Osteosarcoma is the most common type of cancer that originates in bone. (Most bone cancer develops from cancerous cells that have migrated from a tumor in another organ referred to as the primary site). It may also be called osteogenic sarcoma or primary bone cancer.
Description
Osteosarcomas make up about 65% of primary bone cancers and account for about 10% of all childhood cancers. Tumors around the knee (most often just above it) account for almost 75% of osteosarcomas; tumors in the long bone of the upper arm are also relatively common. Osteosarcoma, less commonly, can occur in the back, the skull, and the ribs. In rare instances, it can occur in other bones of the body.
Osteosarcoma is a very aggressive cancer; approximately 90% of all cases are highly malignant. There are several subtypes of osteosarcoma, and some are slightly less aggressive. One rare subtype, called multifocal osteosarcoma, presents with several bony tumors simultaneously; this subtype is very aggressive and has a poor survival rate.
Demographics
About 5.6 new cases of osteosarcoma per million people are reported in the United States every year. It is more common in males than in females. It is far more common in adolescents and young adults (ages 10-25) than in children or older adults. The average age of the osteosarcoma patient is 15 years old, and is very rare after the age of 40. However, osteosarcoma of the jaw, which is rare, is most common in men between the ages of 20 and 40.
Causes and symptoms
All cancers are caused when a mutation occurs in a gene that is involved in the control of cell division. This mutation can occur during normal DNA reproduction and be inherited by future generations, or it can be caused by a virus, radiation, or a chemical carcinogen to which a person is exposed.
In most cases, the cause of osteosarcoma is not known. The fact that it occurs primarily in the area where bone growth takes place has led scientists to hypothesize that osteosarcoma originates where mutations occur in rapidly dividing bone. This is supported by the fact that it is more common in boys than in girls, more common in the bones that grow the fastest, and more common in taller children. The cancer begins in the areas where bone cells are dividing, then spreads out to the surface of the bone. Eventually the cancer grows through the tough outer membrane that covers the bone, then grows into surrounding soft tissue.
For some cases of osteosarcoma, a definite cause can be identified. Some cases appear to be genetically related; there is a strong association of osteosarcoma with hereditary retinoblastoma patients and with LiFraumeni syndrome patients in whom the genetic sequence of a particular gene (p53) has been rearranged. It has been demonstrated that there is an increased risk of osteosarcoma in adults who had survived nuclear accidents, received radiation therapy, or received cyclophosphamidechemotherapy for acute lymphoblastic leukemia as children. In the elderly, osteosarcoma is found in increased incidence in patients with Paget's disease. Contrary to popular belief, osteosarcoma is not caused by a traumatic injury.
The most common symptom of osteosarcoma is a swelling around a bone. Initially the swelling is painless, but as the swelling increases, typically it will become painful and may be warm to the touch. The pain may initially be thought to be the result of an injury, but will persist, and may remain constant at rest. By the time a patient seeks medical help, the pain has often been present for several months, initially mild and transient, but becoming more persistent and severe. The pain is most often described as a deep, dull, aching pain which becomes more severe at night, and is often made worse by standing or moving. In advanced stages, pain may be accompanied by weight loss and fever.
Diagnosis
Diagnosis of osteosarcoma is sometimes difficult, as it can easily be confused with infections, injuries, arthritis, or vitamin deficiencies. When an osteosarcoma is suspected, physicians will typically first obtain a set of x rays of the affected area, which can indicate whether or not a tumor is present. If a tumor is identified, the physician will obtain a biopsy of the tumor (surgically remove a small piece and examine it under microscope for the presence of cancerous cells) for a definite diagnosis of osteosarcoma. In addition, blood tests are often done to measure two substances which may be found in the blood of osteosarcoma patients in greater amounts. Levels of alkaline phosphatase (an enzyme associated with bone growth) are elevated in up to 60% of patients with osteosarcomas; lactic dehydrogenase (an enzyme found commonly in many body tissues that becomes elevated when tissues are injured) is found in greater amounts in about 30% of patients with osteosarcomas.
When an osteosarcoma is diagnosed, surgeons will often also have a patient undergo a bone scan or an MRI (magnetic resonance imaging). MRIs can show the physician how much the tumor has invaded surrounding muscle, fat, joint, and neurovascular tissues. A bone scan will show other areas of bone that may have developed cancerous lesions. In addition, in order to determine if the cancer has spread anywhere else in the body, doctors will order chest x rays or CT (computed tomography) scans.
Treatment team
As the understanding of cancer grows and new treatment approaches are developed, the complexity of cancer treatment also increases. Today, a multidisciplinary approach to cancer treatment is considered necessary for effective patient care. Professionals involved in the treatment of an osteosarcoma will typically include the referring physician, an orthopedic oncologist, a pathologist, and several nurses. If radiation therapy is indicated, a radiation oncologist, radiation therapist, radiation nurse, radiation physicist, and a dosimetrist will also be involved. Treatment may also include a psychologist, nutritionist, social worker, and chaplain. For osteosarcomas, a reconstructive or plastic surgeon may be necessary for optimum cosmetic results after removal of a tumor, and a physical and/or occupational therapist will probably help the patient regain full use of the limb. If amputation is necessary, specialists in prosthetic fitting and design will be necessary as well.
Clinical staging, treatments, and prognosis
When a cancer develops, the original tumor can spread, usually through the blood or lymph system, to other parts of the body. Common places that secondary cancers may appear are the lungs, the liver, other bones, and muscles and tendons.
One of the foremost goals of a doctor's assessment of a cancer patient is to determine how far the cancer has already spread and how likely it is to spread further, both of which are key factors in the likelihood that the patient will be cured. The assessment of how far the cancer has already spread is called staging, and the assessment of how likely the cancer is to spread further (determined by the types of cells found in the tumor on biopsy) is known as grading.
No staging systems have been commonly accepted for osteosarcomas. Tumor grade is considered the most important factor in predicting prognosis for osteosarcoma. Grading, however, is controversial. This is because osteosarcoma tumors often contain many different types of cells, and because osteosarcomas tend to behave similarly regardless of the types of cells identified. An experienced oncologist will often take into account the types of cells in the tumor, how the tumor has grown and responded to previous attempts at treatment, and how the tumor looks on x ray, in order to make the most accurate prognosis. Although an officially accepted staging system has not been established, a TNM system is most commonly used: T refers to the size of the tumor, N refers to lymph nodes, and M refers to whether the tumor has metastasized. The cancer is given various numbered ratings in each letter category, and these are used to create a stage value. Generally, tumors with little or no invasion of local tissues are described as Stage I or Stage II. Tumors that have extensive local invasion or that have spread to the lymph nodes are usually described as Stage III, and any tumors that have metastasized are considered Stage IV. Metastases typically occur in the lungs or in other bones.
Treatment of osteosarcoma is typically a combination of surgical removal of the tumor and chemotherapy. If the cancer is more advanced, physicians may precede surgery with one course of chemotherapy and follow surgery with another course. Chemotherapy consists of a combination of drugs (chemotherapy drugs are used in combinations in order to provide for maximum killing of cancerous cells); chemotherapy for osteosarcoma usually includes methotrexate, adriamycin (doxorubicin), platinum, and/or ifosfamide. Patients with a very advanced cancer or cancer that recurs should consider enrolling in a clinical trial.
Radiation therapy is not usually used in treatment of osteosarcoma, but may be employed if the tumor occurs in an area (like the spine) where surgical removal would be impossible. In that case, radiation therapy would typically be followed by chemotherapy.
Historically, most patients with osteosarcoma could expect to have the cancerous limb amputated, but with better imaging techniques like MRI and CT scans, surgeons can better determine how much tissue needs to be removed. Also, the use of chemotherapy both before and after surgery increases the numbers of patients who can avoid amputation. Limb-sparing surgery (also called limb salvage), which can be performed as long as the cancer has not invaded the adjacent blood vessels and nerves, involves removal of only the affected bone and replacement of the bone with a bone graft or prosthetic bone. If amputation is necessary, treatment will include a prosthetic limb that has been fitted for the patient, as well as rehabilitative therapy in learning to use it.
Approximately 80% of osteosarcomas spread to the lungs or other bones before the disease is diagnosed by a doctor. Osteosarcoma is a highly aggressive disease, but with treatment approaches that combine surgical removal of the tumor with chemotherapy before and/or after surgery, up to 80% of osteosarcoma patients are alive 10 years after treatment. Recurrence after three years is rare.
The chance of cure depends on types of cells which make up the tumor, the location in which it occurs (arms and legs have a better prognosis than spine or skull), the stage at which it is discovered, how long the patient has had symptoms, and the age and general health of the patient. The size and volume of the tumor, whether or not it has recurred locally, and how it has responded to any previous treatment are also important factors.
Alternative and complementary therapies
Alternative therapies are nontraditional treatments that are chosen instead of traditional treatments in an attempt to cure the disease. Alternative therapies have typically not been proven to be effective in clinical trials
the way that traditional treatments are evaluated. Numerous alternative therapies exist in cancer treatment. Laetrile, a product of apricot seeds, is probably one of the most well known. Laetrile contains a form of cyanide that may be released by tumor enzymes and may then act to kill cancerous cells, but it has not shown any anti-cancer effectiveness in NCI clinical trials. It is not approved for use in the United States but is available in Mexico. When taken by mouth, laetrile can produce side effects resembling the symptoms of cyanide poisoning. Vitamins and other nutritional elements like vitamins A, C, and E, and selenium are thought to act as antioxidants. Vitamin E, melatonin, aloe vera, and a compound called beta-1, 3-glucan are reported to stimulate the immune system. Natural substances like garlic, ginger, and shark cartilage are also believed by some to shrink tumors, with less defined modes of action. Alternative therapies must be monitored especially carefully with children, and all therapies must be discussed with the treatment team.
Antineoplastons are believed by some to be another alternative approach to a cancer cure. Antineoplastons are small proteins which may act as molecular messengers and which may be absent from the urine and blood of many cancer patients. Proponents believe that replacing these may have beneficial effects. The FDA and National Cancer Institute (NCI) have permitted clinical trials of antineoplastons in cancer patients. However, the clinical trials were closed in 1995 because of small enrollment numbers in the trials and lack of consensus about how to recruit more patients for the trials. Because of the small numbers in the trials, the NCI draws no conclusions about the effectiveness of antineoplastons.
Complementary therapies are meant to supplement traditional therapies and usually have the objective of relieving symptoms or helping cancer patients cope with the disease or traditional treatments. Common complementary therapies that may be employed by patients with osteosarcoma are aromatherapy, art therapy, massage, meditation, music therapy, prayer, tai chi, and yoga or other forms of exercise, which can reduce anxiety and increase a patient's feeling of well-being.
Coping with cancer treatment
Treatment of osteosarcomas commonly includes surgery, radiation therapy, and chemotherapy. Although the use of chemotherapy and radiation therapy in addition to surgery has improved the chance of survival for osteosarcoma patients, both of these treatments unavoidably result in damage to some healthy tissues and other undesirable side effects.
Fatigue is a common side effect of both radiation therapy and chemotherapy. Side effects of the actual treatment combines with the natural depletion of the body's resources as it fights off the disease (as well as normal psychological consequences of the disease, such as depression) to make coping with fatigue a very significant aspect of dealing with cancer treatment. The best way to deal with these symptoms is to cut back on activities and allow plenty of time for resting to allow the body to heal. It is also important to maintain a well-balanced, nutritious diet. Patients should avoid stress as much as possible and should limit visitors, if needed, to avoid being overtired. At the same time, it is also important for the psychological health of the patient to pursue their interests as much as possible and to avoid becoming isolated.
The biggest problem for those undergoing radiation therapy is the development of dry, sore, "burned" skin in the area being treated (radiation does not cause pain or burning sensations during treatment). Skin in the treatment area may become red, become itchy and sore, and may blister and peel. Patients with fair skin or those who
have undergone previous chemotherapy have a greater risk of more serious reactions. Dry, itchy, or sore skin is temporary, but affected skin may be more sensitive to sun exposure for the rest of the patient's lifetime, so a good sunscreen should be used whenever affected skin is exposed to sunlight.
Some of the more common side effects of chemotherapy include hair loss (alopecia), and nausea and vomiting. Hair loss is a difficult part of dealing with cancer treatment for most patients, especially women. Hair may thin out gradually, or it may fall out in big clumps. To slow down the rate of hair loss, avoid any unnecessary sources of damage to the hair, like curling, blow-drying, or chemical treatments.
Different patients choose different ways of coping with the loss of their hair. Some patients may find they are more comfortable hiding hair loss with a wig; it is a good idea to cut off a lock of hair before hair loss begins in case a wig is later desired. Some patients may choose to remain bald, or may want to choose hats or scarves instead of wigs. In any case, it is important to remember that the loss of hair is a sign that the medication is doing its job, and that hair loss is temporary. Hair usually begins regrowth within a few months of the end of intensive chemotherapy, although it may return in a different color or texture than the original hair.
Nausea and vomiting are also fairly common side effects of many chemotherapy drugs (radiation therapy can cause nausea as well). After a few courses of chemotherapy drugs, some patients may experience anticipatory nausea, which can be triggered by thinking about an upcoming treatment or recognizing hospital smells. Drugs that combat nausea and vomiting (antiemetics) can be prescribed, but are often not effective for anticipatory nausea. However, if nausea and vomiting are a problem, heavy, regular meals should be avoided in favor of small, frequent snacks made up of light but nourishing foods like soup. Avoiding food odors and other strong smells may be of help.
Desensitization, hypnosis, guided imagery, and relaxation techniques may be used if nausea and vomiting are severe. These techniques help to identify the things that trigger the nausea and vomiting, decrease patient anxiety, and distract the patient from thinking about getting sick. Acupressure bands, commonly used for seasickness, have also been helpful for some patients, as has acupuncture.
Both radiation therapy and chemotherapy treatments require a substantial level of commitment from the patient in terms of time and emotional energy. Fear and anxiety are major factors in coping with these cancer treatments and with cancer in general. Some patients find that concentrating on restful, pleasurable activities like hobbies, prayer, or meditation is helpful in decreasing negative emotions. It is also very important that patients have people to whom they can express their fears and other negative emotions. If friends or family members are unable to provide this to patients, support groups may be able to provide an environment where fears can be freely expressed and understood.
Clinical trials
Clinical trials are studies in which new treatments for disease are evaluated in human patients. Current clinical trials for osteosarcoma are evaluating new combinations of chemotherapy. Trials on the combination of chemotherapy with replacement of the patient's blood-producing cells after therapy—called autologous stem cell tranplantation—are done because chemotherapy often destroys many of the patient's immune system cells. Some studies are evaluating evolving therapies like antibodies directed towards specific tumors, or cancer "vaccines." The National Cancer Institute (<http://www.nci.nih.gov>) has information about specific clinical trials that are looking for osteosarcoma patients.
Prevention
Since the known risk factors for osteosarcoma (e.g. height, experiencing rapid growth spurts, having other genetic diseases, or surviving a nuclear accident) are unavoidable, there are currently no ways to prevent osteosarcoma. However, it is important to note that in a healthy body (although mistakes in genetic material happen frequently), most mutations do not result in cancer. This is because a healthy body repairs mistakes and destroys cancers before they take hold. In general, therefore, a healthy lifestyle that includes exercise, plenty of sleep, a diet rich in fruits and vegetables, regular health screenings and the avoidance of stress, excessive sun exposure, tobacco use or excessive alcohol consumption will help to prevent most cancers.
Special concerns
An important aspect of coping with osteosarcoma is the potential need for amputation, especially in a young person. Amputation is often an experience similar to bereavement; the patient has lost the body that was whole and is forced to make emotional adjustments to the permanency of the change and the ramifications it has for future activities and social interactions. Patients may initially feel numb, then experience intense, overwhelming feelings of sadness, fear, and anger. The period characterized by intense, almost unbearable emotions is usually followed by a period of time when the patient feels completely empty, fatigued, and apathetic. Given time, most patients will come to an acceptance of their new reality and begin to enjoy old friends and activities again. It is important not to expect patients in such circumstances to accept their situation immediately or to suppress the natural emotions that accompany the change. Patients can ease the process by trying to focus on one day at a time and by finding others who can help them work through the process by listening and accepting their emotions. It is very important that a patient dealing with changes from amputation have friends or family members to whom they can express their feelings of grief and anger. A support group may be beneficial.
The adoption of a prosthetic limb requires a substantial commitment of emotional energy in learning to use a prosthesis effectively, and requires a level of responsibility with regard to stump care that may be challenging for young patients. In addition, phantom pain in the limb and stump pain may present obstacles to success with the prosthesis. It is important, however, for problems be worked through until success with the prosthetic limb is achieved, since patients who fail due to "poor fit" are very likely to never succeed at fitting a limb, since the underlying problem is a failure to cope with the amputation itself.
Resources
BOOKS
Cook, Allan R., ed. The New Cancer Sourcebook. New York:Omnigraphics, Inc., 1996.
Pizzo, Philip, and David Poplack, ed. Principles and Practice of Pediatric Oncology. Philadelphia:Lippincott-Raven, 1997.
Buckman, R. What You Really Need to Know About Cancer. Baltimore: Johns Hopkins University Press, 1999.
Pinkerton, C. R., and Plowman, P. W., ed. Paediatric Oncology. Chapman and Hall Medical, 1998.
ORGANIZATIONS
American Cancer Society. 1599 Clifton Rd. NE, Atlanta, GA 30329-4251. (800) 586-4872. <http://www.cancer.org>.
