Ewing’s Sarcoma

Ewing’s sarcoma is a rare and aggressive cancer that most often affects children and teenagers, beginning as abnormal cell growth in bones or nearby soft tissues and requiring prompt treatment with chemotherapy, surgery, or radiation therapy.

What is Ewing’s sarcoma?
Types of Ewing’s sarcoma
Who is affected?
Signs and symptoms
Causes and risk factors
How is it diagnosed?
Treatment approaches
Outlook and survival
Possible complications

What is Ewing’s sarcoma?

Ewing’s sarcoma is a type of cancer that begins as abnormal growth of cells in the bones or in the soft tissue surrounding bones^[1]. It is considered a highly aggressive form of cancer that can spread to other parts of the body^[3]. Despite being rare, Ewing’s sarcoma ranks as the second most common primary bone tumor in children and young adults, accounting for approximately 10% to 15% of all bone sarcomas^[3].

The condition was first described in 1921 by James Ewing, a physician who recognized these tumors as a distinct type of cancer^[4]. In the United States, only about 200 to 300 new cases occur each year, with an incidence of approximately 1.7 per million children younger than 15 years old^[5].

Ewing tumor, Ewing’s sarcoma, Ewing sarcoma family of tumors

Types of Ewing’s sarcoma

There are three main types of Ewing’s sarcoma, classified based on where the tumor develops^[2]:

Ewing sarcoma of bone: This is the most common type, developing within bone tissue
Extraosseous Ewing tumor (EOE): These tumors affect the soft tissues that surround bones, including muscles, tendons, and ligaments
Peripheral primitive neuroectodermal tumor (PPNET): This type can start in either bone or soft tissue

The Ewing family of tumors also includes Askin tumor, which is a malignant small cell tumor affecting the chest wall^[3].

Who is affected?

Ewing’s sarcoma predominantly affects adolescents and young adults, with most cases occurring in people between the ages of 10 and 20 years^[1]. The peak age for diagnosis is around 15 years old^[2]. However, the disease can appear at any age, including in younger children and people in their late twenties to early thirties^[2].

The tumors often develop during puberty, when bones are growing very quickly^[2]. Males are affected slightly more often than females^[4]. Regarding race and ethnicity, Ewing’s sarcoma is more likely to affect people who are white (both Hispanic and non-Hispanic) compared to Asian American or Black populations^[2].

Leg bones (femur, tibia)
Pelvis
Chest wall (ribs, shoulder blades)
Arms
Spine
Skull

Signs and symptoms

The most common symptoms of Ewing’s sarcoma typically appear in and around a bone^[1]. Pain is often the first sign that something is wrong. This bone pain tends to come and go at first, but usually gets worse over time and may become more severe at night^[2].

Other symptoms that may indicate Ewing’s sarcoma include^[1]^[2]:

A lump or swelling near the affected area, which may feel warm and soft to the touch
Pain, swelling, or tenderness near the tumor site
A bone fracture that happens without any injury
Fever that doesn’t go away
Tiredness and unexplained weight loss, especially if the cancer has spread

The tumor may appear as a visible bump or lump on the arms, legs, or chest^[2]. It’s important to note that the tumor may be present for many months before it becomes large enough to cause noticeable symptoms^[5].

Causes and risk factors

The exact cause of Ewing’s sarcoma is not known^[4]. However, scientists have discovered that the cancer results from a genetic mutation—a change in genes—that happens after birth^[2]. This change is not inherited from parents but occurs randomly during a person’s life^[5].

The genetic change most commonly involves two genes: the EWSR1 gene and the FLI1 gene. These two genes fuse together to create a new abnormal gene that causes cells to multiply uncontrollably and form cancerous tumors^[2]. About 85% of Ewing’s sarcoma tumors are associated with a specific chromosomal change called t(11;22)(q24;q12), which creates the EWS-FLI1 fusion gene^[3].

Researchers don’t know what triggers this genetic change. However, they have ruled out exposure to cancer-causing substances as a cause, since Ewing’s sarcoma typically affects children and young adults who haven’t had long-term exposure to such substances^[2].

While Ewing’s sarcoma doesn’t appear to be strongly linked to hereditary cancer syndromes, there is growing evidence suggesting an inherited risk factor with multiple chromosome locations associated with susceptibility to the disease^[4].

How is it diagnosed?

Diagnosing Ewing’s sarcoma begins with a physical examination where healthcare providers feel for any lumps or bumps and ask about symptoms^[2]. Several tests are then used to confirm the diagnosis and determine the extent of the disease.

Imaging tests allow doctors to visualize bones and soft tissues to locate tumors. Common imaging tests include^[1]^[2]:

X-rays
MRI scans (magnetic resonance imaging), which use magnets and radio waves to create detailed images
CT scans (computed tomography), which create 3D images of the body
Bone scans
PET scans (positron emission tomography)

A biopsy is essential to confirm the diagnosis^[1]. During this procedure, a sample of tissue is removed—either using a needle inserted through the skin or through surgery—and examined in a laboratory^[1]. The tissue sample undergoes special testing to identify specific DNA changes in the cancer cells, particularly looking for changes in the EWSR1 gene and its fusion with other genes like FLI1^[8].

Treatment approaches

Treatment for Ewing’s sarcoma typically involves a combination of therapies and usually lasts 6 to 9 months^[14]. The treatment approach depends on whether the cancer is localized (confined to one area) or has spread to other parts of the body.

Chemotherapy

Chemotherapy uses powerful drugs to destroy cancer cells throughout the body. It is the first treatment given for Ewing’s sarcoma and is called neoadjuvant chemotherapy when given before other treatments^[13]. This initial chemotherapy is typically given for about 12 weeks to shrink the tumor^[13].

The most common chemotherapy combinations include several drugs given together, such as vincristine, doxorubicin, and cyclophosphamide, alternating with etoposide and ifosfamide^[13]^[14]. After surgery or radiation, more chemotherapy is given, called adjuvant chemotherapy^[13].

Recent research has shown that giving chemotherapy every 2 weeks instead of every 3 weeks can improve outcomes for patients with localized Ewing’s sarcoma, with 5-year survival rates improving from 65% to 73%^[14].

Surgery

After chemotherapy, surgery is performed to remove the tumor. The goal is to remove the entire tumor along with some healthy tissue around it, a procedure called wide resection^[13]. The type of surgery depends on the tumor’s size and location.

For tumors in the arms or legs, doctors try to perform limb-sparing surgery, which removes the tumor without removing the limb^[13]. In cases where limb-sparing surgery isn’t possible, amputation (removal of part or all of the affected limb) may be necessary^[13].

Radiation therapy

Radiation therapy uses high-energy beams to kill cancer cells. It may be used when surgery cannot be performed with minimal impact on the patient, or when the tumor cannot be completely removed by surgery^[8]^[13]. Radiation therapy may also be given after surgery to destroy any remaining cancer cells.

Emerging treatments

Researchers are studying new treatment approaches, including targeted therapy and immunotherapy^[1]. Some promising new therapies include drugs that target specific proteins involved in tumor growth and CAR-T-cell therapy directed at a molecule called GD2 found on Ewing’s sarcoma cells^[10].

Outlook and survival

The outlook for people with Ewing’s sarcoma has improved dramatically over the past four decades. Major advances in chemotherapy and local treatment have increased the 5-year survival rate from less than 20% to greater than 70% for patients with localized disease^[3]. The overall 5-year survival rate is approximately 70%^[4].

However, several factors affect survival rates. Patients with cancer that has spread at the time of diagnosis have poorer outcomes^[3]. About 25% of patients have cancer that has already spread to other parts of the body when they are first diagnosed^[4]. The location and size of the tumor, as well as how well it responds to initial chemotherapy, also influence the prognosis.

If the cancer is caught before it spreads, the chance of long-term survival is much better^[21]. Despite improvements in treatment, the recurrence rate remains a concern, and treatment for recurrent or metastatic disease continues to be challenging^[3].

Possible complications

Ewing’s sarcoma and its treatment can lead to various complications. These include the possibility of cancer spreading to other parts of the body, cancer returning after treatment, or developing a second, different type of cancer^[2].

Children and young adults who have been treated for Ewing’s sarcoma may experience late effects—health problems that develop months or years after completing treatment^[2]. These late effects can affect various aspects of health, including:

Organ and tissue function
Growth and development
Mood, feelings, and mental health
Ability to think, learn, and remember information
Fertility and ability to have children in the future

Because of these potential late effects, healthcare professionals often recommend long-term monitoring and follow-up care for people who have been treated for Ewing’s sarcoma^[1]. Regular check-ups allow doctors to detect and manage any complications early, helping survivors maintain the best possible quality of life after treatment.