Scientists Seek Treatment Options for Brain Tumors in Boxers

Used with permission from the Purina Pro Club Boxer Update, Nestle Purina PetCare Company

A team of scientists at the College of Veterinary Medicine at North Carolina State University (NCSU) is working hard to better understand brain tumors in Boxers. Ultimately, the scientists hope to develop effective new treatment options.

Boxers and other brachycephalic, or short-nosed, breeds have the highest incidence for a type of brain tumor known as gliomas. These tumors start in glial cells (supporting cells) within the brain, and as they grow they cause compression and death of surrounding brain tissue. The tumors can vary in malignancy from slow-growing, relatively benign tumors to high-grade, aggressive tumors known as glioblastoma multiforme. These latter tumors are resistant to current forms of treatment.

Led by Natasha Olby, D.V.M., Ph.D., assistant professor of neurology, the research team at NCSU is focusing on learning what makes tumors grow with the hope that targeting these "growth factors" will provide effective treatment options. There already has been a lot of work done on this type of brain tumor in people, as high-grade gliomas are the leading cause of death among humans with brain tumors.

"In our preliminary work, we've found that the pattern of growth in canine brain tumors is comparable to that seen in human brain tumors," Olby says. "For example, we have found that the epidermal growth factor receptor, a receptor important in mediating tumor growth, is expressed at high levels by high-grade gliomas in dogs as well as people. Blocking the function of this receptor may therefore prevent or slow brain tumor growth, and we plan to investigate the ability of different drugs to achieve this effect."

Identifying Tumor Signs
"Brain tumors tend to occur in older dogs, and tumor signs vary depending on the location of the mass," Olby says. Seizures, behavioral changes, circling and general clumsiness indicate damage to the forebrain. A tumor in the brain stem could trigger head tilting, nystagmus (rapid flicking of the eyes), difficulty swallowing and unsteady walking.

A veterinarian who suspects a brain tumor will first seek an assessment. Ideally, the dog will be referred to a veterinary neurologist for evaluation. If appropriate, the neurologist will order a CT ("cat" scan) or an MRI to identify the presence and location of a mass. "The definitive determination is reached by taking a small piece of the mass (a biopsy), and looking at it histologically," Olby says. "This is critical in order to determine the best treatment for each individual dog."

A CT-guided biopsy or a surgical biopsy can be performed. For a CT-guided biopsy, a small hole is drilled in the skull while coordinates are plotted from the CT scan to guide the neurologist as a needle is inserted into the tumor. The biopsy needle removes a tiny sample of tissue, which is looked at by a pathologist. Biopsies are generally trouble-free, Olby says, but owners should be cautioned about the low risk of bleeding into the brain from the biopsy site. If the tumor is accessible, surgery may be performed to remove as much of the tumor as possible, and at that time a sample of the tumor is evaluated histologically to identify the tumor type.

"Biopsies are an important step in determining the most appropriate treatment for each dog," Olby says. "Many different diseases can appear similar on CT or MRI images, for example, an abscess looks like a mass. It is therefore important to get a definitive diagnosis before embarking on treatment such as radiation."

Current Treatment Options
Once the type of canine brain tumor is known, recommendations for appropriate therapy can be made. If seizures are occurring, the dog will be placed on an anti-epileptic medication, such as phenobarbital, to suppress seizures. "We also will usually start dogs on prednisone, a steroid that reduces fluid around the tumor and can improve signs for a short period of time," Olby says, "although this does nothing for the tumor itself." Surgical removal of the tumor, or as much of it as possible, is attemptedproviding the tumor is in an operable site.

Unfortunately, gliomas tend to be difficult to remove surgically as it is likely other brain tissue will be damaged in the process. The most common treatment for gliomas is radiation. "Radiation therapy can help to shrink and slow the rate of growth, thereby helping to prolong a dog's life," Olby says, noting that 50 percent of treated dogs are alive and well 10 months after their course of radiation is completed. Dogs undergoing radiation at the veterinary teaching hospital at North Carolina State University are given 16 doses in separate treatments on consecutive weekdays, with no treatments on weekends.

Each treatment is administered under anesthesia and lasts about 30 minutes. Though side effects are usually minimal, damage can occur from the radiation beam. For example, the color of the hair in the radiation field may change. "There is a wide range of responses to radiation therapy," Olby says. "Some dogs may die quickly despite world-class care, while others with less malignant tumors can survive for long periods."

Chemotherapy is another treatment option; however, the blood-brain barrier typically makes delivery of the drugs to the tumor inadequate and currently there is a dearth of effective, tumor specific drugs for canine brain tumors. Part of the brain tumor study at NCSU involves looking at different drugs to help block growth factor receptors as potential therapies in dogs. "This work has implications for dogs and also for people, because canine tumors seem so similar to human brain tumors," Olby says. "In addition, the kinds of therapies that target brain tumors may also be effective against other types of cancers that express the same growth factor receptors at high levels."

Future Developments
Several different groups are currently working on different aspects of canine brain tumors. "There are still some very basic facts that we do not know about canine brain tumors," Olby says. "For example, if a brain tumor is not treated, how long can the owner expect their dog to survive? If owners decide not to treat their dogs once they know it has a brain tumor, subsequent tracking to determine how the dog fares is difficult. In addition, many owners understandably are reluctant to have an autopsy when their dogs die or are euthanized, so the type of tumor their dog had is never known if a biopsy was not performed."

Striving to improve the information available, and to provide extra support to affected dogs and their owners, the group at NCSU is trying to touch base with owners of dogs with brain tumors at regular intervals. In addition, the researchers are working to expand the database to help them study treatment options. They are asking owners to bring their animals to the clinic for evaluation, possible biopsy and treatment. From the small biopsy samples, researchers will extract DNA to use in studying mutations (genetic defects) associated with the tumors.

"We are just starting to investigate the genetic conditions that are associated with brain tumors," Olby says. "Identifying mutations may give us more information about specific tumors and how they respond to therapy. Such mutations or conditions are well known in people and provide invaluable information for determining the most appropriate therapy. This work is just getting off the ground in dogs." Owners interested in having their dogs participate in the NCSU brain tumor study should ask their veterinarians to submit a referral to the Department of Neurology at North Carolina State University by calling (919) 513-6692

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