General Information About Normal Bone

The bone is actually an organ system, meaning that it is made up of various tissues, which are in turn made up of specific cells. The bone system functions at two levels, one for structural support of the body (so we don't collapse) and one for the manufacture of blood cells within the "marrow space of the bone. There are specific cells that contribute to each of these two functions. In childhood the outer bone, called the "cortex," is made up of soft cartilage, which in turn is laid down by cartilage-forming cells called "chondroblasts." Gradually, as we mature, the cartilage is calcified into hard bone by cells called gosteoblasts."

Initially, the calcium is laid down in a rather haphazard pattern, so the bone does not have it's optimal strength. A secondary "restructuring" of bone occurs through puberty and young adulthood, where the initial calcified bone is re-absoted cells called "osteoclasts." The restructured bone is then laid down by osteoblasts in "Haversian Canals" which are cylindrical, run along the long axis of the bone, and resemble cement rods. These "canals" have a central blood vessel (bone is living tissue that needs blood for survival).

There are two basic types of bone in the body: flat bone and long long. Flat bones include those in the skull, vertebrae and ribs, while long bones are found in the extremities. The central skeleton contains the flat bones, and is called the 'axial" skeleton; the limbs contain the long bones which are called the "appendicular" skeleton.

While the outer shell, or "Otable" of each bone is the hard cortex, the inside of both flat and long bones is made of up the soft "marrow." The marrow is basically little spicules of bone with blood forming cells clinging to them, so it is very rich in blood. The marrow contains "stem cells," which are the 'precursor (first) blood cells from which all others arise. The cortex of the bone has nerves traveling through it, accounting for bone pain when the bone is injured. When a bone fractures, it forms a hard "callous" around the break, and amazingly this is even stroqger than the bone before breakage!

A balance is kept between the free calcium in the blood and the calcium in bone by hormones. If the blood calcium is too low, then some is reabsorbed from bone through the action of "parathyroid hormone" (PTH), produced by small glands in the thyroid. If the blood calcium is too high, it is deposited into bone by the hormone "Ocalcitonin," also from the thyroid. The laying down of calcium in bone also requires active vitamin D, and a shortage of this during childhood results in "rickets." Vitamin D is converted from its dietary to active form by sunlight, but only requires a very brief exposure. There is a balance between phosphorus and calcium in the blood: when one goes up the other goes down. People with kidney failure, on dialysis, have a difficult time clearing their blood of phosphorus, and this results in calcium being leached out of bone. Too much phosphoric acid in the diet, from soda-pop, can also weaken bone. In women, the deposition of calcium into bone requires estrogen. calcium and exercise. and if lacking these women tend to get "osteoporesis" (brittle bones) after menopause.

What is Bone Cancer?

Normally, the cells informing the bone cortex divide very rapidly from womb life through puberty, and then slow down dramatically during adult life. The major growth occurs at the ends of the long bones, called the "epiphysis": where initially new cartilage grows: this is gradually calcified by osteoblasts into hard bone. If the "epiphyseal plate" is damaged in childhood, by injury or medication, this will stunt that bone's growth. The long shaft of a bone is called the "diaphysis', and the area between the epiphysis and diaphysis is called the "metaphysis." These areas are important to know since particular bone tumors have a predilection to arise in particular areas of the bone, as will be seen. The cells inside the bone marrow, which form the blood cells, must continue to divide very rapidly throughout life, since white blood cells may normally live as little as 10 hours. The types of cancer that arise from these are lymphomas, leukemias, and myelomas, are are NOT considered primary bone cancer; they are different topics.

The control of new bone formation is by the "genes," sequences of DNA which are themselves packed into larger chromosomes in each cell. If there is damage to the genes. a given cell may start dividing out of control. Bone cancer starts in just one cell. This cell starts dividing in a haphazard manner, eventually forming a clump called a "tumor." A tumor simply means a swelling; it can be caused by infection or cancer or injury. If a tumor only grows in it's local area, and does not have the capacity to spread distantly, it is called "benign" and is not cancer. If, however, a tumor has the capability to spread distantly to other organs, it is called "malignant" and this is cancer. The actual process of cancer spread is called "metastasis," and may occur to any place in the body. Sometimes, a tumor in bone may start as benign, but further DNA damage can cause it to become malignant; this process is called "malignant degeneration." Cancer kills by anemia. infection and debility, and by spreading to and interfering with the function of critical body areas, such as the lung and brain. Any cancer that is not successfully treated will eventually lead to the patient's demise, but this may be a very rapid (weeks) or very slow (many years) process. Also, for bone some tumors have a varying degree of aggressiveness, and the same type of tumor (i.e. Giant Cell Tumor) may range from indolent to aggressive in different patients. Thus, even true bone cancers may be classed as merely "bone tumors," which doesn't say if it is a true cancer or not. Ar, essential of the evaluation is to try to detemine how aggressive. or "malignant," the tumor is.

It is important to note that this transcript discusses PRIMARY bone cancers, which means those that arise in the cortex of the bone. Cancers originating in other areas may have a strong predilection to spread to bone. such as prostate, lung and breast cancer. The treatment for these when they have metastasized to bone is discussed under the transcripts dealing with those particular cancers. Also, some cancers arise from cells which normally live in bone, such as lymphomas, myelomas, plasmacytomas. and leukemias from the blood cells within the bone marrow. These are also discussed in their own transcripts, as they are not primary bone cancers.

How Common Is Bone Cancer?

There are about 500 new cases of primary bone cancer each year in the U.S.A, making this a rare cancer. Bone cancers represent 3% of childhood cancers with about 200 new cases per year. The majority of cases are in the second decade (during adolescence), but there is a second peak in the 6th decade. About 3 per 100.000 people will ever develop a primary bone cancer. In children under 10 years old, only 20% of bone tumors are malignant. However, in adults malignant bone tumors are twice as common as benign bone tumors. Recall that most malignant tumors found in bone have spread there from another organ, and so are not primary bone cancer.

What are the Common Types of Bone Cancer?

If multiple myetoma is considered a primary bone tumor (even though it arises in the marrow and not the cortex) then it represents 40% of bone tumors. Classically, the major common types of bone cancer are "Chondrosarcoma" (arising from cartilage), "Osteosarcoma" (arising from bone), "Fibrosarcoma" (arising from scar tissue), "Liposarcoma" (arising from fat), "Ewing's Sarcoma" (from primitive cells) and the increasingly popular "Malignant Fibrous Histiocytoma" (MFH) of disputed origin. Rare types exist, like "Hemangiopericytoma" from blood vessels within the bone, "Malignant Giant Cell Tumor," and "Adamantinoma" (from enamel in teeth). It is important to note that sub-varieties of the above types exist, and there may be a mixture of elements in a given tumor. Primary examples of this are "osteochandrosarcoma" which is made of up both bone and cartilage, and 'fibrochondrosarcoma" made up of both fibrous tissue and cartilage. Another crucial thing to know is that there has been a gradual "reclassification" of bone cancers, so that MFH, which was once a rare diagnosis, is now the most common in many series! Also. various pathologists (doctors who make diagnosis from tissue samples) may give different diagnosis from examining the same bone tumor under the microscope! In fact. there is as much as a 20% disagreement by even expert pathologists when classifying biopsies (samples) of bone tumors from the same patient.

What Causes, or Increases the Risk for Bone Cancer?

The exact reason why one person get's a bone cancer and another does not is unknown. However, "risk factors" have been found that are associated with a greater chance for getting particular bone cancers. Some of these are noted below for the major types of bone cancer:

-Osteosarcoma represents 20% of all bone cancers, with 85% occurring before age 35. 60% occur during adolescence. Males are more likely to be affected than females, with a ratio of 3:2, but under age 15 the ratio is equal. A smaller . peak" of osteosarcoma is noted in the 6th to 7th decades, where it tends to arise from Paget's disease of bone. bone scars or in areas of prior treatment with radiation therapy.

For Osteosarcoma things noted to increase risk include:

Genetic: Patients with the eye disease "retinoblastoma" have a gene alteration (13q) that raises the chance for osteosarcoma by 500 fold.

Constitutional: With unusually active bone growth, the risk increases. This is thought why the disease is more common in males after age 15. Large dcgs like Great Danes have a 13 times higher risk, as well as very tall people. Also, it can arise from "malignant degeneration" of a previously benign bone tumor. Environmental: Local high dose irradiation increases the risk, as well as chronic irritation, as from multiple fractures and screw-in pins for bone fractures.

Chondrosarcoma makes up 15% of bone cancers; the majohty of patients are between 30 and 60 years old. Primary Chondrosarcoma (75% of cases) arises from previously normal bone, while Secondary Chondrosarcoma arises from a pre-existing benign cartilage tumor. Males and females are equally effected.

Several well recognized syndromes give rise to Chandrosarcoma, including: -Ollier's Disease ("Enchondromatosis") 20% of patients get chondrosarcoma. - Maffucci's Syndrome (benign cartilage and blood vessel tumors) 25% of these patients will eventually develop Chondrosarcoma. -Paget's Disease of Bone (abnormal formation and re-absorbtion of bone, over repeated cycles) 1 0% develop Chondrosarcoma. - Irradiation of bone, either normal bone or with a previous bone tumor in it. *** The general risk of developing any bone cancer with radiation is less than 5%.

Fibrosarcoma makes up 5% of bone cancers, and is closely related to MFH (Malignant Fibrous Histiocytoma). It is more common in soft tissues than bone. Fibrosarcoma mostly occurs between the 3rd and 7th decade, with males and females equally effected. Associated conditions including, bone infarcts (blood stoppages) and cysts, Paget's of bone, Osteomyelitis (infection in the bone), benign bone tumors, Fibrous Dysplasia and Irradiation are found in 1/3 of patients.

Ewings Sarcoma makes up 7% of bone cancers. It is the second most common childhood tumor (after osteosarcoma) with 150 new cases per year in the U.S. It is rare in blacks, males are effected twice as commonly as females, and tall people are more often affected. It is rare past the 3rd decade. While no cause is known. a chromosomal "translocation" (switching of genetic material) is often seen between chromosomes # 11 and #22.

Giant Cell Tumor of Bone is 5% of all bone tumors, only 1 0% are cancerous. It is seen mostly in the 3rd and 4rth decades. slightly more females are affected. It is widely reoorte(i to arise from irradiation of previous benign tumors.

How and Where do Bone Cancers Usually Arise?

Osteosarcoma usually arises in the cavity of the metaphyseal end of a long bone, that is that portion between the shaft ("diaphysis") and end ("epiphysis"). The most common sites, in decreasing order. are knee area (60%), hip (1 5%) shoulder (1 0%) and jaw area (8%). After age 25, flat bones are as likely to be involved as long bones. The disease is usually first felt as non-specific, dull local pain, often discovered with and accidental injury (i.e. football). Also seen is some local redness ("erythema") and swelling ("induration"). By the time the disease comes to medical attention, it has spread to the lung in 40% of patients and shown up as another separate area in the same bone ("skip metastasis") in 25%. The tumor can extend along ligaments, and invade into nerve bundles. When an X-ray is taken, a characteristic "sunbursts appearance is seen from the tumor pressing up the cortex of the bone. The tumor often extends into the local soft tissues (i.e. muscle), and actually destroys local bone. A Chest X-ray may show calcified tumors in the lungs from spread; the tumors produce bone-like substance wherever they spread to.

Chondrosarcoma also arises in the metaphyseal Growth plate areas of bone, which have rapidly growing cartilage. Most chondrosarcomas arise in the central ('axial") skeleton. The most common sites, in decreasing order, are pelvis (30%) ribcage (20%), shoulder (1 0%), and spine bones ("vertebrae") (1 0%). About 1 0% occur in the knee area, and may be mixed with osteosarcoma ("osteochondro- sarcoma"). They present the same as osteosarcoma (see above); in children they behave very aggressively as does osteosarcoma, but in adults they often have a less aggressive course ("indolentm). This is especially true of the secondary variety that arise from a pre-existing benign tumor. Interestingly, the cancer may actually change during its course to an osteosarcoma or fibrosarcoma. On X-ray of the area, we see a "fluffy" or"windblown" appearance from new cartilage.

Fibrosarcoma/Malignant Fibrous Histiocytoma arise in the METAPHYSIS or the nearby DIAPHYSIS. Again. the"presentation" is the same as osteosarcoma (see above) and most cases actually arise not in bone, but in soft tissue (i.e. muscle). The aggressiveness depends upon the cancer's 4GRADE." This means what it looks like under the pathologist's microscope: It can appear as very cancerous with rapid cell division, or look fairly benign with not much cell division. On X-ray we see a "sunburst" appearance (like osteosarcoma) with fibrosarcoma. and a area of a hole in the bone ('Iytic lesion"), showing destruction of bone, with MFH.

Ewing's Sarcoma arises in the DIAPHYSIS (i.e. shaft), within the marrow cavity of the bone. It starts as resembling an infection in the bone ('osteomyelitis") with pain. swelling. redness. and fever. The lower body is much more frequently the site of disease. especially the pelvis. thigh and leg bones. There is often a soft tissue mass extending out from the bone tumor, invading into local muscle and fat. The disease has usually already spread to the lungs when first diagnosed. On X-ray of the involved bone. we see "onion skin layering', with no formation of new bone but a reactive. inflamed appearance of bone surface ("periostium").

Giant Cell Tumor of Bone arises in the EPIPHYSIS/METAPHYSIS of rapidly grow- ing bone, and is most commonly seen in the knee area (60%) of young adults. Other common areas are the wrist (1 0%), tailbone, (8%) and ankle (7%). The Opresentation" for malignant Giant Cell Tumors (recall that only 1 0% are cancer) is similar to osteosarcoma (see above). On X-ray alone, we CANNOT distinguish benign from malignant tumors, but see: A thinning and buckling of the cortex, lots of new blood vessel formation, and little or no inflammatory reaction of the bone surface (i.e. little uperiosteal reaction").

Tumors Metastatic to Bone are of course not the PRIMARY bone tumors that we are discussing here, but it is worthwhile to note that cancer spread from lung, breast, prostate. kidney and bladder are usually to the spine and pelvis. It is less frequently seen in the more "distal" (further away from the center of the body) extremities, but is still more common to the feet than the hand. The one cancer that this 'distal extremity" spread is noted for is lung cancer. The point is, a new area of cancer in the elbow, knee or ankle is more likely a primary bone cancer in a patient without lung cancer.

How Is Bone Cancer Detected and Evaluated?

If a patient comes for medical attention for a possible bone cancer, we do:

Complete History and Physical, including careful examination of the tumor area, checking of the local lymph nodes (the bean sized filters that help purify blood, commonly called "glands"). The risk of a bone cancer going to lymph nodes is only about 5%, but infections commonly cause lymph nodes to swell up. The size of the tumor is noted, with a measurement of the affected extremity girth, if the tumor is in the appendicular skeleton. A careful check of the abdomen is made to look for organ swelling, indicating possible spread to the liver and spleen. The lungs are listened to ("auscultated") to see if their is any blocking of the airway from tumor spread. Given the chance that a bone tumor may be a result of spread from another organ, it is appropriate to check the prostate in males with a rectal exam and do a pelvic and breast exam in females.

Routine Laboratory Tests include Complete Blood Count ("CBC") to check for anemia and infection, and a Chemistry Panel ("SMA") to check blood sodium, potassium, bicarbonate, calcium, phosphorus, glucose, cholesterol, and liver and kidney function. The SMA also commonly tells "alkaline phosphatase', an enzyme which rises when bone is being destroyed. A Urinalysis (IIUA") is gotten which tells whether their is blood, glucose, protein or infection in the urine. If a Multiple Myeloma is possible, the doctor will order "Bence Jones" protein check of the urine to identify the tell-tale "light protein chains excreted with the disease. Other tests that may be ordered are a msedimentation Rate" ("ESR") of the whole blood which is a non-specific indicator of inflammation, Prostate Specific Antigen ("PSA") in men to rule out prostate cancer (which commonly spreads to bone), CA-125 in women to help screen for ovarian cancer, thyroid tests ("T3, T4, TSH") since thyroid cancer can spread to bone, and CEA that is a non-specific indicator of possible gastrointestinal cancer that may spread to bone. If surgery is being considered, tests of clofting ability ("PT, PTT, bleeding time") may be requested by the surgeon.

Radiology Tests firstly include a plain X-ray of the affected bone looking for the tell-tale appearances that were discussed previously. Plain Chest X-ray is partly valuable, but not conclusive, in confirming or denying spread to the lungs. The most valuable scans today for bone cancers are CT scan and MRI (Magnetic Resonance Imaging). CT scan of the lungs is more accurate than plain X-ray in determining if lung metastasis is present, and is required for many protocols. CT scan of the bone tumor area itself can help determine if it is malignant by telling if bone is being destroyed, which is a hallmark of malignant processes. MRI is invaluable in telling the extent of a soft tissue component of a bone tumor, and whether ft invades into the nerve trunks. Bone Scan can also help tell if bone is being destroyed. Other tests are only ordered for particular symptoms.

Biopsy (sampling) is the only ultimate way of diagnosing any cancer. Note that the biopsy must be planned to avoid spreading the cancer, if present.

Bone Biopsy is actually getting a piece of the tumor to confirm the suspected diagnosis, It may be easier just to get a piece of the tumor which has grown into the local soft-tissues surrounding the bone. A biopsy must be carefully planned and should be done by the same surgeon who will be operating upon the tumor. A reckless biopsy can actually cause the tumor to spread and then require a more disabling surgery- it may even force later amputation of a limb that could have been saved! In general, the biopsy should be done in just one muscular compartment, along the length of the tumor, and the soft-tissue component should be sampled if one exists. Multiple punctures should be avoided! Samples are often gotten with a "fine-needle" which minimizes the damage to surrounding tissue. If the bone itself must be entered, a "bone-punch" is used to get a sample of the cortex. The biopsy samples are examined by a pathologist, who makes slides from them and may use special stains or look for genetic markers to highlight the features of the cancer. He will identify the particular type of cancer, and also assign a "grade" based upon how aggressive it looks.

How is the Extent of Bone Cancer Gauged?

Like all cancers, the extent of bone cancer is given by the "stage." The most used staging system is by the American Joint Cancer Committee (AJCC):

"Stage I" means the tumor is of low grade and may penetrate the cortex
"Stage II" means the tumor is of high grade and may penetrate the cortex
"Stage III" is not used for bone tumors.
"Stage IV" means the tumor can be of any grade, and either involves local lymph nodes or has spread to other body areas (metastasized).

What is the Conventional Treatment for Bone Cancer?

The conventional treatment for all bone cancers was surgery, usually amputation to remove the involved extremity. The "Cade" procedure for bone sarcomas cut off'the affected limb way above the cancer, to help make sure it would come back at the stump. Often this meant "disarticulating" (removing the whole hip or shoulder joint) which was obviously a very handicapping procedure. Unfortunately, the results of surgery alone for many bone cancers was poor, as shown by the following overall results:

Surgeries less than radical amputation gave even poorer survival results than the ones quoted above. It was heartbreaking for many patients, in the prime of life, to have such disabling surgery and then die shortly there afterward from distant spread of the cancer. It was also realized that, ironically, more aggressive cancers are often easiest to cure, by giving drugs that interfere with cell division. These facts encouraged cancer researchers to develop new approaches, described below, to increase survival and often conserve the affected limb.

What is the Latest Effective Treatment for Bone Cancer?

In general, the latest approach uses "trimodality therapy" of radiation, chemotherapy, and limited surgery (instead of amputation) for many bone cancers. Not all types of cancers will get radiation, and not all limbs can be spared even with modern techniques. However, survival is much better now than in the era of amputation only! We will give an overview of modern radiation treatment and chemotherapy prior to discussing the most effective treatments for particular bone cancers.

Radiation Therapy has improved dramatically in the past 3 decades. It is prescribed and administered by a "Irradiation oncologist" , a cancer doctor specializing in radiation. The patient is first "simulated," meaning they are put on a replica treatment machine and the area to be irradiated is marked out. Special X-rays are taken to confirm position. Watercolor marks, and eventually tiny tattoos, mark out the treatment area. Information from the simulation, as well as from previous scans like CT or MRI, is fed into a special "treatment planning computer" which generates a "plan." This plan describes how much radiation is going to the cancer, and how much to surrounding normal tissues. Special lead blocks, which fit into the head of the treatment machine, may be made to shield normal tissues.

Treatments are given with a "Linear Acceleratoe' ("Linac') which emits radiation of millions of volts. The patient lies still on a hard table and is aligned with laser lights. Treatment takes only several minutes each day, Monday through Friday, for 4 to 6 weeks. The total dose given is usually 50 Gray (units of radiation) at 2 Gray per day when "multimodality treatment is used. Radiation treatment is painless, the patient does not become radioactive or lose their scalp hair. It is usually.very well tolerated.

Possible side-effects of radiation are divided into "acute" or "late" reactions. "Acute' reactions occur during the treatment period, while "late" reactions may occur months to years after treatment is completed. Typical acute reactions are skin redness (which can progress to peeling and soreness) in the area of treatment and fatigue. This will be worsened if chemotherapy is also given, especially with a drug called adriamycin. Acute reactions subside after completion of treatment. Possible late reactions include skin thickening, shortening of the limb in a growing patient, joint stiffness, and limb swelling ("edema"). It is more likely for a limb to swell if it's entire circumference is treated. Giving the treatment as many "fractions" (instead of all at once) reduces late reactiions. It is also possible that a tumor may become more malignant ("malignant degeneration") when treated with radiation, or that an entirely new cancer may arise years later owing to the previous radiation treatment ("radiation carcinogenesis'). Usually, however, radiation is a safe and effective treatment for cancer, and definitely improves survival in many bone cancers, by reducing recurrence in the local area and furthermore helping preserve limbs or cosmetic appearance for head and neck tumors.

Chemotherapy has also become an crucial element of effective treatment for many bone tumors, particularly those of young people. Great improvements have been made in chemotherapy over the past 3 decades. The nausea caused by many drugs can be well controlled in most patients with "Zofran" (ondansetron) which turns off the nausea sensing center in the brain. Low blood counts can be stimulated with special ugrowth factors" (GMCSF) which helps avoid anemia and infections. Chemotherapy is given by a "medical oncologist" for adults or "pediatric oncologist" for children.

The advantage of chemotherapy is that is travels through the entire body, and so can kill cancer cells that have escaped from the primary tumor before they have a chance to grow. This is important, since both surgery and radiation are "local therapies" and can do nothing about the cancer spread that makes it so lethal. Chemotherapy is most effective when any cancer cells that have escaped are too small to detected by any scan. Control of this "micrometastasis" has improved survival considerably in many bone cancers. Common drugs used for chemotherapy are cytoxan, adriamycin, and vincristine. Each of these represents a different class of agents. Cytoxan is related to mustard gas and kills growing cells, including both cancer cells and normal blood and intestinal tract cells. Adriamycin is a red liquid given into the veins which also kills rapidly growing cells, it is toxic to the heart and lungs and increases skin reaction if radiation is given. Vincristine is a plant-derived intravenous drug which arrests cellular division and is toxic to the ears and nervous system. While other drugs may be used, thdy're usually similar to these.

Osteosarcoma: Simple amputation is never enough, with only about 20% survival. The latest treatment is preoperative chemotherapy followed to shrink the tumor with platinum and adriamycin, followed by limb salvage surgery is possible. Radiation is seldom used since osteosarcoma is not very mradiosensitive." The Memorial Sloan Kettehng in New York has pioneered this approach, and which now gets over 70% long term survival! If the tumor has not invaded the nerve bundle in the limb, and has no skip metastasis in the same bone (25% do), the limb can usually be saved. If the tumor has gone to the lungs, the individual tumors growing there may be operated upon ("berry picking') giving 50% survival for even those who relapsed in the lungs. Preventative radiation given to the whole lungs has not been found to be effective, and is not recommended.

Chondrosarcoma: If the tumor is just biopsied, survival is only 5%. Extensive surgery can raise this survival as high as 70% for limb tumors, and 40% for pelvis tumors. While pre-operative chemotherapy is under trials at Memorial Sloan Keftering, (results not yet available) the M.D. Anderson cancer center has noted almost 70% control with radiation. The latest radiation treatment involves either neutrons (which are only given at specialized facilities) or photon-neutron combinations. The total dose is about 70 Gray at 10 Gray per week. This is one of the few tumors where neutron therapy is effective, and it is especially recommended if th6 tumor is at the skull base or other hard to operate area. Fibrosarcoma/MFH: Surgery still remains the standard of care for this rare cancer, with about 33% long term survival vath aggressive resection as done at the Mayo Clinic. Pre- operative chemotherapy is experimental, but radiation has been found effective if given to 70 Gray, producing good relief of symptoms and possible cure. It is recommended that post-operative radiation be given to the area if the margins of tumor removal are uncertain. Another attractive approach (through unproven) is using pre-operative radiation to shrink the tumor, followed by the best possible resection for cure.

Giant Cell Tumor: Surgery also is the preferred therapy with a local recurrence rate of about 40%, depending upon the extensiveness of the operation. Recall that only about 10% of Giant Cell Tumors are malignant. Chemotherapy has no known role in Giant Cell Tumor. Radiation is reserved for cases in which surgery would be disabling, for inoperable lesions, for incomplete surgeries and for symptom relief with advanced disease. Although radiation can control 80% of Giant Cell Tumors, doctors worry that the tumor will undergo "malignant degeneration" into osteosarcoma or fibrosarcoma. This happens about 15% of the time after radiation, but also may occur spontaneously after surgery alone. If malignant transformation occurs, survival is about 20% at 5 years, which tells why doctors are reluctant to use radiation unless it appears absolutely necessary.

Ewing's Sarcoma: Is a classic example of how trimodality therapy has increased survival. The "International Ewing's Sarcoma Studies" ("IESS") has increased 2 year survival from 15% to 75% today! Initial high dose chemotherapy with vincristine, cytoxan and adriamycin is followed by 45 Gray of radiation (plus a 10 Gray uboost") and limited surgery. The NCI has over 90% response with lphosphamide and etoposide. For small cancers of the hands or expendable bones, surgery is preferable to radiation since the cosmetic and functional results are better in children. For radiation, the whole bone need not be treated. This was shown by the eminent Dr. Taft (retired) at Cleveland Clinic. Almost 20% of children radiated will get a secondary cancer, often decades later, in the radiation portal. These secondary cancers are usually sacomas of fat or muscle. Thus, the dose of radiation has been reduced in current protocols, along with the combination chemotherapy, to try to reduce later new cancer risk.

Other Latest Treatments

Heavy Particle, or Neutron bombardment therapy, is about 60% effective (by review of the world literature) at local control for bone tumors. These exotic treatments are only available at a few locations in the U.S., such as Loma Linda University in California. The rationale for these treatments is that bone tumors usually have low oxygen, and oxygen is a requirement for standard External Beam photon radiation to work. However, neutron and heavy particle beams (i.e. Helium, Heavy metal ions) do not have this dependence upon oxygen in the tissue to kill cancer cells. On the other hand, the late effects of these treatments are also greater, and it is more difficult for normal tissues to repair themselves. These treatments should be considered in the face of local relapse which is insensitive to standard External Beam radiation.

Immune Therapy with lnterferons was tried with standard intramuscular doses 3 times per week for seventeen months. The survival analysis showed 58% of these patients were free of disease at 3 years, compared with just 37% in patients who did not get the interferon therapy (study by Strander, H "adjuvant intereron in osteosarcoma"). This treatment has also shown regression of bone tumors metastatic to lung. Another form of immune therapy is "transfer factor" derived from blood of other people living in the patient's home; it's injected under the patient's skin and helps prevent relapse.

Advanced Disease

Sarcomas have a predilection to spread to lung, and if the site of origin ('primary site") is controlled, surgically removing individual lung metastasis ("berry picking") may increase survival, or occasionally even cure the patient. The formal name for removing metastasis is "metastatectomy." It is not our chemotherapy or radiation which kills the last few cancer cells, it is the body's immune system. If the number of cancer cells can be reduced to undectable levels by our current methods, then there is a chance for cure. When sarcomas have spread to lung, an effective chemotherapy regimen is CYVADIC, (Cyclophosphamide, Adriamycin, Vincristine) but it does not work as well for liver or bone metastasis. It is also quite toxic causing heart, lung, ear and nerve damage as well as nausea, vomiting, baldness, sterility, and lowering of blood counts. Injecting it into a local artery Cintra-arterial") is not better than standard intravenous, and is more complicated. Very high dose lfosphamide is dangerous to the kidneys, but has shown success in disseminated sarcomas that were resistant to all other chemotherapy (50% response).

Palliation of Symptoms

For very advanced bone cancer which is widespread, the objective is no longer cure but the comfort of the patient. Surgically removing a painful stump of a previously amputated extremity may produce better pain relief than any drug or radiation. The patient should be made as comfortable as possible, and narcotic medicines like morphine (which Osier called "G-d's own medicine) should never be withheld for fear of causing "addiction." Using "Fentanyl Patches" applied to the skin helps give a continuous amount of narcotic, eliminating the problems of forgotten doses, 'loss' of narcotics, and smoothing out the dosing for less disturbing "highs and lows." Sometimes radiation therapy is used as an emergency measure when the cancer spreads to the spinal column and threatens to cause paralysis by pressing upon the spinal cord. Any patient with bone cancer who experiences new weakness of -the extremities, numbness, or loss of bowel or bladder function must be brought into the Emergency Room immediately to see whether the tumor is compressing the spinal cord causing these syrhptoms. Up to 60% of new back pain in a cancer patient is caused by spread of cancer there. The patient is given a painless Magnetic Resonance Imaging (MRI) scan to check for "epidural spinal cord compression." If this is caught early, and treatment is given, (radiation therapy or surgical decompression) permanent paralysis may be prevented. It is unfortunately uncommon to reverse symptoms of paralysis once they have set it, however, so quick recognition is essential.

Other options for patients in severe pain for multiple areas of spread to bone include "hemi-body" radiation, and "strontium-89." Hemi-Body radiation uses a low dose (6 to 8 Gray) in a single treatment to the upper or lower body to treat multiple areas of bony involvement; some anti-nauseants are usually necessary and it lowers blood counts. It is over 90% effective for pain relief lasting an average of 6 months.

Strontium-89 is an injected radioisotope that goes through the bloodstream to all bony areas, and is especially attracted to cancerous areas. It also lowers blood counts but is very effective at palliating pain. It can only be done once. If no relief is gotten from medications or radiation, neurosurgical techniques to cut sensory nerves can usually afford relief, to this small population of patients. Committina suicide because of unrelieved Dain should NEVER be necessary with oain science todav. The patient with newly diagnosed bone cancer should not rely on any one therapy, but instead should use a combination approach to maximize the chance for success Specifically, besides the conventional medical therapies mentioned above, consider the use of a non-toxic, not over-expensive alternative therapy that you believe in, a program of spiritual renewal, "mind over cancer," nutritional therapy and exercise. Keep the most positive attitude possible; research has shown this to be an important factor in survival. ' CancerAnswers has a transcript available on reasonable alternative treatments which you can order through our website. Using a true "multi-modality" approach will give the confidence that you have done everything possible for a happy outcome, and certainly improve the current quality of life,

New techniques utilizing surgery, radiation therapy and chemotherapy are showing better survival rates than ever before for bone cancer. If cure is the objective, consider getting treatments at a University Academic Center and joining ongoing research trials which offer the latest therapies. The National Cancer Institute has listings of open trials (which change weekly) on their website, these trials are only offered at particular centers. Realize that by joining a trial, you may be giving up the ability to chose the more effective therapy. Most importanly, understand the treatment you are getting, believe in it, and have an up-to-date doctor you feel comfortable asking questions to. Given the survival improvements over the past 2 decades, the future has never looked brighter for bone cancer patients!

Unfortunately, bone cancer is a very serious form of cancer. While not as common as breast cancer, bone cancer is nonetheless a serious condition, and those who suffer should seek some health information from their physicians.

This is the full transcript, offered freely in the spirit of internet sharing, of CancerAnswers' report on Bone Cancers. Much more, including latest additional treatments for Bone Cancers can be found on our order page. Thank you for using CancerAnswers as your information resource.