Ewing sarcoma is the second most common malignant bone tumor in young people, after osteosarcoma. In France, it affects approximately 80 to 100 new patients per year. It can affect the bones of the pelvis, limbs, chest, spine, or, more rarely, other sites.

About 15% of Ewing sarcomas develop in soft tissues without a bone origin. The disease is defined by a characteristic molecular abnormality most often involving the EWSR1 gene and a gene from the ETS family, typically FLI1.

Symptoms vary depending on the location. At first, they may be mistaken for a sports injury or minor pain, but if they persist or worsen, a medical evaluation is necessary.

Imaging

An X-ray may be the first test performed for a bone lesion. An MRI provides detailed information on the local extent of the lesion within the bone, muscles, blood vessels, nerves, and joints. A chest CT scan looks for lung metastases. A PET-CT scan or bone scan may be included in the evaluation of distant disease, depending on the protocols.

Biopsy and Molecular Diagnosis

A biopsy should be performed after imaging and planned in consultation with the team that will provide local treatment. The pathologist analyzes the tumor, and molecular biology testing looks for the characteristic fusion gene. This confirmation is essential, as other round-cell sarcomas—particularly those with CIC or BCOR abnormalities—represent distinct entities.

Staging Evaluation

Staging determines whether the disease is localized or metastatic. The most common sites of metastasis are the lungs, other bones, and the bone marrow. Bone marrow biopsies are not routinely performed when modern imaging provides the necessary information, but may be considered depending on the situation.

The presence of metastases at diagnosis is the major prognostic factor. The site of the metastases is also important: isolated lung involvement does not have the same prognosis as bone or spinal cord involvement. The location and size of the primary tumor, the possibility of complete local control, and the response to chemotherapy also contribute to the assessment.

Treatment always combines systemic chemotherapy with local treatment of the primary tumor through surgery, radiation therapy, or a combination of both. The exact strategy depends on the patient’s age, the extent of the disease, its location, and functional capabilities.

Initial Chemotherapy

Chemotherapy begins before local treatment in order to treat the entire disease early on, reduce the tumor, and target any disseminated cells. Following the results of the EURO EWING 2012 trial, the VDC/IE regimen—combining vincristine, doxorubicin, and cyclophosphamide alternated with ifosfamide and etoposide—has become the European standard of care. The exact number of treatment cycles and their schedule depend on the protocol.

Local Treatment

Surgery aims for complete resection with adequate margins, while preserving function as much as possible. It must be performed by a specialized team. Bone or joint reconstruction may be necessary. Amputation has become rare but sometimes remains the solution offering the best local control and the best possible function.

Radiation therapy may be used alone when complete surgery would result in disproportionate complications or is not feasible. It may also complement surgery in cases of insufficient margins, tumor breakthrough, or an unfavorable histological response, depending on the chosen strategy.

Chemotherapy Following Local Treatment

Chemotherapy continues after surgery or during and after radiation therapy to complete systemic treatment. Analysis of the surgical specimen measures the proportion of tumor cells still alive and helps assess the response, but treatment adjustments depend on the protocol and all risk factors.

Isolated lung metastases may warrant consideration of radiation therapy to both lungs following chemotherapy, depending on the patient’s age, response, and treatment protocol. Bone or bone marrow metastases represent a very high-risk situation that requires an individualized treatment strategy at a specialized center.

High-dose chemotherapy with busulfan and melphalan, supported by stem cell transplantation, may be considered in certain situations, taking into account the location of the metastases and compatibility with radiation therapy. For extrapulmonary metastatic forms, French guidelines recommend induction therapy, expert local treatment, possible high-dose therapy, and metronomic maintenance therapy; however, this strategy must be tailored to the patient and the available data.

The treatment strategy depends on the time elapsed, the number and location of relapses, previous treatments, and the possibility of further local treatment. It may combine chemotherapy, surgery, radiation therapy, and clinical trials. The prognosis for relapses remains generally poor, which justifies consultation at a specialized center and access to clinical research.

The Rego-Inter-Ewing-1 trial, sponsored by Gustave Roussy, is evaluating the addition of regorafenib to standard first-line chemotherapy in patients with metastatic Ewing sarcoma. Preliminary results were presented at ASCO 2025. These results constitute a research signal and do not allow this combination to be presented as a new standard of care.

The upcoming international INTER-EWING-1 program is focusing, in particular, on the role of maintenance therapy with vinorelbine and low-dose cyclophosphamide. A review published in July 2026 emphasizes that the role of maintenance therapy remains to be defined.

Follow-up care is designed to monitor for recurrence and manage the effects of the disease and its treatments. It depends on the location of the tumor, the type of surgery, the medications, and the areas treated with radiation.

Gustave Roussy is one of the coordinating centers of the national NETSARC+ network. The treatment strategy is discussed during sarcoma multidisciplinary team (MDT) meetings and, for children and adolescents, in consultation with the pediatric or AJA team. For certain bone, thoracic, or complex surgeries, the care pathway is coordinated with expert partner institutions.

Depending on the patient’s needs, the care pathway combines pediatric or medical oncology, surgery, radiation therapy, imaging, pathology, nuclear medicine, rehabilitation, pain management, psychological support, educational services, adapted physical activity, and social support.