Ewing Sarcoma

Symptoms of Ewing Sarcoma

Ewing sarcomas are most common in older children and teens, though they can occur in people of any age. These tumors are often detected because of the symptoms they cause.

Pain

Pain is the most common symptom of Ewing sarcoma. Tumors typically develop in the pelvis (hip bones), chest wall (ribs or shoulder blades), or extremities (particularly the middle of the long bones), though they can arise in other parts of the body. Initially, the pain may come and go, often worsening at night or during activity. Over time, the pain tends to become more intense and constant. In some cases, a person may experience sudden, severe pain due to a fracture in a bone weakened by the tumor.

Lump or Swelling

Most Ewing sarcomas eventually cause a lump or swelling. These are more noticeable when the tumor occurs in the arms or legs. The lump is often soft, warm, and may grow over time. Tumors in areas like the chest wall or pelvis might not become apparent until they have grown significantly.

Other Symptoms

Ewing sarcomas can also cause additional symptoms, particularly if the cancer has spread:

• Fever
• Fatigue
• Weight loss

Rarely, tumors located near the spine may press on nerves, causing back pain, weakness, numbness, or even paralysis in the arms or legs. Tumors that spread to the lungs can result in shortness of breath.

Ewing Sarcoma: Diagnosis and Testing

Ewing sarcomas are typically identified after a person experiences concerning symptoms. If a tumor is suspected, diagnostic tests and procedures including biopsy are performed to confirm its presence and determine its characteristics.

Diagnosis Challenges

Many symptoms of Ewing sarcoma resemble those of more common issues like infections or injuries. For instance, a doctor may initially prescribe antibiotics if an infection is suspected. If symptoms persist or worsen, further investigation—such as an X-ray—might reveal the tumor.

Anyone experiencing these symptoms, especially if they do not improve, should consult a doctor to identify the cause and receive appropriate care.

Medical History and Physical Examination

Doctors start by gathering a comprehensive medical history to understand the symptoms and their duration. A physical examination follows, focusing on any pain or swelling. If a tumor is suspected, further tests such as imaging studies, biopsies, and laboratory evaluations are conducted.

Imaging Tests

Imaging tests provide detailed pictures of the body to help identify tumors, evaluate their size, and check for cancer spread. Common imaging methods include:

• X-rays: Often the first step when a bone tumor is suspected, x-rays can reveal abnormalities.
• MRI Scans: MRI uses magnets and radio waves to produce detailed images, particularly helpful in showing tumor extent in bones and nearby tissues. Contrast agents enhance image clarity. A biopsy is needed to confirm a diagnosis.
• CT Scans: These scans create detailed cross-sectional images of the body. They are frequently used to check for lung metastases and evaluate tumor details.
• Bone Scans: Radioactive material highlights areas of bone activity, useful for detecting cancer spread throughout the skeleton.
• PET Scans: PET scans identify active cancer cells using radioactive sugar. These scans are valuable for staging and monitoring tumor spread and treatment progress.

Biopsy Procedures

A biopsy is essential to confirm a diagnosis of Ewing sarcoma. An orthopedic surgeon experienced in treating bone tumors typically performs the biopsy. Careful planning ensures the procedure supports subsequent treatment.

• Core Needle Biopsy: Generally done with imaging guidance, this percutaneous, minimally invasive technique takes a core tissue sample from the tumor. Majority of musculoskeletal tumors are diagnosed in this manner.
• Incisional Biopsy: Involves removing a portion of the tumor, surgically
• Excisional Biopsy: In rare cases, a small tumor may be completely removed during biopsy.

During the biopsy, additional procedures such as sampling nearby tumors or placing a central venous catheter may be performed to streamline treatment preparation.

Bone Marrow Aspiration and Biopsy

These procedures check if the cancer has spread to the bone marrow. A small sample of bone and marrow is taken, usually from the pelvis, under local or general anesthesia.

Lab Testing of Biopsy Samples

Pathologists examine biopsy samples under a microscope and conduct specialized tests, including:

• Immunohistochemistry: Identifies specific protein markers expressed by Ewing sarcoma cells.
• Molecular Tests: Detect translocations in tumor cell DNA or RNA, particularly between chromosomes 11 and 22. Methods include cytogenetics, FISH, PCR, and next-generation sequencing.

Blood Tests

Blood tests can’t diagnose Ewing sarcoma but provide supportive information:

• Complete Blood Count (CBC)
• LDH Levels: High lactate dehydrogenase levels suggest more extensive disease.
• Blood Chemistry Tests: Monitor liver and kidney function during treatment.

These diagnostic steps ensure a thorough understanding of the tumor, guiding effective treatment planning.

Stages

Once Ewing Sarcoma is diagnosed, additional tests help determine its stage, or how much cancer is in the body. The stage indicates the severity of the cancer and helps guide treatment decisions. It is also used when discussing survival statistics. Staging is based on imaging tests and biopsies of the main tumor and any affected tissues, as explained in Ewing Sarcoma.

A staging system provides a standardized way for the care team to summarize the cancer’s extent. Different cancers use different staging systems. For Ewing tumors, the American Joint Committee on Cancer (AJCC) has formal systems for bone cancers and soft tissue sarcomas. However, for treatment purposes, a simpler classification—localized or metastatic—is often used.

Localized vs. Metastatic Ewing Tumors

When planning treatment, doctors typically classify Ewing tumors as localized or metastatic.

• Localized Ewing Tumors: A tumor is considered localized if it is only found in the area where it started or in nearby tissues, such as muscles or tendons. This determination is made after all tests, including x-rays, CT scans, MRIs, PET scans, bone scans, or bone marrow biopsies, show no signs of the cancer spreading to distant parts of the body.
  • Even if tests don’t detect cancer in other areas, many patients likely have micrometastases (small cancerous areas undetectable by imaging tests). This is why chemotherapy, which treats the whole body, is a critical part of treatment for all Ewing Sarcoma.
• Metastatic Ewing Sarcoma: A metastatic Ewing Sarcoma has spread to distant parts of the body. Most commonly, it spreads to the lungs, bones, or bone marrow, though less frequently to the liver or lymph nodes. About 20% of patients show clear signs of cancer spread on imaging tests. However, small amounts of undetectable spread may still exist in others.

Ewing Sarcoma staging can feel overwhelming. Be sure to ask your care team any questions to better understand the stage and what it means for treatment.

Localized Ewing Sarcoma

Localized tumors appear confined to their original area (and possibly nearby tissues), but even then, microscopic cancer cells may be present elsewhere in the body. Chemotherapy (chemo) is essential in these cases, as it targets undetectable cancer cells that could form new tumors if untreated.

1. Initial Treatment: Chemotherapy begins after diagnosis and staging. In the U.S., the typical regimen, VDC/IE (vincristine, doxorubicin, and cyclophosphamide alternated with ifosfamide and etoposide), is administered before and after treatment of the primary tumor with surgery and/or radiation therapy.
2. Assessment: After at least nine weeks of chemo, imaging tests (CT, MRI, PET, or bone scans) Are repeated to assess response to treatment.

If surgery is viable, the tumor is removed, and a pathologist examines the specimen:

• Positive Margins: Tumor is present at the edge of the removed tissues.
• Negative Margins: There are healthy non-tumor tissues present at the edge of the removed tissues.

As Ewing sarcoma is radiation sensitive, the decision for treatment of the primary tumor is a multidisciplinary discussion that takes into account patient and tumor specific variables, disease stage, and impact of local control treatment on near and long-term outcomes and complications.

For tumors unresponsive to the initial regimen, alternative chemo combinations, surgery, or radiation therapy may be tried.

Metastatic Ewing Sarcoma

Metastatic tumors, particularly those spreading beyond the lungs, are harder to treat. Intensive chemotherapy is the first step, followed by tests to evaluate the cancer’s response. If only a few small areas remain, treatment options include:

• Surgery to remove the primary tumor and metastases
• Radiation therapy for remaining areas
• Chemotherapy for several months

For certain cases, high-dose chemo followed by stem cell transplants is being studied. Clinical trials often provide new treatment options for metastatic Ewing tumors.

Recurrent Ewing Sarcoma

If a tumor returns, treatment depends on its size, location, spread, prior treatments, and time since the last treatment. Options include chemo, surgery, radiation therapy, or a combination. Clinical trials for high-dose chemo, stem cell transplants, and targeted or immune therapies may offer hope in these cases.

Chemotherapy

Chemotherapy target cancer throughout the body, making them crucial for Ewing tumors, which often have undetected microscopic spread. Chemo is typically administered in cycles, alternating treatment days with recovery periods.

Common Regimen

The most common regimen, VDC/IE, alternates two drug combinations:

• VDC: Vincristine, doxorubicin, cyclophosphamide
• IE: Ifosfamide, etoposide

Patients receive chemo for at least nine weeks pre-surgery or radiation, with additional cycles afterward, totaling 14–15 cycles over 6–12 months.

Side Effects

Chemo side effects vary based on drugs and doses. Common effects include:

• Hair loss, mouth sores, nausea, vomiting, diarrhea, and appetite loss
• Low blood cell counts, increasing infection risk, bruising, or fatigue
• Specific drugs may cause unique issues:
  • Cyclophosphamide/Ifosfamide: Bladder damage (preventable with fluids and mesna)
  • Doxorubicin: Heart damage, monitored with echocardiograms
  • Vincristine: Nerve damage (numbness/tingling)
  • Etoposide: Rarely linked to later leukemia

Long-term side effects, including fertility issues or secondary cancers, should be discussed with the care team.

Surgery for Ewing Sarcoma

Surgery is key option for removing tumors. The main goal is complete tumor removal with negative margins, often with surrounding healthy tissue, to prevent recurrence. A pathologist examines the tissue margins to confirm whether cancer cells remain.

Limb-Sparing Surgery

For tumors in arms or legs, limb-sparing surgery removes affected bone and replaces it with bone grafts or internal metal prostheses or bone transport. These procedures are complex and require skilled surgeons. Expandable prosthetics are used in children with significant remaining growth in order to help maintain as close as possible limb lengths. Another unique option is rotationplasty for patients who want a biologic surgical option and less need for future surgeries and less activity restrictions.

Challenges

Tumors in areas like the skull base, spine, chest wall, or pelvis can be harder to remove and may require different approaches.

For tumors that cannot be completely removed surgically or in which the complications of surgery is deemed to significant, like in the spine, radiation therapy is typically combined with other treatments.

Radiation Therapy and Stem Cell Transplants for Ewing Tumors

Radiation Therapy

Radiation therapy uses high-energy beams targeted at tumors to destroy cancer cells. Ewing sarcomas are highly sensitive to radiation, making this treatment an option alongside or instead of surgery. When surgery isn’t feasible, radiation therapy, often combined with chemotherapy, can be effective.

How Radiation Therapy is Performed

Administered by a radiation oncologist, treatment begins with a planning session called simulation. Imaging tests like MRI scans determine the tumor's location and the appropriate radiation dose. Patients may wear a plastic mold to maintain consistent positioning during treatments. Sessions occur five days a week over several weeks. Each session involves the patient lying on a table while radiation is delivered from specific angles. Treatments are brief, but setup can take longer, particularly for younger children who may require sedation to prevent movement.

Modern Radiation Techniques

Advances in technology allow for more precise targeting of radiation, minimizing damage to healthy tissue:

• 3D Conformal Radiation Therapy (3D-CRT): Uses imaging to map the tumor and deliver focused beams from various directions.
• Intensity-Modulated Radiation Therapy (IMRT): Adjusts beam strength for complex tumors or those near sensitive areas like the spine.
• Conformal Proton Beam Therapy: Uses proton beams to release energy directly at the tumor, sparing nearby tissues.

Possible Side Effects of Radiation Therapy

Side effects depend on the radiation dose and the targeted area.

• Short-term effects include skin irritation, lowered blood cell counts, nausea, and mouth sores.
• Long-term effects in growing children can involve slowed bone growth, organ damage, fertility issues, or secondary cancers.

Stem Cell Transplants for Ewing Sarcomas

For advanced or recurrent Ewing Sarcomas, high-dose chemotherapy combined with a stem cell transplant may be considered. While still under study, this approach can provide higher chemo doses by rescuing damaged bone marrow with stem cells.

Stem Cell Transplant Procedure

Patients undergo initial chemo and local treatment (surgery or radiation) before the transplant. Blood stem cells are harvested, frozen, and later infused after high-dose chemo to restore bone marrow function.

Side Effects of Stem Cell Transplants

This intensive treatment carries risks like severe side effects from chemotherapy. Long-term concerns, especially in children, include delayed effects on growth and organ function. Stem cell transplants should be performed at specialized centers equipped to manage recovery.

By utilizing cutting-edge techniques and tailored treatments, radiation therapy and stem cell transplants offer hope for managing complex Ewing tumors.

The University of Colorado (CU) Cancer Center partners with UCHealth, Children’s Hospital Colorado, and Rocky Mountain Regional VA to provide clinical care. Please make an appointment with one of our clinical partners to be seen by a CU Cancer Center doctor.

UCHealth:

UCHealth Cancer Care - Anschutz Medical Campus
1665 Aurora Court Anschutz Cancer Pavilion
Aurora, CO 80045
720-848-0300

UCHealth Cherry Creek Medical Center
100 Cook Street
Denver, CO 80206
720-848-0000

Rocky Mountain Regional VA Medical Center:
1700 North Wheeling Street
Aurora, CO 80045-7211
303-399-8020