Colorado State University begins canine study to help save limbs of animal, human bone cancer patients

Colorado State University Animal Cancer Center researchers are embarking on a study that may save limbs of both human and animals with bone cancer that would otherwise be amputated. The study, which uses new state-of-the-art machinery at the university’s James L. Voss Veterinary Teaching Hospital, is seeking dogs with osteosarcoma who may qualify for the study.

The study is designed to deliver doses of radiation to within 2 millimeters of precision to tumors in the legs of dogs with osteosarcoma. The College of Veterinary Medicine and Biomedical Sciences’ Varian Trilogy Linear Accelerator, a highly advanced machine that delivers radiation to tumors, makes such meticulous delivery possible.

Osteosarcoma is the most common primary bone cancer in dogs and people, so this study will benefit both. The most common treatment and current standard of care for this disease in dogs is amputation and chemotherapy said Dr. Stewart Ryan, a researcher at the Animal Cancer Center and professor in the Department of Clinical Sciences.

"This is one of the first studies that uses objective measurements of how well dogs use their legs after this sort of treatment," Ryan said. "The results of this study may help prevent amputations in future veterinary patients and would also have a translational aspect to help humans with bone cancer who don’t want amputation. It may also have a role in decreasing the number of cycles and intensity of chemotherapy before limb-spare surgery in people, giving them a higher quality of life during the treatments.

When veterinarians are able to perform limb-sparing surgery for dogs, there are often complications that can result in additional surgeries and expense or ultimately end up in amputation.

"Now that we have this new equipment, we started to think about how we could develop high-dose radiation therapy as a non-surgical limb salvage treatment and a potential cure," Ryan said.

Bone cancers can be difficult to kill with traditional radiation. Instead, radiation mainly has been used to provide pain control and not to kill all of the tumor. When using radiation on osteosarcoma tumors, doctors must use a low radiation dose to avoid damage to normal tissues such as skin. With too much radiation, the skin can be damaged to varying degrees, including causing wounds that will not heal. If too little radiation is given, the tumor can come back or continue to grow. Radiation also can make the bone weak and susceptible to fracture.

Traditional limb-sparing surgery, which involves implanting canine cadaver bones or artificial metal implants after removing the bone cancer, also carries the risk of the tumor returning, infection in the bone, or screw or plate malfunctions. Options for this sort of surgery also are limited to tumors near the wrist joint in dogs.

The Varian Trilogy Accelerator is so technically advanced it can target a tumor with significantly more radiation than it delivers to the skin and tissue it travels through to reach the tumor. It can also focus more radiation at a tumor than the area of tissue immediately surrounding the tumor, regardless of the complexities of the shape of the tumor. A special computer program is used to make individual plans for patients to control the depth, intensity and duration of each round of radiation, based on each patient’s CT scan and tumor shape.

Because tumors must receive more than one treatment with radiation and because the accelerator can deliver higher doses to tumors without damaging surrounding tissue, dogs in the study would get fewer numbers of radiation doses at levels eight to 10 times stronger than typical treatments. The precision at which the doses are delivered is key to preventing complications in the skin and maximizing the amount of tumor killed.

Ryan and collaborators Dr. Susan LaRue and Dr. Susan Kraft, along with radiation oncology staff at the hospital, have developed a system to ensure that radiation delivered to dogs in the study will be given to exactly the same spot every time. The study is limited to dogs with osteosarcoma in their limbs. Small wires or pins are inserted into the bone of the leg needing radiation. A ring is connected to these wires or pins outside of the leg, which is attached to a frame on the accelerator table when the dog undergoes treatment. The ring, which is protected when the dog is not receiving radiation, is worn like a bracelet for about a week to 10 days until treatment is completed.

The accelerator can take X-ray images of the dog’s leg, which is securely positioned on the frame. The dog is anesthetized during treatment to ensure that he remains still. X-ray images taken at the initial treatment become the template for alignment for each consecutive treatment. X-rays taken at each consecutive treatment are compared to the initial images before radiation is delivered to ensure that the dog is lined up exactly the same way every time. If not positioned correctly, the Varian’s table automatically readjusts the position.

Dogs in the study will be given three radiation treatments each spaced two to three days apart. They also will receive a dose of chemotherapy, which can make tumors more sensitive to radiation. At the end of the third treatment, the bracelet and wires or pins will be removed. Dogs in the study will be candidates for amputation. This treatment is also being offered to clients who do not want to participate in the study because they are not opting for amputation. Valuable information also will be obtained from those cases.

The success of the study will be measured through blood and urine tests that indicate the amount of bone turnover, MRI images, the amount of weight that dogs put on treated legs and the amount of tumor killed.

People interested in enrolling in this study or finding out more about treatment of osteosarcoma with high-dose radiation may contact Dr. Ryan by e-mail at stewart.ryan@colostate.edu or by calling (970) 297-4159.

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