NORD gratefully acknowledges Richard Gorlick, MD, Division Head, Division of Pediatrics, The University of Texas MD Anderson Cancer Center, for assistance in the preparation of this report.
Osteosarcoma is a form of cancer. It is a type of tumor that affects the bones. Osteosarcoma can affect people at any age, but is most common during the teen-aged years, and is the most common bone cancer affecting children and adolescents under the age of 20. The long bones of the legs, usually near where they connect to the knees, and the upper long bone of the arms, near where this bone meets the shoulders are the most common sites for osteosarcoma formation. Symptoms will vary depending upon the exact location and extent of disease. Pain is the most common symptom of osteosarcoma and there is often a mass or bump that can be felt (palpable). Eighty percent of individuals present with localized disease, which means the cancer remains in the area it first developed. Osteosarcoma can spread (metastasize) to other areas of the body, most likely the lungs. The exact cause is unknown in most individuals, but osteosarcoma can be induced by radiation. Most individuals are treated with a combination of chemotherapy and surgery. Sometimes, radiation therapy may be used.
The most commonly affected bones are the long bones of the legs. These are the femur and the tibia. The femur, also called the thighbone, runs from the hip to the knee, and the tibia, or shinbone, runs from the knee to the ankle. The femur and the tibia meet at the knee where they help to form the knee joint. Osteosarcomas can form where these bones are growing the fastest in children and adolescents, which is called the growth plate. About 50% of individuals develop an osteosarcoma around the knee. For the legs this is near the knees and includes the bottom of the femur and the tops of the tibia. Osteosarcomas can also affect the upper part of the long bone of the arms called the humerus. The humerus runs from the elbow to the shoulder. The area near where the humerus connects to the shoulder accounts for about 15% of osteosarcomas.
Less often, the middle portions of the femurs or tibia can be affected. Osteosarcomas can potentially be found in any bone of the body, although this is far less common. Other areas that can be affected include the spine, shoulder, pelvis, skull, or jaw.
Pain is common in the area where the tumor is located. Pain may increase or decrease (wax and wane) over time. Pain may increase when a person does something that requires effort, such as lifting or another activity. A tumor may appear as a mass that can be seen or can be felt (palpable) and may be tender to the touch. Swelling near the tumor is also common. Sometimes, a tumor causes decreased movement in the affected arm or leg or nearby joint. Some people may limp because of a tumor in the leg or near the knee. Bones affected by osteosarcoma are weakened, and they may be more likely to fracture or break, although this is not a common occurrence.
Osteosarcomas can spread (metastasize) to other areas of the body, most often the lungs. Generally, if the cancer has spread to other areas then the prognosis is worse. Researchers are currently working on ways to prevent or treat metastatic osteosarcoma.
Osteosarcomas can be classified as high-grade, intermediate-grade, or low-grade. This refers to how the cancer looks like under a microscope and determines how likely an osteosarcoma is to grow and spread. High-grade osteosarcomas are the most common form in children and adolescents and are the fastest growing form. They also have the greatest tendency to spread (metastasize).
As with many forms of cancer, the exact, underlying cause of osteosarcoma is unknown in most individuals. In most children and adolescents, this cancer is thought to occur randomly, for no specific reason (sporadically). Sporadic occurrence of cancer is thought to occur because of multiple factors acting together. This can include genetic and environmental factors. The cancerous cells in osteosarcomas are usually mesenchymal stem cells or osteoblasts. Mesenchymal stem cells are “adult” stem cells that can grow and change (differentiate) into different types of cells including bone, cartilage, muscle, fat, or connective tissue. Osteoblasts are cells that work to develop new bone. When they become cancerous they may produce an immature form of bone called an osteoid, which is how the pathologist makes the diagnosis.
Changes (variations) in certain genes have been noted to occur in greater frequency in individuals with osteosarcoma than in people without this form of cancer. These genes include the retinoblastoma 1 (RB1) gene, which is associated with a rare childhood eye cancer called retinoblastoma, or the TP53 gene, which is also associated with cancer. A variation in the WWOX gene is also seen in increased frequency in individuals with osteosarcoma. The genetic factors that contribute to the development of osteosarcomas are heterogeneous; this means that there are different genetic abnormalities or mechanisms that result in susceptibility to disease. Although mutations in genes like RB1 or p53 lead to a higher risk of osteosarcoma, most affected individuals do not have changes in these genes. The underlying, genetic factors associated with osteosarcoma are very complex and more research is necessary for doctors to figure out the all of the genetic and environmental interactions that contribute to the development of osteosarcoma.
Because osteosarcomas tend to affect adolescents in their teen years and disproportionately affects the growing portions (growth plates), many researchers believe that there may be problems with bone growth contributing to the development of this form of bone cancer.
Although the causes and genetic aspects of osteosarcoma are not fully understood, several risk factors have been identified. Risk factors are anything that increases a person’s risk of developing a condition. Having a risk factor does not mean a person will definitely develop that condition, and people who do not have any risk factors can still develop a condition.
Individuals who have been treated by radiation therapy or certain anticancer medications called alkylating agents have a greater risk of developing osteosarcoma. Male gender, being tall in height, and people of African-American or Hispanic/Latino descent are aspects that make people more likely to develop an osteosarcoma. Osteosarcomas also occur with greater frequency in people or families that have rare genetic disorders such as hereditary retinoblastoma (RB1), Li-Fraumeni syndrome (p53), Rothmund-Thompson syndrome, Blackfan-Diamond anemia, Bloom syndrome or Werner syndrome.
Some individuals, including many adults, develop osteosarcoma when they have another, noncancerous bone disorder including Paget disease of bone or fibrous dysplasia, which result in increased bone turnover. Bone turnover is a normal process in which bone gradually breaks down and then reforms.
There are estimated to be about 750-1,000 new individuals diagnosed with osteosarcoma each year in the United States. About 450 of those are children or adolescents under the age of 20. Osteosarcoma is a rare disorder, but it is the most common cause of bone cancer in children and adolescents. These tumors usually affect individuals in their second decade of life (10-19 years of age), most often between 13 and 16 years of age, which most likely coincides with adolescent growth spurts. There is a second increase in the number of people with osteosarcoma in people over the age of 60. Overall, osteosarcoma accounts for about 1% of all cancers diagnosed each year in the United States. Osteosarcoma affect slightly more males than females and is slightly more common in African-Americans and Hispanics/Latinos than in Caucasians.
A diagnosis of osteosarcoma is suspected upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. A physical examination may reveal swelling or a mass that is tender to the touch, and limited mobility of a nearby joint.
Clinical Testing and Workup
X-rays should be taken if there is a suspicion of osteosarcoma. Plain x-rays are used to obtain images of the tumor or the affected area. An osteosarcoma typically will have a distinct appearance on an x-ray.
More specialized imaging techniques may be used to help evaluate the size, placement, and extension of the tumor (e.g. into the soft tissue or surrounding areas), to determine whether the tumor has spread (metastasized) to the lungs or other areas of the body, and to serve as an aid for future surgical procedures. Such imaging techniques may include magnetic resonance imaging (MRI), computerized tomography (CT scan), or bone scans. Plain films are most effective in helping to diagnose osteosarcoma. CT scans and MRIs give different information. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues including bone marrow and soft tissue. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. During a bone scan, a relatively harmless radioactive dye is injected into the affected bone. A special camera that can track the dye as it travels through the bone is used to create a picture of the skeleton and determine all affected areas and can help determine whether an osteosarcoma has spread to other areas of the body.
Another advanced imaging technique known as positron emission tomography or PET scan may also be used, although it is not a standard diagnostic tool for osteosarcoma. During a PET scan, a radioactive sugar is injected into the body. This sugar will collect in areas of the body where there is a higher demand for energy. Tumors require a lot of energy to keep growing and spreading, and will soak up the radioactive sugar. When the x-ray (scan) is taken areas that soak up the radioactive sugar including an osteosarcoma show up as bright spots on the film.
A diagnosis of osteosarcoma is confirmed through the surgical removal (biopsy) and microscopic study of a portion of affected tissue. A biopsy can reveal characteristic changes in the tumor tissue that are diagnostic of osteosarcomas. A malignant cell produces osteoid, which typically leads to the diagnosis of osteosarcoma.
Some individuals may have their blood tested to detect elevated levels of chemicals called alkaline phosphatase and lactate dehydrogenase. These chemicals are sometimes high in people with an osteosarcoma. Although they may indicative of osteosarcoma, there are other conditions that can cause these chemicals to be high. Therefore, these blood tests cannot diagnose osteosarcoma. However, if people with an osteosarcoma have high levels of these chemicals, it may help to reveal how advanced the cancer is. However, this does not supplant imaging, which is used to stage the cancer.
The therapeutic management of individuals with osteosarcoma may require the coordinated efforts of a team of medical professionals, such as specialists in the diagnosis and treatment of disorders of the skeletal system (orthopedists), orthopedic surgeons, orthopedic surgeons who specialize in treating cancer (orthopedic oncologists), physicians who specialize in the diagnosis and treatment of cancer in children (pediatric oncologists), physicians who specialize in the diagnosis and treatment of cancer (oncologists), physicians who specialize in the use of radiation therapy for treatment of cancer (radiation oncologists), oncology nurses, psychiatrists, nutritionists, and other healthcare specialists. Psychosocial support for the entire family is essential as well.
Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as disease stage; tumor size; specific tumor subtype; whether the cancer has spread; the presence or absence of certain symptoms; an individual’s age and general health; and/or other elements. Decisions concerning the use of particular drug regimens and/or other treatments should be made by physicians and other members of the health care team in careful consultation with the patient based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors.
The main treatment option for individuals with osteosarcoma is a combination of chemotherapy and surgery. Chemotherapy is the use of certain medications to stop the growth or kill cancer cells. Cancers cells grow and divide rapidly, which makes them susceptible to chemotherapy medications. In osteosarcoma, chemotherapy may be given before surgery to shrink a tumor or following surgery to eliminate any remaining cancer cells and lessen the risk of a recurrence. Usually, chemotherapy is given before and after surgery. Different combinations of medications may be used; this is called a chemotherapy regimen. When chemotherapy is given, the specific chemotherapy regimen used can vary. Different medical centers may have their own preferences as to the best way to approach treatment and what chemotherapeutic regimen is best for each individual.
Surgical removal (resection) of a tumor is a mainstay for the treatment of osteosarcoma. Ideally, doctors will perform limb-sparing surgery. This surgery is designed to remove the tumor, but preserve the function of the limb as well as the physical appearance of the limb. Sometimes, this surgery can leave a limb fragile and affected individuals may need to avoid high-stress, physical activities. If doctors cannot remove the entire tumor, or can only do so without preserving the function of the affected limb, amputation may be recommended. This eliminates the tumor and will prevent the cancer from spreading further.
Sometimes, doctors may recommend radiation therapy for individuals in whom a tumor could not be completely removed by surgery. There is a risk for side effects following radiation therapy.
Late Effects of Osteosarcoma Therapy
Late effects of cancer therapy refer to the risk that survivors of childhood cancer may develop problems later in life because of treatment they received during childhood. Children treated with chemotherapy or radiation therapy have a risk of developing various issues later in life including heart problems, toxicity to the kidneys or central nervous system, infertility, and an increased risk of developing a second, different cancer later in life.
Targeted therapies are being explored as potential treatments for individuals with osteosarcoma. Targeted therapies are drugs and other substances that prevent the growth and spread of cancer by blocking or inhibiting certain specific molecules (often proteins) that are involved in the development of specific cancers. Generally, targeted therapies are less toxic than other treatments for cancer. Targeted therapy for osteosarcoma has been hindered because doctors do not yet fully understand the complex genetic changes that underlie the growth and development of this form of cancer. More research is necessary to determine what genetic factors (e.g. altered genes) play a role in the development of osteosarcoma and what types of targeted therapies may be possible to treat these tumors.
Some affected individuals may be treated with samarium or radium 223. Samarium and radium 223 are radioactive drugs that target areas where bone cells are growing. This includes tumor cells in osteosarcoma. Samarium is given to relieve bone pain in individuals who have cancer that returns and cannot be removed surgically or for some people in whom cancer has spread (metastasized). Some doctors believe that samarium may have a role in reducing tumor growth or spread in osteosarcoma as well. More research is necessary to determine what role, if any, that samarium has in the treatment of osteosarcoma, beyond that of pain reduction in certain affected individuals.
Many other types of cancer are treated with a new therapy called immunotherapy. This type of treatment aims to enhance the body’s innate ability to fight cancer cells using the immune system. For example, the most common form of immunotherapy called PD-1 or PD-L1 blockade releases the “brakes” on the immune system that some cancers use to try to evade the immune cells. Researchers are currently studying whether immunotherapy could potentially be used to treat osteosarcoma. At present (as of July 2018), researchers do not yet know if these agents do or do not work.
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