What is Ewing Sarcoma?

Ewing sarcoma is a rare cancer that affects the bones. It is most prevalent in children and teenagers. Although its incidence rate is low, it is the second most common bone cancer.  Ewing sarcoma is associated with significant mortality, thus having a huge impact on society. Therefore, it is important to increase the population’s awareness about this cancer. This article will explore the different characteristics, causes and symptoms of  Ewing sarcoma while also exploring the tools used for its diagnosis and the treatments available. Overall, the aim of this article is to answer the following question: what is Ewing sarcoma?

Overview

Ewing sarcoma is an uncommon but highly aggressive primary bone cancer that can affect the bones and the soft tissue around them. There are different types of this cancer: Ewing sarcoma of the bone extraosseous Ewing sarcoma, primitive neuroectodermal tumour, and Askin’s tumour.¹ In terms of its incidence, Ewing sarcoma can be considered a childhood cancer as it is mainly diagnosed in children and young adults, affecting the long bones in regions such as the legs, the arms, the chest, and the pelvis. The sarcoma can be either localised, where the tumour is only found in a specific region and has not spread to other parts of the body, or metastatic, which means that the cancer cells have spread to different organs and tissues. Although the survival rate for patients with localised Ewing sarcoma is approximately 80%, for those with metastasis, only 3 out of 10 patients will survive.² Therefore, metastasis is the primary cause of mortality in patients with Ewing sarcoma.³  Despite being linked to considerably high mortality and being the second most frequent bone cancer in children, following osteosarcoma,⁴ the prevalence of Ewing sarcoma is fortunately low, only affecting approximately 2.93 per million individuals who are younger than 19 years old.

Causes of ewing sarcoma

The exact cause of Ewing sarcoma is unknown. However, although this bone cancer is not inherited, as other childhood cancers are, its development seems to be linked to non-random and unusual gene rearrangements. Furthermore,patients with Ewing sarcoma commonly have genetic modifications affecting the EWSR1 gene. Nevertheless, the cause of these gene alterations is still not known. Yet, studies have outlined that, unlike some other types of cancers, radiation exposure does not seem to increase its incidence.⁵

Signs and symptoms of ewing sarcoma

Signs and symptoms characteristic of this bone cancer include:

• Intermittent bone pain that progressively becomes more constant and usually worsens at night
• Local swelling and stiffness
• Fatigue
• Development of visible lumps on the skin which are usually soft and warm
• Fever that does not go away and cannot be explained
• Unintentional weight loss
• Weakness of the bones, making them more likely to break

Management and treatment for ewing sarcoma

The treatment for this bone cancer involves one or more approaches, the most common being chemotherapy, radiotherapy, and local surgery.⁶

For localised sarcoma, the most typical approaches are:

• A combination of surgery and radiation therapy: surgery is used for the partial or complete removal of a tumour, sometimes requiring limb amputation if the tumour is too large. Radiation therapy is used after undergoing surgery as a maintenance therapy, to kill any remaining cancer cells that could not be removed surgically. Radiotherapy can be delivered internally or externally. Radioactive substances are used to f direct energy to an external target or to produce high doses of radiation in a focal area⁷
• A combination of radiation therapy with adjuvant chemotherapy: radiotherapy can be used together with chemotherapy to increase the effectiveness of the treatment. Chemotherapy usually uses a combination of drugs that inhibit the proliferation of cancer cells. Chemotherapy treatment is sometimes continued after the rest of the treatments are completed to ensure that the remaining cancer cells are killed

On the other hand, for metastasised Ewing’s sarcoma, the main approach is to use systemic chemotherapy. However, treatments for metastatic cancers are not as effective as with localised sarcoma. However, there are many clinical trials and studies being conducted which show promise for developing more effective treatments for metastatic Ewing sarcoma. For example, stem cell transplantation is currently being tested.⁸

Diagnosis of ewing sarcoma

Doctors specialised in clinical oncology use a combination of different tests to diagnose Ewing sarcoma. These include:¹

Imaging tests 

These are essential for the diagnosis of cancers as they are able to provide morphological, structural, functional, and metabolic information about the tumour.⁹ There are different imaging tests that can be combined for diagnostic purposes. Some of the most common ones includethe following:

• X-rays: this test provides an image of the bones, allowing doctors to identify the presence of tumours on the surface of a bone
• Computed tomography (CT) scans: these scans are similar toX-ray imaging but they differ in that they can produce cross-sectional images of bones and tissues.¹⁰ In this way, these scans create more detailed images than X-rays do
• Positron emission tomography (PET) scans: this imaging technique uses radiopharmaceuticals to allow doctors to differentiate between normal and malignant tissues. Nowadays, the hybrid PET/CT system is becoming quite popular as, apart from providing the information that PET scans provide, complementary CT images can be used for the anatomic localisation of tumours¹¹
• Magnetic Resonance Imaging (MRI) scan: this anatomical imaging method uses magnetic fields and radio waves to produce images. It is used in cases in which the tumour is not found in the bone. It can be really useful as it provides higher-definition images than CT scans

Biopsies

Biopsies are medical procedures that involve surgically taking a small piece of the patient’s bone or tissue from an area that is suspected to be cancerous. By doing this, doctors are able to examine the pieces of bone or tissue under a microscope and check them for any signs of cancer cells and genetic changes that have been associated with Ewing sarcoma.

Risk factors

There are different factors that can increase the risk of developing  Ewing sarcoma. However, as outlined by the American Cancer Society, none of them are environmental. This includes:

• Age: teenagers and young children have been found to be  at a greater risk of developing the cancer than adults, the incidence peaking between the age of 15 and 20¹²
• Race: studies have shown that Caucasians are more likely to develop this bone cancer compared to Asians and Africans. Furthermore, within Asiatic populations, those from East Asia are at a lower risk of developing Ewing sarcoma. Hence, individuals from India are more likely to develop Ewing sarcoma than Chinese and Malay people¹²
• Sex: people assigned male at birth seem to be at a slightly higher risk of developing Ewing sarcoma compared to people assigned female at birth

Complications

Ewing sarcoma and its treatment have been associated with complications that include:⁶

• Secondary malignancies can develop approximately 9.5 years after the diagnosis of Ewing sarcoma¹³
• Metastasis of Ewing sarcoma makes it more difficult to treat this cancer. The most common site for metastasis is the lungs (50%), which can lead to symptoms such as shortness of breath. The second most common site of metastasis includes other bones, different from the one in which the cancer originated in, and the bone marrow.¹⁴ Bone metastasis has the worst prognosis, the survival rate of patients with bone marrow metastasis being lower than 25%⁴
• Pathological fractures are a complication of Ewing sarcoma but donot reduce the survival rate of patients¹⁵
• Recurrent sarcoma can occur in 1 in 5 patients¹⁶
• Radiotherapy and chemotherapy are very aggressive treatments that can give rise to quite serious toxic effects on individuals.¹⁷ To overcome this problem, there are currently some clinical trials being conducted with the aim of finding treatments with less toxic effects²

FAQs

How can I prevent ewing sarcoma?

Unfortunately, it is still unclear what causes Ewing sarcoma, and the only risk factors known (age, race, and sex)cannot be changed. Hence, there are no ways of preventing Ewing sarcoma at present. However, future research might provide information about the exact causes of Ewing sarcoma, promising the development of prevention strategies for this cancer.

How common is ewing sarcoma?

Luckily, Ewing sarcoma is quite uncommon. It is diagnosed only in approximately 2.93 per million individuals younger than 19. In fact, as the risk of developing Ewing sarcoma is higher for teenagers and children, its incidence is even lower for those older than 20.

When should I see a doctor?

If you notice an unusual change that worries you and/or have persistent signs and symptoms characteristic of Ewing sarcoma, making an appointment to see your GP is recommended. The incidence of this bone cancer is really low and, thus, it is more likely that something else is causing your symptoms. However, if the symptoms are actually being caused by Ewing sarcoma, the earlier it is picked up, the higher the chances of treating it successfully.

Summary

Ewing sarcoma, although rare, is an aggressive bone cancer that has a considerable impact on our society. The main symptoms are pain, swelling and stiffness. Treatments are based on combinations of chemotherapy, radiotherapy, and surgery. Although these are effective for localised sarcoma, they have many toxic effects. Furthermore, when the cancer has metastasised, the effectiveness of the treatments is lowered and the survival rate decreases dramatically. In terms of the causes, it is known that the development of Ewing sarcoma is related to a change in gene arrangements. But, the exact cause is unclear. Thus, future cancer research on Ewing sarcoma is needed and should be directed towards finding out the causes of Ewing sarcomaand developing novel treatments that have less toxic side effectsand that effectively treat metastatic disease.