une meilleure prise en charge initiale (imagerie, biopsie), une meilleure qualite de chirurgie et un meilleur acces aux traitements innovants. Cette organisation permet egalement de structurer la recherche, d’optimiser l’utilisation de techniques diagnostiques et la prescription de traitements couteux et de standardiser la collecte de donnees de prise en charge et de suivi a l’echelle nationale.

Background Prediction of metastatic outcome in sarcomas is challenging for clinical management since they are aggressive and carry a high metastatic risk. A 67-gene expression signature, the Complexity INdex in SARComas (CINSARC), has been identified as a better prognostic factor than the reference pathological grade. Since it cannot be applied easily in standard laboratory practice, we assessed its prognostic value using nanoString on formalin-fixed, paraffin-embedded (FFPE) blocks to evaluate its potential in clinical routine practice and guided therapeutic management. Methods A code set consisting of 67 probes derived from the 67 genes of the CINSARC signature was built and named NanoCind®. To compare the performance of RNA-seq and nanoString (NanoCind®), we used expressions of various sarcomas (n=124, frozen samples) using both techniques and compared predictive values based on CINSARC risk groups and clinical annotations. We also used nanoString on FFPE blocks (n=67) and matching frozen and FFPE samples (n=45) to compare their level of agreement. Metastasis-free survival and agreement values in classification groups were evaluated. Results CINSARC strongly predicted metastatic outcome using nanoString on frozen samples (HR=2.9, 95% CI: 1.23–6.82) with similar risk-group classifications (86%). While more than 50% of FFPE blocks were not analyzable by RNA-seq owing to poor RNA quality, all samples were analyzable with nanoString. When similar (risk-group) classifications were measured with frozen tumors (RNA-seq) compared with FFPE blocks (84% agreement), the CINSARC signature was still a predictive factor of metastatic outcome with nanoString on FFPE samples (HR=4.43, 95% CI: 1.25–15.72). Conclusion CINSARC is a material-independent prognostic signature for metastatic outcome in sarcomas and outperforms histological grade. Unlike RNA-seq, nanoString is not influenced by the poor quality of RNA extracted from FFPE blocks. The CINSARC signature can potentially be used in combination with nanoString (NanoCind®) in routine clinical practice on FFPE blocks to predict metastatic outcome.

Nodular fasciitis is a benign reactive lesion, often mistaken for a soft-tissue sarcoma in clinical practice. Involvement of the finger is rare, and a finger joint even rarer. We report on the clinical, radiological and histological features of intra-articular nodular fasciitis in a 52-year-old man, originating from the proximal interphalangeal joint of the right ring finger, with cortical erosion of adjacent bone. The discussion is focused on the tumor diagnosis and therapeutic approach, the differential diagnosis and the importance of immunohistochemical staining to establish the final diagnosis.

The natural history of localized high-grade sarcomas of the digestive tract (SDT) excluding GIST has been rarely considered owing to their low incidence and heterogeneity. We describe the histoclinical characteristics of SDT and correlate them with patients' outcomes.We retrospectively collected medical files from a European database covering connective tissue tumors listed in Europe for about twenty years. Only untreated localized primary high-grade SDT were included. A central histological review was performed for each case. Patients' characteristics were compared and correlated with clinical outcomes.A total of 45 patients were identified. Leiomyosarcomas (LMS) and undifferentiated sarcomas (UDS) were predominant, the former having better overall survival (OS) and progressionfree survival (PFS) while the latter having a worse outcome than the other histological types. Complete remission was obtained in 34 patients (75%) and was associated with male sex, age over 40 years and monofocal tumor. Complete surgery and LMS histology were associated with a better prognosis without any significant difference in baseline characteristics or in treatment modalities.Complete surgery and histological type seem to be prognostic indicators of SDT. These results suggest the importance of treating these patients in a reference center.

Background Sarcomas are rare but aggressive diseases. Specialized multidisciplinary management is not implemented for all patients in most countries. We investigated the impact of a multidisciplinary tumor board (MDTB) presentation before treatment in a nationwide study over 5 years. Patients and methods NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized MDTB, funded by the French National Cancer Institute to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma patients in France. Patients' characteristics and follow-up are collected in a database regularly monitored and updated. The management and survival of patients presented to these MDTB before versus after initial treatment were analyzed. Results Out of the 12 528 patients aged ≥15 years, with a first diagnosis of soft tissue and visceral sarcoma obtained between 1 January 2010 and 31 December 2014, 5281 (42.2%) and 7247 (57.8%) were presented to the MDTB before and after the initiation of treatment, respectively. The former group had generally worse prognostic characteristics. Presentation to a MDTB before treatment was associated with a better compliance to clinical practice guidelines, for example, biopsy before surgery, imaging, quality of initial surgery, and less reoperations (all P

BACKGROUND: Soft tissue sarcomas of the trunk wall (STS-TW) are usually studied together with soft tissue sarcomas of other locations. We report a study on STS-TW forming part of the French Sarcoma Group database. PATIENTS AND METHODS: Three hundred and forty-three adults were included. We carried out univariate and multivariate analysis for overall survival (OS), metastasis-free survival (MFS) and local recurrence-free survival (LRFS). RESULTS: Tumor locations were as follows: thoracic wall, 82.5%; abdominal wall, 12.3% and pelvic wall, 5.2%. Median tumor size was 6.0 cm. The most frequent tumor types were unclassified sarcoma (27.7%) and myogenic sarcoma (19.2%). A total of 44.6% of cases were grade 3. In all, 21.9% of patients had a previous medical history of radiotherapy (PHR). Median follow-up was 7.6 years. The 5-year OS, MFS and LRFS rates were 60.4%, 68.9% and 58.4%, respectively. Multivariate analysis retained PHR and grade for predicting LRFS and PHR, size and grade as prognostic factors of MFS. Factors influencing OS were age, size, PHR, depth, grade and surgical margins. The predictive factors of incomplete response were PHR, size and T3. CONCLUSIONS: Our results suggest similar classical prognostic factors as compared with sarcomas of other locations. However, a separate analysis of STS-TW revealed a significant poor prognosis subgroup of patients with PHR.

BACKGROUND The role of adjuvant radiotherapy (RT) in the management of atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WD-LPS) remains controversial. METHODS Two hundred eighty-three patients with operable ALT/WD-LPS, no history of previous cancer, chemotherapy (CT) or RT, treated between 1984 and 2011 registered in the Conticabase database were included and described. Overall (OS), progression-free survival (PFS) and time to local relapse (TTLR) were evaluated from the time of first treatment. RESULTS Three of 20 centers enrolled 58% of the patients. Median age at diagnosis was 61 (range 25-94) years, 147 patients (52%) were males, 222 (78%) patients had their primary tumor located in an extremity while 36 (13%) and 25 (9%) had tumors involving the girdle and the trunk wall, respectively. The median size of primary tumors was 17 cm (range 2-48 cm). Adjuvant RT was given to 132 patients (47%). Patients who received adjuvant RT had larger tumors (P = 0.005), involving more often the distal limbs (P < 0.001). Use of adjuvant RT varied across centers and along the study period. Other characteristics were balanced between the two groups. Median follow-up was 61.7 months. None of the patients developed metastasis during follow-up. The 5-year local relapse-free survival rates were 98.3% versus 80.3% with and without adjuvant RT, respectively (P < 0.001). Once stratified on time period (before/after 2003), adjuvant RT, tumor site and margin status (R0 versus other) were independently associated with TTLR. No OS difference was observed (P = 0.105). CONCLUSION In this study, adjuvant RT following resection of ALT/WD-LPS was associated with a reduction of LR risk.

Objectives To retrospectively evaluate the diagnostic performance of morphological signs observed on conventional magnetic resonance (MR) imaging to differentiate benign from malignant peripheral solid tumors of soft tissue with myxoid stroma. Methods MR images from 95 consecutive histopathologically proven tumors (26 benign and 69 malignant) of soft tissues with myxoid components were evaluated in our tertiary referral center. Two radiologists, blind to pathology results, independently reviewed conventional MR sequences including at least a) one T2-weighted sequence with or without fat suppression; b) one T1-weighted sequence without fat suppression; and c) one T1-weighted sequence with gadolinium-complex contrast enhancement and fat suppression. Multiple criteria were defined to analyze morphology, margins, architecture and tumor periphery and evaluated for each lesion. Intra- and inter-observer reproducibility and Odds ratios were calculated for each criterion. Results The most relevant and reproducible criteria to significantly predict malignancy were: (1) ill-defined tumor margins, (2) a hemorrhagic component, (3) intra-tumoral fat, (4) fibrosis and (5) the “tail sign”. A lesion is classified as malignant if any of these 5 criteria is present, and benign if none of them are observed. Therefore, this combination provides a sensitivity of 92.9% and a specificity of 93.3%. Conclusion Conventional MR imaging provides reproducible criteria that can be combined to differentiate between benign and malignant solid tumors of soft tissue with myxoid stroma.

BACKGROUND: Data regarding the role of systemic therapy in patients with advanced well-differentiated/dedifferentiated liposarcomas (WDLPS/DDLPS) are limited. METHODS: From 2000 to 2010, 208 patients with advanced WDLPS/DDLPS received chemotherapy in 11 participating institutions. Clinical and pathological data were collected by reviewing medical records. RESULTS: Median age was 63 years (range 32-84). Combination chemotherapy was delivered in 85 cases (41%) and single agent in 123 cases (59%), respectively. One hundred and seventy-one patients (82%) received an anthracycline-containing regimen. Using RECIST, objective response was observed in 21 patients (12%), all treated with anthracyclines. Median progression-free survival (PFS) was 4.6 months [95% confidence interval (CI) 3.3-5.9]. On multivariate analysis, age and performance status (PS) were the sole factors significantly associated with poor PFS. Median overall survival (OS) was 15.2 months (95% CI 11.8 -18.7). On multivariate analysis, grade and PS were the sole factors significantly associated with OS. CONCLUSIONS: Chemotherapy was associated with clinical benefit in 46% of patients with advanced WDLPS/DDLPS. OS remains poor, even though visceral metastatic disease is less frequent than in other sarcomas.

Clear cell sarcomas are aggressive, rare soft tissue tumors and their classification among melanoma or sarcoma is still undetermined due to their clinical, pathologic, and molecular properties found in both types of tumors. This is a retrospective study of 52 patients with CCS seen between April 1979 and April 2005 in two institutions. The EWS-ATF-1 fusion transcript was studied in 31 patients and an activating mutation of theBRAForNRASgene was researched in 22 patients. 30 men and 22 women, with a mean age of 33 were studied. Forty-three tumors (82.69%) were located in the extremities, specially the foot (19 tumors). Median initial tumor size was 4.8 cm (1 to 15 cm). Necrosis involving more than 50% of the tumor cells was found in 14 cases (26.92%). High mitotic rate (>10) was found in 25 cases (48.07%). The EWS/ATF-1 translocation was found in 28 (53.84%) of 31 patients studied, and mutation ofBRAForNRASwas found in only 2 of 22 patients analyzed cases (3.84%). Among the tumor-associated parameters, only tumor size (>4 cm) emerged as a significant prognostic factor. Forty-nine patients had a localized disease at diagnosis (94.23%) and underwent surgical resection immediately (90%) or after neoadjuvant chemotherapy (CT) (10%). Various CT regimens were used in 37 patients (71.15%) with no significant efficacy. The 5- and 10-year OS rates were 59% and 41%, respectively. Tumor size was the only emerging prognosis factor in our series. Complete surgical resection remains the optimal treatment for this aggressive chemoresistant tumor.

Introduction Nous rapportons 2 observations de dermatomyofibromes (DMF) cervicaux mimant un dermatofibrosarcome de Darier–Ferrand (DFSP). Observations Cas 1 : une femme de 32 ans presentait depuis 10 ans une plaque infiltree cervicale erythemateuse de 7 cm de grand axe ( Fig. 1 ). L’echographie montrait une masse hypoechogene s’etendant a l’hypoderme mais respectant l’aponevrose et les muscles sous-jacents. L’examen histologique d’une biopsie profonde mettait en evidence une proliferation infiltrant le derme reticulaire constituee de cellules fusiformes, sans atypie, disposees en faisceaux paralleles a la surface de l’epiderme. En immunohistochimie (IHC), le marquage avec le CD34 etait negatif, l’actine musculaire lisse (AML) etait positive de meme que le MMP11 (reactivite nucleaire) alors que les marquages avec la calponine, la desmine et la caldesmone etaient negatifs. La recherche d’une translocation (17;22) par hybridation in situ en fluorescence (FISH) etait negative. Le diagnostic de dermatomyofibrome (DMF) etait retenu et une chirurgie de type « slow-Mohs » proposee avec marges laterales de 1 cm. L’exerese etait incomplete. Il etait decide de ne pas poursuivre la chirurgie compte tenu de la benignite de la tumeur. Cas 2 : une femme de 28 ans presentait une plaque infiltree cervicale posterieure de 8 cm ( Fig. 2 ). L’imagerie en resonance magnetique (IRM) revelait une masse de 21 × 50 mm infiltrant le muscle trapeze. L’examen anatomopathologique de la biopsie profonde etait similaire a celui de la premiere patiente. En IHC le CD34 etait negatif, l’AML positive, la caldesmone negative. La calponine etait positive. La recherche de translocation (17;22) en FISH etait negative. Le diagnostic DMF etait donc retenu. Un suivi sans exerese etait decide. Discussion Le DMF est une tumeur benigne rare, avec seule une centaine de cas publies. Chez l’adulte, il survient le plus souvent chez des femmes jeunes alors que le sex-ratio est equilibre chez l’enfant. Cette difference entre enfants et adultes serait liee a une influence hormonale, non prouvee. Cliniquement ce sont des plaques infiltrees de couleur chair a brun-rouge habituellement de 1 a 2 cm de grand axe predominant sur les epaules. Histologiquement le DMF est constitue de cellules fusiformes monomorphes, sans atypie, sans mitose, regroupees en faisceaux allonges et entrelaces dans le derme reticulaire. Aucune anomalie cytogenetique n’a ete identifiee. Le profil immunohistochimique est stereotype : CD34−, AML+, desmine−, caldesmone−. La calponine serait un marqueur plus specifique, comme le suggere une etude pediatrique recente, meme si negative dans un de nos cas. Une exerese chirurgicale est le plus souvent preconisee, mais celle-ci est discutable pour une tumeur benigne surtout en cas de lesions etendues comme dans nos observations, ou l’exerese serait delabrante. Conclusion Le DMF est une pathologie rare pouvant mimer dans les formes evoluees un DFSP. Le diagnostic repose alors sur un faisceau d’arguments histologiques, immunohistochimiques et cytogenetiques.

International audience; Gastrointestinal stromal tumors (GISTs) are the most common human sarcoma. Most of the data available on GISTs derive from retrospective studies of patients referred to oncology centers. The MolecGIST study sought to determine and correlate clinicopathological and molecular characteristics of GISTs. Tumor samples and clinical records were prospectively obtained and reviewed for patients diagnosed in France during a 24-month period. Five hundred and ninety-six patients were included, of whom 10% had synchronous metastases. GISTs originated from the stomach, small bowel or other site in 56.4, 30.2 and 13.4% of cases, respectively. The main prognostic markers, tumor localization, size and mitotic index were not independent variables (P

Parmi les ossements recueillis dans une grotte sepulcrale du sud de la France, nous avons reconnu un cas de maladie de Paget polyostotique. La datation C14, apres calibration, donne un âge d’environ 3350 ans avant J.-C. Apres la description macroscopique, radiologique et microscopique de ces pieces, nous rapportons les elements de la revision des deux cas les plus anciens publies auparavant. Ces cas concernent des individus ayant vecu en Europe entre la fin du Neolithique et le Chalcolithique. Il est donc avere que la maladie de Paget etait deja presente a cette epoque, et au sud de l’Europe occidentale; aucun cas plus ancien n’a ete signale a ce jour.

Resume Introduction Nous rapportons trois nouveaux cas de fibromyxome acral superficiel (FAS) et discutons, d’une part, des caracteristiques anatomocliniques qui definissent cette tumeur fibreuse acrale peu frequente et, d’autre part, des diagnostics differentiels a evoquer devant un aspect de nodule ferme touchant les extremites. Observations Les trois lesions presentaient l’aspect clinique habituel d’un volumineux nodule solitaire de couleur chair deformant l’appareil ungueal d’un orteil ou d’un doigt. Les biopsies montraient, sur un fond fibromyxoide, une proliferation de cellules fusiformes sans atypies exprimant CD 34 de maniere diffuse et, de maniere focale et plus inconstante, l’ epithelial membrane antigen (EMA) et le CD 99. La recherche par FISH d’une translocation t(17 ; 22) est restee negative dans nos observations. Discussion Cette tumeur fibreuse acrale non exceptionnelle est meconnue. Elle peut parfois faire discuter histologiquement un dermatofibrosarcome myxoide, au pronostic radicalement different.

Background The predictive value of grade for benefit from adjuvant chemotherapy (AC) in soft tissue sarcoma (STS) patients has never been explored. Patients and methods From 1980 to 1999, 1513 adult patients with non-metastatic STS were included prospectively in the French Sarcoma Group database. Grade was assessed according to the Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) system after central review. Results AC was delivered to 13 grade 1 patients (3%), 145 grade 2 patients (35%) and 262 grade 3 patients (62%). Young age, non-well-differentiated liposarcoma histology, deep location, bone and/or neurovascular invasion and grade 2 or 3 were significantly associated with a higher likelihood to receive AC. Median follow-up was 9 years. On multivariate analysis, AC was significantly associated with improved metastasis-free survival (MFS) [5-year MFS: 58% versus 49%, hazard ratio (HR) 0.7 (95% confidence interval (CI) 0.6–0.9), P = 0.01] and overall survival (OS) [5-year OS: 58% versus 45%, HR 0.6 (95% CI 0.5–0.8), P = 0.0002] in grade 3 patients. This was not observed in grade 2 patients [5-year MFS: 76% versus 73%, HR 0.8 (95% CI 0.5–1.2), P = 0.27; 5-year OS: 75% versus 65%, HR 0.8 (95% CI 0.6–1.1), P = 0.15]. Conclusions This large cohort-based analysis with long-term follow-up indicates that patients with FNCLCC grade 3 disease may benefit from AC.

Resume Introduction Le fibroblastome a cellules geantes est une tumeur rare de malignite intermediaire appartenant au spectre du dermatofibrosarcome de Darier et Ferrand. Nous en rapportons une observation de presentation atypique. Observation Un enfant de quatre ans etait amene en consultation pour une masse perineoscrotale qui evoluait depuis l’âge de un an. D’apres les parents, la lesion initiale etait une macule bleutee perineale qui avait rapidement augmente de volume au decours d’un traumatisme. A l’examen clinique, on constatait une volumineuse tumefaction mollasse bilobee, s’etendant du rebord posterieur de la bourse gauche jusqu’a la marge anale. Le diagnostic d’hemolymphangiome etait evoque cliniquement. Les resultats de l’echographie et de l’imagerie en resonance magnetique (IRM) etaient compatibles avec cette hypothese. Compte tenu de la gene fonctionnelle et de la presentation clinique atypique, une exerese chirurgicale etait realisee. L’examen histologique de la piece operatoire concluait au diagnostic de fibroblastome a cellules geantes. En raison de la localisation de cette tumeur, la prise en charge chirurgicale du reliquat tumoral etait effectuee par la technique de Mohs lente. Trois ans apres l’intervention, aucun signe de recidive locale n’etait constate. Discussion L’interet de l’observation reside dans le caractere trompeur de cette presentation clinique pseudo-angiomateuse. Le recours a la technique de Mohs lente a permis de limiter le sacrifice tissulaire.

Gastrointestinal stromal tumours (GISTs) are the most frequent mesenchymal tumours of the digestive tract and occur typically in the stomach for two-third or in the small intestine for 25% in most series (Emile et al, 2004). Gain of function mutations of either KIT or platelet-derived growth factor receptor alpha polypeptide (PDGFRA) receptor tyrosine kinases play a critical role in GIST pathogenesis, and are found in 85% of GISTs (Rubin et al, 2007). Many types of gain of function mutations of KIT and PDGFRA have been described in GISTs, but 60% occurred within the exon 11 of KIT (Corless et al, 2004; Emile et al, 2004), which comprises 33 codons (codons 550–582). The two tyrosines Tyr568 and Tyr570, first residues to be phosphorylated during activation, are consensus sites for binding of Src family kinases and could be implicated in activation of different signalling pathways (Roskoski, 2005). More than 90 mutations of exon 11 have been published, and consist in insertions, substitutions and deletions; however, delWK557–558, in the proximal part of exon 11, is the most frequent, accounting for 8–25% of KIT exon 11 mutations. Others deletions, in the distal part of the exon, include in particular deletions of Tyr568 and/or Tyr570, and may thus have more specific effects on KIT signalling pathways and degradation. Such deletions account for 3–8% of exon 11 mutations in published series (Ernst et al, 1998; Taniguchi et al, 1999; Debiec-Rychter et al, 2004, 2006; Wardelmann et al, 2004; Martin et al, 2005; Penzel et al, 2005; Andersson et al, 2006; Emile et al, 2006; DeMatteo et al, 2008). After surgical resection, the type of KIT mutations may be a prognostic factor of relapse. KIT exon 11 deletions and deletions affecting codons 557–558 of KIT exon 11 were described to be independent adverse prognostic factors in patients with GIST (Wardelmann et al, 2003; Martin et al, 2005; DeMatteo et al, 2008). Conversely, in another study, GISTs in which the last part of exon 11 (codons 562–579) was deleted were most frequently associated with malignancy than GISTs with deletion of the first part of exon 11 (codons 550–561; Emile et al, 2004, 2006). So, the prognostic value of some types of KIT exon 11 mutations for risk of relapse is still debated. The mutational status of KIT or PDGFRA is predictive of clinical response to imatinib (Glivec, Gleevec, Novartis, Basel, Switzerland) and best results are obtained in patients with GISTs harbouring KIT exon 11 mutations (Heinrich et al, 2003; Debiec-Rychter et al, 2006). Nevertheless, the role of the type of KIT exon 11 mutations for the response and survival under imatinib remains to be determined. Thus, to better understand the prognostic significance of the type of KIT exon 11 deletions, we have compared the clinical characteristics and outcome of patients with GIST and deletion of both Tyr568 and Tyr570 with the most frequent deletion of KIT exon 11, delWK557–558.

Les sarcomes sont des tumeurs rares et variees representant un modele pour la mise en commun des donnees et du materiel tumoral collectes pour la realisation de travaux de recherche. Le Groupe Sarcome Francais a organise une banque de tumeurs virtuelle annotee nationale comportant actuellement 3 900 cas. Cette banque de tumeurs constitue l’un des axes principaux du reseau d’expertise de biopathologie des sarcomes soutenu par l’INCa. Le projet est maintenant de realiser une banque de tumeurs sur les sarcomes partages via Internet au niveau europeen dans le cadre du reseau d’excellence Conticanet.

Background Angiosarcomas are rare, heterogeneous and a retrospective study was conducted to describe their natural history. Patients and methods We reviewed 161 files of angiosarcoma treated in three institutions of the French Sarcoma Group from 1980 to 2004. Survival and prognostic factors for survival were analyzed. Results Median age was 52 years. Primary sites were the breast (35%), skin (20%) and soft tissues (13%). At initial diagnosis, 31 (19%) had metastases. Surgery was the first treatment in 121 (75%) patients combined with chemotherapy or radiotherapy in 34 and 32, respectively. Ninety (74%) of these 121 patients relapsed, mostly locally (50). With an average time since initial diagnosis of 8.1 years, 123 (76%) patients progressed and 76 (47%) died. Median survival was 3.4 years [95% confidence interval (CI) 2.4–5.8], and the 5-year overall survival (OS) rate was 43% (95% CI 33–53). In multivariate analysis, liver primary site [relative risk (RR) = 12.62], performance status (PS) of two or more (RR = 3.83), presence of metastases at diagnosis (RR = 2.50), soft tissue tumor (RR = 0.31) were correlated to OS. PS, liver and soft tissue tumors were identified as independent prognostic factors for progression-free survival. Conclusions Angiosarcomas have an overall poor outcome, but with a clearly distinct prognosis depending on the primary site.

Contexte La mise a jour des recommandations pour la pratique clinique (RPC) pour la prise en charge des patients atteints d’un sarcome des tissus mous a ete elaboree par la Federation nationale des centres de lutte contre le cancer (FNCLCC), en collaboration avec le Groupe sarcome francais et le Groupe d’etude des tumeurs osseuses (GSF-GETO), des partenaires des secteurs publics (CHU, CHG), prive et de l’Institut national du cancer sur la base de la methodologie developpee par les SOR.

Les tumeurs stromales du tube digestif (GIST) sont des tumeurs mesenshymateuses malignes rares, liees a une mutation fonctionnelle de c-kit ou de PDGFα. La prise en charge et le pronostic de ces tumeurs ont ete profondement modifies par un traitement cible specifique, l’imatinib mesylate. En effet, si la chirurgie reste le traitement essentiel des formes localisees, l’imatinib permet d’obtenir une reponse tumorale chez pres de 85% des patients metastatiques et une mediane de survie de cinq ans, contre 12 mois auparavant. L’evolution sous-traitement, comme l’histoire naturelle de la maladie, est etroitement correlee a la biologie tumorale et en particulier au statut mutationnel. La poursuite des efforts pour une meilleure comprehension des processus moleculaires impliques doit permettre d’optimiser la prise en charge des malades, que ce soit par une meilleure utilisation des traitements existants, en particulier en precisant la place de la chirurgie dans la maladie metastatique, le role eventuel du niveau d’exposition a l’imatinib dans la cinetique de survenue de resistances, l’interet en traitement adjuvant de l’imatinib, ou la place des nouvelles molecules disponibles telles que le sunitinib.

Context The National French Federation of Comprehensive Cancer Centres (FNCLCC) initiated the update of clinical practice guideline for the management of patients with soft tissue sarcoma in collaboration with the French Sarcoma Group (GSF-GETO), specialists from French public universities, general hospitals and private clinics and with the French National Cancer Institute. This work is based on the methodology developed in the "Standards, Options and Recommendations" (SOR) project. Objectives To update SOR guidelines for the management of patients with soft tissue sarcoma previously validated in 1995. Methods The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGsaccording to the definitions of the Standards, Options and Recommendations project. Once the guidelines have been developed, they are reviewed by independent reviewers. Results This article presents the updated recommendations for radiotherapeutic management. The main recommendations are: 1) irradiation before or after surgical treatment is the standard for soft tissue sarcoma of the extremity and uterine sarcoma; 2) no systematic irradiation should be done in case of retroperitoneal sarcoma.

Resume Objectifs. – Analyse retrospective du traitement et identification des facteurs pronostiques des premieres rechutes locales isolees de sarcomes des tissus mous (tronc ou extremites). Patients et methodes. – Il s’agit d’une etude retrospective portant sur une cohorte de 83 patients adultes traites entre 1980 et 1999. La taille tumorale moyenne etait de 6 cm. La plupart des sarcomes etaient situes au niveau des extremites (n = 74), etaient profonds (n = 60), et proximaux (n = 53) ; trente etaient au contact des axes vasculonerveux. Il s’agissait principalement de 49 % d’histocytofibrosarcomes et de liposarcomes (20 %), de grade 2 (42 %) ou 3 (36 %), selon les criteres de la Federation nationale des centre de lutte contre le cancer (FNCLCC). Le traitement chirurgical de la rechute locale a consiste en une exerese large dans 32 cas, une resection marginale dans 46 cas, et cinq patients ont du avoir une amputation. Les tranches de section d’exerese ont ete classees R0 (n = 33), R1 (n = 47) et R2 (n = 3). Six patients ont recu une chimiotherapie neoadjuvante et sept patients une chimiotherapie adjuvante. Vingt-trois patients ont recu une irradiation externe postoperatoire de dose moyenne 55 Gy et 26 une curietherapie interstitielle de bas debit de dose par iridium 192 de dose moyenne de 45 Gy si delivree seule, et de 22 Gy si associee a la radiotherapie externe, 19 patients ayant ete re-irradies. Resultats. – Avec un suivi en mediane de 59 mois, 37 patients (45 %) ont souffert d’une rechute, uniquement locale pour 61 % d’entre eux. Dix-neuf patients ont eu secondairement des metastases a distance. En analyse multifactorielle, seule la profondeur tumorale (p = 0,05) et la reintervention chirurgicale lors de la prise en charge de la recidive apres une premiere chirurgie incomplete (p = 0,018) etaient des facteurs pronostiques de survie sans rechute, la radiotherapie (externe et/ou interstitielle) etant significative uniquement apres analyse unifactorielle (p = 0,05). Les taux de survie globale etaient respectivement de 73, 54 et 47 % a 3, 5 et 10 ans et decroissaient respectivement a 65, 35 et 32 % apres la seconde rechute locale. Apres analyse multifactorielle, la localisation tumorale au niveau du tronc (p = 0,0001) ou des membres inferieurs (p = 0,023), les tumeurs symptomatiques (p = 0,001), profondes (p = 0,01) et de haut grade (p = 0,01), ainsi que la survenue d’une seconde rechute locale (p = 0,004) etaient des facteurs pronostiques independants de survie globale. Conclusion. – L’analyse des resultats obtenus dans cette serie montre qu’une premiere rechute locale isolee de sarcome des tissus mous augmente considerablement le risque de developper une nouvelle rechute locale. La qualite du traitement local de la premiere rechute est capitale. Lorsqu’un traitement conservateur est envisageable, il doit autant que possible associer exerese chirurgicale et radiotherapie externe, la curietherapie etant prioritairement reservee aux rechutes en territoire irradie. Les efforts doivent etre poursuivis pour ameliorer la qualite de la prise en charge des tumeurs primitives au mieux realisee dans des centres experimentes.

We have earlier devised a system for soft tissue sarcoma (STS), based on three negative prognostic features: large tumour size, vascular invasion, and microscopic tumour necrosis, the SIN-system. Tumours which exhibit 2 or 3 of these features are categorised as high-risk, the others as low-risk. We have now tested this system for reproducibility both as regards recognition of its components, and as regards prognostic strength in patients from another institution. We have also compared it with the American Joint Committee on Cancer (AJCC) system. 200 patients with STS were analysed, all had been treated by surgery, in 97 patients combined with radiotherapy. The median follow-up for the 117 survivors was 10 (1.5-27) years. Without knowledge of the clinical data, three groups of pathologists independently reviewed original slides from all of the tumours. Based on the factors, the tumours were classified as high-risk or low-risk. The prognostic strength was compared using the results obtained by the different observers. Concordance in recognition of vascular invasion, tumour necrosis, and overall grading was seen in 156 (78%), 154 (77%), and 167 (84%) of the 200 tumours, respectively. Based on the different observers' grading, the cumulative 5-year metastasis-free survival rate (MFSR) varied for patients with low-risk tumours between 0.85 and 0.80, and for patients with high-risk tumours between 0.48 and 0.43. The Kappa-value for grading between all three groups of observers was 0.77. The SIN-system gave more clinically useful prognostic information than the AJCC system. Useful prognostic information in STS can be obtained by using tumour size, vascular invasion and microscopic tumour necrosis. This system provides two distinct prognostic groups, and has a high reproducibility.

Introduction Chez l’adulte, les sarcomes des tissus mous forment un groupe heterogene de tumeurs malignes rares. L’histoire naturelle de ces tumeurs differe en fonction de facteurs pronostiques intrinseques (sous type histologique, grade…) et extrinseques (qualite de la chirurgie, centre de prise en charge…). Les sarcomes dits a translocation recurrente constituent un sous-ensemble de tumeurs (Synovialosarcome, Ewing…) qui possede une mutation caracterisee par un echange reciproque de materiel chromosomique. Ils representent 20 % des sarcomes, surviennent generalement chez les personnes jeunes, sont agressifs et ont un potentiel metastatique important. L’objectif de cette etude est de decrire les caracteristiques diagnostiques et les traitements des patients atteints d’un sarcome a translocation et de comparer ces caracteristiques dans les deux groupes de patients : sarcomes a translocation versus les autres. Methodes Cette etude retrospective multicentrique a ete conduite chez les patients atteints d’un sarcome traite dans l’un des 22 centres de reference du Groupe Sarcome Francais (GSF) et enregistres dans la « Conticabase ». Cette base de donnees clinico–biologique a grande dimension comporte 16 422 patients dont 12 711 atteints de sarcomes, sur la periode 1980–2016. Elle contient les informations liees a la tumeur primaire, au traitement et au suivi des patients. Dans cette base, les diagnostics ont ete relus de maniere systematique par des pathologistes experts et codes selon la classification de l’Organisation mondiale de la sante 2013. Les comparaisons entre les deux groupes de patients (sarcomes a translocation versus les autres) ont ete realisees a l’aide de test non parametrique pour les variables quantitatives et test du Chi-deux pour les variables qualitatives. Resultats Parmi les 10 262 patients presentant un sarcome et inclus dans la Conticabase entre le 1er janvier 1980 et le 31 decembre 2013, 2143 (20,8 %) sont atteints d’un sarcome a translocation, dont 1135 hommes (53,0 %). Ces patients ont principalement des tumeurs dites profondes (93,3 %) et localisees dans les membres (60,5 %). Compare aux autres sarcomes, les patients avec un sarcome a translocation ont un âge median plus faible (40,6 versus 60,0 ; p Conclusion Les sarcomes a translocation presentent un profil specifique et different en termes de caracteristiques initiales (demographiques, traitements anterieurs, caracteristiques de la tumeur primaire). La qualite des donnees bio-pathologiques comme des donnees cliniques enregistrees dans cette base au niveau national via les reseaux de tumeurs rares est un apport pour identifier ou valider des caracteristiques utiles pour etudier le pronostic des patients.

Soft-tissue sarcomas (STSs) are rare tumors with varied histological presentations. Management and treatment are thus complex, but crucial for patient outcomes. We assess adherence to adult STS management guidelines across two French regions (10% of the French population). We also report standardized incidence.STS patients diagnosed from 1 November 2006 to 31 December 2007 were identified from pathology reports, medical hospital records, and cancer registries. Guideline adherence was assessed by 23 criteria (validated by Delphi consensus method), and age and sex-standardized incidence rates estimated. Associations between patient, treatment, and institutional factors and adherence with three major composite criteria relating to diagnostic imaging and biopsy as well as multidisciplinary team (MDT) case-review are reported.Two hundred and seventy-four patients were included (57.7% male, mean age 60.8 years). Practices were relatively compliant overall, with over 70% adherence for 10 criteria. Three criteria with perfect Delphi consensus had low adherence: receiving histological diagnosis before surgery, adequacy of histological diagnosis (adherence around 50% for both), and MDT discussion before surgery (adherence30%). Treatment outside of specialized centers was associated with lower adherence for all three composite criteria, and specific tumor sites and/or features were associated with lower adherence for diagnostic imaging, methods, and MDT meetings. STS standardized incidence rates were 4.09 (European population) and 3.33 (World) /100 000 inhabitants.Initial STS diagnosis and treatment across all stages (imaging, biopsy, and MDT meetings) need improving, particularly outside specialized centers. Educational interventions to increase surgeon's sarcoma awareness and knowledge and to raise patients' awareness of the importance of seeking expert care are necessary.

Pre-clinical data have suggested a therapeutic role of Hedgehog (Hh) pathway inhibitors in chondrosarcoma.This phase II trial included patients with progressive advanced chondrosarcoma. They received GDC-0449 150 mg/day (days 1-28, 28-day cycle). The primary end point was the 6-month clinical benefit rate (CBR) defined as the proportion of patients with non-progressive disease at 6 months. A 6-month CBR of 40% was considered as a reasonable objective to claim drug efficacy.Between February 2011 and February 2012, 45 patients were included. Twenty had received prior chemotherapy. Thirty-nine were assessable for efficacy. The 6-month CBR was 25.6% (95% confidence interval 13.0-42.1). All stable patients had grade 1 or 2 conventional chondrosarcoma with documented progression within the 6 months before inclusion. All but one with available data also had overexpression of the Hh ligand. Median progression-free and overall survivals were 3.5 and 12.4 months, respectively. The most frequent adverse events were grade 1 or 2 myalgia, dysgeusia and alopecia.GDC-0449 did not meet the primary end point of this trial. Results suggest some activity in a subset of patients with progressive grade 1 or 2 conventional chondrosarcoma. Further studies assessing its role in combination with chemotherapy are warranted.NCT01267955.

PDGFRA is mutated in 5%–10% of gastrointestinal stromal tumors (GISTs), the PDGFRA D842V mutation accounting for ∼60% of all PDGFRA mutations known in GISTs [1]. The DIMH842–845 and the IMH843–846 deletions represent ∼15% of all PDGFRA mutations. While the latter have been associated with sensitivity to imatinib, the PDGFRA D842V mutation confers primary resistance to imatinib [1–4], sunitinib [5], and nilotinib [6]. In vitro data suggested that dasatinib is a potent inhibitor of PDGFRA D842V [7]. Sorafenib also displayed some intermediate efficacy even if it was significantly lower than for PDGFRA ΔDIM842–844 [7]. Given the rarity of metastatic GIST with PDGFRA mutation, clinical data in this setting are almost nonexistent [8]. We report here a series of five patients with metastatic GIST bearing a mutation of the exon 18 of PDGFRA and treated with sorafenib (400 mg twice daily).

Background:Data regarding the role of chemotherapy (CT) in patients with recurrent and/or unresectable desmoid tumors (DTs) are scarce. Patients and methods:Records of patients with DT who were treated with CT in centers from the French Sarcoma Group were reviewed. Results:Sixty-two patients entered the study. The two most common locations were extremities (35.5%) and internal trunk (32.5%). Twelve patients (19.5%) were diagnosed with Gardner syndrome. Thirty-seven patients (54.7%) received previously one or more lines of systemic therapies (nonsteroidal anti-inflammatory drugs: 43.5%, antiestrogens: 43.5% and imatinib: 30.5%). Combination CT was delivered in 44 cases (71%) and single agent in 18 patients (29%), respectively. Thirteen patients (21%) received an anthracycline-containing regimen. The most frequent nonanthracycline regimen was the methotrexate‐vinblastine combination (n=27). Complete response, partial response, stable disease and progressive disease were observed in 1 (1.6%), 12 (19.4%), 37 (59.6%) and 12 (19.4%) patients, respectively. The response rate was higher with anthracycline-containing regimens: 54% versus 12%,P= 0.0011. Median progression-free survival (PFS) was 40.8 months. The sole factor associated with improved PFS was the nonlimb location: 12.1 months (95% confidence interval 5.6‐18.7) versus not reached,P=0.03. Conclusions:CT has significant activity in DT. Anthracycline-containing regimens appear to be associated with a higher response rate.

This review reports the main gene signature specific for the diagnosis, prognosis or prediction of drug response in sarcomas. Almost half of sarcomas show a simple genetic lesion which is specific for the diagnosis: recurrent translocations in 10 to 15% of sarcomas, specific activating and inactivating mutations in GIST and rhabdoid tumor respectively, and MDM2 amplification in well-differentiated and dedifferentiated liposarcomas as well as in intimal sarcoma. A recent study reported a gene expression signature which is much better than histological grading for predicting metastasis outcome. This signature is composed of 67 genes all belonging to pathways involved in chromosome integrity suggesting an important role of these mechanisms in the development of metastases. On the other hand, and except for GIST with KIT and PDGFRA mutations, there is no validated predictive gene signature so far.