Ewing Sarcoma

What is Ewing Sarcoma?

Ewing sarcoma is a serious type of cancer that typically affects teenagers and young adults. It accounts for 10% to 15% of all bone cancers. This cancer was first identified by James Ewing in 1921. Various types of cancers fall under the Ewing sarcoma family, including ‘classic’ Ewing sarcoma of the bone, extra-skeletal Ewing sarcoma (cancer outside the bone), malignant small cell tumor of the chest wall (also called Askin tumor), and soft tissue-based primitive neuroectodermal tumors (tumors starting from cells in the nervous system). All these types of cancers are believed to originate from the same type of early-stage cells due to their similar characteristics.

Characteristics of Ewing sarcoma include specific chromosomal changes that lead to the creation of abnormal regulatory proteins. The most common anomaly, found in 85% of cases, involves a switch of genetic material between chromosomes 11 and 22, leading to the production of a protein called EWS-FLI-1. Other less common anomalies make up the remaining 10% to 15% of cases. Ewing sarcoma can occur in almost any bone or soft tissue, but the most commonly affected parts are the pelvis, spinal column, and thigh bone. Patients typically experience pain and swelling in the affected area.

In the past 40 years, there has been significant progress in treating localized Ewing sarcoma, meaning cancer that hasn’t spread. The combination of localized treatments and chemotherapy has increased the 5-year survival rate from less than 20% to over 70%. Despite this, the cancer often comes back, and almost all cases have microscopic cancer spread that might not be initially detected. Around 25% of patients with originally localized cancer eventually experience a recurrence. There is no standard treatment for recurrent and difficult-to-treat Ewing sarcoma. Survival rates are less than 30% for those with cancer spread to the lungs, and less than 20% if it’s spread to the bones or bone marrow. Given the treatment side effects and low survival rates for advanced-stage disease, there is an immediate need for the development of new treatments for Ewing sarcoma.

What Causes Ewing Sarcoma?

Ewing sarcoma, a type of cancer, has no validated relationship with factors such as exposure to certain environments, drugs, radiation, or history of cancer in the family. The studies that have researched these potential connections are primarily small, and look back at patients’ histories after they’ve been diagnosed, which makes it hard to firmly establish any such relationships.

Risk Factors and Frequency for Ewing Sarcoma

Ewing sarcoma is the second most usual type of bone cancer found in adolescents and young adults, typically around 15 years old. It makes up less than 5% of all soft tissue cancers. More than 200 cases are reported in the United States every year. However, when it comes to Ewing sarcoma’s rate of occurrence, it was 2.93 in a million between 1973 and 2004.

• Most cases occur between the ages of 10 and 15.
• About 30% of the cases occur in children under 10 and another 30% in adults over 20.
• Ewing sarcoma is more common in males, with a 3 to 1 ratio of males to females.
• It’s more commonly seen in whites than in Blacks, Asians, Hispanics, or Africans.
• The exact occurrence of Ewing sarcoma in older age groups isn’t known.

Signs and Symptoms of Ewing Sarcoma

Ewing sarcoma is a type of cancer that often shows symptoms such as pain, stiffness, or swelling that can go on for weeks or even months. Over half the patients with Ewing sarcoma experience occasional pain that gets worse at night. This cancer mostly affects the middle section of long bones, but it can show up in different areas with different symptoms. If the cancer is in a long bone, it can cause fractures. If it’s in the pelvis, it can cause back pain. Systemic symptoms like fever and weight loss usually suggest that the cancer has spread. Around 20% of patients already have metastatic disease, meaning the cancer has spread, when they are diagnosed, and more than 20% of these cases affect the lung or the lining of the lungs.

• Pain, stiffness, or swelling
• The pain tends to worsen at night
• The cancer often affects the middle of long bones
• Fractures can occur if a long bone is involved
• Back pain can occur if the cancer is in the pelvis
• Systemic symptoms like fever and weight loss can indicate metastatic disease
• About 20% of patients already have metastatic disease when they are diagnosed
• Among these cases, over 20% involve the lung or its lining

Doctors conduct a thorough physical exam, especially checking the nervous system if it’s involved. If the cancer has spread to the lungs, the patient’s breathing might be uneven, and there might be pleural signs or crackling sounds. People with bone marrow metastases might have petechiae or purpura, which are small bruise-like spots, due to a low platelet count. If the nervous system is involved, a neurological exam is vital. The first steps in diagnosing Ewing sarcoma usually include an x-ray of the affected area, which might show the “onion skin” appearance of periosteal reaction. Other necessary tests include a bone scan, MRI, and CT scan for initial staging.

Testing for Ewing Sarcoma

When it comes to diagnosing and assessing your condition, imaging tests play a critical role. They help doctors see what’s happening in the affected area and can also detect if the disease has spread to other parts of your body. Some common imaging techniques include plain X-rays, CT scans, MRI scans, and PET scans.

Plain X-rays of the affected area may show unique patterns, like holes that look like a moth has eaten through the bone, or an “onion-skin” pattern where the outer layer of the bone has a multi-layered appearance. Such findings can give clues to your problem.

MRI, often used with or without CT scans, is particularly important. It can show how far the disease has spread, whether it can be surgically removed, if there is swelling, or if the disease involves surrounding organs. CT scan of your chest, PET/CT scan, bone scan, and MRI of your spine and pelvis are other imaging methods that can help check potential spread to lymph nodes or other organs.

If you have specific symptoms, your doctor may suggest a biopsy, which involves removing a small sample of tissue for further study. This could be done by an orthopedic surgeon or by using a CT scan to guide a needle to collect the tissue sample. Further analysis of the biopsy sample would potentially reveal the rearrangement of chromosomes often seen in some diseases.

Your initial tests might include checking the level of lactate dehydrogenase (a type of protein) in your blood, as its level can hint at the severity of your condition. You may also undergo a bone marrow aspiration and biopsy, where a small amount of bone marrow tissue is taken from your bone for testing.

It’s also important to discuss the potential effects of your treatment on your ability to have children in the future. Therefore, fertility counseling might be offered before your treatment begins.

Treatment Options for Ewing Sarcoma

People who have Ewing sarcoma, whether or not the cancer has spread to other parts of their body, usually undergo a team-based treatment approach. This involves chemotherapy, and sometimes, local therapies such as surgery and radiation therapy.

Chemotherapy, which is a type of treatment that uses strong drugs to kill cancer cells, is the key element of treatment for all patients with Ewing sarcoma. In the US, the usual combination of chemotherapy drugs used includes vincristine, doxorubicin, and cyclophosphamide (known together as VDC), along with ifosfamide and etoposide (known as IE). These drugs are given in alternating cycles, which means they are given one after the other over a period of time.

Once the initial (induction) chemotherapy has been completed, doctors usually suggest a local therapy. This could be radiation therapy, surgery, or both put together. Radiation therapy uses high-energy rays (like X-rays) to kill cancer cells, while surgery involves physically removing the cancer.

The five-year survival rate, which is a standard measure of how successful the treatment has been, differs based on whether the cancer has spread or not. For patients whose cancer hasn’t spread beyond the original location, 75% to 80% are still living five years later. But for those whose cancer has spread to other parts of their body, the five-year survival rate drops to around 30%.

What else can Ewing Sarcoma be?

By looking at clinical history and considering findings from certain tests, doctors can rule out other conditions when diagnosing Ewing sarcoma. These conditions may have similar features and include:

• Neuroblastoma
• Rhabdomyosarcoma
• Lymphoma
• Neuroectodermal tumors
• Desmoplastic small round cell tumor
• Synovial sarcoma
• Osteomyelitis
• Osteogenic sarcoma
• Eosinophilic granuloma

Considering these potential diagnoses helps ensure the most accurate diagnosis of Ewing sarcoma.

Surgical Treatment of Ewing Sarcoma

Ewing sarcoma is a type of cancer and its surgical removal is a key part of its treatment. Surgery not only helps to diagnose the disease but also evaluate how well the tumor responds to treatment. Compared to radiation therapy, surgery is believed to cause fewer long-term health problems like growth restrictions and the development of other cancers. Now, with the introduction of 3D printing systems, the need for amputations has decreased greatly, and surgeries that use custom-made implants to preserve function have increased.

Surgery is often the preferred method for treating tumors that come from non-essential bones like the ribs, fibula, small bone in the lower leg, iliac wings, large bones in the pelvis, distal four-fifths of the clavicle, and the scapula or shoulder blade. There is no clear evidence to suggest that radiation therapy is better than surgery. However, analyses of various studies suggest that combined postoperative radiation therapy and surgery may provide better local control in certain cases.

Biopsy, the procedure where a small sample of tissue is taken for testing, is recommended. While a core needle biopsy can provide enough tissue for a diagnosis, more tissue might be required for biological studies, which might not be adequately obtained through multiple needle biopsies. Any suspected areas of cancer spread, like lymph nodes or bone lesions, should also be biopsied.

Before surgery, detailed imaging is critical to understand the extent of the tumors and how resectable they are. Tumors that cross the middle line of the sacrum are usually not able to be removed, nor are tumors that require the removal of a visceral organ, an organ located within the main cavities of the body, like the stomach or liver. Cases of spinal tumors are treated selectively: only patients who respond well to chemotherapy are considered.

If a patient is considered a suitable surgical candidate, removal of the main tumor and its surrounding area is recommended. Amputations are performed less frequently but might be considered if complete cancer removal is not possible with less invasive methods, or in cases of limbs with poor function or locally recurrent disease.

When the disease has spread extensively, surgical removal of the main tumor may be difficult to justify, unless performed for pain relief or when the spread of the disease is limited. On a case by case basis, surgery might be possible on patients who have isolated lung metastasis.

About 70% of relapses occur within two years of diagnosis. Although distant spread is more common, a small percentage of patients may have an isolated local recurrence or a single metastatic site and might be considered for further localized treatment.

Complications can occur in about 25% of patients from surgery or a combination of treatments. These include delayed wound healing, fibrosis (scarring), thrombosis (blood clots), abscess formation (pockets of pus), or problems with surgical implants. The risk of postoperative complications seems to relate to the tumor site.

What to expect with Ewing Sarcoma

Ewing sarcoma is a type of cancer, and when it’s found in the farther parts of the limbs (like the hands and feet), it’s usually associated with a better outlook than when the cancer is in the closer parts of the limbs. How much the cancer has spread is also essential in determining the patient’s outlook.

People with this cancer who have isolated spread to their lungs generally fare better than those with cancer that has spread to other parts of the body. Among those with lung spread, patients with the disease in one lung have a better outlook than those with involvement in both lungs. However, if the cancer has spread to both the bone and lung or if the tumor is extensive, the outlook tends to be poorer.

Tumor size and age are also influential factors in prognosis. Research suggests that patients under 15 years old tend to have a better outlook. Studies have shown that patients who have little or no detectable cancer left after initial rounds of chemotherapy before surgery seem to fare better than those with more considerable amounts of cancer remaining.

Additionally, if the body doesn’t respond positively to the initial rounds of chemotherapy, there’s a higher chance that the cancer might come back. Important to think about, but not a deal-killer since the presence of a particular genetic re-arrangement (EWSR1-ETS translocation) is no longer viewed as a predictor for a poor outlook.

Possible Complications When Diagnosed with Ewing Sarcoma

Ewing sarcoma, a type of cancer, can potentially have multiple complications. These include the spreading of the cancer to other parts of the body, regrowth in the same area, developing another type of cancer, breaking of bones, and potential side effects related to both surgery and treatments involving radiation and chemotherapy.

For more details about complications pertaining to the specific treatment used, refer to relevant subsections.

Common Complications of Ewing Sarcoma:

• Metastases or the spread of cancer
• Local recurrence or cancer regrowth in the same area
• Secondary malignancies or another type of cancer
• Pathological fractures or breaking of bones
• Surgery-related complications
• Side effects from radiation-associated treatments
• Side effects from chemotherapy-associated treatments

Preventing Ewing Sarcoma

Ewing sarcoma is a type of disease that we unfortunately don’t have ways to prevent yet. But it’s crucial for patients and their parents to understand the importance of sticking to all the prescribed treatments. This consistency in following the treatment plans can greatly help to improve the health results.