Osteosarcoma

Risk Factors for Osteosarcoma

A risk factor is anything that can increase your chance of getting cancer. Different cancers have different risk factors, and not all people with risk factors develop cancer. 

Unlike many other cancers, osteosarcoma is not thought to be linked in a significant way to lifestyle-related risk factors, such as body weight, physical activity, diet, and tobacco use. Still, there are several factors that can increase the chance of a person getting osteosarcoma. Among the most notable:

Age: The risk of osteosarcoma is higher for people between ages 10 and 30, and it’s especially high during the teenage growth spurt, suggesting a possible link to rapid bone growth. The risk decreases after age 30 but rises again after age 60. Osteosarcoma in older adults is often linked to another cause, such as a long-standing bone disease.

Height: Osteosarcoma risk is higher among children who are unusually tall for their age.

Sex: The risk of osteosarcoma is higher among males than among females. Females who develop osteosarcoma often do so at a slightly earlier age than males.

Race and ethnicity: In the United States, osteosarcoma is slightly more common among Black and Hispanic children than among white children.

History of radiation treatment: People treated with radiation for another cancer can have a higher risk of later developing osteosarcoma in an area that was exposed to radiation.

History of certain bone diseases: People with certain non-cancerous bone diseases have an increased risk of developing osteosarcoma. These diseases include Paget’s disease of the bone, hereditary multiple osteochondromas, and fibrous dysplasia.

Family history of rare cancer syndromes: People with certain rare, inherited cancer syndromes have an increased risk of osteosarcoma. These can include hereditary retinoblastoma, Li-Fraumeni syndrome, and Rothmund-Thomson syndrome.

> Socioeconomic Status and Ethnicity Shown to Impact Pediatric Bone Cancer Outcomes

Symptoms of Osteosarcoma

Osteosarcomas are usually detected because of symptoms they are causing. These include: 

Bone pain and swelling: The most common symptoms of osteosarcoma are pain in the bone at the site of the tumor and swelling in the area. For younger people, these occur most commonly around the knee or in the upper arm. Initially, the pain might not be constant, but it often increases with activity. Limb pain and swelling are common among active children for reasons other than cancer, but if they don’t go away within a few weeks, consult a doctor. These symptoms are less common in adults, so if they occur, it could be a sign to see a doctor sooner. 

Bone fractures: In the case of rare telangiectatic osteosarcomas, bones tend to weaken more. than in other forms of osteosarcoma, which may lead to bone breaks at the tumor site. 

Diagnosing Osteosarcoma

Here are some key ways that osteosarcoma is diagnosed:

Medical history and physical exam: A doctor will take a complete medical history to find out more about the symptoms. A physical exam can allow a doctor to see or feel an abnormal lump or mass. The doctor may also look for problems in other parts of the body, because when people have cancer in the bones, often it’s the result of cancer that started somewhere else.

If the doctor suspects a person could have osteosarcoma, more tests will be done, possibly including imaging tests, biopsies, and lab tests.

Imaging tests: X-rays, magnetic fields, or radioactive substances can be used to create images of the body’s interior. A bone x-ray may be the first test done if a bone tumor is suspected. Imaging tests might be done for a number of reasons, such as:

• To help find out if a suspicious area might be cancer.
• To help determine if a cancer might have started in another part of the body.
• To learn how far cancer has spread.
• To help determine if treatment is working.
• To look for signs that the cancer might have come back.

If results of imaging tests suggest a person has osteosarcoma, a biopsy (see below) usually will be performed to confirm that it is cancer rather than some other problem, such as an infection.

Other imaging tests might be performed:

• A computed tomography (CT) scan combines x-ray pictures to make detailed cross-sectional images of parts of the body. If a bone x-ray shows a tumor, CT scans are sometimes used to see if the tumor has grown into nearby muscle, fat, or tendons. A CT scan of the chest is often done to look for spread of the cancer to the lungs or other parts of the body.
• A magnetic resonance imaging (MRI) scan creates images of soft tissues in the body using radio waves and strong magnets instead of x-rays, so no radiation is involved. An MRI is often performed to get a more detailed look at a bone mass seen on an x-ray, showing if the mass is likely to be a tumor, an infection, or some type of bone damage from another cause. MRIs can also help determine the extent of a tumor.
• A bone scan can show if a cancer has spread to other bones. For this test, a small amount of low-level radioactive material is injected into the blood and travels to the bones. A special camera that can detect the radioactivity then creates a picture of the skeleton.
• In a positron emission tomography (PET) scan, a form of radioactive sugar (known as FDG) is injected into the blood. Because cancer cells in the body are growing quickly, they absorb large amounts of the sugar. A special camera can then create a picture of areas of radioactivity in the body. PET scans can help show the spread of osteosarcomas to the lungs, other bones, or other parts of the body.

Biopsy: If imaging tests suggest osteosarcoma or some other type of bone cancer is present, a biopsy may be performed to confirm those results. A biopsy involves removing some of the tumor for viewing under a microscope and for other lab testing. When bone tumors are suspected, a biopsy should be performed by doctors experienced in treating bone tumors, such as those at the CU Cancer Center.

There are two main types of biopsies used for bone tumors:

• In a core needle biopsy, the doctor uses a hollow needle to remove a small cylinder of tissue from the tumor. If the tumor is near the surface of the body, often the doctor can aim the needle by feeling the area. If the tumor can’t be felt because it’s too deep, the doctor can guide the needle into the tumor using an imaging test such as a CT scan. This kind of biopsy is usually done with local anesthesia, but in some cases, sedation or general anesthesia (putting the patient into a deep sleep) may be needed.
• In an open (surgical) biopsy, a surgeon cuts through the skin, exposes the tumor, and then cuts out a piece of it. These biopsies are usually done in an operating room with the patient under general anesthesia or using a nerve block, numbing a large area of the body.

Lab tests: Biopsy samples are sent to a pathologist (a doctor specializing in lab tests) to be examined through a microscope. Tests looking for chromosome or gene changes in the tumor cells might also be performed. These tests can help tell osteosarcoma from other cancers that look like it under the microscope, and they can sometimes help predict whether the osteosarcoma is likely to respond to treatment.

If osteosarcoma is diagnosed, the pathologist will assign it a grade, which is a measure of how quickly the cancer is likely to grow and spread, largely based on how the tumor cells look. (See Types of Osteosarcoma.)

Stages of Osteosarcoma

After diagnosing the presence of osteosarcoma, the doctor will identify the stage (or extent) of the cancer. That information can aid in decisions on the best way to treat the cancer. Different stages also have different survival rates.

Doctors often categorize osteosarcoma in two main groups: localized and metastatic.

Localized osteosarcoma: This is a cancer confined to the bone it started in and possibly the tissues next to the bone, such as muscle, tendon, or fat. About 80% of osteosarcomas appear to be localized when they are first found, but there still may be small areas of cancer that have spread elsewhere but can’t be detected by tests. For that reason, chemotherapy is often administered after surgery.

Doctors further divide localized osteosarcomas into two groups: Resectable osteosarcomas, in which all of the tumor can be removed (resected) by surgery; and non-resectable (or unresectable) osteosarcomas, which can’t be removed completely by surgery.

Metastatic osteosarcoma: This is a cancer that has spread to other parts of the body, typically the lungs, but also to other bones, the brain, or other organs. About 20% of osteosarcomas have spread already when they are first diagnosed. These cancers are harder to treat, but some can be cured if the metastases can be removed by surgery. The cure rate for these cancers improves markedly if chemotherapy is also given.

There is another, more detailed system used to stage osteosarcomas, known as the Musculoskeletal Tumor Society (MSTS) staging system. It’s also known as the Enneking system). This system uses three pieces of information to categorize osteosarcoma:

• The grade (G) of the tumor, which is a measure of how likely it is to grow and spread. (See Types of Osteosarcoma.)
• The extent of the primary tumor (T), which is classified as either intracompartmental (T1), meaning it has basically remained within the bone, or extracompartmental (T2), meaning it has extended beyond the bone into other nearby structures.
• If the tumor has metastasized (M), which means it has spread to other areas, either to nearby lymph nodes or other organs. Tumors that have not spread to the lymph nodes or other organs are considered M0, while those that have spread are M1.

When combined, these factors are assigned a Roman numeral from I to III:

• Low-grade, localized tumors are stage I.
• High-grade, localized tumors are stage II.
• Metastatic tumors (regardless of grade) are stage III.

Stages I and II are further divided into A for intracompartmental tumors or B for extracompartmental tumors.

Treatments for Osteosarcoma

Surgery for Osteosarcoma

The main goal of surgery is to remove all of the cancer. If even a small amount of cancer is left behind, it might continue to grow and make a new tumor, and it might even spread to other parts of the body. To lower the risk of this happening, surgeons remove the tumor plus some of the normal tissue that surrounds it.

The type of surgery done in cases of osteosarcoma depends mainly on the location and size of the tumor. All surgeries to remove osteosarcomas are complex, but tumors in the limbs are generally not as difficult to remove as those in the jawbone, at the base of the skull, in the spine, or in the pelvic bone.

For tumors in the arms and legs, depending on the extent of the cancer, it may be possible to remove the cancer and some surrounding tissue but leave the rest of the limb intact (limb-salvage or limb-sparing surgery). But if the tumor is very large or if it extends into the nerves and blood vessels, it might not be possible to save the limb, and amputation may be needed. In such cases, reconstructive surgery may be possible.

In cases of osteosarcoma in other locations, surgery may be performed in combination with other therapies, such as chemotherapy and radiation.

Osteosarcoma often spreads to the lungs. Whether surgery can remove these metastases depends on a number of factors, including the number of tumors, their location, their size, whether they occur in one lung or both, how well the tumors responded to chemotherapy, and the person’s overall health.

Chemotherapy for Osteosarcoma

Chemotherapy (chemo) is the use of drugs to treat cancer. The drugs are usually given into a vein and can reach and destroy cancer cells throughout the body.

Chemo is an important part of the treatment for most people with osteosarcoma, although some patients with low-grade osteosarcoma may not need it. Giving chemo along with surgery helps lower the risk of tumors returning.

Most osteosarcomas are treated with chemo before surgery (neoadjuvant chemotherapy) for about 10 weeks. In some people with osteosarcoma in an arm or leg bone, this can shrink the tumor, which might help make surgery easier. Chemo is then given again after surgery (adjuvant chemotherapy) for up to a year. Usually, two or more chemo drugs are administered together.

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

Chemo drugs administered to people with osteosarcoma can cause side effects, particularly among adults. These can include:

• Nausea and vomiting.
• Loss of appetite.
• Diarrhea.
• Hair loss.
• Mouth sores.

Chemo can damage the bone marrow, where new blood cells are made. This can lead to 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).

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 doesn’t play a major role in treating this type of cancer. But sometimes radiation can be useful if the tumor can’t be removed completely by surgery, such as osteosarcoma in hip bones or in the bones of the face, particularly the jaw.

After as much of the tumor is removed as possible, radiation is given to try to kill the remaining cancer cells. Chemotherapy is then often given after the radiation.

Radiation can also be used to help slow tumor growth and control symptoms like pain and swelling if surgery is not possible, or if the cancer has returned.

Targeted Therapy for Osteosarcoma  

Targeted therapy uses drugs or other substances to block the action of specific enzymes, proteins, or other molecules involved in the growth of tumor cells. There are different kinds of targeted therapy that have been used or are being tested for use to treat certain cases of osteosarcoma:

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 (which has returned after treatment) in certain cases. Other kinds of kinase inhibitors are being studied for treatment of 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.

The University of Colorado (CU) Cancer Center partners with UCHealth, Children’s Hospital Colorado, and Rocky Mountain Regional VA to provide clinical care. Please make an appointment with one of our clinical partners to be seen by a CU Cancer Center doctor.

UCHealth:

UCHealth Cancer Care - Anschutz Medical Campus
1665 Aurora Court Anschutz Cancer Pavilion
Aurora, CO 80045
720-848-0300

UCHealth Cherry Creek Medical Center
100 Cook Street
Denver, CO 80206
720-848-0000

Rocky Mountain Regional VA Medical Center:
1700 North Wheeling Street
Aurora, CO 80045-7211
303-399-8020