5th Bone Sarcoma Networking Meeting: What’s new in Ewing sarcoma and osteosarcoma?

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5th Bone Sarcoma Networking Meeting:
What’s new in Ewing sarcoma and osteosarcoma?

“Collaboration is not something that just happens, it needs to be worked on.”
Jeremy Whelan, UK

The 5th Bone Sarcoma Networking Meeting was held May 23/24, 2019, in Prague, Czech Republic, within the framework of the 1. Annual Meeting of the European Society for Pediatric Oncology (SIOP Europe). It brought together scientific and clinical researchers and representatives from sarcoma charities from Europe and the USA, to present and discuss new developments on bone sarcoma.

It focused on both Ewing sarcoma, including the work and achievements of the Euro Ewing Consortium (EEC), and on osteosarcoma.

Ewing sarcoma

Ewing sarcoma is the third most common bone sarcoma. It occurs most frequently in children and adolescents, but is also seen in young adults. Therapy encompasses surgery, chemotherapy and radiotherapy and is mostly conducted within clinical trials.

The EuroEwing Consortium, a collaborative EU project, is currently running two clinical trials:

  • EuroEwing 2012, investigating treatment for newly diagnosed Ewing sarcomas
  • and rEECur, a trial comparing different treatments in recurrent and primary refractory Ewing sarcomas

Professor Jeremy Whelan, UK, and EEC project coordinator, opened the session with an overview of what has been achieved within the consortium over the past five years:

  • The EuroEwing 2012 trials has recruited over 600 patients in 112 sites across 10 countries, over 3.800 biological samples have been collected.
  • The rEECur trial has recruited over 300 patients in 15 countries and nicely demonstrates the advantages of a complex trial design.

An EuroEwing 2012 update was given by Keith Wheatley, UK. The trial compares two different chemotherapy regimens – one primarily used in Europe (VIDE) vs. a regimen mostly applied in the US (VDC/IE). In a second step, the application of zoledronic acid is investigated to see whether or not it improves the outcome for patients.

On May 3rd, the first phase (known as R1) has closed recruitment – enough patients have been involved in the study. Data will be monitored and published within the upcoming months.

The study rEECur was presented by Marin McCabe, UK. The study has a complex trial design (multi-arm, multi-stage = MAMS): It compares four different chemotherapy regimens with the intention of dropping the least effective one after stage 1 and another arm in stage 2. The remaining two arms will progress to phase III evaluation. Patients aged 4-50 years with recurrent and primary refractory Ewing sarcoma and fit to receive chemotherapy were randomized between topotecan plus cyclophosphamide (TC), irinotecan plus temolozomide (IT), gemcitabine plus docetaxel (GD) or high-dose ifosfamide (IFOS). rEECur could now demonstrate that gemcitabine plus docetaxel (GD) is a less effective treatment than the other three tested regimens in reducing tumour burden or prolonging PFS (Update from ASCO 2019). This arm will be closed. The study design also allows the introduction of novel agents into the study, a decision on the new compound will follow soon.

Professor Uta Dirksen, Germany, introduced a study currently in development and following the EuroEwing 2008 trial: iEuroEwing. The aim of the new trial is to improve outcome, get results within a quicker timescale, randomize upfront and only include one randomization per risk group. For standard risk patients, the aim is to improve survival while reducing toxicity. Patients will be randomized to standard chemotherapy (VIDE) with or without Temozolomide Irinotecan (TEMIRI) and then following local therapy to another chemotherapy regimen (VAI1/VAC2) with or without TEMIRI. Poor responders will receive additional high dose chemotherapy (BuMel3). For high risk patients, there is no broadly accepted standard of care and there are no new drugs available with good clinical evidence.

The role of radiotherapy in Ewing Sarcomas was discussed by Prof. Beate Timmermann, Germany. While radiotherapy is accepted and has proven to be an integral part of a multimodal treatment concept in Ewing sarcoma, some questions remain to be answered: When is the right timing of radiotherapy in Ewing and should it be applied preoperatively? Can safety margins be reduced, should scars be treated? Consequences of the interaction of chemotherapy and radiotherapy e.g. on fertility?


The second part of the meeting was dedicated to osteosarcomas and included presentations on developments in the understanding of osteosarcoma genetics and immunology as well as discussion of recent and ongoing clinical trials.

Osteosarcoma is the most frequent primary cancer of bone. It is estimated that per year, 2-3 persons in one million are affected by it. It occurs more often in adolescents (age 15-19), where it accounts for >10 % of all solid cancers. There is another peak of incidence at age >70. Osteosarcoma therapy usually includes surgery, chemotherapy and in some cases radiotherapy. The need for new treatments is high, as prognosis in advanced osteosarcomas remains poor.

Studies in osteosarcoma are scarce on an international level. Dr. Nathalie Gaspar, France, introduced studies in osteosarcomas that have been or are currently conducted by the “Innovative Therapies for Children with Cancer” (ITCC), among them the Regobone study, which only recently proved efficacy of regorafenib in metastatic osteosarcomas. Further studies are planned in bone sarcomas including osteosarcomas, both in France alone, but also internationally, testing novel treatment options with a rationale in osteosarcomas.

Osteosarcomas are rare and are characterized by a high genomic instability, explained Professor Daniel Baumhoer, Switzerland. That means that the tumor evolves quickly and primary tumor mutations can differ from mutations in metastasis. This makes it hard to identify genetic targets for the development or application of targeted therapies.

Dr. Sandra Strauss, UK, introduced the ICONIC study. ICONIC is the UK’s first patient registry and clinical study to capture patient samples and complete medical data from osteosarcoma patients of all ages. Studying both of these in combination gives the biggest chance of uncovering novel treatments and understanding which patients will benefit from these.

Professor Stefan Bielack summarized that there’s no existing infrastructure in osteosarcomas. “We need to urgently establish such an infrastructure to improve the situation of osteosarcoma patients.”




1 Vincristine, actinomycin and ifosfamide
2 Vincristine, Doxorubicin, Cyclophosphamide
3 Busulfan and melphalan


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