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When a soft-tissue sarcoma, a type of cancer, develops in an arm or leg, amputation of that limb is sometimes necessary. Chemotherapy and radiation therapy are sometimes used in an attempt to spare the limb. Now, researchers from Italy report that they have used an alternative method: to heat the temperature of the blood in the affected arm or leg and deliver high doses of chemotherapy and tumor necrosis factor to the limb only. The researchers say that this treatment may be effective and the amputation avoided.

Soft-tissue sarcomas are characterized by the growth of cancer cells in the soft tissue of the body, that is, in the muscles, tendons, fibrous tissue, fat, blood vessels, nerves, or the tissues around the joints. Treatment for these soft-tissue sarcomas varies, depending on the type of cancer, the place in the body where the cancer started, and the stage of disease (extent of disease at diagnosis). Treatment may include surgery to remove the cancer if this is possible, chemotherapy, and/or radiation therapy. When this type of cancer develops in an arm or leg, amputation is sometimes needed.

Techniques called hyperthermia and isolated perfusion, along with chemotherapy, radiation therapy, and/or surgery, can also be used to treat soft-tissue sarcomas of the arm and leg effectively, without amputation.

Hyperthermia is a therapy in which the temperature of the blood in the affected limb is increased to a point that could not be tolerated by the whole body. This is done to make the subsequent chemotherapy more effective, as cancer cells are more vulnerable to attack at high temperatures.

Isolated perfusion is a method by which researchers can deliver chemotherapy directly to the affected limb, and not to the rest of the body. Recently, a biologic therapy, called

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tumor necrosis factor, was also found to be effective as an anti-cancer agent for persons with soft-tissue sarcoma; however, this agent is too toxic to administer intravenously to the whole body.

The Italian researchers used hyperthermia, followed by isolated perfusion to deliver the chemotherapy drug doxorubicin and tumor necrosis factor to the limb only. In an initial study, they treated 18 persons with advanced soft-tissue sarcoma of the arm or leg with doxorubicin by isolated perfusion. In a second study, they treated 29 persons with hyperthermia plus doxorubicin by isolated perfusion. In a third study, they used hyperthermia, plus doxorubicin and tumor necrosis factor by isolated perfusion. After this treatment, all patients underwent surgical removal of the remaining cancer, or, if still needed, amputation. Results showed that 92% of patients were able to avoid amputation, with the best results occurring in the third study. In those receiving tumor necrosis factor, better local control of cancer was achieved, with only 2 recurrences, fewer cases of spreading to distant parts of the body, and better survival rates.

These researchers concluded that doxorubicin plus tumor necrosis factor, with hyperthermia and followed by surgery, may be an effective alternative to amputation for persons with advanced soft-tissue sarcomas of the limb. (

Cancer, Vol 86, No 9, pp 1731-1749, 1999) November

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