Background

This article focuses on high-grade intramedullary osteosarcoma (also referred to as simply osteosarcoma), including its classic osteoblastic form and its fibroblastic and chondroblastic forms. Osteosarcoma is the most common malignant bone tumor.[1, 2] This disease is thought to arise from primitive mesenchymal bone-forming cells, and its histologic hallmark is the production of malignant osteoid. Other cell populations may also be present, as these types of cells may also arise from pluripotential mesenchymal cells, but any area of malignant bone in the lesion establishes the diagnosis as osteosarcoma. The mainstay of therapy is surgical removal of the malignant lesion. Most often, limb-sparing (limb-preserving) procedures can be used to treat patients with this disease and, thus, preserve function. Chemotherapy is also required to treat micrometastatic disease, which is present but often not detectable in most patients (about 80%) at the time of diagnosis.[3] An image depicting osteosarcoma can be seen below.

Chest radiograph of patient with osteosarcoma who died from pulmonary metastatic disease. Note the presence of a pneumothorax as well as radiodense (bone-forming) metastatic lesions.

History of the Procedure

Osteosarcoma is an ancient disease that is still incompletely understood. The term "sarcoma" was introduced by the English surgeon John Abernathy in 1804 and was derived from Greek roots meaning "fleshy excrescence." [4] In 1805, the French surgeon Alexis Boyer (personal surgeon to Napoleon) first used the term "osteosarcoma."[4, 5] Boyer realized that osteosarcoma is a distinct entity from other bone lesions, such as osteochondromas(exostoses). Evidence of further organized thought and purposeful investigation regarding this disease was found by the mid 1800s. Peltier recorded that in 1847, the Baron Guillaume Dupuytren demonstrated his intimate knowledge of the gross pathologic appearance of osteosarcoma when he wrote the following[4] : "Osteosarcoma, which is a true cancerous degeneration of bone, manifests itself in the form of a white or reddish mass, lardaceous and firm at an early stage of the disease; but presenting at a later period, points of softening, cerebriform matter, extravasating blood, and white or straw colored fluid of a viscid consistence in its interior." [4] Under the auspices of the American College of Surgeons, Ernest Amory Codman (along with James Ewing and Joseph Bloodgood) created the Registry of Bone Sarcoma in 1921.[6] This was a significant step forward in studying these rare and ominous tumors, as individual surgeons had only limited experience to guide them. Another major institution that began to take shape in the early 1900s was the Rizzoli Institute in Bologna, Italy. This institute, whose bone tumor roots were nurtured by Vittorio Putti (1880-1940), prospered under the later guidance of persons such as Scaglietti and Campanacci.[7] Major contributions from this institution have included innovative treatment for unicameral bone cysts (Scaglietti) and intense study of osteofibrous dysplasia (Campanacci tumor). By the mid 1900s, great strides were being made in the United States in the field of bone pathology by Henry L. Jaffe (1896-1979) and his colleague Louis Lichtenstein (1906-1977). Each of these men published textbooks devoted to bone pathology. Jaffe is also often credited with bringing order to the chaos that was orthopedic pathology. Together, Jaffe and Lichtenstein established virtually all of the key histologic criteria that are used to diagnose most of the commonly encountered bone tumors. A different Dr Jaffe (Norman Jaffe), along with other researchers, helped expand the use of a variety of effective chemotherapeutic agents in the 1970s and early 1980s.[8] Not the least of these agents were Adriamycin and methotrexate. These medications (and others that followed) dramatically improved the treatment of patients with osteosarcoma through their ability to treat the micrometastatic disease that was thought to be present in approximately 80% of patients.[9] These drugs were found to be useful both preoperatively and postoperatively in patients with osteosarcoma, a discovery made at the Sloan-Kettering Memorial Cancer Center somewhat serendipitously while custommade prostheses were being fabricated for patients awaiting surgery. [10] Such preoperative use of chemotherapy came to be referred to as neoadjuvant chemotherapy.

An orthopedic surgeon from Gainesville, Florida, William F. Enneking, MD, introduced his surgical staging system for musculoskeletal sarcomas.[11, 12]This staging system helped organize the orthopedic surgical approach to both biopsy and definitive tumor resection for osteosarcoma, as well as for other musculoskeletal sarcomas. Dr. Enneking's influence extended far beyond his staging system because of his intense commitment to educating others regarding musculoskeletal tumors. He has educated numerous orthopedic oncology fellows, published numerous research articles, and continued to conduct a yearly continuing medical education course focusing on benign and malignant tumors.

Problem
Osteosarcoma is a deadly form of musculoskeletal cancer that most commonly causes patients to die from pulmonary metastatic disease.[4, 7, 13, 14, 15] The first image below illustrates the chest radiograph of a patient who died from pulmonary metastatic disease. Most osteosarcomas arise as solitary lesions within the fastest growing areas of the long bones of children. The top 3 affected areas are the distal femur, the proximal tibia, and the proximal humerus, but virtually any bone can be affected. The other images below illustrate the clinical and radiologic findings of a patient who presented with osteosarcoma of the proximal humerus.

Chest radiograph of patient with osteosarcoma who died from pulmonary metastatic disease. Note the

presence of a pneumothorax as well as radiodense (bone-forming) metastatic lesions. Clinical appearance of a teenager who presented with osteosarcoma of the proximal humerus (same patient as in the following i mages). Note the impressive swelling throughout the deltoid region, as well as the disuse atrophy of the pectoral musculature.

Not all osteosarcomas arise in a solitary fashion, as multiple sites may become apparent within a period of about 6 months (synchronous osteosarcoma), or multiple sites may be noted over a period longer than 6 months (metachronous osteosarcoma).[13] Such multifocal osteosarcoma is decidedly rare, but when it occurs, it tends to be in patients younger than 10 years.[13]

Epidemiology
Frequency
In the United States, the incidence of osteosarcoma is 400 cases per year (4.8 per million population < 20 y). [16] The overall 5-year survival rate for patients diagnosed between 1974 and 1994 was 63% (59% for males, 70% for females). The incidence is slightly higher in blacks than in whites. Data from the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Pediatric Monograph 1975-1995 are as follows[16] : Blacks 5.2 cases per million per year (persons < 20 y) Whites 4.6 cases per million per year The incidence of osteosarcoma is slightly higher in males than in females. In males, it is 5.2 per million per year. In females, the incidence is 4.5 per million per year.

Osteosarcoma is very rare in young children (0.5 cases per million per year in children < 5 y). However, the incidence increases steadily with age, increasing more dramatically in adolescence, corresponding with theadolescent growth spurt.[17] Age 5-9 years 2.6 (black) or 2.1 (white) cases per million per year Age 10-14 years 8.3 (black) or 7 (white) cases per million per year Age 15-19 years 8.9 (black) or 8.2 (white) cases per million per year

Etiology
The exact cause of osteosarcoma is unknown. However, a number of risk factors are apparent, as follows [4, 7, 13, 14, 15, 18, 19, 20, 21, 22, 23, 24, 25] : Rapid bone growth: Rapid bone growth appears to predispose persons to osteosarcoma, as suggested by the increased incidence during theadolescent growth spurt, the high incidence among large-breed dogs (eg, Great Dane, St. Bernard, German shepherd), and osteosarcoma's typical location in the metaphyseal area adjacent to the growth plate (physis) of long bones. Environmental factors: The only known environmental risk factor is exposure to radiation. Radiation-induced osteosarcoma is a form of secondary osteosarcoma and is not discussed further in this article. Genetic predisposition: Bone dysplasias, including Paget disease, fibrous dysplasia, enchondromatosis, and hereditary multiple exostoses and retinoblastoma (germ-line form) are risk factors. The combination of constitutional mutation of the RB gene (germline retinoblastoma) and radiation therapy is associated with a particularly high risk of developing osteosarcoma, Li-Fraumeni syndrome (germline p53 mutation), and Rothmund-Thomson syndrome (autosomal recessive association of congenital bone defects, hair and skin dysplasias, hypogonadism, andcataracts).

Pathophysiology
Osteosarcoma is a bone tumor and can occur in any bone, usually in the extremities of long bones near metaphyseal growth plates. The most common sites are the femur (42%, 75% of which are in the distal femur), tibia (19%, 80% of which are in the proximal tibia), and humerus (10%, 90% of which are in the proximal humerus). Other significant locations are the skull and jaw (8%) and pelvis (8%). A number of variants of osteosarcoma exist, including conventional types (osteoblastic, chondroblastic, and fibroblastic), telangiectatic, multifocal, parosteal, and periosteal. This article only addresses conventional osteosarcoma.

Presentation
Symptoms may be present for weeks or months (occasionally longer) before patients are diagnosed. The most common presenting symptom of osteosarcoma is pain, particularly pain with activity. Patients may be concerned that their child has a sprain, arthritis, or growing pains. Often, there is a history of trauma, but the precise role of trauma in the development of osteosarcoma is unclear. Pathologic fractures are not particularly common. The exception is the telangiectatic type of osteosarcoma, which is more commonly associated with pathologic fractures. The pain in an extremity may result in a limp. There may or may not be a history of swelling, depending on the size of the lesion and its location. Systemic symptoms, such as fever and night sweats, are rare. Tumor spread to the lungs only rarely results in respiratory symptoms and usually indicates extensive lung involvement. Metastases to other sites are extremely rare, and, therefore, other symptoms are unusual. Physical examination findings are usually limited to the site of the primary tumor, as follows: Mass: A palpable mass may or may not be present. The mass may be tender and warm, although these signs are indistinguishable from osteomyelitis. Increased skin vascularity over the mass may be discernible. Pulsations or a bruit may be detectable. Decreased range of motion: Involvement of a joint should be obvious on physical examination. Lymphadenopathy: Involvement of local or regional lymph nodes is unusual. Respiratory findings: Auscultation is usually uninformative unless the disease is extensive.

Indications
The 2 main procedures performed by orthopedic surgeons in patients with osteosarcoma are biopsy and wide resection. Neither of these procedures should be undertaken unless complete tumor staging has been completed preoperatively. Such staging would typically include (but not be limited to) the following: Plain radiography of the involved bone, including the joint above and the joint below the affected region Total body bone scanning Magnetic resonance imaging (MRI) of the primary tumor area to include the entire bone of origin Computed tomography (CT) scanning of the lungs

The biopsy of malignant bone lesions is not an insignificant procedure. An improperly performed biopsy can result in the amputation of an otherwise salvageable extremity. It has also been shown repeatedly that oncologic outcomes are optimized when the biopsy is performed by the same surgeon who will be responsible for the definitive tumor resection (if one is needed).[26, 27] Incisional biopsies or core needle biopsies (Craig needle biopsy) are the most common types of biopsies performed by orthopedic surgeons.[28] Open lines of communication between the orthopedic surgeon and the pathologist are vital to help ensure that adequate tissue is obtained for diagnostic purposes, as seen in the images below.

Intraoperative consultation with the pathologist, in which the surgeon and pathologist view the

microscopic appearance of the biopsy specimen. the biopsy specimen is being performed.

Intraoperative consultation with the pathologist. A frozen section of

Wide resection is the goal for patients in whom primary tumor resection is contemplated. Simply defined, a wide resection means that the entire malignant tumor has been surgically excised, and no microscopic evidence of tumor cells at the resection margins remains (ie, negative margins). Over the years, many authors have suggested variable and arbitrary amounts of the normal tissue cuff to remove along with the primary tumor to increase the likelihood of negative margins. No universally accepted definition exists of the appropriate thickness of the normal cuff. In a technical sense, a wide margin still exists even if the distance between the normal tissue and tumor is 1 cell thick. From an oncologic standpoint, the width achieved is less important (limb-sparing surgery vs amputation) than the achievement of a negative margin. In other words, a limb-sparing surgery without wide margins could do the patient less of a service than an amputation with wide margins. This would apply in most cases in which maximal preservation of life is considered the primary goal.

Relevant Anatomy
See Surgical therapy.

Contraindications
Because osteosarcoma is a deadly form of cancer, no absolute contraindications to treatment exist. Relative contraindications would include situations in which the patient is so frail that the risks of general anesthesiaoutweigh any potential benefits of surgery. Another relative contraindication would be a situation in which the patient has extensive, overwhelming metastatic disease, and the benefits of comfort and/or hospice care outweigh the potential benefits of surgical intervention.

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 teenagers. It commonly forms in the ends of the long bones of the body, which include bones of the arms and legs. In children and teenagers, 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 raretumor of the bone. It is treated like osteosarcoma. Ewing sarcoma is another kind of bone cancer, but it is not covered in this summary. See the PDQ summary onEwing Sarcoma Family of Tumors for more information.

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 doesnt mean that you will not get cancer. People who think they may be at risk should discuss this with their doctor. 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: Hereditary retinoblastoma. Paget disease. Diamond-Blackfan anemia. Li-Fraumeni syndrome. Rothmund-Thomson syndrome. Bloom syndrome. Werner syndrome.

Possible signs of osteosarcoma and MFH include pain and swelling over a bone or a bony part of the body.
These and other symptoms may be caused by osteosarcoma or MFH. Other conditions may cause the same symptoms. A doctor should be consulted if any of the following problems occur: 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 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 patients 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 beinjected 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 surgeryto 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 three types of biopsy that may be used: Fine-needle aspiration (FNA) biopsy: The removal of tissue or fluid using a thin needle. 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. Excisional biopsy: The removal of an entire lump or area of tissue that doesnt look normal. The following tests 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 highpowered microscopes to look for certain changes in the cells. Cytogenetic analysis: A laboratory test in which cells in a sample of tissue are viewed under a microscope to look for certain changes in the chromosomes. Immunocytochemistry study: A laboratory test in which a substance such as an antibody, dye, orradioisotope is added to a sample of cancer cells to test for certain antigens. This type of study is used to tell the difference between different types of cancer.

What is osteosarcoma?
Osteosarcoma is a type of cancer that starts in the bones. To understand osteosarcoma, it helps to know something about the normal structure of bones.

Normal bones
Many people may think of bones as just being part of the skeleton, like the steel girders that support a building. But bones have a number of different functions.

Some bones help support and protect our vital organs. Examples include the skull bones, breast bone (sternum), and ribs. These types of bones are often referred to as flat bones. Other bones, like those in the arms and legs, make a framework for our muscles that helps us move. These are calledlong bones.

Bones also make new blood cells. This is done in the soft, inner part of some bones called the bone marrow. Bones also provide the body with a place to store minerals such as calcium. Because bones are very hard and don't change shape (at least in adults) we may think of bones as being dead. But bones are really living tissue made up of living cells.

There are 2 main types of cells in our bones:

Osteoblasts help build up bones by forming the matrix of the bones, that is, the connective tissue and minerals that give the bones strength. Osteoclasts break down bone matrix to keep it from building up. These cells help bones keep their shape. They also help control the amount of minerals in the blood.

Osteosarcoma
Osteosarcoma is the most common type of cancer that starts in the bone. Most osteosarcomas happen in children and young adults, but it can happen at any age. Like other cancers, osteosarcoma can spread beyond the bone into nearby tissues. Cancer cells can also break away from the main tumor and spread through the blood to other bones or to the lungs or other organs. This process is called metastasis. When this cancer starts in the cells that make bone, the cancer-filled bone is not as strong as normal bones. Osteosarcoma often starts near the ends of the long bones in the legs, especially in the part of the thigh bone next to the knee, and the part of the lower leg bone next to the knee. The arm bone near the shoulder is the second most common place for this cancer to start. But it can start in other bones, too. Osteosarcoma that starts in places like the hip bone (pelvis), shoulder, or jaw (and other places where it's hard to do surgery) tends to have a worse outcome.

Subtypes of osteosarcoma
There are several subtypes of osteosarcoma. The subtype is based on how the cancer looks on x-rays and under the microscope. Some subtypes have a much better outlook for survival than others. Osteosarcomas can be grouped as low grade, intermediate grade, or high grade. If the tumor has few dividing cells and looks more like normal bone, it is called a low-grade osteosarcoma. If it has many dividing cells and is growing quickly, it is high grade. Most osteosarcomas in children and teens are high grade. The grade is important because it tells the doctor how likely the cancer is to grow and spread to other parts of the body. It helps the doctor figure out the stage of the tumor and the best type of treatment to use. For more on staging, see the section, "After the tests: Staging."

Other types of bone tumors

Ewing tumors are the second most common kind of bone cancer in children. They are described in the American Cancer Society document, Ewing Family of Tumors. Most other types of bone cancers are usually found in adults and are rare in children. Many types of cancer that start in other places can spread to the bones, but they are not true bone cancers. They are sometimes called metastatic bone cancers. For instance, prostate cancer that spreads to the bones is still prostate cancer and is treated like prostate cancer. For more information, see our document called Bone Metastasis. Many bone tumors are not cancer. These are called benign (be-nine) bone tumors. Benign bone tumors do not spread to other parts of the body and most of the time they are not dangerous.

What are the risk factors for osteosarcoma?

The exact cause of most osteosarcomas is not known. But we do know that certain risk factors are linked to this disease. A risk factor is something that affects a person's chance of getting a disease. Some risk factors, like smoking, can be controlled. Others, like a person's age or race, can't be changed. So far, lifestyle-related factors (like bad diets, lack of exercise, or obesity) have not been linked to osteosarcoma in children or in adults.

Risk factors for osteosarcoma

Age and height: The risk of osteosarcoma is highest during the teenage growth spurts. Children with osteosarcoma are usually tall for their age. There may be a link between rapid bone growth and the risk of tumors forming. Osteosarcoma in older adults is often linked to a different cause, such as a long-standing bone disease. Gender: Osteosarcoma is more common in males than in females. Race/ethnicity: Osteosarcoma is slightly more common in African Americans than in whites.

Radiation to bones: Young people who were treated with radiation for an earlier cancer have a higher risk of getting osteosarcoma later. It is not clear if tests that such as x-rays, CT scans, and bone scans, raise the risk of osteosarcoma. The amount of radiation used for these tests is many times lower than that used for treatment. If there is any increased risk it is likely to be very small, but doctors try to limit the use of these types of tests in children whenever they can, just in case. Certain bone diseases: People with certain non-cancer bone diseases have an increased risk of getting osteosarcoma. Some of these diseases include Paget disease of bone and multiple hereditary osteochondromas. Certain cancer syndromes: Some people inherit gene changes from their parents that put them at increased risk for some types of cancer. People with certain rare, inherited cancer syndromes have an increased risk of getting osteosarcoma. One of these syndromes is Li-Fraumeni syndrome. When children with retinoblastoma (a rare eye cancer) are treated with radiation it raises the chance of osteosarcoma in the bones of the skull. There are several other rare syndromes that increase the risk of osteosarcoma in children. It is important to keep in mind that most people with osteosarcoma do not have any known risk factors. We do not know the cause of this cancer.

How is osteosarcoma found?

Most cases of osteosarcoma are found at an early stage, before they have clearly spread to other parts of the body. Symptoms like bone pain or swelling often cause a person (or a child's parents) to see a doctor. The sooner it is found, the better the chance of a cure. At this time there are no special tests to find osteosarcoma in people without symptoms. The best thing to do is to watch for any symptoms of this disease and see a doctor right away.

Signs and symptoms of osteosarcoma

Pain and swelling
Pain in a bone is the most common symptom of osteosarcoma. At first, the pain may come and go. It may be worse at night. The pain gets worse with activity and may cause a limp if the tumor is in a leg. Swelling in the area of the pain may not happen until weeks later. Depending on where the tumor is, you may be able to feel a lump. The cancer may weaken the bone it is in, but the bones usually do not break. Because limb pain or swelling is fairly common in normal, active children and teens it's easy to see why this cancer might not be found right away. These symptoms are less common in adults and should be a sign to see a doctor.

Bone fractures (breaks)

Although osteosarcoma may weaken the bone it develops in, the bones often do not break. People with a fracture next to or through an osteosarcoma often describe a limb that was sore for a few months and suddenly became very painful when the fracture occurred. If there are signs or symptoms that suggest a tumor, the doctor will want to take a complete medical history. A physical exam will be done to learn more about the tumor and other health problems. If the doctor thinks it may be osteosarcoma, more tests will be done, such as those listed below.

Imaging tests
Imaging tests are done to get pictures of the inside of the body to look for problems. These tests can be done to find the cancer, to figure out how far it has spread, to see how well treatment is working, or to see if the cancer has come back after treatment. Bone x-rays: Doctors can often spot osteosarcoma on a regular x-ray, but only a biopsy (see below) can show if cancer is really there. MRI (magnetic resonance imaging): MRI scans use radio waves and strong magnets instead of x-rays to make very detailed pictures. An MRI can help show if a bone tumor has grown into nearby areas. Sometimes the MRI can help find small tumors several inches away from the main tumor. Knowing how far the tumor has grown is important for planning the best type of surgery. An MRI scan may take up to an hour. You (or your child) have to lie on a table that slides inside a narrow tube, which can be upsetting. Newer, more open MRI machines can help with these feelings, but the test still means staying still for a long time. The machine also makes a thumping noise that you may find disturbing. Some places will give you headphones with music to block out the noise. Sometimes, younger children are given medicine to help keep them calm or even asleep during the test. CT (computed tomography) scans: In this test many x-rays of the body are taken from different angles. These images are combined by a computer to make cross-sectional pictures of your insides. A CT scan of the bone can show if the tumor has spread into nearby tissues like muscle or fat, although MRI is often better for this. A chest CT scan can show whether the cancer has spread to the lungs. Before the scan, you (or your child) may be asked to drink a liquid or have a contrast dye put into your vein. This helps better outline places in the body. The dye may cause some a feeling of warmth, especially in the face. Some people are allergic and get hives.

Rarely, problems like trouble breathing or low blood pressure can occur. Be sure to tell the doctor if you (or your child) have any allergies or have ever had problem with any contrast dye used for x-rays. CT scans take longer than normal x-rays, but not as long as MRIs. You (or your child) will need to lie still on a table while they are being done. During the test, the table slides in and out of the scanner, a ring-shaped machine that goes around the table. Some people feel a bit confined by the ring they have to lie in while the pictures are being taken. In some cases, children may be given medicine before the test to help stay calm and stay still while the scan is done. Spiral CT (also known as helical CT) is now used in many medical centers. This type of CT scan uses a faster machine that uses less radiation and gives more detailed pictures. Chest x-ray: An x-ray is sometimes done to see if the cancer has spread to the lungs. It can find larger tumors, but it is not as good as a CT scan for spotting smaller tumors. If a CT scan of the chest is done, a chest x-ray may not be needed. Bone scan: A bone scan can help show if a cancer has spread to other bones. This test is useful because it gives a picture of the whole skeleton at once. For a bone scan, a radioactive tracer is put into a vein and travels through the blood. Areas of damaged bone, such as tumors, absorb this tracer. You (or your child) then lie on a table for about 30 minutes while a special camera makes pictures of the bones that show the radioactive spots. Younger children may be given medicine to help keep them calm or even asleep during the test. A computer puts the pictures together showing the whole skeleton. Osteosarcoma will usually look like a darker spot in the bone, showing where there is more radioactivity. PET scan: For a PET scan, a form of sugar that contains a radioactive atom is put into the blood. The amount of radioactivity used is very low. Because cancer cells in the body are growing quickly, they take in a lot of the sugar. A special camera can then make a picture of places of radioactivity in the body. PET scans can be helpful in showing the spread of the cancer to the lungs, other bones, or other parts of the body. They are sometimes done at the same time as CT scans.

Biopsy
A biopsy involves taking a sample of the tumor to be looked at under a microscope. If the tumor is in a bone, it is very important that a surgeon experienced in treating bone tumors does the biopsy. When the biopsy is done right, it can prevent later problems and reduce the amount of surgery needed later on. The biopsy may be done after the area around the tumor is numbed or with the patient in a deep sleep (under general anesthesia). There are 2 different types of biopsies, the needle biopsy and the open (surgical) biopsy. A needle biopsy can be done with a thick or a thin (fine) needle. With the thick needle biopsy, the surgeon takes out a round core of tissue. The fine needle biopsy, which is not used much for bone tumors, removes very small pieces of tissue. In an open biopsy, the doctor cuts through the skin, exposes the tumor, and then cuts out a piece of it. This type of biopsy must be done by an expert in bone tumors.

Lab tests
Testing the biopsy samples
All biopsy samples are sent to a doctor with special training in lab tests (a pathologist) to be looked at under a microscope. Tests to find chromosome or gene changes in the tumor cells may also be done. These tests may help tell osteosarcoma from other cancers that look like it under the microscope. If an osteosarcoma is found, the doctor will give it a grade, which is a measure of how quickly the cancer is likely to grow and spread. Cancers that look somewhat like normal bone tissue are described as low grade, while those that look very different from normal cells are called high grade. For more on grading, see the section, "After the tests: Staging."

Blood tests
Blood tests are not used to find osteosarcoma, but they may be helpful later. For instance, high levels of certain chemicals in the blood can suggest that the osteosarcoma may be more advanced than it looks. Other tests are done before surgery and other treatments to get a sense of a person's overall health. These tests are also important to keep track of a person's health while getting chemo.

Staging of osteosarcoma
Staging is the process the doctor uses to find out if and how far the cancer has spread. The stage of the cancer is based on the results of physical exams, imaging tests, and any biopsies that have been done. The treatment and outlook for survival depend mostly on the stage of the cancer.

Localized or metastatic
As a rule, doctors divide osteosarcomas into 2 groups when deciding on the best course of treatment localized ormetastatic. A localized osteosarcoma affects only the bone it started in and maybe the tissues next to the bone, such as muscles and tendons. But even when tests do not show that the cancer has spread to distant places, most patients are likely to have very small areas of cancer spread that can't be found with tests. This is why chemotherapy ("chemo") is an important part of treatment for most patients. A metastatic osteosarcoma has clearly spread to other parts of the body not directly connected to the bone the tumor started in. Most often the spread is to the lungs, but it can also spread to other bones, the brain, or other organs. Patients with metastases (mets) at the time the cancer is found have a worse outlook, although some can be cured if the mets can be removed by surgery. The cure rate for these patients is much better if chemo is also given.

Musculoskeletal Tumor Society (MSTS) staging system

This system is a more detailed way to stage osteosarcoma. It is also known as the Enneking system. It takes into account the grade of the tumor, if the tumor has grown outside of the bone, and whether the cancer has spread to nearby lymph nodes or other organs. The grade is found by looking at the cancer cells under a microscope and is used to predict how likely the cancer is to grow and spread. These factors are combined to give an overall stage, expressed in Roman numerals from I to III (1 to 3). Some of these stages are further divided into A or B. As a rule, the higher the number, the more serious the cancer.

AJCC staging system

A second staging system, the AJCC system (American Joint Commission on Cancer), divides osteosarcoma into 4 stages using Roman numerals I to IV (1 to 4). Again, the higher the number, the more advanced the cancer. Ask your doctor to explain the stage of your (or your child's) cancer to you in terms you can understand.

TREATMENT:

Surgery for osteosarcoma

Surgery for this type of cancer includes both the biopsy to confirm the cancer and the surgery to take out the tumor(s). When possible, it is very important that the biopsy and surgical treatment be planned together, and that the same orthopedic surgeon at a cancer center does both the biopsy and the surgical treatment. The main goal of surgery is to remove all of the cancer. If even a few cancer cells are left behind, they can grow and make a new tumor. To try to be sure that this doesn't happen, surgeons remove the tumor plus some of the normal tissue around it. This is known as wide excision. Taking out some normal-looking tissue raises the chance that all of the cancer has been removed. The type of surgery done depends on the place of the tumor. Some tumors are much harder to treat. These include tumors at the base of the skull, or in the spine or hip bone (pelvis).

Tumors in the arms or legs

Surgery can be either the kind that saves the arm or leg (limb-sparing) or removes the cancer and all or part of an arm or leg (amputation). Limb-sparing surgery (limb-salvage surgery): Most patients with tumors in the arms or legs can have limb-sparing surgery, but this depends on where the tumor is and how big it is. This type of surgery is very complex and should be done by a doctor with special skill and experience. The challenge for the surgeon is to remove all of the tumor while saving the nearby tendons, nerves, and blood vessels. The part of the bone that is removed is replaced with a bone graft (piece of bone from a different part of the body or from another person) or with a device made of metal or other materials. Some metal rods are designed to grow with the child and can be made longer without any extra surgery. They have tiny devices in them that can lengthen the "bone" whenever needed to make room for a child's growth. But even these may need to be replaced with something stronger once the child's body stops growing.

More surgery may be needed during the years after the first operation, and some patients might still need an amputation later on. There can be a danger of infection, and grafts or rods can become loose or break. It takes about a year, on average, for patients to learn to walk again after this surgery on a leg. If the person does not keep up with rehabilitation, the arm or leg may become useless. Amputation: If there is a large tumor that involves the nerves or the blood vessels, an amputation might be the best choice. Surgery is planned so that muscles and the skin will form a cuff around the end of the remaining arm or leg bone. This cuff will fit into an artificial limb (prosthesis). With physical therapy, the patient is often walking within 3-6 months after a leg amputation. Reconstructive surgery: Sometimes, if the bone has to be removed in the middle of the thigh, the lower leg and foot is turned and attached to the thigh bone. The ankle now functions as a knee joint. Of course, the person will need an artificial leg to make the leg long enough. If the cancer is in the upper arm, the tumor may be removed and the lower arm reattached. Then the person will have a working, but shorter, arm. Rehabilitation after surgery: This might turn out to be the hardest part of all. Patients (and the parents, if the patient is a child) should meet with a rehabilitation expert before surgery to learn what needs to be done. If a limb has been removed, they must learn how to deal with the artificial limb. This can be hard for growing children when the artificial limb needs to be changed to keep up with their growth. If limb-sparing surgery is done, the situation is even more complex. Further operations might be needed to replace the metal rod with one more suited to their growing body size. Each of these surgeries has problems as well as benefits. People with amputations can often actually be more physically active, as the artificial limb may be able to take more physical stress than one with a bone graft or metal rod. It turns out that there is little difference in the approaches in terms of how people react and quality of life. Often the biggest problem has been for teens who fear the social effects of their operation. These feelings and concerns are very important, and support and encouragement are needed for all patients. (Please see the section, "What happens after treatment for osteosarcoma?").

Tumors that start in other places

Pelvic tumors can often be hard to remove with surgery. But if the tumor responds well to chemo first, then surgery (sometimes followed by radiation treatment) may get rid of all of the cancer. Pelvic bones can often be reconstructed after surgery. For a tumor in the lower jaw bone, the whole lower half of the jaw may be removed and later replaced with bones from other parts of the body. If the surgeon can't remove all of the tumor, radiation treatment may be used as well. For tumors in areas like the spine or the skull, it may not be possible to remove all of the tumor safely. Cancers in these bones may need a combination of treatments like chemo, surgery, and radiation.

Surgery for metastases

If the osteosarcoma has spread to other parts of the body, these tumors need to be removed for there to be a chance of curing the cancer Surgery to remove cancer that has spread to the lungs must be planned very carefully. The doctor must have a plan in case there are more tumors than the CT scan showed. There could be some areas of spread that cannot be removed because they are too big or are too close to structures in the chest, such as large blood vessels. Also, some patients may not be healthy enough to go through such surgery. A small number of osteosarcomas spread to other bones or to the kidneys, liver, or brain. Whether or not these tumors can be removed with surgery depends on their size, place, and other factors.

Chemotherapy for osteosarcoma

Chemotherapy (chemo) is the use of drugs to kill cancer cells. Most often the drugs are given into a vein. Once the drugs enter the bloodstream, they go throughout the body, which makes this a useful treatment for osteosarcoma that has spread to the lungs or other organs, or is likely to do so. Doctors give chemo in cycles, with each round of treatment followed by a rest to allow the body time to recover. Each chemo cycle lasts for a few weeks. Chemo is part of the treatment for most osteosarcomas, although some patients with low-grade osteosarcoma may not need it. Often, chemo is given both before (for about 10 weeks) and after surgery for up to a year. Most of the time 2 or 3 drugs are given together.

Side effects of chemo

Chemo kills cancer cells, but it also harms some normal cells. Side effects from chemo will depend on the type of drugs given, the amount taken, and how long treatment lasts. Side effects could include:

Nausea and vomiting Loss of appetite Hair loss (the hair grows back after treatment ends) Mouth sores Increased chance of infection (caused by a shortage of white blood cells) Bleeding or bruising after small cut or injuries (from a shortage of platelets) Tiredness or shortness of breath (from a shortage of red blood cells) Children seem to do better than adults when it comes to chemo. They tend to have less severe side effects and to get over side effects faster. Because of this, doctors can give them higher doses of chemo to try to kill the cancer. Rarely, chemo may cause a second type of cancer (such as leukemia) years after the osteosarcoma is cured. But the need for chemo in treating osteosarcoma far outweighs this risk. Some side effects, such as damage to the heart and not being able to have children (infertility), happen with certain drugs. Serious side effects are rare, but they do happen. Side effects can often be prevented or controlled. Anyone who has problems with side effects should talk with their doctor or nurse about them. Some of these long-term effects are described in the section, "Moving on after treatment" Tests to check for side effects of chemo: Before giving chemo, the doctor will check your (or your child's) lab results to be sure the liver, kidneys, and bone marrow (which makes blood cells) are working well. The complete blood count (CBC) includes counts of white blood cells, red blood cells, and blood platelets. White blood cells fight infections, so it is important to know the white blood cell count before chemo starts. Platelets are small cells that plug up holes in blood vessels and stop bleeding. Red blood cells carry oxygen from the lungs to the rest of the body. Routine blood chemistry panels measure certain blood chemicals that tell doctors how well the liver and the kidneys are working. A test may be done to check the patient's hearing, which can be affected by certain chemo drugs.

Radiation treatment for osteosarcoma

Radiation therapy is treatment with high-energy rays to kill cancer cells. For the most part, radiation is not often used to treat osteosarcoma. Sometimes, though, it may be useful when the tumor cannot be completely removed by surgery. It can also help control symptoms like pain and swelling if the cancer has come back and surgery cannot be done.

What`s new in osteosarcoma research?

Research on the causes and treatment of this cancer is now being done at many medical centers across the nation. Researchers are making progress in learning about the causes of osteosarcoma and the DNA changes that cause this cancer. This knowledge could lead to treatments to correct these changes.

Treatment
Surgery
Doctors now know much more about the growth and spread of osteosarcomas than they did in the past. This, along with newer imaging tests, allows them to plan surgeries that remove the cancer while leaving as much normal tissue as they can. Some newer, man-made devices used to replace pieces of bone (internal prostheses) can now be made longer without the need for further 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.

Chemotherapy
Clinical trials are being done to figure out the best combinations of chemo drugs, as well as the best time to give them. Newer chemo drugs are being studied, too. 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. Early results have shown promise.

Other new forms of treatment

Clinical trials are looking into ways to help the patient's immune system recognize and attack the osteosarcoma cells. A new drug called muramyl tripeptide (MTP) has been shown to help some patients when added to chemo. Doctors are also looking at new medicines that are aimed at certain molecules on the cancer cells. These are known as targeted therapies. Some of these are man-made versions of immune system proteins called monoclonal antibodies. Other drugs that target the bone cells called osteoclasts may also be useful against osteosarcoma. Bisphosphonates are a group of drugs that are already used to treat bone thinning and certain cancers that have spread to the bone. Some of these drugs, as well as others, are now being studied for use in patients with osteosarcoma.

Osteosarcoma

Type of bone cancer that develops in the cells (forms the outer covering of the bone). Most common and fatal in children and males between 10-25 years old.

5% of all childhood cancers. Common sites: long bones, knee, upper leg, thigh bone, lower leg and upper arm. Etiology Causes: Unknown DNA mutation either inherited or acquired after birth. Familial susceptibility Injury

Infection Metabolic or hormonal disturbance Risk Factors: Children Teenage growth spurt Tall for the age Previous treatment with radiation Benign and non-cancerous bone tumors

Retinoblastoma Adult High fat diet Lack of exercise

Smoking Drinking alcohol Pathophysiology Osteoblast DNA mutation Malignant osteoblast (abnormal) Proliferation of abnormal osteoblast Formation of osteoid or immature bone

1. 2. 3. 4. 5.

6. Signs and symptoms are then observed such as pain, swelling, and tenderness. Assessment 1. 2. 3. 4. Encourage patient to discuss problem and course of symptoms. Note patient and familys understanding of the disease, coping with the problem andmanagement of pain. Palpate mass gently on physical examination. Note size and associated soft-tissue swelling, pain and tenderness of the mass.

5. Assess neuromascular status and range of motion extremity. 6. Evaluate motility and ability to perform activities of daily living. Diagnostic Procedures

X-ray

MRI CT scan Biopsy CBC Blood chemistry

Urine analysis Sternal marrow puncture Nursing Diagnosis Acute or chronic pain Risk for injury: pathologic fracture related to tumor Ineffective coping

Activity intolerance Nursing Intervention Provide quiet environment and calm activities to prevent or lessen pain. Provide comfort measure such as back rub, change position and use of heat or cold application. Encourage diversional activities Administer analgesics as indicated to maximal dose as needed. Encourage the patient to increase fluid intake. Encourage rest periods to prevent fatigue. Provide accurate information about the situation, medication and treatment. Assess muscle strength, gross and fine motor coordination.

1. 2. 3. 4. 5. 6. 7. 8.

9. Provide pillows for cushion and support. 10. Keep side rails up all the time. Complications

Alopecia Reduction in number of leucocytes and platelets Septicemia Bleeding Anemia Kidney damage Hearing loss