You are here

Print

World Sarcoma Network

The Synergy Lyon Cancer Foundation is hosting the World Sarcoma Network (WSN): this international network facilitates the implementation of research projects on sarcomas, which are rare cancers.

The WSN wanted to retain its lightweight and reactive structure while being able to receive projects and funds in an environment acceptable to our sponsors. The Synergy Lyon Cancer Foundation is an ideal host for the WSN. It’s a clearly visible entity that acts as a template for organising and structuring national and international research programmes and it matches ours. WSN benefits from what Synergy Lyon Cancer has set up and can continue to work efficiently with the same light structure”, Prof Jean-Yves Blay, Director of the Cancer Research Centre of Lyon, founder of the WSN and Member of the Management Board of Synergy Lyon Cancer.

Sarcoma research is strong in Lyon and Prof J.Y. Blay is acknowledged around the world. It was possible to set up the WSN quickly thanks to funding obtained by the CRCL  from cancer research centres. The network is now functional. The fact that SLC is hosting it is perfectly justifiable, since one of its main missions, announced from the beginning of its project, is to structure tools in the service of research and the patient”. Marina Rousseau-Tsangaris, Treasurer of Synergy Lyon Cancer.

Why set up a sarcoma research network?

Sarcomas are rare cancers (about 0.5 cases per 100,000 people/year), but with many and various molecular characteristics (more than 150). Therefore it is difficult for research teams to recruit patients for clinical trials devoted to sarcomas, even when the teams group together. These difficulties are further confounded if the sarcoma studied does not belong to the ten most frequent sarcomas– gastrointestinal stromal tumours, leiomyosarcomas, osteosarcomas, synovial sarcomas, etc.

To overcome these problems, research into rare sarcomas requires a global and systematised “intergroup” approach.

The World Sarcoma Network (WSN) was set up to promote and accelerate the development of drugs to combat sarcomas and permit carrying out clinical tests that could not be performed nationally. To do this, it positions itself as:

  • a platform for communication between groups performing clinical research on sarcomas wherever they are based, all over the world;
  • a facilitator of collaborations to organise clinical tests.

The project to set up the World Sarcoma Network (WSN) sprang from the ambition of Prof Jean-Yves Blay and the involvement of global opinion leaders associated with the Conticanet Network of Excellence*. In 2009, the WSN was founded with the support of European sarcoma experts.

The effort to forge collaborations initiated by Prof Blay and funded by the Rhône-Alpes Region brought together opinion leaders in Europe and other regions of the world such as North America, Australia and Asia. A college of 25 experts from11 different countries now determines and drives WSN’s activities.

* Launched in 2006, the Conticanet network (www.conticanet.com) groups anti-cancer centres, hospitals, industrial companies and European patient associations recognised for their expertise and knowledge of diagnostics, research and caring for adults and children  suffering from sarcomas.

The WSN’s missions are to:

  • bring together all clinical and translational sarcoma research groups.
  • develop and promote a list of key clinical studies,
  • improve the visibility of specific pathologies for the pharmaceutical industry,
  • optimise the use of funds from the industry for key clinical trials.

In particular its aims are to:

  • optimise interactions to facilitate starting multicentre studies,
  • develop protocols for different subtypes of sarcoma,
  • develop a set of protocols for using targeted therapies for well-defined nosological entities of sarcomas,
  • facilitate the training of future actors in clinical research,
  • improve collaboration with patients’ associations and their networks.

Academic studies

 

Industrial studies

  • Tumours with perivascular epitheloid cells and BEZ235 (J.Y. Blay)
  • Nutlins, well-differentiated liposarcomas and RG7112 (supervised by J.Y. Blay)
  • Cediranib to treat alveolar soft part sarcomas (I. Judson)

 

Collaborations between the National Cancer Institute (NCI) - European Organisation for Research and Treatment of Cancer (EORTC)

  • Adjuvant therapy in hormone receptor positive leiomyosarcomas (EORTC)
  • High grade undifferentiated uterine sarcomas (I. Ray-Coquard)

 

EuroSARC (European Clinical trials in Rare Sarcomas

  • EORTC 62092: preoperative radiation therapy for retroperitoneal sarcoma (A. Le Cesne)
  • ISG test: Randomised clinical trial of neoadjuvant chemotherapy adapted to a histotype (A. Gronchi)
  • LINES/MEMOS: Linsitinib in advanced Ewing’s sarcoma and Mifamurtide in advanced osteosarcoma.

 

New projects:

  • International Rare Cancers Initiative Project - endometrial stromal sarcoma (IRCI - ESS): Letrozole in low grade endometrial stroma sarcoma.
  • IMadGIST: Multicentre  phase 3 study to assess the pertinence of stopping or continuing Imatinib as an adjuvant following three years in gastrointestinal stromal tumours.

 

Prof Jean-Yves Blay is the Director of the Cancer Research Centre of Lyon, the founder of WSN and a member of the Management Board of the Synergy Lyon Cancer Foundation.

Why are you interested in sarcomas?

A few years ago, sarcomas were a group of orphan diseases: these rare cancers with multiple features were completely unknown to research. In parallel, biological knowledge on sarcomas was increasing, leading to the possibility that it would result in innovative therapeutic solutions. This is in fact what happened.

What were WSN’s objectives and have they changed since 2009?

WSN’s first goal was to set up a think tank to bring researchers together and exchange upstream on research programmes and forge and implement a global strategy for these rare diseases that require collaboration between each team. This has always been our vision. Then we completed it by opening out to more networks and widening it to specific missions, though we were careful not to take the place of existing structures and add another floor to the edifice. Our real strength lies in sharing ideas.

Could you give me an example of a successful research project resulting from the network’s exchanges?

In 2008, no one had yet focused on pigmented villonodular synovitis and no prospective or retrospective studies existed on the subject. Since then, different American and European research programmes have been performed around the WSN’s actors, involving industrial partners. They have led to the development of standard treatments for these diseases.

Could the WSN be used as a model for other diseases?

When the scope of application is already structured, which is the case for national sarcoma teams, a space where minds can meet and exchange ideas is certainly useful if not essential. This model can be adapted to several diseases, especially rare ones.

•    Sarcomas represent 1% of all cancers and 4,000 new cases a year in France

•    Sarcomas are a group of heterogenic tumours, clinically and histologically, and regarding their prognosis.

•    They develop from the tissues that support the body (muscles, bones, adipose tissue, nerves, etc.). A distinction is made between the sarcomas of “soft tissues” which include the viscera and bone sarcomas.

•    There are at least 150 different subtypes with liposarcomas, leiomyosarcomas, fibrosarcomas, angiosarcomas, GIST, osteosarcomas, and so forth. They can affect many parts of the body (limbs, torso, neck, etc.).

•    They are subject to a new WHO classification dating from 2013.

•    According to their type, they can affect persons of all ages, from children to the elderly.

•    They are now better understood thanks to the progress made in molecular biology

•    Very often, they present genetic abnormalities: translocation, amplification, inactivation, mutation or rearrangement. Researchers specialised in the study of sarcomas have discovered and are still discovering abnormalities specific to one or more sarcomas. Their findings can improve the diagnosis of these tumours and lead to the development of more targeted therapies.

Advances: At the end of 2015, two teams of the Inserm (Centre Léon Bérard and the Institut Curie) highlighted a new genetic variant of sarcomas, the “SMARCA4-deficient thoracic sarcoma”. Their results, published in Nature Genetics, permit better diagnosis for this cancer and thus speed up the care process. The researchers validated a biomarker, SOX2, overexpressed by this new cancerous entity. Prof. Jean-Yves Blay, the co-director of this study, founder of the WSN and member of the Management Board of Lyon Synergy Cancer, declares, “Our priority is to refine the classifications of tumours used in clinical practice in order to provide patients with a more adapted therapeutic choice”. Molecular investigations have demonstrated inactivations of the SMARCA4 gene in twenty samples of sarcomas with similar clinical and pathological characteristics. SMARCA4 codes for the BAF complex, which participates in the regulation of chromatin structure. It presents modifications in 1 cancer out of 5 and is now the subject of research on its therapeutic targeting. 

•    40% of sarcomas can now be characterised by a specific modification of DNA during examination by anatomical pathology.

•    According to WHO, up to 20% of sarcomas have not yet been classified.

•    Diagnosis problems persist for about 15% of sarcomas, even following review by a panel of anatomical pathology experts.