Ewing sarcoma is the second most common primary bone cancer in children and young people after osteosarcoma. Ewing sarcoma most commonly occurs in the bone, but in rare cases can develop in surrounding soft tissue (extraosseous Ewing sarcoma). It requires aggressive treatment, often involving a combination of chemotherapy, surgery and radiotherapy.
Ewing sarcoma is rare, with less than 100 cases diagnosed each year in the UK and more commonly affects males.1 The second decade of life, where bone growth is at its greatest, is the most common age for diagnosis. Ewing sarcoma can occur in adults, however, it is extremely rare in those older than 30 years.
Ewing sarcoma is a small, round blue cell tumour.2 It most commonly develops in flat bones such as the tibia and fibula around the knee joint, the femur, pelvis and ribs. In approximately 95% of cases of Ewing sarcoma, there is a genetic mutation detected which is responsible for tumour development. The most common mutation is a translocation between chromosome 11 and 22 – t(11;22)(q24:q11), however, there are several variations that have been detected. This translocation results in the formation of a fusion gene known as EWS-FLI1, which codes for the production of the EWS-FLI1 fusion protein. This is a transcription factor that upregulates cell proliferation leading to uncontrolled cell turnover and tumour formation.2
The symptoms of Ewing sarcoma can often be misinterpreted as growing pains or sports injuries in young people and therefore a low index of suspicion for further investigation is important. NICE guidelines advise that children, teenagers and young adults with an unexplained bony lump should be referred for an urgent x-ray within 48 hours. If an x-ray suggests possible bone cancer then an urgent referral for an appointment within 48 hours for specialist assessment should be made.3
- Bone pain – often progressive over time and worse at night, often resistant to over the counter analgesia
- Restricted movement of a joint
- Weight loss
- Tender palpable mass
- Increased susceptibility to fracture – this can often be how Ewing sarcoma is diagnosed
- Osgood-Schlatter disease
- Slipped epiphysis
- Osteomyelitis – more constant pain than with Ewing sarcoma, blood and x-ray results can help distinguish
- Growing pains – no systemic symptoms and pain will be relieved by analgesia
A series of blood tests should be ordered including FBC, U&Es, LFTs, ESR, CRP, ALP and a bone profile. Results that could be seen with Ewing sarcoma include anaemia, leucocytosis, elevated white cell count, elevated ESR, elevated LDH, elevated ALP and elevated CRP.4
Imaging and Invasive Tests
The imaging modalities often used include x-ray, MRI, CT and PET. X-ray is used in the initial assessment and Ewing sarcoma appears as a destructive, diaphyseal lesion with layered periosteal calcification4 (Figure 1). MRI can be used to gain a more detailed view and CT and PET are often used as part of the staging process. Bone biopsy provides the definitive diagnosis.
Management of Ewing sarcoma needs to be aggressive and typically involves a combination of chemotherapy, surgery and radiotherapy.
Chemotherapy is used both neoadjuvantly to shrink the tumour prior to surgery and adjuvantly to destroy any remaining tumour cells which may have spread from the primary tumour site. After the Euro Ewing 2012 clinical trial, the standard chemotherapy regimen is usually VDC/IE (vincristine, doxorubicin, cyclophosphamide/ifosfamide, etoposide)1. Novel therapeutic agents include those targeting the genetic mutations most commonly seen.
Limb-sparing surgery with resection of the tumour and either a metal implant or autologous bone graft is the preferred surgical method. However, in certain circumstances where the tumour is too widely spread, or the site is not amenable to resection, amputation is performed. This is required in around 10% of individuals.
Radiotherapy is not used in every patient, however, it can be used before surgery to shrink the tumour, which is especially useful for tumours in regions that are difficult to resect, such as the pelvis.
Radiotherapy can also be used after surgery to destroy any remaining tumour cells and is utilised in individuals where the resection did not result in the removal of the entire tumour.5
Prognostic factors associated with decreased survival rates include:6
- Metastatic disease at diagnosis
- Large tumour size (≥200ml in volume or ≥8cm in diameter)
- Primary tumour located in the axial skeleton, especially the pelvis
- Histological response of less than 100%
Metastatic disease is a complication of Ewing sarcoma, with the most common sites for metastases being the lungs, other bones, and the bone marrow. Additionally, in around 30% of individuals, Ewing sarcoma recurs in later life and in these cases the disease is often fatal.7 Around 60% of individuals with Ewing sarcoma live at least 5 years after diagnosis.
|1||Bone Cancer Research Trust – Ewing sarcoma. Available at www.bcrt.org.uk/information/information-by-type/ewingsarcoma/.
|2||Bernstein, M., Kovar, H., Paulussen, M., Lor Randall, R., Schuck, A., Teot, L.A., Jeurgensg, H. 2006. Ewing’s Sarcoma Family of Tumours: Current Management. The Oncologist. 11(5); 503-519.
|3||NICE – bone and soft tissue sarcoma: recognition and referral. Available at www.cks.nice.org.uk/topics/bone-soft-tissue-sarcoma-recognition-referral/
|4||Ozaki, T. 2015. Diagnosis and treatment of Ewing sarcoma of the bone: a review article. Journal of Orthopaedic Science. 20(2); 250-263.
|5||Sarcoma UK – Ewing’s sarcoma. Available at www.sarcoma.org.uk/sarcoma-types/ewings-sarcoma.
|6||Bosma, S.E., Ayu, O., Fiocco, M., Gelderblom, H., Dijkstra, P.D.S. 2018. Prognostic factors for survival in Ewing sarcoma: A systematic review. Surgical Oncology. 27(4); 603-610.
|7||Dirksen, U., Jurgens, H. 2010. Approaching Ewing sarcoma. Future Oncology. 6(7); 1155-1162.