How is osteosarcoma 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 osteosarcoma, 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 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 osteosarcoma, 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. By looking at the cells under the microscope, an expert pathologist can make the diagnosis of osteosarcoma. Pathologists are doctors that use laboratory techniques to diagnose disease. The pathologist can also find out the 'subtype' and 'grade' of the cancer. The 'grade' describes how different the cells of the tumour look when compared to normal cells and helps predict how quickly the cancer may grow or spread to other parts of the body.

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 20-25% of patients with osteosarcoma, the scans show the cancer has spread, usually to the lungs. Sometimes the cancer may have spread to other bones or more unusual sites. Cancer that has spread away from the primary site is called 'secondary cancer' and doctors called these secondary tumours 'metastases' (meh-TAS-tuh-sees).

Up to the 1970s the only successful treatment for osteosarcoma was surgery to remove the tumour. This was usually an amputation (complete removal of a limb). This resulted in very poor long-term survival rates as low as 12%. This is probably because at the time of diagnosis, most patients have some cancer cells that have spread outside of the bone but are too small to detect on the scans and x rays.

During the late 1970s and 1980s, treatment of osteosarcoma changed to include chemotherapy (KEY-mo-THERA-pee), and survival rates started to improve. Because chemotherapy is given into the bloodstream and travels around the whole body, cells that have spread outside of the bone can also be killed. The overall 5-year survival rates for osteosarcoma are now around 55%, meaning around 55 out of every hundred people with Ewing's will be alive 5 years after diagnosis.

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

During the 1980s the way osteosarcoma is treated became the same throughout much of the world.

The main treatments for osteosarcoma are chemotherapy and surgery.

1. - Following the diagnosis and the first tests, patients are given a combination of chemotherapy drugs. The number of drugs and how long for and how many times they are given can be different from country to country. The number of chemotherapy drugs can vary from 2 to 4 and these can be given for between 6 and 12 weeks.

In the UK, Ireland, much of Europe and the USA the current standard treatment before surgery is made up of 3 chemotherapy drugs given over 10 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.

2. - Following this first lot of chemotherapy, the aim is to treat the main tumour site. 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.

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 limb preservation surgery may be possible. 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. This is bone, which is taken from another part of the body to replace the bone, which has been removed. Even with these advances in surgery around 10 per cent 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.

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

4. - Following removal of the tumour, patients will go on to receive further chemotherapy courses. Once again, the number of drugs and length of treatment may be different from country to country. Most treatment courses last for a further 16 -30 weeks after surgery.

In the UK, Ireland, much of Europe and the USA, current standard treatment is made up of the same 3 drugs and lasts for 18 weeks after surgery. Chemotherapy given after the surgery is known as adjuvant (AJOO-vant) chemotherapy.

5. - 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.

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

Chemotherapy

• In most cases, chemotherapy is used before surgery to kill the tumour cells. This helps control any spread of the tumour outside of the bone and may make it easier for the surgeon to remove in the bone. 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 patients may be supplied with a prosthetic (false) joint
  
  
• Limb sparing surgery: is complex surgery, which aims to keep as much normal function in the limb as possible.
  
  
• Autologous bone graft: this is bone, which is taken from another part of the body to replace the bone, which has been removed.
  
  
• Other surgical techniques include resection alone, allografts (non-self tissue), irradiation/ reimplantation.
  
  
• Amputation: sometimes because of the position or size of the tumour, the surgery involves removal of the whole limb. If possible 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.
  
  
• Not all osteosarcomas are found in the limbs. Tumours from the pelvis, skull, spine and jaw can be difficult to remove completely by surgery. Radiotherapy is used occasionally in special situations where it is not possible to remove the whole tumour surgically.
  
  
• 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

• Because osteosarcomas are not very sensitive to radiation, this type of treatment is not used very often for osteosarcoma. Occasionally, in special circumstances, radiotherapy might be recommended to treat osteosarcoma following surgery.
  
  

What are the chemotherapy drugs called that are used to treat osteosarcoma?

• Methotrexate (METH-oh-TREX-ate)
• Doxorubicin(dox-oh-ROOB-issin)
• Cisplatin (SISS-plattin)
• Ifosfamide(eye-FOSS-fam-ide)
• Etoposide(ee-tow-POH-side)

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 (instructions).

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, diarrhoea, hair loss, mouth sores, a nasty taste and tiredness (fatigue). Medications can be given before and 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.

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 2½ 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.

Mifamurtide (mih-FAM-yoor-tide) marketed as Mepact, is a new drug for osteosarcoma treatment. A clinical trial in the USA showed that the drug used alongside chemotherapy and surgery may improve long-term survival in patients with non-metastatic disease (no spread of the cancer). The drug stimulates a type of white blood cell to attack the cancer cells.

In the Republic of Ireland Mepact is available as a treatment for osteosarcoma.

In the UK, Mepact recently underwent appraisal by the National Institute for Clinical Excellence (NICE). BCRT is now pleased to report that NICE has now approved the drug Mepact for use by the NHS in England & Wales for the treatment of osteosarcoma in suitable patients. This follows similar approval by the Scottish Medicines Consortium.

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

Phase 1 or I: 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 or II: 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 or III: If a drug in a phase II trial looks as if it works as well or better than an existing treatment, a phase III 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 nor the patients know which treatment they have received.

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

At the moment, a large clinical trial by the European and American Osteosarcoma Study (EURAMOS) called EURAMOS-1 is in progress in patients with tumours that can be surgically removed, to find out if treatment and disease outcome (survival) can be improved.

In this study, patients are divided into two groups based on response to chemotherapy. Patients' response to chemotherapy is worked out by using a microscope to check the amount of cells that have been killed by the chemotherapy given before surgery. Response is considered either "good" or "poor" based on the number (percentage) of cells that have died.

Patients that respond well to pre-surgery chemotherapy are split into two groups randomly. One group will be given Methotrexate, Doxorubicin and Cisplatin; the other group will also receive the three chemotherapy drugs along with a further drug called alpha-interferon. The aim of this is to see if adding this drug can help prevent the cancer returning.

Patients that respond poorly will also be split into two groups randomly. One group carries on with the 3-drug combination chemotherapy. The other group receives the three drugs along with two other chemotherapy drugs called ifosfamide and etoposide. These two drugs are currently used to treat osteosarcoma that has returned (recurrent).

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 give the patient information to read about the trial and time to think about whether they wish to take part in the trial.

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 osteosarcoma 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.

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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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