Osteosarcoma

General treatment information

Great advances have been made in the treatment of osteosarcoma during the past several decades. In the 1960s the only treatment available was amputation, and only a small number of patients survived 2 years or more after diagnosis.

Since that time, doctors have found that chemotherapy given before and after surgery will cure many people with osteosarcoma. It may also allow some people who previously would have needed to have the affected limb amputated to have limb-sparing surgery instead.

Making treatment decisions

Once osteosarcoma is found and staged, the cancer care team will talk with you about treatment options. It is important to take time and think about your options. Because osteosarcoma is rare, only doctors in major cancer centers have a lot of experience treating these cancers.

For children, a team approach is recommended that includes the child’s pediatrician as well as children’s cancer specialists. Treatment is best done at a children’s cancer center. For adults with osteosarcoma, the treatment team typically includes the patient’s primary care doctor, as well as specialists at a major cancer center. Doctors on the treatment team might include:

An orthopedic surgeon (a surgeon who specializes in muscles and bones) experienced in treating bone tumors

A medical or pediatric oncologist (a doctor trained to treat cancer with chemotherapy and other drugs)

A radiation oncologist (a doctor trained to treat cancer with radiation therapy)

A pathologist (a doctor specializing in lab tests to diagnose and classify diseases)

A rehabilitation/physical therapy expert

For both adults and children, the team would also include other doctors, nurses, rehabilitation therapists, and technologists who have essential roles in diagnosing and treating the disease and assisting in recovery after surgery.

The types of treatment used for osteosarcomas include:

Surgery

Chemotherapy

Radiation therapy (in certain cases)

In most cases, both chemotherapy and surgery are needed.

All of these treatments may have side effects, but many of them can be made less troublesome. Your medical team will help you take care of the side effects and will help you work closely with nutritionists, psychologists, and social workers to understand and deal with the medical problems, stress, and scheduling issues related to the treatment.

Because many of these things can be more complicated for cancer in children, many people will be involved in your child’s overall care. As a parent, taking care of a child with cancer can be a very big job. It is important to remember that you will have a lot of help. It is also important for you to know that the health care professionals who treat children with osteosarcoma are using the experience and knowledge gained from many decades of detailed scientific study of treating this disease.

The next few sections describe the types of treatment used for osteosarcomas. This is followed by a discussion of when these treatments are used in different situations.

Surgery for osteosarcoma

Surgery for osteosarcoma includes both the biopsy to diagnose the cancer and the surgical treatment. Surgery is an important part of treatment for virtually all osteosarcomas.

Whenever possible, it is very important that the biopsy and surgical treatment be planned together, and that the same orthopedic surgeon at a cancer center does both the biopsy and the surgical treatment.

The main goal of surgery is to remove all of the cancer. If even a few cancer cells are left behind, they can grow and multiply to make a new tumor. To try to be sure that this doesn’t happen, surgeons remove the tumor plus some of the normal tissue that surrounds it. This is known as wide excision. Removing some normal-looking tissue around the tumor raises the chance that all of the cancer is removed.

A pathologist will look at the removed tissue under a microscope to see if the margins (outer edges) contain cancer cells. If cancer cells are seen at the edges of the tissue, the margins are called positive. Positive margins can mean that some cancer was left behind. When no cancer cells are seen at the edges of the tissue, the margins are said to be negative, clean, or clear. A wide excision with clean margins minimizes the risk that the cancer will grow back where it started.

The type of surgery done depends on the location of the tumor. Although all operations to remove osteosarcomas are complex, tumors in the limbs (arms or legs) are generally not as hard to remove as those at the base of the skull, in the spine, or in the pelvis.

Tumors in the arms or legs

Tumors in the arms or legs might be treated with either limb-salvage (limb-sparing) surgery (removing the cancer without amputation) or amputation (removing the cancer and all or part of an arm or leg).

Limb-salvage surgery: Most patients with tumors in the arms or legs can have limb-sparing surgery, but this depends on the location and extent of the tumor.

Limb-salvage surgery is a very complex operation. The surgeons who do this type of operation must have special skills and experience. The challenge for the surgeon is to remove the entire tumor while still saving the nearby tendons, nerves, and blood vessels to keep as much of the limb’s function and appearance as possible. But if the cancer has grown into these structures, they will need to be removed along with the tumor. In such cases, amputation may sometimes be the best option.

The section of bone that is removed along with the osteosarcoma is replaced with a bone graft (piece of bone from another part of the body or from another person) or with an internal prosthesis (a man-made device used to replace part or all of a bone) made of metal and other materials.

Complications of limb-salvage surgery can include infections and grafts or rods that become loose or broken. Limb-salvage surgery patients might need more surgery in the following years, and some could eventually need an amputation.

Using an internal prosthesis in growing children is especially challenging. In the past, it has required occasional operations to replace the prosthesis with a longer one as the child grows. Newer prostheses have become very sophisticated and can often be made longer without any extra surgery. They have tiny devices in them that can lengthen the prosthesis when needed to make room for a child’s growth. But even these prostheses may need to be replaced with a stronger adult prosthesis once the child’s body stops growing.

It takes about a year, on average, for patients to learn to walk after limb-salvage surgery on a leg. This physical rehabilitation is more intense than after amputation. If the patient does not take part in the rehabilitation program, the salvaged arm or leg may become useless.

Amputation: For some patients, amputation may be the best option. For example, if the patient has a large tumor that extends into the nerves and/or the blood vessels, it might not be possible to save the limb.

Results of MRI scans and examination of the tissue by the pathologist during surgery can help the surgeon decide how much of the arm or leg needs to be amputated. Surgery is planned so that muscles and the skin will form a cuff around the remaining bone. This cuff will fit into the end of a prosthetic (artificial) limb.

Reconstructive surgery can help some patients who lose a limb to function as well as possible. For example, if the leg must be amputated mid-thigh (including the knee joint), the lower leg and foot can be rotated and attached to the thigh bone, so that the ankle functions as a new knee joint. This surgery is called rotationplasty. Of course, the patient would still need a prosthetic limb to extend the leg.

With proper physical therapy, the patient is often able to walk on his/her own 3 to 6 months after leg amputation.

If the osteosarcoma is located in the upper arm, in some cases the tumor may be removed and the lower arm reattached so that the patient has a functional, but much shorter, arm.

Rehabilitation after surgery: This may be the hardest part of all the treatments, and this discussion cannot describe it completely. Patients and parents should meet with a rehabilitation specialist before surgery to learn about their options and what may be required after surgery.

If a limb is amputated, the patient must learn to live with and use a prosthetic limb. This can be particularly hard for growing children if the prosthetic limb needs to be changed to keep up with their growth.

When only the tumor and part of the bone is removed in a limb-sparing operation, the situation can be even more complicated, especially in growing children. Further operations might be needed to replace the internal prosthesis with one more suited to their growing body size.

Both types of surgery can lead to problems as well as having possible benefits. For example, limb-sparing surgery, although more acceptable to most patients than amputation, tends to lead to more complications because of its complexity. Growing children who have limb-sparing surgery are also more likely to need further surgery later. Perhaps surprisingly, people with amputations can often be more physically active, as the affected limb can tolerate more physical stress than one with an internal prosthesis.

When researchers have looked at the final results of the different surgeries in terms of quality of life, there has been little difference between them. Perhaps the biggest problem has been for teens, who may worry about the social effects of their operation. Emotional issues can be very important, and support and encouragement are needed for all patients.

Tumors that start in other areas

Pelvic tumors can often be hard to remove completely with surgery. But if the tumor responds well to chemotherapy first, surgery (sometimes followed by radiation therapy) may get rid of all of the cancer. Pelvic bones can often be reconstructed after surgery.

For a tumor in the lower jaw bone, the entire lower half of the jaw may be removed and later replaced with bones from other parts of the body. If the surgeon can’t remove all of the tumor, radiation therapy may be used as well.

For tumors in areas like the spine or the skull, it may not be possible to remove all of the tumor safely. Cancers in these bones may require a combination of treatments such as chemotherapy, surgery, and radiation.

Surgical treatment of metastases

If the osteosarcoma has spread to other parts of the body, these tumors need to be removed to have a chance at curing the cancer.

When osteosarcoma spreads, most often it is to the lungs. Surgery to remove these metastases must be planned very carefully. Before the operation, the surgeon considers the number of tumors, their location (one lung or both lungs), their size and response to chemotherapy, and the general health of the patient. Since the chest CT scan done before surgery may not show all of the lung tumors, the surgeon will have a treatment plan in case more tumors are found during the operation.

Patients who have tumors in both lungs and respond well to chemotherapy can have surgery on one side of the chest at a time. Removing tumors from both lungs at the same time may be another option.

Some lung metastases may not be able to be removed because they are too big or are too close to important structures in the chest (such as large blood vessels). Patients whose general health is not good (because of poor nutritional status or heart, liver, or kidney problems) may not be able to withstand the stress of anesthesia and surgery to remove metastases.

A small number of osteosarcomas spread to other bones or to the kidneys, liver, or brain. Whether or not these tumors can be removed with surgery depends on their size, location, and other factors.

Chemotherapy for osteosarcoma

Chemotherapy (chemo) is the use of drugs for treating cancer, which are usually given into a vein or artery. The drugs enter the bloodstream and reach and destroy cancer cells throughout the body.

In many cases, osteosarcoma has spread to the lungs and/or other organs or has a high risk of doing so, even if tumors can’t be seen on imaging tests. Because of this, chemotherapy is an important part of the treatment for most osteosarcomas, although some patients with low-grade osteosarcoma may not need it.

Doctors give chemotherapy in cycles, with each period of treatment followed by a rest period to allow the body time to recover. Each cycle typically lasts for a few weeks.

Most osteosarcomas are treated with chemotherapy given before surgery (neoadjuvant chemotherapy) for about 10 weeks and again after surgery (adjuvant chemotherapy) for up to a year. People with high-grade osteosarcomas that responded well to chemo before surgery usually get the same chemo after surgery. People whose tumors responded poorly usually will get different chemo after surgery.

The drugs used most often to treat osteosarcoma include:Methotrexate (given in high doses along with leucovorin to help prevent side effects),Doxorubicin (Adriamycin), Cisplatin or carboplatin,Etoposide,Ifosfamide,Cyclophosphamide,Epirubicin, Gemcitabine,Topotecan

Usually, several drugs are given together. Some common combinations of drugs include:

High-dose methotrexate, doxorubicin, and cisplatin (sometimes with ifosfamide)

Doxorubicin and cisplatin

Ifosfamide and etoposide

Ifosfamide, cisplatin, and epirubicin

Many experts recommend that the drugs be given in very high doses, which can affect the bone marrow, where new blood cells are made. In these cases, other drugs called growth factors (such as filgrastim, also known as Neupogen) may be given to help the body make new blood cells as quickly as possible.

Before starting chemotherapy, the doctor might advise putting a venous access device into a large vein in the chest. The device is a catheter (hollow tube) that is inserted surgically while the patient is under general anesthesia (asleep). One end of the catheter stays in the vein, while the other end lies just under or outside the skin. This lets the health care team give chemo and other drugs and to draw blood samples without having to stick needles into the veins each time. The device can usually remain in place for several months, and can make having chemo less painful. If such a device is used, the health care team will teach you how to care for it to reduce the risk of problems such as infections.

Side effects of chemotherapy

Chemo drugs attack cells that are dividing quickly, which is why they work against cancer cells. But other cells in the body, such as those in the bone marrow, the lining of the mouth and intestines, and the hair follicles, also divide quickly. These cells are also likely to be affected by chemotherapy, which can lead to side effects.

Children seem to have an advantage over adults when it comes to chemotherapy. They tend to have less severe side effects and recover from side effects more quickly. Because of this, doctors can give them higher doses of chemotherapy to try to kill the tumor.

The side effects of chemotherapy depend on the type and dose of drugs given and the length of time they are taken.

General side effects: Many chemo drugs can cause side effects, such as:Nausea and vomiting,Loss of appetite,Diarrhea,Hair loss,Mouth sores

Because chemotherapy can damage the blood-producing cells of the bone marrow, patients may have low blood cell counts, which can result in:

Increased chance of infection (from a shortage of white blood cells)

Bleeding or bruising after minor cuts or injuries (from a shortage of platelets)

Fatigue or shortness of breath (from low red blood cell counts)

Most of these side effects are short-term and tend to go away after treatment is finished. Often there are ways to lessen these side effects. For example, drugs can be given to help prevent or reduce nausea and vomiting, or to help get blood counts back to normal levels. Be sure to discuss any questions you have about side effects with the cancer care team, and tell them about any side effects so that they can be controlled.

Side effects of certain drugs: Some side effects are specific to certain drugs. Many of these side effects are rare, but they are possible. Before treatment, ask your cancer care team about the possible side effects of the drugs you or your child will be getting.

Ifosfamide and cyclophosphamide can damage the lining of the bladder, which can cause blood in the urine. The chance of this happening can be lowered by giving a drug called mesna during chemotherapy, along with plenty of fluids.

Cisplatin and carboplatin may cause nerve damage (called neuropathy) leading to numbness, tingling, or pain in the hands and feet. Kidney damage can also occur after treatment. Giving lots of fluid before and after the drug is infused can help prevent this side effect. These drugs can sometimes affect hearing. Most often patients with this problem notice problems hearing high-pitched sounds.

Etoposide can also cause nerve damage. It can also increase the risk of later developing a cancer of white blood cells, known as acute myeloid leukemia. Fortunately, this is not common.

High-dose methotrexate can damage the white matter of the brain (called leukoencephalopathy) and the liver or kidneys. Before starting high-dose methotrexate, medicines are given to help protect the kidneys. Methotrexate blood levels may be checked to see how much leucovorin (also called folinic acid) should be given to help stop any damage to normal tissues.

Doxorubicin (Adriamycin) and epirubicin can cause heart damage over time. The risk of this happening goes up as the total amount of the drug that is given goes up, so doctors are careful to limit the total dose. Your (child’s) doctor may order a heart function test before and during treatment to see if this drug is affecting the heart. Another drug called dexrazoxane may be given along with the chemotherapy to help lessen the possible damage.

Some chemo drugs may affect your (child’s) ability to have children later in life. Talk to your (or your child’s) cancer care team about the risks of infertility with treatment, and ask if there are options for preserving fertility, such as sperm banking.

The doctors and nurses will watch closely for side effects. Do not hesitate to ask your cancer care team any questions about side effects.

Tests to check for side effects of chemotherapy: Before each treatment, your (or your child’s) doctor will check lab test results to be sure the liver, kidneys, and bone marrow are functioning well.

The complete blood count (CBC) includes counts of white blood cells, red blood cells, and blood platelets. Chemotherapy can lower the numbers of these blood cells, so blood counts will be watched closely during and after chemo. The cells usually reach their lowest point about 2 weeks after chemo is given, though this can occur earlier with high-dose regimens.

Blood chemistry panels measure certain blood chemicals that tell doctors how well the liver and the kidneys are working. Some chemo drugs can damage the kidneys and liver.

An audiogram might be done to check hearing, which can be affected by certain chemo drugs.

If doxorubicin or epirubicin is to be given, tests such as an echocardiogram (an ultrasound of the heart) may be done before and during treatment to check heart function.

Radiation therapy for osteosarcoma

Radiation therapy uses high-energy rays or particles to kill cancer cells. Osteosarcoma cells are not easily killed by radiation, so radiation therapy does not play a major role in treating this disease.

External beam radiation therapy

This is the type of radiation therapy most often used to treat osteosarcoma.

Before treatments start, the radiation team takes careful measurements with imaging tests such as MRI scans to determine the correct angles for aiming the radiation beams and the proper dose of radiation.

External radiation therapy is much like getting an x-ray, although the dose of radiation is much higher. For each session, you (or your child) will lie on a special table while a machine delivers the radiation from a precise angle. The treatment is not painful.

Each actual treatment lasts only a few minutes, although the setup time – getting you (or your child) into place for treatment – usually takes longer. Young children may be given medicine to make them fall asleep so they will not move during the treatment. Most often, radiation treatments are given 5 days a week for several weeks.

Newer radiation techniques, such as intensity modulated radiation therapy (IMRT) and conformal proton beam therapy, may allow doctors to aim treatment at the tumor more precisely while reducing how much radiation nearby healthy tissues get. This may offer a better chance of increasing the success rate and reducing side effects. Many doctors now recommend using these approaches when they are available.

Radiation therapy may be useful in some cases where the tumor cannot be completely removed by surgery. For example, osteosarcoma can start in hip bones or in the bones of the face, particularly the jaw. In these situations, it is often not possible to completely remove the cancer. As much as possible is removed, and then radiation is given to try to kill the remaining cancer. Chemotherapy may be used after radiation.

Radiation can also help control symptoms like pain and swelling if the cancer has come back or surgery is not possible.

The possible side effects of external radiation therapy depend on the dose of radiation and where it is aimed. Short-term problems can include effects on skin areas that receive radiation, which can range from mild sunburn-like changes and hair loss to more severe skin reactions. Radiation to the abdomen or pelvis can cause nausea, diarrhea, and urinary problems. Talk with your (child’s) doctor about the possible side effects because there may be ways to relieve some of them.

In children, radiation therapy can interfere with the growth of normal body tissues, including the bones. For example, radiation to the bones in one leg might result in it being much shorter than the other. Radiotherapy of facial bones may cause uneven growth, which might affect how a child looks. But if a child is fully or almost fully grown, this is less likely to be an issue.

Depending on where the radiation is aimed, it can also damage other organs. Radiation to the chest wall or lungs may affect lung and heart function. Radiation to the pelvis may damage the bladder or intestines. It can also damage reproductive organs, which could affect a child’s fertility later in life, so doctors do their best to protect these organs by shielding them from the radiation or moving them out of the way whenever possible.

Another major concern with radiation therapy is that it may cause a new cancer to form in the part of the body that was treated with the radiation. The higher the dose of radiation, the more likely this is to occur, but the overall risk is small and should not keep children who need radiation from getting treatment.

To lower the risk of serious long-term effects from radiation, doctors try to use the lowest dose of radiation therapy that is still effective. Still, it’s important to continue follow-up visits with your (child’s) doctor so that if problems come up they can be found and treated as early as possible.

Radioactive drugs (radiopharmaceuticals)

Bone-seeking radioactive drugs, such as samarium-153, are also sometimes used to treat symptoms such as pain in people with advanced osteosarcoma. These drugs are injected into a vein and collect in bones. Once there, the radiation they give off kills the cancer cells and relieves some of the pain caused by bone metastases.

These drugs are especially helpful when cancer has spread to many bones, since external beam radiation would need to be aimed at each affected bone. In some cases, these drugs are used together with external beam radiation aimed at the most painful bone metastases.

The major side effect of these drugs is a lowering of blood cell counts, which could increase the risk for infections or bleeding, especially if the blood counts are already low.

Treatment based on the extent of the osteosarcoma