What is Ewing's Sarcoma?

Sarcoma is a cancer of the bone or soft tissue . It is a rare form of cancer representing about 1.3% of all cancer diagnoses in Australia and New Zealand. (www.sarcoma.com.au)

Ewing's Sarcoma represents 15% of all sarcomas. It is more common amongst children and young adults, but can affect people of all ages. Ewing's sarcoma is a highly aggressive cancer that most often occurs in the long bones of the pelvis, legs, arms and chest, but it can occur in any bone. Less often, it starts in the soft tissues of the chest, abdomen, limbs or other locations.

Image [https://www.orthobullets.com/pathology/8047/ewings-sarcoma]

Symptoms

The most common symptom of Ewing's Sarcoma is pain in a bone or tissue which may be associated with a lump or swelling. The pain might become constant and refer to other nerves in the body. Often the pain is worse at night or with activity and cannot be relieved with pain medications. Other symptoms might include problems with movement, unexplained fatigue and weight loss, fever without a cause. These symptoms do not always lead to a diagnosis of sarcoma but it is recommended that if any of these symptoms last more than two weeks, you should seek medical consultation.

Risk Factors

Because Ewing's sarcoma is such a rare cancer , it remains difficult to understand. This is partly because there are fewer patients to study, and it is underfunded. There are currently no known lifestyle changes that can prevent Ewing's Sarcoma. One of the known risk factors is age. Ewing's sarcoma occurs most often in teenagers during puberty or younger children. Males and Caucasians are at a slightly greater risk. None of these factors can be changed in an individual and don't contribute enough statistical information to truly assess a person's risk of developing the disease.

Causes

As a rare childhood cancer with a scarcity of funding and research, the causes of Ewing's Sarcoma are still unclear. This condition is not inherited but arises from a mutation in the body's cells.

"The most common mutation that causes Ewing sarcoma involves two genes, the EWSR1 gene on chromosome 22 and the FLI1 gene on chromosome 11. A rearrangement (translocation) of genetic material between chromosomes 22 and 11, written as t(11;22), fuses part of the EWSR1 gene with part of the FLI1 gene, creating the EWSR1/FLI1 fusion gene. This mutation is acquired during a person's lifetime and is present only in tumor cells. This type of genetic change, called a somatic mutation, is not inherited.

The protein produced from the EWSR1/FLI1 fusion gene, called EWS/FLI, has functions of the protein products of both genes. The FLI protein, produced from the FLI1 gene, attaches (binds) to DNA and regulates an activity called transcription, which is the first step in the production of proteins from genes. The FLI protein controls the growth and development of some cell types by regulating the transcription of certain genes. The EWS protein, produced from the EWSR1 gene, also regulates transcription. The EWS/FLI protein has the DNA-binding function of the FLI protein as well as the transcription regulation function of the EWS protein. It is thought that the EWS/FLI protein turns the transcription of a variety of genes on and off abnormally. This dysregulation of transcription leads to uncontrolled growth and division (proliferation) and abnormal maturation and survival of cells, causing tumor development.

The EWSR1/FLI1 fusion gene occurs in approximately 85 percent of Ewing sarcomas. Translocations that fuse the EWSR1 gene with other genes that are related to the FLI1 gene can also cause these types of tumors, although these alternative translocations are relatively uncommon. The fusion proteins produced from the less common gene translocations have the same function as the EWS/FLI protein. " (https://medlineplus.gov/genetics/condition/ewing-sarcoma/#causes)

Diagnosis

The delayed diagnosis or misdiagnosis rate for patients with Ewing's sarcoma is far too high. The disease is inherently difficult identify and few specialists, let alone general practitioners, have experience interpreting the symptoms. A diagnosis usually begins with one or more types of imaging ; MRIs, X Rays, Bone scans, CT scans and Pet Scans. However a diagnosis can only be confirmed with a biopsy of cancerous tissue which is sent off to pathology.

Staging

Diagnosis and regular imaging can assess the extent of cancer. In Ewing's Sarcoma this is usually staged as localised or metastatic. The sarcoma is localised if it is contained in the part of the body where it was detected. Even when imaging tests don't show that the cancer has spread to distant areas, most patients are likely to have micrometastases (very small areas of cancer spread that can’t be detected with tests).

A metastatic Ewing's tumor has clearly spread from where it started to distant parts of the body. Most of the time, it spreads to the lungs or to other bones or the bone marrow. Unfortunately the prognosis is poor for metastatic Ewing's Sarcoma .

Recurrent Ewing sarcoma means the cancer has returned after it has been treated. The cancer may come back in the bone or soft tissue where it began or in another part of the body. Unfortunately this is not uncommon and can also result in a poor prognosis.

Treatment

Childhood cancers are not the same as adult cancers, and they need to be treated differently. However unlike many adult cancers, there have been very few advances in the treatments of childhood cancers. Many of the chemotherapies used to treat Ewing's Sarcoma are the same as those used twenty or thirty years ago and many of those treatments put the child at risk of serious heart conditions and other debilitating conditions later in life. The chemotherapies can also cause other cancers such as acute myeloid leukemia and myelodysplastic syndrome and the radiation can cause other sarcomas.

Because Ewing's Sarcoma is such an aggressive cancer a multimodal approach is used for treatment.

That typically involves multiple rounds of chemotherapy, surgery to remove the affected area of bone and or tissue and often radiation as well.

Prognosis

While it is not possible to predict the exact course of the disease, it is sometimes possible to predict a prognosis based on the rate and depth of tumour growth, susceptibility to treatment, age, overall fitness and medical history. Generally, early-stage Ewing's sarcomas have a better prognosis and survival rates. If the cancer is advanced and has spread, the prognosis may not be as good and there may be a higher risk of cancer recurrence.

The Tragedy

Unfortunately too many people do not survive a diagnosis of Ewing's Sarcoma. Statistically the chances of survival of localised disease is 70% and that rate is dramatically lower for someone who presents with metastatic or recurrent disease. That toll weighs heavily on our young population and their loved ones. It is imperative that more targeted treatments be developed to treat this aggressive disease and save young lives and that these treatments involve less gruelling and debilitating side effects.