Osteosarcoma and undifferentiated pleomorphic sarcoma (UPS) of 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. 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 long 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. UPS (formerly called malignant fibrous histiocytoma [MFH]) is a rare type of bone cancer that usually starts in soft tissue, but it may form in bone. In bone, UPS cells look similar to osteosarcoma under a microscope. UPS 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 RB1 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 UPS include swelling over a bone or a bony part of the body and joint pain.

These and other signs and symptoms may be caused by osteosarcoma 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 to detect (find) osteosarcoma.

Imaging tests are done before a biopsy. 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 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:

• 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.

After osteosarcoma 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. Most patients with osteosarcoma and UPS are grouped according to whether cancer is localized or metastatic.

• Localized osteosarcoma or UPS 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 UPS 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.

The following tests and procedures may be used to find out if the cancer has spread:

• 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 with cancer 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 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, the cancer cells in the lung are actually osteosarcoma cells. The disease is metastatic osteosarcoma, not lung cancer.

Sometimes osteosarcoma and UPS of bone come back after treatment.

The cancer may recur (come back) in the bone or in other parts of the body. Osteosarcoma and UPS 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 undifferentiated pleomorphic sarcoma (UPS).

Different types of treatment are available for children with osteosarcoma or UPS 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 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 who specialize in certain areas of medicine. These may include the following specialists:

• Pediatrician.
• Orthopedic surgeon who has experience treating bone tumors.
• Radiation oncologist.
• Rehabilitation specialist.
• Pediatric nurse specialist.
• Social worker.
• Child-life specialist.
• Psychologist.

Five 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 tissueneeds to be removed and there are fewer problems after surgery.

The 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 the time of diagnosis or 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 is the same whether the first surgery done is a limb-sparing surgery or an amputation.

After the doctor removes all the cancer that can be seen at the time of the surgery, patients are given chemotherapy 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).

Combination chemotherapy is the use of more than one anticancer drug.

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 growing. There are two types of radiation therapy:

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

Osteosarcoma and UPS 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

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 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.

Targeted therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells. Targeted therapies usually cause less harm to normal cells than chemotherapy or radiation therapy do. There are different types of targeted therapy:

• Kinase inhibitor therapy blocks a protein needed for cancer cells to divide. Sorafenib is a type of kinase inhibitor therapy used to treat recurrent osteosarcoma. Regorafenib is a type of kinase inhibitor that is being studied in adults for the treatment of metastatic osteosarcoma that has recurred. Lenvatinib is a type of kinase inhibitor that is being studied in combination with ifosfamide and etoposide for relapsed and refractory osteosarcoma.
• Mammalian target of rapamycin (mTOR) inhibitors block a protein called mTOR, which may keep cancer cells from growing and prevent the growth of new blood vessels that tumors need to grow. Everolimus is an mTOR inhibitor used to treat recurrent osteosarcoma.

Treatment for osteosarcoma or UPS 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 treatment may include the following:

• Physical problems, such as infertility.
• Changes in mood, feelings, thinking, learning, or memory.
• Second cancers (new types of cancer), such as breast cancer or acute myeloid leukemia.

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.

New types of treatment are being tested in clinical trials.

Information about ongoing clinical trials is available from the NCI website.

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.

Clinical trials are taking place in many parts of the country. Information about clinical trials supported by NCI can be found on NCI’s clinical trials search webpage. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website.

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.

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

The prognosis may be affected by certain factors before and after treatment.

The prognosis of untreated osteosarcoma and UPS may depend on the following:

• Where the tumor is in the body and whether tumors formed in more than one bone.
• Whether the patient has two or more tumors in the same 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 sex, age, and weight at the time of diagnosis.
• Whether the patient has had treatment for a different cancer.
• Whether the patient has certain genetic diseases.

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

• How much of the cancer was killed by chemotherapy.
• Whether the tumor has been completely removed by surgery.
• Whether the cancer has recurred (come back) within 2 years of diagnosis.

Treatment options for osteosarcoma and UPS depend on the following:

• Where the tumor is in the body and if it has spread.
• The size of the tumor.
• The grade 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 take part in activities such as sports or to look a certain way.
• Whether the cancer is newly diagnosed or has recurred after treatment.