Osteosarcoma and Malignant Fibrous Histiocytoma of Bone

• Osteosarcoma and malignant fibrous histiocytoma (MFH) of the bone are diseases in which malignant (cancer) cells form in bone.
• Having past treatment with radiation can increase the risk of osteosarcoma.
• Signs and symptoms of osteosarcoma and MFH include swelling over a bone or a bony part of the body and joint pain.
• Imaging tests are used to detect (find) osteosarcoma and MFH.
• A biopsy is done to diagnose osteosarcoma.
• Certain factors affect prognosis (chance of recovery) and treatment options.

Osteosarcoma and malignant fibrous histiocytoma (MFH) of the bone are diseases in which malignant (cancer) cells form in bone.

Osteosarcoma usually starts in osteoblasts, which are a type of bone cell that becomes new bone tissue. Osteosarcoma is most common in adolescents. It commonly forms in the ends of the long bones of the body, which include bones of the arms and legs. In children and adolescents, it often forms in the bones near the knee. Rarely, osteosarcoma may be found in soft tissue or organs in the chest or abdomen.

Osteosarcoma is the most common type of bone cancer. Malignant fibrous histiocytoma (MFH) of bone is a rare tumor of the bone. It is treated like osteosarcoma.

Ewing sarcoma is another kind of bone cancer, but it is not covered in this summary.

Having past treatment with radiation can increase the risk of osteosarcoma.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn't mean that you will not get cancer. Talk with your child's doctor if you think your child may be at risk. Risk factors for osteosarcoma include the following:

• Past treatment with radiation therapy.
• Past treatment with anticancer drugs called alkylating agents.
• Having a certain change in the retinoblastoma gene.
• Having certain conditions, such as the following:
• Bloom syndrome.
• Diamond-Blackfan anemia.
• Li-Fraumeni syndrome.
• Paget disease.
• Hereditary retinoblastoma.
• Rothmund-Thomson syndrome.
• Werner syndrome.

Signs and symptoms of osteosarcoma and MFH include swelling over a bone or a bony part of the body and joint pain.

These and other a signs and symptoms mamay be caused by osteosarcoma or MFH or by other conditions. Check with a doctor if your child has any of the following:

• Swelling over a bone or bony part of the body.
• Pain in a bone or joint.
• A bone that breaks for no known reason.

Imaging tests are used to detect (find) osteosarcoma and MFH.

Imaging tests are done before the biopsy. The The following tests and procedures may be used:

• Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient's health habits and past illnesses and treatments will also be taken.
• X-ray : An X-ray of the organs and bones inside the body. An X-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.
• CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an X-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
• MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).

A biopsy is done to diagnose osteosarcoma.

Cells and tissues are removed during a biopsy so they can be viewed under a microscope by a pathologist to check for signs of cancer. It is important that the biopsy be done by a surgeon who is an expert in treating cancer of the bone. It is best if that surgeon is also the one who removes the tumor. The biopsy and the surgery to remove the tumor are planned together. The way the biopsy is done affects which type of surgery can be done later.

The typeThe type of biopsy that is done will be based on the size of the tumor and where it is in the body. There are two types of biopsy that may be used:

• Core biopsy: The removal of tissue using a wide needle.
• Incisional biopsy : The removal of part of a lump or a sample of tissue that doesn't look normal.

The following test may be done on the tissue that is removed:

• Light and electron microscopy: A laboratory test in which cells in a sample of tissue are viewed under regular and high-powered microscopes to look for certain changes in the cells.

Treatment options for osteosarcoma and MFH depend on the following:

• Where the tumor is in the body.
• The size of the tumor.
• The stage of the cancer.
• Whether the bones are still growing.
• The patient's age and general health.
• The desire of the patient and family for the patient to be able to participate in activities such as sports or have a certain appearance.
• Whether the cancer is newly diagnosed or has recurred after treatment.

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) is affected by certain factors before and after treatment.

The prognosis of untreated osteosarcoma and MFH depends on the following:

• Where the tumor is in the body and whether tumors formed in more than one bone.
• The size of the tumor.
• Whether the cancer has spread to other parts of the body and where it has spread.
• The type of tumor (based on how the cancer cells look under a microscope).
• The patient's age and weight at diagnosis.
• Whether the tumor has caused a break in the bone.
• Whether the patient has certain genetic diseases.

After osteosarcoma or MFH is treated, prognosis also depends on the following:

• How much of the cancer was killed by chemotherapy.
• How much of the tumor was taken out by surgery.
• Whether chemotherapy is delayed for more than 3 weeks after surgery takes place.
• Whether the cancer has recurred (come back) within 2 years of diagnosis.

• After osteosarcoma or malignant fibrous histiocytoma (MFH) has been diagnosed, tests are done to find out if cancer cells have spread to other parts of the body.
• There are three ways that cancer spreads in the body.
• Cancer may spread from where it began to other parts of the body.
• Osteosarcoma and MFH are described as either localized or metastatic.

After osteosarcoma or malignant fibrous histiocytoma (MFH) has been diagnosed, tests are done to find out if cancer cells have spread to other parts of the body.

The process used to find out if cancer has spread to other parts of the body is called staging. For osteosarcoma and malignant fibrous histiocytoma (MFH), most patients are grouped according to whether cancer is found in only one part of the body or has spread.

The following tests The following tests and procedures may be used:

• X-ray : An X-ray of the organs, such as the chest, and bones inside the body. An X-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body. X-rays will be taken of the chest and the area where the tumor formed.
• CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, such as the chest, taken from different angles. The pictures are made by a computer linked to an X-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography. Pictures will be taken of the chest and the area where the tumor formed.
• PET-CT scan: A procedure that combines the pictures from a positron emission tomography (PET) scan and a computed tomography (CT) scan. The PET and CT scans are done at the same time on the same machine. The pictures from both scans are combined to make a more detailed picture than either test would make by itself. A PET scan is a procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.
• MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).
• Bone scan: A procedure to check if there are rapidly dividing cells, such as cancer cells, in the bone. A very small amount of radioactive material is injected into a vein and travels through the bloodstream. The radioactive material collects in the bones and is detected by a scanner.

There are three ways that cancer spreads in the body.

Cancer can spread through tissue, the lymph system, and the blood:

• Tissue. The cancer spreads from where it began by growing into nearby areas.
• Lymph system. The cancer spreads from where it began by getting into the lymph system. The cancer travels through the lymph vessels to other parts of the body.
• Blood. The cancer spreads from where it began by getting into the blood. The cancer travels through the blood vessels to other parts of the body.

Cancer may spread from where it began to other parts of the body.

When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph sand travel through the lymph system or blood.

• Lymph system. The cancer gets into the lymph system, travels through the lymph vessels, and forms a tumor (metastatic tumor) in another part of the body.
• Blood. The cancer gets into the blood, travels through the blood vessels, and forms a tumor (metastatic tumor) in another part of the body.

The metastatic tumor is the same type of cancer as the primary tumor. For example, if osteosarcoma spreads to the lung, are actually osteosarcoma cells. The disease is metastatic osteosarcoma, not lung cancer.

Osteosarcoma and MFH are describOsteosarcoma and MFH are described as either localized or metastatic.

• Localized osteosarcoma or MFH has not spread out of the bone where the cancer started. There may be one or more areas of cancer in the bone that can be removed during surgery.
• Metastatic osteosarcoma or MFH has spread from the bone in which the cancer began to other parts of the body. The cancer most often spreads to the lungs. It may also spread to other bones.

Recurrent osteosarcoma and malignant fibrous histiocytoma (MFH) of bone are cancers that have recurred (come back) after being treated. The cancer may come back in the bone or in other parts of the body. Osteosarcoma and MFH most often recur in the lung, bone, or both. When osteosarcoma recurs, it is usually within 18 months after treatment is completed.

There are different types of treatment for patients with osteosarcoma or malignant fibrous histiocytoma (MFH) of bone.

Different types of treatment are available for children with osteosarcoma or malignant fibrous histiocytoma (MFH) of bone. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment.

Because cancer in children is rare, taking part in a clinical trial should be considered. Some clinical trials are open only to patients who have not started treatment.

Children with osteosarcoma or MFH should have their treatment planned by a team of health care providers who are experts in treating cancer in children.

Treatment will be overseen by a pediatric oncologist, a doctor who specializes in treating children with cancer. The pediatric oncologist works with other pediatric health care providers who are experts in treating osteosarcoma and MFH and who specialize in certain areas of medicine. These may include the following specialists:

• Pediatrician.
• Orthopedic surgeon.
• Radiation oncologist.
• Rehabilitation specialist.
• Pediatric nurse specialist.
• Social worker.
• Psychologist.

Treatment for osteosarcoma or malignant fibrous histiocytoma may cause side effects.

Side effects from cancer treatment that begin after treatment and continue for months or years are called late effects. Late effects of cancer treatmeeffects. Late effects of cancer treatment may include the following:

• Physical problems.
• Changes in mood, feelings, thinking, learning, or memory.
• Second cancers (new types of cancer).

Some late effects may be treated or controlled. It is important to talk with your child's doctors about the effects cancer treatment can have on your child.

Four types of standard treatment are used:

Surgery

Surgery to remove the entire tumor will be done when possible. Chemotherapy may be given before surgery to make the tumor smaller. This is called neoadjuvant chemotherapy. Chemotherapy is given so less bone tissue needs to be removed and there are fewer problems after surgery.

The following types of surgery may be doThe following types of surgery may be done:

• Wide local excision: Surgery to remove the cancer and some healthy tissue around it.
• Limb-sparing surgery: Removal of the tumor in a limb (arm or leg) without amputation, so the use and appearance of the limb is saved. Most patients with osteosarcoma in a limb can be treated with limb-sparing surgery. The tumor is removed by wide local excision. Tissue and bone that are removed may be replaced with a graft using tissue and bone taken from another part of the patient's body, or with an implant such as artificial bone. If a fracture is found at diagnosis oor during chemotherapy before surgery, limb-sparing surgery may still be possible in some cases. If the surgeon is not able to remove all of the tumor and enough healthy tissue around it, an amputation may be done.
• Amputation: Surgery to remove part or all of an arm or leg. This may be done when it is not possible to remove all of the tumor in limb-sparing surgery. The patient may be fitted with a prosthesis (artificial limb) after amputation.
• Rotationplasty: Surgery to remove the tumor and the knee joint. The part of the leg that remains below the knee is then attached to the part of the leg that remains above the knee, with the foot facing backward and the ankle acting as a knee. A prosthesis may then be attached to the foot.

Studies have shown that survival done is a limb-sparing surgery or an amputation.

Even if the doctor removes all the cancer that can be seen at the time of the surgery, patients are also given chemotherapy after surgery to kill any cancer cells that are left in the area where the tumor was removed or that have spread to other parts of the body. Treatment given after the surgery, to lower the risk that the cancer will come back, is called adjuvant therapy.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). Combination chemotherapy is the use of more than one anticancer drug. The way the chemotherapy is given depends on the type and stage of the cancer being treated.

In the treatment of osteosarcoma and malignant fibrous histiocytosis of bone, chemotherapy is usually given before and after surgery to remove the primary tumor.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy X-rays or other types of radiation to kill cancer cells or keep them from growito kill cancer cells or keep them from growing. There are two types of radiation therapy:

• External radiation therapy uses a machine outside the body to send radiation toward the cancer.
• Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer.

The way the radiation therapy is given depends on the type and stage of the cancer being treated.

Osteosarcoma and MFH cells are not killed easily by external radiation therapy. It may be used when a small amount of cancer is left after surgery or used together with other treatments. Samarium is a radioactive drug that targets areas where bone cells are growing, such as tumor cells in bone. It helps relieve pain caused by cancer in the bone and it also kills blood cells in the bone marrow. It also is used to treat osteosarcoma that has come back after treatment in a different bone.

Treatment with samarium may be followed by stem cell transplant. Before treatment with samarium, stem cells (immature blood cells) are removed from the blood or bone marrow of the patient and are frozen and stored. After treatment with samarium is complete, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body's blood cells.

New types of treatment are being tested in clinical trials.

Targeted therapy

Targeted therapy is a treatment that uses drugs or other substances to find and attack specific cancer cells without harming normal cells. Kinase inhibitor therapy and monoclonal antibody therapy are types of targeted therapy being studied in clinical trials for osteosarcoma.

Kinase inhibitor therapy blocks a protein needed for cancer cells to divide. Sorafenib is a type of kinase inhibitor therapy being studied for the treatment of recurrent osteosarcoma.

Monoclonal antibody therapy is a cancer treatment that uses antibodies made in the laboratory, from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal substances that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells. Denosumab, dinutuximab, and glembatumumab are monoclonal antibodies being studied for the treatment of recurrent osteosarcoma.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your child's condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Treatment may include the following:

• Surgery. Combination chemotherapy is usually given before and after surgery.
• Surgery followed by radiation therapy when the tumor cannot be completely removed by surgery.

Lung Metastasis

When osteosarcoma or malignant fibrous histiocytoma (MFH) spreads, it usually spreads to the lung. Treatment of osteosarcoma and MFH with lung metastasis may include the following:

• Combination chemotherapy followed by surgery to remove the primary cancer and the cancer that has spread to the lung.

Bone Metastasis or Bone with Lung Metastasis

Osteosarcoma and malignant fibrous histiocytoma may spread to a distant bone and/or the lung. Treatment may include the following:

• Combination chemotherapy followed by surgery to remove the primary tumor and the cancer that has spread to other parts of the body. More chemotherapy is given after surgery.
• Surgery to remove the primary tumor followed by chemotherapy and surgery to remove cancer that has spread to other parts of the body.