Everything Comes Up Rosey
Nancy Gustafson, DVM, MS, DACVR
Rosie was a 9 year old, female spayed retriever mix of 48 lbs, who had a long term history of increased panting and increased urination. She had recently become uncertain on her feet, was acting disoriented, and was anxious. Routine blood tests, chest radiographs, and abdominal ultrasound were performed by the referring veterinarian. These tests were normal. The referring veterinarian then referred Rosie to an internal medicine specialist. An MRI was performed, which revealed that Rosie had a mass in her pituitary gland (part of the brain). The internist started Rosie on prednisone, which resolved her neurologic deficits, but she continued to be anxious. She was referred to our Oncology service at the Regional Veterinary Referral Center on October 31, 2006 for a consultation and more definitive treatment.
The two most common pituitary tumors are adenoma and carcinoma. Adenomas are benign tumors whereas carcinomas are malignant. Malignant tumors are generally more aggressive locally and have an ability to metastasize (spread to other organs). A recently published study suggested that pituitary tumors with a larger, taller, narrower appearance are most likely carcinoma, which unfortunately has a poorer prognosis. The smaller, shorter, rounder pituitary tumors are more likely to be adenomas and a better prognosis. Previous published studies reported that dogs with pituitary tumors (adenoma versus carcinoma not specified) treated with radiation therapy alone have an average survival time of one to three years. Prognostic factors that predict a poorer outcome include size of tumor, neurologic abnormalities and endocrine abnormalities.
Rosie’s tumor size was large and tall (probably carcinoma), she was stumbling and not mentally herself (neurologic abnormalities) and she was drinking and urinating excessively (endocrine abnormalities). Therefore, her prognosis should have been six to eight months. Pituitary carcinoma is more likely to respond to radiation therapy and chemotherapy than the adenoma because the cells are more rapidly dividing. However, the cells that are not killed by treatment are also more likely to repopulate more quickly than adenomas. Chemotherapy agents have limited access to brain tumors because many agents will not cross the blood-brain barrier. The agents that will cross the barrier include CCNU (Lomustine), Cytarabine and Hydroxyurea.
Radiation therapy was discussed as the best treatment for Rosie. Surgery was not an option, because of the location of the tumor, and the published survival times with radiation therapy are significantly longer than chemotherapy alone. Full course radiation was proposed, which would require that Rosie receive 18 daily (Monday-Friday) treatments, using our linear accelerator. The images from the MRI can be imported to our computerized treatment planner to create a radiation plan that maximizes the dose to the tumor and minimizes the dose to the surrounding normal brain and other tissues. All pets require anesthesia for radiation therapy in order to achieve exact positioning for each treatment. Extensive anesthetic monitoring is standard for our radiation patients. Rosie’s owner decided to pursue full course radiation therapy.
Rosie responded well to radiation, and there were no problems with her daily anesthesias. The owner reported a decrease in urinary accidents and an overall brightening of her attitude by the fourth treatment. By the final treatment on 11/22/06, Rosie was acting like her old self again, so the prednisone dose was able to be decreased. Rosie returned for a recheck exam 2 weeks later, and her exam and blood work were normal. The owner decided to be more aggressive with Rosie’s treatment since she responded so well to the radiation and her tumor was likely a carcinoma, which meant it was predicted to recur relatively quickly. Therefore, Lomustine (CCNU) was started with plans to increase the dose as tolerated, for a total of 5 treatments. Lomustine is an oral chemotherapy drug that is administered every 3 weeks. The dose of prednisone was also decreased further and eventually stopped. Rosie handled the Lomustine very well and only had a few urinary tract infections develop as side effects from the chemotherapy-induced immunosuppression.
In September of 2007, eleven months after her initial presentation, Rosie began to show some of the previous neurologic signs. On examination she was slow and had muscle wasting on the left side of her skull. A follow-up MRI showed that the pituitary tumor was about 60% of the previous size with little inflammation and no evidence of necrosis from the previous radiation. In veterinary medicine, routine follow-up MRI’s are rarely performed because of the expense and in some cases anesthetic risk. Although the tumor at this time was smaller than seen on the original MRI, it was likely even smaller at some point and was now regrowing. Additionally, the recurrent tumor was probably caught at a smaller size because Rosie’s owner was now more aware of the clinical signs resulting from a pituitary tumor. Her owner was again given treatment options including reirradiation of the tumor, additional doses of Lomustine, or prednisone alone. The ability to reirradiate is limited by many factors including response to the initial radiation, time between the courses of radiation and the tissues within the irradiated field. In Rosie’s case, she had a great response to treatment and 11 months had passed between courses. Therefore, her only significant limiting factor was that the brain was the major tissue in the field. It is generally accepted that reirradiation of brain tissue should be 85% of the original dose because the brain, in a sense, takes a long time to “forget” the original dose.
Rosie’s owner chose to reirradiate the tumor. Prednisone was also restarted. Rosie rapidly improved again and continued to feel well until late February 2008, when her owner noticed a bit of wobbliness. Radiation therapy for a 3rd course was not an option because the time between courses was not long enough (only 4 months). Lomustine was restarted and administered every 3 weeks. Prophylactic antibiotics were administered because she had low white blood cell counts after chemotherapy. Rosie again improved until at her 6th dose (late June 2008) her owner reported that she was stumbling again and had difficulty focusing on objects. A different chemotherapy drug, Cytarabine, was started and administered under her skin every 2 weeks. This was administered three times and improved her attitude and stumbling, but she still had difficulty focusing on objects.
Rosie passed away at home in August of 2008, just shy of 2 years after beginning her valiant fight against her pituitary cancer. Her quality of life during the 2 years of treatment was wonderful. She did begin to show clinical signs of progressive disease at 10 months after the first course of radiation therapy finished. If her owner had decided not to pursue any more treatment after the first course of radiation, Rosie would have survived as predicted. The reirradiation and chemotherapy allowed her to have another year. Rosie’s success was due to her amazing spirit and strong will, as well as the decisions made by her owner. We all miss Rosie and will always think of her as a miracle girl.