Improved nationwide survival of sarcoma patients with a network of reference centers.

BACKGROUND: We investigated the impact of the implementation of a network of reference centers for sarcomas (NETSARC) on the care and survival of sarcoma patients in France since 2010. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTBs), funded by the French National Cancer Institute (INCa) since 2010. Its aims are to improve the quality of diagnosis and care of sarcoma patients. Patients' characteristics, treatments, and outcomes are collected in a nationwide database. The objective of this analysis was to compare the survival of patients in three periods: 2010-2012 (non-exhaustive), 2013-2015, and 2016-2020. RESULTS: A total of 43 975 patients with sarcomas, gastrointestinal stromal tumors (GISTs), or connective tissue tumors of intermediate malignancy were included in the NETSARC+ database since 2010 (n = 9266 before 2013, n = 12 274 between 2013 and 2015, n = 22 435 in 2016-2020). Median age was 56 years, 50.5% were women, and 13.2% had metastasis at diagnosis. Overall survival was significantly superior in the period 2016-2020 versus 2013-2015 versus 2010-2012 for the entire population, for patients >18 years of age, and for both metastatic and non-metastatic patients in univariate and multivariate analyses (P < 0.0001). Over the three periods, we observed a significantly improved compliance to clinical practice guidelines (CPGs) nationwide: the proportion of patients biopsied before surgery increased from 62.9% to 72.6%; the percentage of patients presented to NETSARC MDTBs before first surgery increased from 31.7% to 44.4% (P < 0.0001). The proportion of patients with R0 resection on first surgery increased (from 36.1% to 46.6%), while R2 resection rate decreased (from 10.9% to 7.9%), with a better compliance and improvement in NETSARC centers. CONCLUSIONS: The implementation of the national reference network for sarcoma was associated with an improvement of overall survival and compliance to guidelines nationwide in sarcoma patients. Referral to expert networks for sarcoma patients should be encouraged, though a better compliance to CPGs can still be achieved.

Sclerosing Epithelioid Fibrosarcoma (SEF) versus Low Grade Fibromyxoid Sarcoma (LGFMS): Presentation and outcome in the nationwide NETSARC+ series of 330 patients over 13 years.

Sclerosing Epithelioid Fibrosarcoma (SEF) and Low Grade Fibromyxoid Sarcoma (LGFMS) are ultrarare sarcomas sharing common translocations whose natural history are not well known. We report on the nationwide exhaustive series of 330 patients with SEF or LGFMS in NETSARC+ since 2010. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTB). Since 2010, (i) pathological review has been mandatory for sarcoma,and (ii) tumour/patients' characteristics have been collected in the NETSARC+ nationwide database. The characteristics of patients with SEF and LGFMS and their outcome are compared. RESULTS: 35/73 (48%) and 125/257(49%) of patients with SEF and LGFMS were female. More visceral, bone and trunk primary sites were observed in SEF (p < 0.001). 30% of SEF vs 4% of LGFMS patients had metastasis at diagnosis (p < 0.0001). Median size of the primary tumor was 51 mm (range 10-90) for LGFMS vs 80 (20-320) for SEF (p < 0.001). Median age for LGFMS patients was 12 years younger than that of SEF patients (43 [range 4-98] vs 55 [range 10-91], p < 0.001). Neoadjuvant treatment was more often given to SEF (16% vs 9%, p = 0.05). More patients with LGFMS were operated first in reference centers (51% vs 26%, p < 0.001). The R0 rate on the operative specimen was 41% in LGFMS vs 16% in SEF (p < 0.001). Median event-free survival (EFS) of patients with SEF and LGFMS were 32 vs 136 months (p < 0.0001). The median overall survival (OS) was not reached. Fifty-months OS was 93% vs 81% for LGFMS vs SEF (p = 0.05). Median OS was 77 months after first relapse, similar for SEF and LGFMS. In multivariate analysis, age, tumor size, metastasis at diagnosis were independent prognostic factors for OS in LGFMS. CONCLUSIONS: Although sharing close molecular alterations, SEF and LGFMS have a different natural history, clinical presentation and outcome, with a higher risk of metastatic relapse in SEF. Survival after relapse is longer than with other sarcomas, and similar for SEF and LGFMS.

Epithelioid hemangio-endothelioma (EHE) in NETSARC: The nationwide series of 267 patients over 12 years.

EPITHELIOID HEMANGIOENDOTHELIOMA: A NATIONWIDE STUDY: Epithelioid hemangioendothelioma (EHE) is an ultrarare sarcoma whose natural history and treatment is not well defined. We report on the presentation and outcome of 267 patients with EHE in the NETSARC+ network since 2010 in France. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centres with specialised multidisciplinary tumour boards (MDTB), funded by the French National Cancer Institute (NCI), Institut National du Cancer (INCA). Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma patients. Patients' characteristics are collected in a nationwide database regularly monitored with stable incidence since 2013. The characteristics of patients with EHE at diagnosis are presented as well as progression-free survival (PFS), overall survival (OS), and outcome under treatment. RESULTS: Two hundred and sixty-seven patients with EHE were included in the NETSARC+ database since 2010. Median age in the series was 51 (range 10-90) years, 58% were women. Median tumour size was 37 mm (4-220). Forty-eight percent, 42%, and 10% were visceral, soft parts, or bone primaries. The most frequent sites were liver (28%), lung (13%). 40% were reported to have systemic (i.e. multifocal or metastatic disease) at diagnosis. With a median follow-up of 20 months, OS and PFS rates at 24 months were 82% and 67%, with 10-year projected OS and PFS of 62% and 21% respectively. Male and M+ patients at diagnosis had a significantly worse OS, but not PFS. Local treatment was associated with a favourable survival in localised but not in patients with advanced stage at diagnosis. For 23 patients receiving medical treatment, PFS and OS were 50.2% and 33.2% at 60 months were respectively. CONCLUSIONS: EHE is a frequently metastatic sarcoma at diagnosis with a unique natural history. This study shows in a nationwide series over 12 years that most patients progressed but are still alive at 10 years, both in localised and metastatic stages.

Patterns of care and outcomes of 417 patients with METAstatic SYNovial sarcoma (METASYN): real-life data from the French Sarcoma Group (FSG).

BACKGROUND: Synovial sarcoma (SS) occurs in both adult and pediatric patients. The primary aim of this study is to describe the outcomes, prognostic factors, and treatment of patients with metastatic SS within a nationwide cohort. PATIENTS AND METHODS: All pediatric and adult patients with metastatic SS are registered in the French Sarcoma Group database. Data were collected from the national database https://conticabase.sarcomabcb.org/ up to March 2020. Descriptive and comparative analyses were conducted using SAS 9.4 and Stata Special Edition 16.1 software. RESULTS: Between January 1981 and December 2019, 417 patients with metastatic SS from 17 French sarcoma centers were included, including 64 (15.3%) under the age of 26 years. Median age was 42.5 years (range 9-87 years). The metastases were synchronous (cohort 1) or metachronous (cohort 2) in 18.9% (N = 79) and 81.1% (N = 338) patients, respectively. Median overall survival (OS) from the date of metastasis was 22.3 months (95% confidence interval 19.7-24.1 months). First-line chemotherapy without ifosfamide and/or doxorubicin was unfavorable for progression-free survival and OS (P < 0.001). Concerning cohort 1, young age, surgery of the primary tumor, and single metastatic site were independent favorable prognostic factors for OS. In cohort 2, surgery within an expert French Sarcoma Group center, absence of chemotherapy in the perioperative setting, the lungs as a single metastatic site, time to first metastasis >12 months, local therapy, and ifosfamide in the first metastatic line were independent favorable prognostic factors. CONCLUSIONS: The outcome of patients with metastatic SS is influenced by local treatment, management in reference centers, and cytotoxic treatments given in the perioperative and metastatic setting.

Improved survival using specialized multidisciplinary board in sarcoma patients.

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 < 0.001). Local relapse-free survival and relapse-free survival were significantly better in patients presented to a MDTB before initiation of treatment, both in univariate and multivariate analysis. CONCLUSION: The compliance to clinical practice guidelines and relapse-free survival of sarcoma patients are significantly better when the initial treatment is guided by a pre-therapeutic specialized MDTB.

Prediction of local and metastatic recurrence in solitary fibrous tumor: construction of a risk calculator in a multicenter cohort from the French Sarcoma Group (FSG) database.

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.

Multicentric neoadjuvant phase II study of panitumumab combined with an anthracycline/taxane-based chemotherapy in operable triple-negative breast cancer: identification of biologically defined signatures predicting treatment impact.

BACKGROUND: Triple-negative breast cancer (TNBC) is a heterogeneous group of tumors for some of which the epithelial growth factor receptor (EGFR) pathway may play an important role. We investigated the efficacy and toxicity of an anti-EGFR antibody (panitumumab) combined with a standard neoadjuvant anthracycline-taxane-based chemotherapy in patients with operable, stage II-III, TNBC. PATIENTS AND METHODS: Treatment in this multicentric neoadjuvant pilot study consisted of panitumumab (9 mg/kg) for eight cycles q.3 weeks combined with four cycles of 5-fluorouracil, epidoxorubicin and cyclophosphamide (FEC100: 500/100/500 mg/m(2)) q.3 weeks, followed by four cycles of docetaxel (T: 100 mg/m(2)) q.3 weeks. Following therapy, all patients underwent surgical resection. Pathologic complete response (pCR) in assessable patients was the main end point while clinical response, toxicity and ancillary studies were secondary end points. Paraffin-embedded and frozen tumor samples were systematically collected with the aim to identify predictive biomarkers of efficacy and resistance in order to select biologically defined subpopulations for potential further clinical development of the anti-EGFR antibody. RESULTS: Sixty patients were included with 47 assessable for pathologic response. The pCR rates were 46.8% [95% confidence interval (CI): 32.5% to 61.1%] and 55.3% [95% CI: 41.1% to 69.5%] according, respectively, to Chevallier and Sataloff classifications. The complete clinical response (cCR) rate was 37.5%. Conservative surgery was carried out in 87% of cases. Toxicity was manageable. The association of high EGFR and low cytokeratin 8/18 expression in tumor cells on one hand and high density of CD8+ tumor-infiltrating lymphocytes on the other hand were significantly predictive of pCR. CONCLUSIONS: Panitumumab in combination with FEC100 followed by docetaxel appears efficacious, with acceptable toxicity, as neoadjuvant therapy of operable TNBC. Several biomarkers could help define large subsets of patients with a high probability of pCR, suggesting a potential interest to further develop this combination in biologically defined subgroups of patients with TNBC. CLINICAL TRIAL NUMBER: NCT00933517.