Diagnosis and Treatment of Ewing Sarcoma

Sheba Medical Center is dedicated to providing the best treatment and care to patients with Ewing sarcoma prior to diagnosis through specialized treatment plans. Our oncologists, hematologists, radiation oncologists, pathologists, and other specialists work closely together to diagnose and determine the type of your disease.

At Sheba, we keep you informed every step of the way as our experienced doctors guide you through the critical diagnostic part of your cancer care. Once a diagnosis is made, we come up with an individualized treatment plan tailored to your specific needs.

The diagnosis of Ewing sarcoma typically involves a series of medical evaluations and tests to confirm the presence of the disease. Initially, a thorough physical examination is conducted to assess the symptoms and potential risk factors, and the following blood tests may be employed:

• A Complete Blood Count (CBC) and Peripheral Blood Smear: A CBC is a blood test that provides a count of the red blood cells, white blood cells, and platelets in your blood. During a peripheral blood smear, doctors look at the blood under a microscope for changes in the number and appearance of cells. This test looks at the patient’s overall health and can find a wide range of conditions, including Ewing sarcoma.
• Lactate Dehydrogenase (LDH) Test: this test measures the level of lactate dehydrogenase (LDH), also known as lactic acid dehydrogenase, in your blood or sometimes in other body fluids. LDH is a type of protein, known as an enzyme. LDH plays an important role in making your body’s energy.
• Comprehensive Metabolic panel: is a blood test with 14 different measurements, which is often used to evaluate liver and kidney function, as well as nutrient levels.

Following this, imaging tests are performed to identify any suspicious tumors or abnormalities:

• X-Ray Scan: also called a radiograph, an x-ray is a type of medical imaging (radiology) that creates pictures of your bones and soft tissues, such as organs.
• Bone Scan: a bone scan is a test that uses nuclear imaging to help diagnose and track several types of bone disease.
• Computed Tomography (CT) Scan: a computerized tomography (CT) scan combines a series of X-ray images taken from different angles around your body and uses computer processing to create cross-sectional images (slices) of the bones, blood vessels and soft tissues inside your body. CT scan images provide more information than X-rays do.
• Positron Emission Tomography (PET) Scan: A positron emission tomography (PET) scan is a type of imaging test that shows how organs and tissues are working. It is different from MRI and CT scans because it shows the structure of, and blood flow to and from organs.
• Magnetic Resonance Imaging (MRI): MRI is a non-invasive imaging technology that produces three dimensional detailed anatomical images. It is often used for disease detection, diagnosis, and treatment monitoring.

To establish a definitive diagnosis, a biopsy is usually conducted, where a small tissue sample is taken from the affected area and examined under a microscope by a pathologist.

There are three types of biopsies that are usually performed:

• Bone Marrow Biopsy and Aspiration: These procedures collect and examine bone marrow that show whether your bone marrow is healthy and making normal amounts of blood cells. This data can help to diagnose and monitor blood and marrow diseases.
• Bone Biopsy: A bone biopsy is a procedure in which bone samples are removed (with a special biopsy needle or during surgery) to find out if cancer or other abnormal cells are present. A bone biopsy involves the outer layers of bone, unlike a bone marrow biopsy, which involves the innermost part of the bone.
• Tumor Biopsy: In this type of biopsy, a surgeon cuts through the skin to remove the entire tumor (called an excisional biopsy) or a small part of a large tumor (called an incisional biopsy). This is often done using local or regional anesthesia (drugs are used to numb the area).

Various laboratory tests may also be performed, such as:

• Cytogenetic Analysis: A process for analyzing cells in a sample of tissue, blood, bone marrow or amniotic fluid to look for changes in chromosomes, including broken, missing, rearranged or extra chromosomes.
• Flow Cytometry: A technique used to detect and measure physical and chemical characteristics of a population of cells or particles.
• Immunohistochemistry (IHC): A widely used ancillary testing method in anatomic surgical pathology for cell classification and diagnosis that utilizes antibodies targeted against certain antigens in specific tissues and cells to facilitate determination of cell type and organ of origin. A sample of cells is treated with antibodies that only stick to proteins found on Ewing sarcoma tumor cells. A dye causes them to change color so that they can be seen under a microscope.

Additionally, molecular testing may be employed to detect the specific genetic changes associated with Ewing sarcoma:

• Fluorescence in Situ Hybridization (FISH): This laboratory test uses fluorescent dyes that attach to certain genes or chromosomes. It can pick up on small changes that are not seen in other kinds of testing, mapping the genetic material in a person’s cells.
• Polymerase Chain Reaction (PCR): A laboratory technique used to make many copies of a specific piece of DNA to more easily identify certain changes in a gene or chromosome, which can help locate and diagnose a malignancy.
• Additional methods include next generation sequencing (NGS), such as gene panel sequencing (DNA and RNA), mutation profile characterization, methylation profile, and response markers for immunotherapies.

Overall, the process of diagnosing Ewing sarcoma requires the collaboration of medical professionals from various fields, including oncology, radiology, and pathology, to accurately identify the disease and develop an appropriate treatment plan for the patient.

Once a diagnosis of Ewing sarcoma is made, doctors try to figure out how advanced the cancer is by determining whether it has spread, and if so, how much. Sheba’s specialists will gather all the information from the diagnostic tests, and perform further testing if necessary.

Stages 1 through 4 are used to signify how advanced the cancer is, with stage 1 being the least advanced, and stage 4 indicating that the cancer has spread to other parts of the body.

Instead of the traditional staging system used for most cancers, Ewing Sarcoma staging is usually classified into four types:

• Localized Ewing Sarcoma: The cancer is confined to the primary site where it started, and it has not spread to other parts of the body. In this stage, only the bone in which the tumor developed and the tissues next to the bone, such as muscle and tendon. It has the highest 5-year relative survival rate of all stages (82%).
• Regional Ewing Sarcoma: In this stage, the cancer has spread to the nearby regions, and the 5-year relative survival rate drops to 71%.
• Metastatic Ewing Sarcoma: The cancer has spread from the primary site to other distant parts of the body, and the 5-year relative survival rate is 39%.
• Relapsed/Refractory Ewing Sarcoma: The cancer hasn’t responded to treatment or has returned after an initial response to treatment. The most common site for recurrence is the lungs. A long interval between the primary diagnosis and the appearance of recurrent disease is associated with a better prognosis.

Ewing sarcoma treatment options depend on the type, size, and location of the tumor. Usually, treatment for Ewing sarcoma involves a combination of the following:

Cancer Removal Surgery

In the majority of Ewing sarcoma cases, surgery is an important part of treatment. It may be performed to obtain a biopsy sample and to remove the tumor. The goal of surgery is to remove the whole tumor, and doctors may remove some tissue around the tumor as well just to be sure.

Chemotherapy

Often referred to as “chemo”, chemotherapy is a cancer treatment method that employs either a single medication or a blend of various drugs. The primary aim of chemo is to halt or significantly slow down the proliferation of cancer cells. In some instances, chemotherapy stands as the sole treatment, while in other cases, it is administered in combination with either radiation therapy, surgery, or both.

Contrasting with surgical and radiation therapies which target specific areas, chemo is a systemic therapy, impacting the body as a whole. This suggests that chemotherapy is capable of eliminating cancer cells that have metastasized, or spread, beyond the original tumor to other parts of the body.

Chemotherapy can fulfill four key functions:

• it can completely eradicate cancer cells, offering a potential cure
• it can control the growth and spread of the disease
• it can alleviate symptoms by reducing the size of a tumor
• it can prevent a recurrence of the disease

The exact role that chemo plays is largely dependent on the specific type of cancer and the stage it has reached.

Radiotherapy

Radiation therapy, also called radiotherapy or irradiation, is one of the most common approaches to cancer therapy. Over half of all people with cancer will be treated with radiation therapy; sometimes the head area is also treated by radiotherapy or radiosurgery.

In contrast to chemotherapy, which can expose your entire body to drugs that fight cancer, radiation therapy is typically localized. Radiation aims high-energy rays precisely to destroy cancer cells, thereby minimizing the harm to healthy surrounding tissues. Radiotherapy damages the DNA inside cancer cells so they cannot continue to grow and divide, and they die instead.

There are several different reasons radiation therapy may be used:

• To shrink or cure early-stage cancer: Some cancers are highly sensitive to radiation, and this therapy may therefore be enough to cure your cancer completely. Radiation may also be administered in order to shrink a tumor before surgery, or used after surgery to help prevent the cancer from recurring. Sometimes, radiation is used along with chemotherapy, as specific chemo drugs (radiosensitizers) can enhance the effects of radiation by increasing the sensitivity of cancer cells to radiation.
• To destroy cancer cells before bone marrow/stem cell transplantation: Prior to undergoing a stem cell transplant, radiation therapy may be administered to the entire body to destroy cancer cells in the bone marrow.
• To prevent cancer from recurring: Cancer can spread from where it originated to other parts of your body. Sometimes, radiation may be used to treat the organ that your specific cancer spreads to most often, thereby killing any cancer cells before they form tumors.
• To treat the symptoms of advanced cancer: When cancer has spread too extensively to be cured, the tumors can sometimes be treated with radiation in order to alleviate pain or other symptoms. This type of radiation therapy is called palliative radiation.
• To treat a recurrence of cancer: Radiation may be used to treat a cancer that has returned, or to treat the resulting symptoms.

The following treatments are not necessarily readily available everywhere, but Sheba’s Hemato-Oncology Division offers advanced techniques for Ewing sarcoma treatment.

Bone Marrow Transplantation

When necessary, bone marrow transplants can be performed as part of Ewing sarcoma treatment. The procedure involves depleting a diseased bone marrow with chemotherapy or radiation and then intravenously infusing healthy donor stem cells into the patient. The new stem cells travel to the bone marrow, where they begin to produce new blood cells.

At Sheba Medical Center, the Department of Bone Marrow Transplants features 14 private rooms, alongside comprehensive, high-tech laboratories and clinics – enabling all steps of the transplant procedure to be completed efficiently on-site. The department has performed more than 2,000 transplants to date and employs a diverse team of world-renowned specialists, including hematologists, medical oncologists, and radiation oncologists.

Targeted Therapy

Targeted therapy is an innovative approach to cancer treatment that is officially classified as biological treatment, using specialized drugs that target cancer cells while leaving healthy cells alone.

Targeted therapy destroys cancer cells by blocking chemical signals that tell them to grow; changing proteins within the cells so they die; preventing new blood vessels from forming that would otherwise feed cancer cells; triggering the immune system to kill cancer cells; or sending toxins to the cancer cells to destroy them.

Since these specialized drugs are made to only target specific cancer cells, targeted drugs can, in many cases, be more effective than chemotherapy, and they often have fewer side effects. Unlike traditional chemotherapy, which affects all rapidly dividing cells in the body, targeted therapies are designed to act more precisely, identifying and attacking specific cancer cells, thus reducing the harm to healthy cells.

These therapies function by interfering with specific proteins or processes that cancer cells rely on for their survival and proliferation. For instance, some target the protein receptors on the surface of cancer cells, while others interfere with the signals that stimulate cancer cells to grow and divide uncontrollably.

One of the significant advantages of targeted therapy is that it can be more effective and have fewer side effects than traditional chemotherapy.

Learn more about the benefits of targeted therapy for Ewing sarcoma.

Based on the factors above, Sheba’s team of oncologists, hematologists, hematopathologists, and radiation oncologists will build a holistic personalized treatment for every patient, accounting for the physical and emotional aspects of the patient’s well-being.

Individuals who have undergone treatment for Ewing sarcoma during their childhood or teenage years may experience lingering health issues known as late effects. These can surface months or years following the completion of the treatment. The specific late effects that a survivor might experience are typically determined by the original location of the tumor and the method of treatment utilized.

Late effects could encompass issues with the heart and lungs, emotional and cognitive challenges, problems with growth, and secondary malignancies stemming from chemotherapy or radiation therapy. For instance, individuals who were treated for Ewing sarcoma as children have a greater probability of developing solid tumors or leukemia in later life, compared to the general population.

Certain treatments could also have an impact on fertility in the future. If this adverse effect is enduring, it results in infertility, defined as the inability to conceive children. This concern pertains to both males and females, as they can equally be impacted by issues related to fertility.

Being a relatively rare malignancy, quality treatment for Ewing Sarcoma can be hard to find. Therefore, it is critical to choose a medical center staffed with top tier cancer specialists and medical experts with experience in a wide range of disciplines for treatment.

At Sheba, we prioritize a holistic approach to healthcare, placing the patient and their family’s well-being at the forefront. We understand that cancer treatment impacts various aspects of one’s life, and we are dedicated to providing the best possible care.

Our Hemato-Oncology Division is dedicated to applying precision medicine for bone and soft tissue sarcomas. As a rule, we strive to customize the most effective treatment program for each individual patient. Sheba’s compassionate team of Ewing Sarcoma experts will ensure you are well-informed at every step of the way to healing.

The Hemato-Oncology Division at Sheba is home to some of the world’s leading Ewing sarcoma treatment specialists, experienced in treating patients of all ages and stages. Our dedicated team of experts includes oncologists, hematologists, and other healthcare professionals whose collective mission is to provide the best possible care for Ewing sarcoma patients by creating a customized treatment plan that addresses all of their medical and emotional needs.