How is Ewing's Sarcoma Treated?



This information has been written for patients, their families and friends and the general public to help you learn more about and understand the treatments used for Ewing's sarcoma, what they are and how they are given or carried out.

Once an abnormality is found in a bone that suggests the possibility of cancer, the medical team will carry out tests in order to answer two essential questions:

1 - What is it? and
2 - Where is it?

The type of treatment for Ewing's sarcoma and how likely it is that treatment is successful depends on the answers to these two questions.

1 - What is it?

X-rays and scans may show that the patient is very likely to have Ewing's sarcoma, doctors cannot be fully certain without taking a small piece of the suspected tumour (biopsy). The biopsy goes to a special laboratory so that it can be examined under a microscope and have other tests carried out on it, such as cytogenetic tests. Patients will also have a bone marrow aspirate (removal of a sample of bone marrow fluid). By looking at the cells under the microscope, and from the results of these other tests, an expert pathologist can make the diagnosis of Ewing's sarcoma.

2 - Where is it?

X-rays and scans help the doctors to see the size and exact place in the body of the tumour and to look for evidence if the cancer has spread to any other parts of the body. This is known as 'staging' of the cancer.

In around 25-30% of patients with Ewing's sarcoma, the scans show the cancer has spread, usually to the lungs. Sometimes the cancer may have spread to other bones, bone marrow or more unusual sites. Cancer that has spread away from the primary site is called 'secondary cancer' and doctors called these secondary tumour 'metastases' (met-AS-ta-seas).

Treatment of Ewing's Sarcoma

Treatment for Ewing's sarcoma, involves treatment to the whole body (systemic) with chemotherapy and local (site of the tumour) treatment by surgery and radiotherapy. Before chemotherapy drugs were developed and widely used to treat cancer, Ewing's sarcoma was treated with radiation alone to the local tumour site. Without chemotherapy, over 90% of patients died because their cancer spread. The overall 5-year survival rate for Ewing's sarcoma is now around 60%, meaning around 60 out of every hundred people with Ewing's will be alive 5 years after diagnosis.

Detailed survival and incidence rates for Ewing's sarcoma will be available on BCRT's pages for healthcare professionals, which will also be fully accessible to patients, families and the general public.

Patients undergoing treatment for Ewing's sarcoma will be under the care of the treatment and rehabilitation part of the multidisciplinary team including:

  • Oncologists, radiologists, radio oncologists, orthopaedic surgeons other doctors, specialist nurses.

  • Physiotherapists and occupational therapists will help with rehabilitation (rehab) after surgery.

  • Social workers and psychologists will help with patients' emotional, social and educational needs.

Your doctor (oncologist) is the best person to describe to you the treatment choices. Your doctors will also tell you what is to be expected from the treatment. Treatment of cancer involves patients and the doctors working together to find a care or treatment plan that fits your needs.

Following the diagnosis and the first tests, patients are given a combination of chemotherapy drugs before surgery. The number of drugs and how long for and how many times they are given can be different from country to country.

In the UK, and much of Europe the current standard treatment before surgery is made up of four chemotherapy drugs (Vincristine, Ifosfamide, Doxorubicin, Etoposide, (VIDE)). Each course of these four drugs is given over 3-4 days every 3 weeks (1 cycle) for 6 cycles. This takes about 18 weeks.

Chemotherapy given before surgery is called neo-adjuvant (NEE-oh-AJOO-vant) chemotherapy. The aim of this course of chemotherapy is to shrink the primary tumour, and to kill any cells that have spread to other parts of the body.

Following the first few cycles of chemotherapy, the main tumour site has to be treated. Where possible patients have surgery to remove the primary tumour. This is more likely to be possible if the main (primary) tumour is in a limb (arm or leg) or easily accessible position in the body. For many patients the main tumour is not easily removable, for example, if the tumour is in the pelvis or spine.

The decision about whether surgery is possible is usually taken by the multidisciplinary team, which includes expert surgeons.

The aim of surgery is to remove the primary tumour safely and at the same time try to keep the body working as normally as possible. If the primary tumour is in a limb then it is usually possible to remove the tumour without removing the limb. There are many different ways that surgeons have developed to preserve limbs, the main one being replacement of the affected bone with a metal implant and false joint. Another technique is to carry out an autologous (aw-TOH-low-gus) bone graft in which bone is taken from another part of the body to replace the bone, which has been removed. Even with these advances in surgery around 10% of patients require an amputation (removal of the limb) to safely remove the tumour.

Tumour removal from other sites can be very complicated and requires very careful individual planning for each patient.

When the tumour is removed, it is examined under a microscope by the pathologist, to make sure that the tumour has been completely removed and to find out how much of the tumour has been killed. The results of this examination may affect treatment after surgery.

Radiotherapy is often also used to control the primary tumour site, either after or instead of surgery if surgical removal is not possible. Radiotherapy means treating the tumour with high doses of concentrated radiation.

After surgery, radiotherapy is given if

  • a) Not all the tumour is completely removed, or

  • b) If more than 10% of the tumour is still alive when examined under a microscope.

The exact dose and length of radiotherapy treatment will also be decided by a special team of doctors, but it is usually given as a single dose each day (a few minutes) for approximately 5 - 6 weeks. Chemotherapy will usually continue during radiotherapy treatment.

Once again, the number of drugs and length of treatment may be different from country to country. Most treatment courses last for a further 8 cycles over about 24 weeks after surgery.

In the UK, Ireland and much of Europe the current standard chemotherapy treatment after surgery is made up of the four drugs (Vincristine, Actinomycin D, Ifosfamide, Cyclophosphamide) and lasts for 24 weeks after surgery, (VAI for 1 cycle, VAC for 7 cycles). Chemotherapy given after the surgery is known as adjuvant (a-JOO-vant) chemotherapy.

If there is evidence that the tumour has spread to other parts of the body then an oncologist and surgeon may want to think about the possibility of removing the secondary cancers by surgery.

Treatment Overview

Chemotherapy

  • In most cases, chemotherapy is used before surgery to kill the tumour cells. This helps control any spread of the tumour outside the bone and usually makes it easier for the surgeon to remove the primary tumour. It is also used after surgery to kill any remaining cancer cells.

  • Chemotherapy may be given as part of a clinical trial - a study used to investigate new or different treatments or side effects of treatments.

  • In some patients, chemotherapy is given to help slow down the growth of the tumour and decrease symptoms when their cancer is advanced and unable to be cured. This is known as palliative chemotherapy.

Surgery

  • Surgery is used to remove the primary tumour.

  • If a joint has to be removed it is usually possible to replace it using an implant with a joint replacement.

  • Limb sparing surgery: is complex surgery, which aims to keep as much normal function in the limb as possible.

  • Autologous (aw-TOH-low-gus) bone graft: this is bone , which is taken from another part of the body to replace the bone that has been removed.

  • Other surgical techniques include resection alone, allografts (donated tissue), irradiation/ reimplantation.

  • Amputation: sometimes because of the position or size of the tumour, the surgery involves removal of the whole limb. If possible, then a prosthetic (false) arm or leg can be made for the patient. Amputation may also be needed if the cancer has spread to major blood vessels or nerves or if the patient develops a bad infection or other serious complications after limb-sparing surgery.

  • For many patients the main tumour is not easily removable by surgery, for example, if the tumour is in the pelvis or spine. Compared with other sarcomas, Ewing's tumours respond well to radiotherapy. Sometimes when surgical removal is not reasonable, radiotherapy can be used alone.

  • Surgery may also be used to remove tumour that has spread to the lungs.

  • Surgery may be needed in future if the reconstruction of the limb wears out or if the tumour comes back.

Radiotherapy

  • Radiotherapy is administered by a radiation oncologist.

  • Radiotherapy involves the patient receiving high doses of concentrated radiation.

  • Radiotherapy is usually given as a single dose each day (a few minutes) for approximately 5 - 6 weeks.

  • It is used alone when removal of the primary tumour may not be possible, for example if it is in the pelvis or spine. Radiotherapy may also be used after surgery if not all the tumour is completely removed or more than 10% of the tumour is still alive when examined under a microscope.

What are the chemotherapy drugs called that are used to treat Ewing's sarcoma?

Types of chemotherapy drugs used to treat Ewing's sarcoma:

  • Doxorubicin (dox-oh-ROOB-issin)
  • Etoposide (ee-tow-POH-side)
  • Vincristine (vin-KRIS-teen)
  • Actinomycin D (AK-tin-oh-MY-sin)
  • Cyclophosphamide (SY-kloh-FOSS-fam-ide)
  • Ifosfamide (eye-FOSS-fam-ide)
What is chemotherapy and how does it work?

Chemotherapy, often called chemo (key-mo) for short, is the name for drugs used for the treatment of cancer. These drugs kill cancer cells or stop their growth by interfering with the way cells divide and grow (also known as the cell cycle), or by damaging the cell's DNA.

Cancer cells divide and grow rapidly, so chemotherapy drugs target rapidly dividing cells. Different chemotherapy drugs affect different parts of cells and that is why more than one drug may be given. This is called combination chemotherapy.

Most healthy cells are not dividing rapidly. However, some cell types do divide rapidly, such as hair follicle cells, skin cells, bone marrow cells, and those lining the digestive system. This means chemotherapy drugs can also affect these 'healthy' cells and this is what causes side effects.

Side effects can be unpleasant, such as,

  • Nausea and vomiting,
  • Diarrhoea,
  • Hair loss,
  • Mouth sores and ulcers,
  • Taste changes, (metallic taste, bitter taste),
  • Tiredness (fatigue).

Medications can be given after chemotherapy to help with some of these side effects. There are also tips on some good websites about dealing with side effects such as mouth sores, skin care and coping with hair loss.

Coping with hair loss: Teenage Info on Cancer (TIC) and Teenage Cancer Trust

Mouth sores and eating problems: Teenage Cancer Trust and TIC and Macmillan

A book written by a former osteosarcoma patient, Megan Blunt called Chemotherapy, Cakes and Cancer is available to download in PDF format published by CLIC Sargent.

How is chemotherapy given?

There are different ways patients are given chemotherapy: tablets, liquid medicine, injection or directly into the blood.

When a patient is given chemotherapy directly into their blood, the drug is given through a cannula (venflon), which is a flexible thin plastic tube that sits in a vein in the arm or hand. Alternatively, patients may have a central line, PICC or implantable ports (Portacath®).

Portacaths®, PICCs and central lines can be kept in for weeks or even a few months. These lines enable the number of needles required during treatment to be minimised and more than one drug or treatment (such as fluids or nutrition) can be given at the same time because the lines can have multiple openings or 'lumens'. Because central lines, PICCs and Portacaths® are all slightly different; the decision on which type of line will best suit the patient's needs can be discussed with the nurses and the doctor.

Figure 1(a). A Central Line. Image Courtesy of The Christie NHS Foundation Trust.

Figure 1(b). Peripherally Inserted Central Catheter (PICC). Image Courtesy of The Christie NHS Foundation Trust.

Figure 1(c). Implantable Port, (Portacath®). Image Courtesy of The Christie NHS Foundation Trust.

The chemotherapy drug enters the blood through the cannula by an infusion usually called a drip. An infusion or drip is a method of giving a set amount (dose) of I.V. medications such as chemotherapy over a set period. This period can be hours or days. The infusion can also be controlled by an infusion pump, which is connected to a central line or a PICC line. Some of the pumps are small enough to fit in a pocket meaning that patients can use them at home.

Chemotherapy is given in 'cycles.' A cycle is the treatment time plus a resting time. For example, a patient may be given a combination of chemotherapy drugs over 3-4 days and then there may be a resting period of 2 and a half weeks. Therefore, the cycle is 3 weeks long. The resting period helps the healthy cells of the body to recover before the next treatment cycle begins.

Complementary or Alternative Medicine (CAM)

Although complementary and alternative medicines are often called CAM for short as if they mean the same thing, there are differences between them. Other names you may see to describe CAMs are 'traditional medicines,' 'unconventional medicines' and 'integrated healthcare/ medicine.'

Alternative medicines or therapies, such as extract of mistletoe (iscador) and laetrile (bitter almonds) are used 'instead' of what are called conventional medicines. Conventional medicines for cancer are the treatments prescribed by doctors, for example, chemotherapy and radiotherapy.

Some people may chose to stop taking conventional medicines because they may no longer be working, or they may not wish to begin their treatment using conventional medicines for many different reasons. However, alternative medicines do not have to go through the very careful testing (trials) that conventional medicines do, and therefore may not be safe.

Adverts for alternative medicines on websites may claim to cure cancer. However, there is no scientific evidence to back these claims up. It is always best to talk to an oncologist if people are thinking about trying alternative therapies.

Complementary medicines are used alongside conventional medical treatment. Some patients use complementary medicine to help with symptoms or to aid relaxation.

Techniques used by some Ewing's sarcoma patients include:

  • Acupuncture
  • Massage therapy
  • Herbal products
  • Vitamins* or special diets*
  • Visualization
  • Meditation
  • Spiritual healing.

* Patients should make sure they tell their doctors about any supplements they may be taking. Some complementary medicines, such as antioxidants may interfere with conventional treatments.

The importance of clinical trials

Doctors use clinical trials to test new treatments or changes to existing ones. Clinical trials usually have three stages called phases:

Phase 1: If a drug looks promising in laboratory studies, a phase 1 trial may be carried out. This is usually the first time a new drug is tried in people. These types of trials do not usually look at the effect on specific types of cancer but look at things such as side effects and the safest and most effective dose. These types of trials are usually done with a small number of people, usually 10-30.

Phase 2: This type of trial may be open to people with specific types of cancer or a number of different cancers. They are usually carried out on more patients than phase I trials, usually around 100; mainly to look at, which type of cancer the drug works best against, to look at the best dose and side effects again, and to find out if the drug is worth taking to a much larger phase 3 trial.

Phase 3: If a drug in a phase 2 trial looks as if it works as well or better than an existing treatment, a phase 3 trial is carried out. These trials are usually open to people with a specific type of cancer. Many more people are included in these trials, this helps to make sure doctors can see how well the drug may or may not help.

The new drug or treatment is usually compared to an existing treatment. Patients will be put into one of at least two groups. For example, either the 'new drug group' or the 'existing treatment group.' This is done randomly by a computer. Randomisation reduces bias and also helps doctors to be certain that it was the drug that caused the effect and it did not just happen by chance.

You may see the terms 'blind' or 'double blind' randomised clinical trial. A blind trial means the patient does not know if they are receiving the existing treatment or the new one. In a double blind trial neither the doctors or the patients know which treatment they have received.

A single phase 3 trial can be carried out in hospitals in many countries.

An ongoing randomised international trial known as EURO-E.W.I.N.G.99 is aiming to improve disease outcome (survival) in patients with Ewing tumours. Its main aim is to increase survival by improving the response to chemotherapy by an increase in its intensity without increasing toxicity (side effects).

Clinical trials may not always be available, as the patient may not meet some of the requirements to be treated on a trial. If a clinical trial is suggested by the doctor, they will speak to, or give the patient information to read, about the trial.

Doctors will describe what taking part in the trial will mean for the patient, what happens before and during the trial and about possible risks. Patients will be given time to think about whether they wish to take part in the trial.

If a clinical trial is suggested by a doctor, as part of making a decision, patients or parents may want to think about the benefits and risks involved in taking part in a clinical trial. Benefits may be that parents and patients will have an active role in his or her health care, may have access to new treatments before they become generally available, and helping others by contributing to medical research.

Risks could include side effects of the drug, which may be unpleasant, or the treatment may not be safe or effective for the patient. The trial may involve frequent stays in hospital and extra cost. Upon contacting a trial coordinator, it may be helpful to have a list of questions written down.

Research into future treatments

Although Ewing's sarcoma survival has dramatically increased compared to the 1970s since chemotherapy has been used, the survival rate has only slightly improved over the last 20 years. Therefore, there is a need to find new treatments to improve outcome in patients, especially those in which their tumour has spread.

Research into the biology of Ewing's sarcoma, helps scientists to find specific targets for treatments. The biology of cancer is what is happening at the cellular and molecular level to start and promote the cancer. Targeted or specific treatments given alongside chemotherapy may help to improve outcomes. Also, the more specific or targeted the treatment, the chance of side effects and toxicity is reduced.

The Bone Cancer Research Trust is actively involved in funding research, especially translational research to help to find new treatments. Translational research is research that bridges the gap between promising findings in the laboratory from basic research and their clinical use in patients.

Research into targeted treatments is still at a very early stage; however, some promising results have been shown with the following.

Antibodies against insulin-like growth factor receptor-1 (IGF-1R)

  • There have been some promising results from preclinical and clinical studies looking at the anti-tumour effects of antibodies such as Figitumumab (fig-I-tue-mm-YOO-mab) in Ewing's sarcoma. However, not all Ewing's sarcoma patients responded well to this treatment so it may only be effective in certain patients.
mTOR inhibitors

Phase 1 clinical trials looking at mTOR inhibitors have shown it to have anti-tumour activity against Ewing's sarcomas. mTOR or mammalian target of rapamycin, is an enzyme involved switching on and off processes involved in cell division and growth, and cell survival.

Bisphosphonates & Fenretinide
  • Bisphosphonates are drugs usually given to patients to help with bone loss in certain diseases.

  • From the results of laboratory studies, it is thought Bisphosphonates may also help to slow down the spread of Ewing's when used as an add on treatment.

  • Fenretinide (fen-RET-in-ide) is a drug related to vitamin A, laboratory studies have shown that it may be toxic to cells of Ewing's sarcomas.
TRAIL Receptor Agonists
  • Preclinical experimental studies using cells from Ewing's Family of Tumours have shown that TRAIL Receptor Agonists selectively bring on cell death (apoptosis).
Gene therapy
  • DNA molecules with known genetic sequences may possibly be directed against particular genes or translocations. These genetic sequences are called 'anti-sense' oligonucleotides (OL-lee-go-NEW-clee-oh-tides).

Last reviewed: October 2010; Version: 1.1
Review due: October 2011

The authors and reviewers of this information are committed to producing reliable, accurate and up to date content reflecting the best available research evidence, and best clinical practice. We aim to provide unbiased information free from any commercial conflicts of interest. This article is for information only and should not be used for the diagnosis or treatment of medical conditions. BCRT can answer questions about primary bone cancers, including treatments and research but we are unable to offer specific advice about individual patients. If you are worried about any symptoms please consult your doctor.

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