How Bone Cancer Is Treated

The most common cancers of bone in the first three decades of life are osteosarcoma, Ewing sarcoma, and chondrosarcoma. Overall, however, cancer that begins in the bones, or primary bone cancer, is relatively rare. This rarity can be challenging from the treatment point of view. That is, less is known about the optimal treatment of bone cancer, and there are fewer clinical studies compared to more common malignancies such as breast cancer or prostate cancer.

Such challenges aside, remarkable progress has been made in many areas of bone cancer treatment in recent years.

Preparing for Treatment

Treatment for bone cancer can be determined after proper diagnosis and staging.

Genetic Testing

In preparation for treatment, genetic testing or counseling may be offered, as certain genetic changes such as a TP53 aberration may be relevant.

The TP53 gene has the code for making a protein called tumor protein p53, or p53. This protein acts as a tumor suppressor, which means that it regulates cell division by keeping cells from growing and dividing too fast or in an uncontrolled way.

Some mutations in this gene can reduce its function, the equivalent of taking the foot off the brakes of cell division, which can favor malignancy. People who have p53 mutations may be at risk for cancers other than bone cancers, as well.

Additional Consultations

Also at this point, consultation with other professionals to address future plans and other considerations may be helpful. For instance, although it might not be a person’s first thought in connection with “cancer treatment,” the preservation of fertility in young people is generally now considered part of the whole treatment package. This may entail sperm banking for young men past the age of puberty as well as newer techniques for maintaining fertility in women.

Before chemotherapy, your doctor will also discuss the long-term risks of therapy, including infertility, but also potential damage to the heart muscle and increased rates of second cancers.

Because the treatment of bone cancer may produce side effects and toxicities, doctors will want to gauge the performance of your key organs in advance of treatment to get baseline reading. Baseline readings are taken for things like heart function, kidney function, and hearing since some chemotherapies have toxicity profiles that may lead to impairment in these areas. Baseline readings are obtained through tests such as an echocardiogram, which shows heart function; audiology testing, which measures hearing; and blood tests that show how well the key organs are functioning, including the kidneys and bone marrow.

In addition to chemotherapy and surgical options, clinical trial options may also be discussed as part of the process of understanding the risks and benefits of treatment. This entire process is known as informed consent.

Treating Osteosarcoma

For the sake of simplicity, “bone cancers” are sometimes lumped together in educational materials that are geared toward patients. However, the precise type of bone cancer may become more important when considering treatment.

Osteosarcoma is the most common primary malignant bone tumor in children, adolescents, and young adults.

Localized Osteosarcoma

Localized osteosarcoma affects only the bone in which it developed and the tissues next to the bone, such as muscle and tendon. In the case of localized osteosarcoma, there is no detectable spread of the cancer to other areas of the body. In young adults, most localized osteosarcomas occur around the knee.

The current standard treatment for localized osteosarcoma involves multiple steps: first, treatment with chemotherapy that will battle the cancer and shrink it (referred to as neoadjuvant chemotherapy); then, surgery to take out the primary disease; and then, what’s called adjuvant chemotherapy, ideally in a clinical trial when one is available.

Adjuvant chemotherapy is so called because it is in addition to the surgery—even though the surgery seems to have gotten rid of the cancer, there may be microscopic remnants of the cancer left behind. That is where the adjuvant chemotherapy comes in—to kill any remnant cancer cells.

Chemotherapy

Methotrexate, doxorubicin, and cisplatin (MAP) chemotherapy may be used for first-line treatment.

Standard MAP therapy includes a doxorubicin dose that can put people at risk for long-term problems with toxicity toward the heart, and so an agent called dexrazoxane may be used in some capacity to help protect the heart. A common regimen is two 5-week cycles of neoadjuvant MAP therapy, which can facilitate saving the limb (limb salvage)

Surgery

Limb salvage is a surgical procedure that replaces a cancerous bone and reconstructs a functional limb by using a metal implant, a bone graft from another person (allograft), or a combination bone graft and metal implant (allo-prosthetic composite).

When going for cure, regardless of the location of the cancer, a complete surgical removal of all disease is the goal. In the arms and legs, limb-preserving surgery and reconstruction with an artificial device (endoprostheses) may be performed.

In some cases, when a portion of a limb is removed, the remaining limb below the involved portion is rotated and reattached (rotationplasty). In other cases, tissue from a donor is used. An amputation may be performed when the limb cannot be preserved or in cases in which the outcome, in terms of function, will actually likely be better with the amputation than not.

Radiation Therapy

When osteosarcoma occurs in the skull, ribs, spine, or certain other areas, the surgery is complex. When the disease would be extremely challenging to remove surgically or when the margins of the surgery are positive for cancer, radiation therapy has been shown to improve outcomes. Higher total radiation doses or larger daily doses (called hypofractionation) may improve control of the cancer.

Stereotactic radiosurgery involves the use of radiation therapy to deliver precisely targeted radiation in fewer high-dose treatments than traditional therapy, which can help preserve healthy tissue.

Response to Therapy

The response or shrinkage of the tumor (tumor necrosis) after receiving neoadjuvant chemotherapy can be telling in terms of the prognosis.

Differing subtypes of high-grade osteosarcoma have also been identified (e.g. osteoblastic, chondroblastic, and fibroblastic), but there does not appear to be any link between these different subtypes and the treatment or prognosis that one can expect.

Recently, the European and American Osteosarcoma Study (EURAMOS) group completed a large study that failed to demonstrate improved outcomes with modified treatment based on tumor necrosis, and so continuing MAP adjuvant chemotherapy regardless of tumor necrosis has been recommended.

Treating Metastatic Osteosarcoma

When most patients with osteosarcoma are first diagnosed, the cancer is localized and hasn’t spread. However, up to 30 percent of patients have cancer that has already spread, or metastasized, at diagnosis, and this spread occurs most commonly in the lungs.

Known as “equivocal pulmonary lesions,” suspicious lung spots are actually quite common in current high-resolution scans, according to Reed and colleagues.

There are guidelines that help doctors determine the significance of such findings on scans: one or more lung spots over or equal to 1 cm or three or more lung spots more than or equal to 0.5 cm should be considered consistent with a diagnosis of metastatic osteosarcoma, whereas smaller lesions are indeterminate without biopsy and confirmation.

Patients with equivocal lung spots on imaging, or nodules, have two treatment options: wedge resection or observation during chemo.

The first option, wedge resection, is a form of surgical treatment that involves removing the suspected cancerous cells in the lung as well as removing a margin of surrounding healthy tissue. It is preferred to taking a biopsy sample through a needle, for instance, because it will confirm whether or not the lung spots are indeed cancer and, simultaneously, it’s the optimal therapy in the case of cancer, since you've just had it removed.

The alternative to wedge resection is to observe the lung spots and see how they respond to chemotherapy. If they don’t change in size after chemotherapy while the primary tumor does shrink with chemo, then the lung spot is less likely to be a tumor. Continued close monitoring after adjuvant chemotherapy is very important in these case, though. In contrast, if the lung spots decrease in size or mineralize (become more white or opaque on imaging) in response to the chemotherapy, then this is more indicative of something that will be recommended for surgical removal.

The optimal timing for removal of metastatic disease, such as lung spots, is not known. Reed and colleagues recommend proceeding with surgical removal of the lung metastases after four cycles of MAP chemotherapy (followed by two more cycles after surgery) or at the end of treatment.

Treating Relapsed Osteosarcoma of the Lung

Sometimes it is not always clear if a spot on the lung in imaging scans is an actual metastasis or some other finding. Recent expert recommendations state that taking some time to make sure suspicious spots are, indeed, cancer is not felt to compromise the quality and goals of therapy.

If the spot or spots are confirmed as relapsed cancer, experts recommend enrollment in a clinical trial. Ifosfamide and etoposide are sometimes used, but they have considerable toxicity.

Relapsed/refractory bone metastatic osteosarcoma is very challenging to treat and the prognosis is bleak. Clinical trial enrollment in these situations is often recommended in order to strive for the best possible outcomes.

Treating Ewing Sarcoma

The treatment for Ewing sarcoma is similar to that of osteosarcoma in that it typically involves taking out the primary tumor (via surgery and/or radiation) combined with chemotherapy that is designed to kill any remaining microscopic cancer sites.

Neoadjuvant chemotherapy may be given, followed by radiation, surgery, or both. Further chemotherapy is then given. Agents involved include ifosfamide and etoposide (IE) plus vincristine, doxorubicin, and cyclophosphamide (VDC) for younger patients with localized tumors. This schedule involving the administration of VDC-IE is now the standard of care in North America.

Treating Metastatic Ewing Sarcoma

At the time a person is diagnosed with Ewing sarcoma, about 25 percent will have metastatic disease in the lungs. Reed and colleagues recommend whole-lung radiotherapy after the completion of chemotherapy; and they say that, since small nodules often disappear with chemotherapy, a biopsy before treatment is started should be considered, if feasible.

Those with metastases limited to the lungs have an expected five-year overall survival rate of 40 percent, whereas fewer than 20 percent of patients with bone and/or bone marrow metastases are long-term survivors.

Clinical trial enrollment can be an especially attractive option for patients with metastatic sarcoma. Investigations are ongoing combining conventional chemotherapy with targeted drugs, and hopefully some of these combinations will yield better results than currently available therapy.

Treating Relapsed Ewing Sarcoma

As with relapsed osteosarcoma, recurrent Ewing sarcoma is, overall, associated with a very poor prognosis. Subsets within the overall group can be extremely important, however. For instance, Reed and colleagues note that although patients with an early relapse (within 2 years of the initial diagnosis) have less than a 10 percent chance of long-term survival, up to one-fourth of those with a later relapse may potentially be cured.

Sometimes, when the recurrence is not metastatic, a local therapy such as radiation or surgery can be administered in addition to chemotherapy. In patients with metastatic or recurrent disease with better long-term prognoses, stereotactic body radiotherapy can be an option, as is the case in some instances with osteosarcoma.

One difference between the treatments of recurrent osteosarcoma versus Ewing sarcoma is that chemotherapy is generally recommended for all recurrent Ewing sarcoma patients, whereas surgical removal of the metastasis may be the only therapy used for some patients with metastatic osteosarcoma.

As with osteosarcoma, consideration of enrollment in a clinical trial is strongly recommended, even at the first relapse.

Treating Chondrosarcoma

Surgery to take out the cancer is required for any chance of a cure in the case of chondrosarcoma, and lung metastases that can be removed are also taken out.

There are different subtypes of chondrosarcoma. However, conventional chondrosarcoma does not respond to chemotherapy. Another type of chondrosarcoma that may be more sensitive to chemotherapy includes dedifferentiated chondrosarcoma.

Chondrocytes are the cells in your body that make cartilage, and chondrosarcomas tend to have a unique tumor environment, just as cartilage is somewhat of a unique tissue. It has been theorized that the reason chemotherapy doesn’t seem to work on chondrosarcoma is that something about the cartilaginous tumor prevents delivery of chemotherapy to the malignant cells.

Radiation therapy is sometimes recommended after a surgery that didn’t get all of the cancer out (called positive margins). If someone with chondrosarcoma develops metastases or the disease comes back in an area that cannot be surgically removed, it’s recommended that the tumor genetics be tested and clinical trials would be the main consideration at that point.

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