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.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.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.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. 

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

Considering the molecular heterogeneity of sarcomas and their immunologically quiet character, immunotherapy (e.g., immune checkpoint inhibitors) plays a viable role in only a subset of these tumors. This study aimed to determine the immune subtypes (IMSs) of sarcomas for selecting suitable patients from an extremely heterogeneous population.By performing consensus clustering analysis of the gene expression profiles of 538 patients with sarcomas in online databases, we stratified sarcomas into three IMSs characterized by different immune cell features, tumor mutational burdens (TMBs), gene mutations, and clinical outcomes. IMS1 showed an immune "hot" and immunosuppressive phenotype, the highest frequencies of CSMD3 mutation but the lowest frequencies of HMCN1 and LAMA2 mutations; these patients had the worst progression-free survival (PFS). IMS2 was defined by a high TMB and more gene mutations, but had the lowest frequency of MND1 mutations. IMS3 displayed the highest MDN1 expression level and an immune "cold" phenotype, these patients had the worst PFS. Each subtype was associated with different expression levels of immunogenic cell death modulators and immune checkpoints. Moreover, we applied graph learning-based dimensionality reduction to the immune landscape and identified significant intra-cluster heterogeneity within each IMS. Finally, we developed and validated an immune gene signature with good prognostic performance.Our results provide a conceptual framework for understanding the immunological heterogeneity of sarcomas. The identification of immune-related subtypes may facilitate optimal selection of sarcoma patients who will respond to appropriate therapeutic strategies. 

https://bmcimmunol.biomedcentral.com/counter/pdf/10.1186/s12865-022-00522-3

The immune subtypes and landscape of sarcomas

Benchmarking is crucial for healthcare providers to enhance quality and efficiency, notably for complex conditions like sarcomas. Multidisciplinary teams/sarcoma boards (MDT/SBs) are vital in sarcoma management, but differences in their processes can affect patient outcomes and treatment costs, despite adherence to international guidelines. To address this issue, this study aimed to compare two MDT/SBs and establish an interoperable digital platform, Sarconnector®, for real-time-world data assessment and automated analysis. The study included 983 patients, 46.0% of whom female, with a median age of 58 years, and 4.5% of patients presented with metastasis at diagnosis. Differences were observed in the number of first-time presentations, follow-up presentations, primary sarcomas, biopsies and chemotherapy indications between the two MDT/SB. The results highlight the importance of benchmarking and utilizing a harmonized data approach, such as the RWT approach provided by the Sarconnector®, to standardize and evaluate quality and cost metrics. By identifying areas of improvement and making data-driven decisions on the meta-level, healthcare providers can optimize resources and improve patient outcomes. In conclusion, benchmarking with the RWT harmonized data approach provided by the Sarconnector® can help healthcare providers improve the overall effectiveness of the healthcare system and achieve better outcomes for their patients in terms of both outcomes and costs.

Unlocking the Power of Benchmarking: Real-World-Time Data Analysis for Enhanced Sarcoma Patient Outcomes.

<h2>Abstract</h2> 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. <h3>Patients and methods</h3> NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTB), funded by the French NCI (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. <h3>Results</h3> 267 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 tumor size was 37mm (4-220). 48%, 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-years 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 favorable survival in localized 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. <h3>Conclusions</h3> 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 localized and metastatic stages. 

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

The administration of adjuvant imatinib during 3 years is indicated after resection of primary localized GIST at high risk of recurrence, but many patients relapse afterwards. 

A randomized study of 6 vs 3 years of adjuvant imatinib in patients with localized GIST at high risk of relapse.

SELNET clinical practice guidelines for soft tissue sarcoma and GIST.

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SELNET clinical practice guidelines for soft tissue sarcoma and GIST.