E. Stoeckle

A critical analysis of treatment strategies in desmoid tumours: a review of a series of 106 cases

BACKGROUND The management of desmoid tumours, previously based on strategies employed for sarcomas, should be reassessed, given the morbidity of interventions used in their treatment. METHODS Long-term follow-up (median 123 months) of a series of 106 treated patients with 69 primary and 37 recurrent desmoids, in order to study natural history and outcome. RESULTS Desmoids typically evolved actively over a median period of 3 years, and stabilised thereafter. Recurrences or progression most commonly occurred between 14 and 17 months. Risk factors for recurrence were presentation (primary vs. recurrent), gender, tumour location and resection margins. However, survival was independent from these factors, with equivalent survival whether resection had been performed or not. Tumour control and functional outcome depended on location and presentation. Functional impairment was proportional to number of operations and whether patients had received radiotherapy. Recurrences were observed in 12/23 patients after radiotherapy. CONCLUSION Desmoids are relatively indolent tumours needing different approaches than sarcomas. Direct surgery is advisable only in primary lower trunk wall/girdle locations. Wait-and-see and medical treatment is preferable in other types of presentations.

Sporadic desmoid-type fibromatosis: a stepwise approach to a non-metastasising neoplasm—a position paper from the Italian and the French Sarcoma Group

Desmoid-type fibromatosis (DF) is a rare locally aggressive monoclonal proliferation of myofibroblasts lacking metastatic capacity. It may be observed in nearly every part of the body. Considering the variable clinical presentations, anatomic locations, and biologic behaviors, an individualized treatment approach is required. The pathogenesis of DF is not completely understood even if a high prevalence (∼85%) of CTNNB1 mutations discovered in sporadic DF underlies the importance of the Wnt/&bgr;-catenin pathway. No established and evidence-based approach for the treatment of this neoplasm is available as of today. Considering the unpredictable behavior and the heterogeneity of this disease, we propose a treatment algorithm approved by the French and the Italian Sarcoma Group, based on a front-line wait and see approach and subsequent therapy in the case of progression. A careful counseling at a referral center is mandatory and should be offered to all patients affected by sporadic DF from the time of their diagnosis.Desmoid-type fibromatosis (DF) is a rare locally aggressive monoclonal proliferation of myofibroblasts lacking metastatic capacity. It may be observed in nearly every part of the body. Considering the variable clinical presentations, anatomic locations, and biologic behaviors, an individualized treatment approach is required. The pathogenesis of DF is not completely understood even if a high prevalence (∼85%) of CTNNB1 mutations discovered in sporadic DF underlies the importance of the Wnt/β-catenin pathway. No established and evidence-based approach for the treatment of this neoplasm is available as of today. Considering the unpredictable behavior and the heterogeneity of this disease, we propose a treatment algorithm approved by the French and the Italian Sarcoma Group, based on a front-line wait and see approach and subsequent therapy in the case of progression. A careful counseling at a referral center is mandatory and should be offered to all patients affected by sporadic DF from the time of their diagnosis.

Retroperitoneal sarcomas: patterns of care in advanced stages, prognostic factors and focus on main histological subtypes: a multicenter analysis of the French Sarcoma Group

BACKGROUND Retroperitoneal sarcomas (RPS) are heterogeneous. Advanced stages include unresectable locoregional (LR) disease, abdominal sarcomatosis and distant metastasis. There is no available report assessing palliative chemotherapy in advanced RPS. This study analyzes management and outcome in a large cohort of patients with advanced RPS, considering main histological subtypes separately. PATIENTS AND METHODS We conducted a retrospective analysis of adult patients diagnosed with a RPS between 1 January 1988 and 31 December 2008 across 12 centers of the French Sarcoma Group. All cases were centrally reviewed by an expert pathologist. RESULTS Five-hundred eighty-six patients were included, 299 patients received palliative chemotherapy, with a median of two lines (range 0-8). Fifty patients underwent palliative surgery. Two hundred fifty-five patients (85%) were assessable for response after first line of chemotherapy. Among them, 69 patients (27%) had progressive disease, 145 (57%) had stable disease, 37 (14.5%) had partial response and 4 (1.5%) complete response. Median time from first line of palliative chemotherapy to progression was 5.9 months [4.9-7.3] and median overall survival (OS), 15.8 months [13-18]. In multivariate analysis, prognosis factors independently associated with poor OS were male gender, performance status (PS) >1 and grade >1. There was no difference according to stage of disease. Palliative surgery did not appear to add any survival benefit. CONCLUSION These results emphasize the scarcity of available options for RPS in the advanced setting and the urgent need to develop new strategies. Patients with good PS should be included in clinical trials and best supportive care should be considered in those with poor PS.BACKGROUND Retroperitoneal sarcomas (RPS) are heterogeneous. Advanced stages include unresectable locoregional (LR) disease, abdominal sarcomatosis and distant metastasis. There is no available report assessing palliative chemotherapy in advanced RPS. This study analyzes management and outcome in a large cohort of patients with advanced RPS, considering main histological subtypes separately. PATIENTS AND METHODS We conducted a retrospective analysis of adult patients diagnosed with a RPS between 1 January 1988 and 31 December 2008 across 12 centers of the French Sarcoma Group. All cases were centrally reviewed by an expert pathologist. RESULTS Five-hundred eighty-six patients were included, 299 patients received palliative chemotherapy, with a median of two lines (range 0-8). Fifty patients underwent palliative surgery. Two hundred fifty-five patients (85%) were assessable for response after first line of chemotherapy. Among them, 69 patients (27%) had progressive disease, 145 (57%) had stable disease, 37 (14.5%) had partial response and 4 (1.5%) complete response. Median time from first line of palliative chemotherapy to progression was 5.9 months [4.9-7.3] and median overall survival (OS), 15.8 months [13-18]. In multivariate analysis, prognosis factors independently associated with poor OS were male gender, performance status (PS) >1 and grade >1. There was no difference according to stage of disease. Palliative surgery did not appear to add any survival benefit. CONCLUSION These results emphasize the scarcity of available options for RPS in the advanced setting and the urgent need to develop new strategies. Patients with good PS should be included in clinical trials and best supportive care should be considered in those with poor PS.

Clinical outcome of leiomyosarcomas of vascular origin: comparison with leiomyosarcomas of other origin

BACKGROUND There are no data about the natural history of leiomyosarcoma of vascular origin (vLMS) in comparison with leiomyosarcoma (LMS) of other origin and about the management of advanced disease. METHODS Among 1472 patients diagnosed with sarcoma from January 1980 to December 2008 at our institution, 195 patients (13%) had LMS. LMS had a vascular origin in 14 cases (7%). RESULTS Patients with vLMS had a significantly worse median metastasis-free survival (MFS) (0.25 versus 9.6 years, P = 0.001) and overall survival (OS; 2.1 versus 7 years, P < 0.0001) than patients with LMS of other origin. On multivariate analysis, grade and vascular origin were the sole independent adverse prognostic factors for OS. Eight metastatic patients with vLMS received a first-line anthracycline chemotherapy regimen. Two patients had partial response, four had stable disease and two had progressive disease. OS of patients with metastatic vLMS was not significantly different from that observed in patients with metastatic LMS of other origin (22.1 versus 16.5 months, P = 0.84). CONCLUSIONS Vascular origin is an independent adverse prognostic factor for MFS and OS in patients with LMS. Patients with metastatic vLMS had a similar outcome than patients with metastatic LMS of other origin.

YWHAE rearrangement identified by FISH and RT-PCR in endometrial stromal sarcomas: genetic and pathological correlations

Endometrial stromal sarcomas represent the second most common mesenchymal uterine tumor. The 2003 WHO classification distinguishes low-grade and undifferentiated endometrial stromal sarcomas with different prognoses. Endometrial stromal sarcomas are a genetically heterogeneous group of sarcomas harboring different cytogenetic anomalies. Recently, a fusion between the YWHAE and FAM22A/B genes subsequent to a t(10;17) (q22;p13) has been described in endometrial sarcomas with high-grade histology. We examined YWHAE rearrangements by FISH break-apart and RT-PCR in a series of 27 undifferentiated uterine stromal sarcoma without JAZF1 rearrangements. Immunohistochemistry (IHC) was carried out with a panel of antibodies (estrogen (ER) and progesterone (PR) receptors, CD10, Cyclin D1, β-catenin, p53, and Ki-67). We identified a subgroup of endometrial sarcomas with high-grade histology and uniform morphology harboring YWHAE rearrangements. FISH break-apart was interpretable in 20 cases (74%). Twelve cases (60%) showed <10% of tumor cells with a YWHAE rearrangement, 4 cases (20%) showed between 10 and ≤20%, and 4 (20%) >20%. RT-PCR was tested on 24/27 cases (88%) and 19 cases were interpretable (79%). Five cases (26%) showed a specific fusion transcript YWHAE–FAM22A/B sequence. The best concordance rate between FISH and RT-PCR (94%) was obtained with the threshold of 20% of cells with a YWHAE rearrangement. The YWHAE-rearranged cases showed high-grade morphology with uniform appearance, spindle or round epithelioid cells, low ER and PR, CD10 expression, and a high and diffuse positivity for Cyclin D1, p53, and nuclear β-catenin negativity. Cyclin D1 was the most sensitive marker for high-grade endometrial sarcomas with YWHAE rearrangement. All undifferentiated uterine sarcomas with pleomorphic appearances did not harbor any YWHAE rearrangements, except for one case. Overall, for endometrial sarcoma cases with high-grade morphology we recommend to test for YWHAE rearrangements by FISH break-apart, a cost- and time-efficient method, and to complete the investigation by RT-PCR in borderline cases.

Soft tissue sarcomas of the trunk wall (STS-TW): a study of 343 patients from the French Sarcoma Group (FSG) database

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.

Soft tissue sarcoma in France in 2015: Epidemiology, classification and organization of clinical care.

Four thousand new cases of soft tissue sarcomas are diagnosed each year in France, 23% of which are localized in the abdomen and pelvis; the treatment of non-metastatic tumor is based on wide surgical resection, the quality of which determines the long-term outcome. To ensure appropriate care, the European Society of Medical Oncology (ESMO) recommends that any patient with an unexplained soft tissue mass (of any size for deep lesions or of>5cm for superficial lesions) be referred to a specialized center with capacities for multidisciplinary team decision; appropriate imaging should be performed prior to treatment and a percutaneous image-guided needle biopsy should be routinely performed. In France, clinical and pathology networks (NetSarc and RRePS) currently offer patients a structured means to make a systematic diagnosis of soft tissue sarcoma and help to provide access to appropriate treatment in a specialized center.

Adjuvant radiotherapy for extremity and trunk wall atypical lipomatous tumor/well-differentiated LPS (ALT/WD-LPS): a French Sarcoma Group (GSF-GETO) study

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 17cm (range 2-48cm). 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.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.

Recommandations pour la prise en charge des tumeurs stromales gastro-intestinales

Resume Contexte La prise en charge des tumeurs stromales gastro-intestinales (GIST) a considerablement evolue recemment, avec notamment la mise a disposition de l’imatinib. Les standards de prise en charge restaient mal definis. Nous rendons compte du travail d’un groupe d’experts francais sur l’adaptation francaise des recommandations de pratiques de l’Europeen Society of Medical Oncology (ESMO) recemment rapportees. Materiels et methodes Un groupe de vingt-deux experts francais s’est reuni pour analyser le document de consensus ESMO et l’adapter a la pratique francaise. Quatre groupes de travail ont ainsi revu les propositions concernant : l’anatomopathologie et la biologie moleculaire, l’imagerie en situation localisee ou metastatique et la prise en charge diagnostique des tumeurs de petite taille, la chirurgie des GIST localisees et metastatiques, le traitement systemique des GIST. Resultats L’examen histologique standard doit etre complete par une analyse immunohistochimique a l’aide des marqueurs CD117, CD34, PS100, Desmine et SMA. Le recours a la biologie moleculaire pour l’identification de la mutation des genes KIT et PDGFRA, est souhaitable pour les GIST presentant un immunomarquage negatif avec CD117 et pour predire la reponse au traitement, mais reste un examen de recherche. La chirurgie de la tumeur primaire doit comprendre une resection tumorale complete, incluant des marges tumorales negatives. L’administration d’imatinib en traitement adjuvant ou neoadjuvant est consideree comme une approche experimentale, a effectuer dans le cadre d’etudes cliniques prospectives. La resection des metastases est egalement consideree comme une procedure experimentale, avant, pendant ou apres echec d’un traitement par imatinib. Il est recommande d’instaurer l’imatinib des le diagnostic de recidive metastatique et de le poursuivre jusqu’a l’intolerance ou la progression multifocale de la maladie. Les criteres optimaux de reponse tumorale a l’imatinib font encore l’objet de travaux prospectifs. Ils peuvent inclure : une reduction de taille de la tumeur ou une stabilisation de la maladie, une diminution de la densite tumorale (unites Hounsfield) sur la TDM, une diminution de l’activite metabolique (mesuree par la captation de FDG sur TEP), la diminution de la vascularisation tumorale, mesuree par echo-Doppler avec injection de produit de contraste. Une augmentation de la taille de la tumeur ne traduit pas necessairement une progression et doit donc etre soigneusement evaluee, sans interrompre le traitement par imatinib avant confirmation definitive. Conclusion Les recommandations francaises pour la prise en charge des GIST adoptent la plupart des recommandations etablies par l’ESMO, et les completent du point de vue du gastroenterologue. Ce travail collegial a ete soumis a une revue de pathologie, de gastroenterologie et d’oncologie et son impact sur les pratiques sera evalue prospectivement.

Lymph node involvement in epithelial ovarian cancer: sites and risk factors in a series of 355 patients.

Objectives: To perform a cartography of lymph node metastases in epithelial ovarian cancer and to determine predictive factors of lymph node metastases. Method: The charts of 355 patients with epithelial ovarian cancer who underwent lymphadenectomy during a primary (n = 252) or secondary debulking surgery (n = 103) were analyzed. The topography of the lymph node metastases was notified for the whole group according to the stage of the disease, the histological type, and the moment of surgery. In patients who underwent a primary surgery before chemotherapy, independent prognostic variables for the risk of lymph node involvement were tested with a multivariate analysis. Independent prognostic factors were combined to determine risk profiles in individual patients. Results: The main area of the lymph node metastases was para-aortic. Isolated pelvic lymph node involvement was 10%. Three variables independently predicted lymph node invasion: advanced T stage, high-risk histological profile, and metastases. Conclusions: When lymphadenectomy is recommended, systematic lymph node dissections in the aortic and pelvic areas are warranted. An isolated pelvic lymph node assessment, particularly in the early stages, is inappropriate. By combining independent risk factors, a useful tool for individual risk assessment of lymph node involvement could be established, helping to decide whether to perform a lymph node dissection, especially at restaging surgery.