What’s New in Osteosarcoma Research?

Research on osteosarcoma is now being done at many medical centers, university hospitals, and other institutions around the world.

Understanding osteosarcoma

Researchers are learning more about what makes osteosarcoma cells different from normal bone cells. Knowing more about the changes in osteosarcoma cells might eventually result in specific treatments based on these changes.

For example, researchers have found that osteosarcoma cells often have large amounts of a substance called GD2 on their surfaces. Drugs that target GD2 are already used to treat neuroblastoma (another cancer often seen in children). Newer immunotherapy treatments that target GD2 are now being studied for use against osteosarcoma as well (see below).

Lab tests of the gene changes inside osteosarcoma cells might help predict the behavior of each tumor, such as how they will respond to certain types of chemotherapy or targeted therapy drugs. This type of testing is now being studied in clinical trials.

Treatment

Many advances have been made in treating osteosarcoma in the past few decades. Still, more research is needed to learn how best to manage hard-to-treat osteosarcomas, such as those that have already spread when they are found. Many clinical trials are focusing on treating osteosarcoma using a variety of strategies.

Surgery

The typical patterns of osteosarcoma growth and spread are much better understood now than they were. Newer imaging tests can also better define the extent of tumors. These advances, along with sophisticated computer programs that help surgeons map out the best surgical approach before and during the operation (known as computer-assisted tumor surgery, or CATS), can help surgeons remove the cancer while sparing as much normal tissue as possible.

Some newer types of internal prostheses (man-made replacements for pieces of bone) can now be extended without the need for more surgery. This is especially important for children, who in the past often needed several operations to replace the prosthesis with a larger one as they grew.

Radiation therapy

Osteosarcoma cells are not killed easily by radiation, so high doses are needed to have an effect. Because high doses can often cause unacceptable side effects, this has limited the use of radiation therapy. Newer forms of radiation let doctors focus radiation more precisely on the tumor. Limiting the doses that reach nearby healthy tissues may allow higher doses to be used on the tumor itself.

Intensity-modulated radiation therapy (IMRT) is an example of an advanced form of therapy. In this technique, radiation beams are shaped to fit the tumor and aimed at it from several angles. The intensity (strength) of the beams can also be adjusted to limit the dose reaching nearby normal tissues. Many hospitals and cancer centers now use IMRT, especially for tumors in hard-to-treat areas such as the spine or pelvis (hip bones).

Stereotactic radiosurgery (SRS) gives a large (usually one-time) dose of radiation to a small tumor area. Once imaging tests have shown the exact location of the tumor, a thin beam of radiation is focused on the area from many different angles. The radiation is very precisely aimed so that it has as little effect on nearby tissues as possible. Sometimes doctors give the radiation in several smaller treatments to deliver the same or slightly higher dose. This is called fractionated stereotactic radiotherapy.

Another newer approach is to use radioactive particles instead of x-rays to deliver the radiation. One example is conformal proton beam therapy, which uses positive parts of atoms. Unlike x-rays, which release energy both before and after they hit their target, protons cause little damage to normal tissues they pass through and then release their energy after traveling a certain distance. Doctors can use this property to deliver more radiation to the tumor and to do less damage to nearby normal tissues. Proton beam therapy may be helpful for hard-to-treat tumors, such as those on the spine or pelvic bones, but only a limited number of centers in the United States offer this treatment at this time.

An even newer approach uses carbon ions, which are heavier than protons and cause more damage to cancer cells. This therapy is still in the earliest stages of development and is only available in a small number of centers around the world.

Doctors are also studying newer forms of radioactive drugs to treat osteosarcoma that has spread to many bones. One example is radium-223 (Xofigo), which works slightly differently than the other radioactive drugs now being used.

Chemotherapy

Clinical trials are being done to determine the best combinations of chemotherapy (chemo) drugs, as well as the best time to give them. Newer chemo drugs are being studied as well.

The lungs are the most common place for osteosarcoma to spread. Inhaled forms of some chemo drugs (such as cisplatin) are being studied for patients whose cancer has spread to their lungs.

Other forms of treatment

Chemo drugs are often helpful in treating osteosarcoma, but sometimes they don’t work, or the cancer becomes resistant to them over time. Researchers are studying newer types of drugs that attack osteosarcoma cells in different ways.

Immunotherapy drugs

Clinical trials are looking into ways to help the patient’s own immune system recognize and attack the osteosarcoma cells. For example:

• Drugs called immune checkpoint inhibitors can sometimes help the body’s immune system recognize and attack cancer cells. These drugs have already been shown to be helpful against many types of cancer, and some of them are now being studied for use against osteosarcoma.
• An experimental immune-stimulating drug called muramyl tripeptide (also known as MTP or mifamurtide) has been shown to help some patients when added to chemotherapy.
• Monoclonal antibodies are man-made versions of immune system proteins that attach to a specific target in the body, which can help the immune system find and destroy cancer cells. Antibodies directed against GD2 and other substances on osteosarcoma cells are now being tested in clinical trials.
• Researchers are also studying a newer form of immunotherapy known as CAR-T cell therapy for osteosarcoma that is no longer helped by other treatments.

Targeted therapy drugs

Doctors are also studying new medicines that target specific molecules on or in cancer cells. These are known as targeted therapies.

Monoclonal antibodies, discussed above, can also be considered a type of targeted therapy. These antibodies attach to certain substances on cancer cells, which can kill them or help to stop their growth. An example is dinutuximab (Unituxin), an antibody that attaches to GD2, a substance that is important for cancer cell growth.

Many other targeted drugs are being studied for use against osteosarcoma, including drugs that affect a tumor’s ability to make new blood vessels, such as sorafenib (Nexavar), pazopanib (Votrient), lenvatinib (Lenvima), and cabozantinib (Cabometyx).

Drugs that affect the bones

Drugs that target bone cells called osteoclasts may also be useful against osteosarcoma:

• Bisphosphonates are a group of drugs that are already used to treat osteoporosis (bone thinning) and certain cancers that have spread to the bones. Some of these drugs, such as pamidronate and zoledronic acid, are now being studied for use in osteosarcoma as well.
• Denosumab is a monoclonal antibody that targets the RANKL protein, which normally helps bones grow. It is now being studied for use against osteosarcoma.