From the Guidelines
Ewing's sarcoma is a rare and aggressive type of cancer that forms in bones or soft tissues, typically affecting children and young adults, and requires a multidisciplinary approach for treatment, including chemotherapy, surgery, and radiation therapy, as recommended by the most recent guidelines 1.
Overview of Ewing's Sarcoma
Ewing's sarcoma is a malignant bone tumor that arises from primitive neural elements in the bone marrow, constituting about 10% of all bone sarcomas 1. It is characterized by specific genetic mutations, including a chromosomal translocation between chromosomes 11 and 22, which creates an abnormal fusion gene called EWS-FLI1 that drives tumor growth.
Symptoms and Diagnosis
Symptoms of Ewing's sarcoma include pain, swelling, and tenderness at the tumor site, fever, fatigue, and sometimes fractures due to bone weakening. Diagnosis is made through a combination of radiological findings, histological examination, and detection of specific genetic translocations involving the EWS gene 1.
Treatment Approach
The treatment of Ewing's sarcoma should involve a multidisciplinary approach, including chemotherapy, surgery, and radiation therapy, with the goal of achieving local control and preventing metastatic spread 1. Chemotherapy regimens such as VDC/IE have demonstrated superiority over other regimens, and local treatment decisions require thorough discussion by a multidisciplinary team 1. Surgery and radiation therapy may be used alone or in combination to treat the primary tumor, and patients with newly diagnosed or relapsed disease should be considered for clinical trials.
Prognosis and Outcomes
The prognosis for Ewing's sarcoma varies depending on whether the cancer has spread, with five-year survival rates ranging from about 70% for localized disease to around 30% for metastatic cases 1. Early diagnosis and treatment are crucial for improving outcomes, and persistent bone pain in children and adolescents should be evaluated promptly. The most recent guidelines recommend considering all patients with Ewing's sarcoma for clinical trials to improve treatment outcomes and survival rates 1.
From the Research
Definition and Characteristics of Ewing's Sarcoma
- Ewing's sarcoma is a rare and highly aggressive tumor belonging to a family of neoplasms of neuroectodermal origin, which primarily affects the bones or soft tissues 2, 3.
- It is characterized by strong membrane expression of CD99 in a chain-mail pattern and negativity for lymphoid, rhabdomyosarcoma, and neuroblastoma markers 2.
- Pathognomonic translocations involving the EWS gene on chromosome 22 and an ETS-type gene, most commonly the FLI1 gene on chromosome 11, are implicated in the great majority of cases 2.
Clinical Presentation and Diagnosis
- Clinical presentation is usually dominated by local bone pain and a mass 2.
- Imaging reveals a technetium pyrophosphate avid lesion that, on plain radiograph, is destructive, diaphyseal, and classically causes layered periosteal calcification 2.
- Magnetic resonance best defines the extent of the lesion, and biopsy should be undertaken by an experienced orthopedic oncologist 2.
- Primary extraosseous Ewing's sarcoma of the lung is extremely rare, with less than 40 cases reported in the English literature 3.
Treatment and Management
- Management, preferably at a specialist center with a multi-disciplinary team, includes both local control (either surgery, radiation, or a combination) and systemic chemotherapy 2.
- Chemotherapy includes cyclic combinations, incorporating vincristine, doxorubicin, cyclophosphamide, etoposide, ifosfamide, and occasionally actinomycin D 2.
- New approaches include anti-angiogenic therapy, particularly since vascular endothelial growth factor is an apparent downstream target of the EWS-FLI1 oncogene 2.
- Investigational therapies for Ewing sarcoma are being explored, including targeted therapies such as insulin-like growth factor receptor (IGF1R) inhibitors, Mammalian Target of Rapamycin (mTOR) inhibition, and vascular endothelial growth factor (VEGF) inhibition 4.
Rare Origins and Cases
- Extraskeletal Ewing sarcoma (EES) is extremely rare, accounting for less than 1% of all sarcomas, and can occur in any part of soft tissue, mostly in the trunk and lower limbs, and rarely in the pleura 5.
- Cases of extraskeletal Ewing sarcoma have been reported in rare locations, such as the posterior chest, and can display a positive EWSR1 gene rearrangement via fluorescence in situ hybridization 6.