Introduction

The term Ewing's sarcoma was first used in 1921¹ and describes a cancer which mainly occurs in the bones of the extremities and the surrounding soft tissue.² It accounts for about 1.4% of all childhood cancers and is classified as a primitive neuroectodermal tumour (PNET).³ Although not hereditary, it is associated with reciprocal translocations at chromosomes 11 and 22.⁴ 90% of affected children will demonstrate an abnormality at two particular gene sites, a finding which helps to establish the diagnosis.

Ewing's sarcoma and peripheral PNET are considered to be two ends of a spectrum of neoplasms termed Ewing family of tumours.⁵
Research using bone marrow suggests that Ewing's sarcoma may arise from mesenchymal stem cells.⁶

Epidemiology

Ewing's sarcoma is rare, affecting in the region of 30 children per year in the UK. It occurs most frequently between the ages of 5 and 20 being most common in the adolescent years. It is slightly more frequent in males than females.²

One series based on 4 UK population-based registers found that there were 144 Ewing's sarcomas in a total of 374 cases of childhood bone tumours registered in the period 1981-2002. The incidence of Ewing's sarcoma declined at an average rate of 3.1% per annum which was thought to be due to tumour reclassification. Survival rate showed a considerable improvement over the twenty years.⁷

Rarely, the condition can present in adults but is extremely rare over the age of 40.⁸

Presentation^9,10

The symptoms and signs of Ewing's sarcoma are not in themselves diagnostic but may include:

• Mass or swelling - most commonly in the long bones of the arms and legs, pelvis or chest but also in the skull and flat bones of the trunk
• Pain in the area of the tumour
• Redness in the area surrounding the tumour
• Malaise
• Anorexia
• Weight loss
• Fever (poor prognostic sign)
• Paralysis and/or incontinence if affecting the spine
• Numbness or tingling as a result of nerve compression by the tumour

Differential Diagnosis¹⁰

• Trauma
• Benign tumours, e.g. neurofibroma
• Other malignancies, e.g. lymphoma

Investigations^9,10

• X-ray of the affected bone - shows bone destruction with overlying onion-skin layers of periosteal bone formation
• FBC and lactic dehydrogenase measurement (LDH) - anaemia and raised LDH levels at diagnosis suggest the presence of metastases and are an indication of poor prognostic outcome¹¹
• CT/MRI scan to assess extent of disease and local structures involved
• Bone scintigraphy - useful in identifying metastases and assessing response to treatment
• Genetic studies - looking at chromosomes 11 and 22
• Biopsy of tumour site - molecular pathology techniques can be used on fresh, frozen formalin-fixed paraffin-embedded tissues¹²
• Bone marrow aspiration

Staging¹³

Staging of the tumour is undertaken to determine the treatment and also give some indication of the likely prognosis:

• Stage 1A - Low-grade tumour found only within the hard coating of the bone
• Stage 1B - Low-grade tumour extending locally into the soft tissues
• Stage 2A - High-grade tumour found only within the hard coating of the bone
• Stage 2B - High-grade tumour extending locally to the soft tissues
• Stage 3 - Low- or high-grade tumour which has metastasised

Management²

Non-Drug

• The family of a child with Ewing's sarcoma will require long-term support from a number of professionals in both primary care and the hospital setting. It is important that all members of the family know where to access information, support and practical help when required and it is vital that there is good communication between all professionals involved in the care of the child.
• Radiotherapy may be used in conjunction with surgery and/or chemotherapy. Radiotherapy may occasionally be used in place of surgery where removal of the bone is not possible, e.g. in the spine.
• Peripheral blood stem cell harvest may be undertaken midway through chemotherapy. The recovered cells are stored in case of future need following further courses of chemotherapy.
• Physiotherapy ±/ prosthetic limb fitting may be required following surgery.

Drugs⁹

Chemotherapy is usually the first line of treatment and is currently initiated using a combination of vincristine, ifosamide, doxorubicin and etopiside (VIDE).The treatment usually takes the form of 6 courses of treatment at intervals of 3 weeks following which further management decisions will be based partly on the response to treatment. Further courses of chemotherapy using different combinations of drugs are generally used following surgery or radiotherapy.

Some patients are treated with radiotherapy alone but one trial suggests that there is a higher rate of treatment failure and relapse compared to surgery.¹⁴

Allogenic stem cell transplantation may offer a way forward in refractory metastatic patients.¹⁵

Surgical

Surgery is often required to remove the tumour. Limb-sparing surgery, where only a part of the bone is removed and replaced if necessary with a segment of prosthetic bone, is increasingly carried out, although amputation of the limb may be required if the tumour is affecting one of the long bones of the arm or leg.

Prognosis^16,17

The overall 5-year survival rate for Ewing's sarcoma is 66%. The initial response to induction chemotherapy is a good prognostic indicator, those with a good response having a 75% disease-free survival at 5 years and those with a poor response having a disease-free survival rate of only 20% at 5 years. Patients with metastases at the time of diagnosis had a worse survival than those that did not and those with lung metastases did better than those with bone metastases. Leaving in inadequate margin of healthy tissue after surgery and over-expression of papilloma virus binding-factor - as identified by antibody staining techniques of biopsy tissue - were also factors associated with a poor prognosis.¹⁸

One study found that relapse did not necessarily mean a poor prognosis. Specific subgroups of patients could be cured, even after 2 or 3 relapses.¹⁹ These included:

• Relapse 2 or more years after primary treatment
• Patients who relapse with only lung metastases
• Patients whose recurrences can be surgically treated

Recurrence of chest wall tumour was associated with a high mortality rate.²⁰