Survival analysis of 97 cats with nasal lymphoma: a multi-institutional retrospective study (1986-2006).

BACKGROUND: Feline nasal lymphoma (NLSA) is a condition for which no standard of care exists. HYPOTHESIS: There is no difference in survival times of cats with NLSA treated with single or multimodality therapy. ANIMALS: Records from 97 cats diagnosed with NLSA were examined. METHODS: The purpose of this retrospective study was to compare the survival times of cats with NLSA treated with radiation therapy (RT) alone, chemotherapy alone, or RT + chemotherapy and identify potential prognostic variables that affected survival. Cats were grouped according to therapy: RT + chemotherapy (n = 60), RT alone (n = 19), or chemotherapy alone (n = 18). RESULTS: Survival was calculated with 2 methods. The 1st survival analysis (method A) included all cats, but counted only deaths caused by progressive NLSA. The median survival time (MST), regardless of therapy modality, was 536 days. The 2nd survival analysis (method B) also included all cats and counted all deaths, regardless of cause, as events. The overall MST calculated for all deaths was 172 days. A negative independent prognostic variable identified was anemia (P < .001), and positive independent prognostic variables were a complete response to therapy (P < .001) and total radiation dose >32 Gy (P= .03). CONCLUSIONS AND CLINICAL IMPORTANCE: There were no significant differences in survival times among the 3 treatment groups but these results suggest that the addition of higher doses of RT to a cat's treatment protocol may control local disease and therefore influence survival.

Clinical and lymphohematologic responses after bone marrow transplantation in sibling and unrelated donor-recipient pairs of cats.

Conditions necessary for establishment of a graft, posttransplant supportive care and complications, and lymphohematopoietic reconstitution after bone marrow transplantation were evaluated in 7 cats. Donor-recipient pairs were selected on the basis of low mutual reactivity in one-way mixed lymphocyte reactions. Before transplantation, cats were given marrow ablative (7 Gray) total-body gamma irradiation. Cyclosporine A was administered to cat 7, which was given marrow from an unrelated donor. Rapid hematologic recovery was attained in 5 of 5 (cats 1 to 5) sibling bone marrow recipients and 1 (cat 7; cyclosporine A-treated) of 2 recipients from unrelated donors. Lymphocyte recovery was prolonged, requiring up to 100 days to attain reference concentrations. Lymphocyte blastogenic responses were below reference range in 2 of 3 cats (cats 1 and 3) examined approximately 1 to 3 months after transplantation. Serum IgG concentrations determined 1 to 6 months after transplantation were within reference range in cats 1 to 5 which were given sibling bone marrow. Fatal infections did not develop in cats that had established grafts. Antimicrobial-responsive fevers did develop, but were generally detected only when granulocyte counts were low (less than 1 x 10(9) cells/L). Clinical signs of disease in the immediate posttransplant period consisted of hepatic lipidosis (fatal) in cat 4, hepatitis (mild graft-vs-host disease) in cat 3, and immune-mediated hemolytic anemia and thrombocytopenia in cat 7. Cats with hepatitis and immune-mediated disease responded to immunosuppressive therapy.

Neurologic abnormalities as the predominant signs of neoplasia of the nasal cavity in dogs and cats: seven cases (1973-1986).

Neurologic abnormalities were the predominant historic and physical findings in 5 dogs and 2 cats with primary nasal cavity tumors that had invaded the cranial vault. Seizures, behavior changes, and obtundation were the most common signs. Other neurologic signs included paresis, ataxia, circling, visual deficit, and proprioceptive deficit. Although 1 dog and 2 cats had historic findings of mild respiratory disease, no physical abnormalities related to the respiratory tract were found in any of the 7 animals. Nasal cavity neoplasia was suggested by radiographic and computed tomographic studies and was confirmed histopathologically in each case. The nasal tumor types in the 5 dogs were epidermoid carcinoma (n = 1), adenocarcinoma (n = 2), solid carcinoma (n = 1), and anaplastic chondrosarcoma (n = 1). An esthesioneuroblastoma was found in each cat. Radiation therapy was effective for 3 months in palliating the clinical signs in the 2 dogs in which it was used. Neoplasia of the nasal cavity should be considered in the differential diagnosis for animals with neurologic signs suggestive of cerebral disorders.

Thrombocytosis associated with a myeloproliferative disorder in a dog.

A dog with a myeloproliferative disorder and thrombocytosis had clinical signs that were consistent with a diagnosis of essential thrombocythemia. The dog was treated with aspirin, radioactive phosphorus, and melphalan. Eighteen months after referral, the disorder progressed to chronic granulocytic leukemia, and treatment was switched to hydroxyurea. Fourteen months later, the dog was euthanatized because of uncontrollable atrial fibrillation.

Probable essential thrombocythemia in a dog.

Essential thrombocythemia (ET) in an 11-year-old dog was characterized by persistently high platelet counts (range, 4.19 X 10(6)/microliters to 4.95 X 10(6)/microliters, abnormal platelet morphology, marked megakaryocytic hyperplasia in the bone marrow, absence of circulating megakaryoblasts, and history of splenomegaly and gastrointestinal bleeding. Increased numbers of megakaryocytes and megakaryoblasts (15% to 20%) in the bone marrow were confirmed by a positive acetylcholinesterase reaction. Another significant finding was the presence of a basophilia in blood (4,836/microliters) and bone marrow. The marked persistent thrombocytosis, absence of reactive (secondary) thrombocytosis, abnormal platelet morphology, and quantitative and qualitative changes in the megakaryocytic series in the bone marrow suggested the presence of a myeloproliferative disease. Cytochemical and ultrastructural findings aided in the diagnosis of ET. The dog was treated with radiophosphorus. The results was a rapid decline in the numbers of megakaryoblasts and megakaryocytes in the bone marrow and platelets and basophils in the peripheral blood. The dog died unexpectedly of acute necrotizing pancreatitis and diabetes mellitus before a complete remission was achieved.

Radiophosphorus (32P) treatment of bone marrow disorders in dogs: 11 cases (1970-1987).

Between March 1970 and February 1987, radiophosphorus (32P) was used to treat bone marrow disorders in 6 dogs; 4 had polycythemia vera and 2 had essential thrombocythemia. Activities of 32P given initially ranged from 2.4 to 3.3 mCi/m2. Four dogs responded well to 32P treatment, with gradual resolution of high RBC or platelet counts. Two of these dogs died of intercurrent disease unrelated to their bone marrow disorder, before blood counts could be stabilized. Two dogs did not respond to the initial 32P treatment nor to additional treatments with 32P, and had clinical signs and blood counts stabilized by use of phlebotomy or chemotherapeutic agents. We reviewed and analyzed 5 other cases of bone marrow disorders in dogs treated with 32P and included the findings from their records with the records of our 6 dogs in this retrospective analysis. Of the 8 dogs with polycythemia vera treated with 32P, 5 were given a single treatment that controlled clinical signs and blood counts for the remainder of the follow-up period. Of the 3 dogs treated for thrombocytosis with 32P, 2 had blood counts that responded to a single treatment.

Response to radiation therapy of recurrent lymphangioma in a dog.

A recurrent lymphangioma in a 5-year-old Airedale Terrier was treated successfully with cobalt-60 radiation. The neoplasm had been excised twice before being treated with radiation.

Prognostic factors for radiation treatment of mast cell tumor in 85 dogs.

Ninety-five mast cell tumors in 85 dogs were therapeutically irradiated. Median and mean tumor-free times for dogs were 17 and 62.7 months, respectively. Percentages of dogs tumor-free at 1 and 2 years were 78.8 and 77%, respectively. Factors significantly affecting tumor-free time were clinical stage (P less than 0.001) and neoplasm location (P = 0.019). Median and mean survival times were 19 and 61.2 months, respectively. Survival rates at 1 and 2 years were 76.2 and 73.2%, respectively. Prognostic factors that significantly affected survival rates were clinical stage (P less than 0.001), neoplasm grade (P = 0.006), and neoplasm location (P = 0.034). Radiation therapy was an effective treatment of mast cell tumor in dogs.

Reirradiation of tumors in cats and dogs.

Fifty-one cats and dogs with tumor recurrence after irradiation were treated with a second course of radiotherapy, using either teletherapy or brachytherapy. Eighty-six percent of the tumors had partial or complete response at 2 months after reirradiation. Tumor response was significantly (P = 0.041) affected when the interval between the 2 courses of irradiation was greater than 5 months. The estimated local tumor control rate was 38% at 1 year after reirradiation. Of all the factors examined, complete response at 2 months, reirradiation field size less than or equal to 10 cm2, and reirradiation dose greater than 40 gray emerged as predictors of local tumor control. The estimated overall survival rate was 47% at 2 years. Tumor location had a significant (P = 0.001) influence on overall survival; animals with cutaneous tumors had the longest survival times, and those with oral tumors had the shortest survival times. The other significant (P = 0.001) factor affecting overall survival time was the field size of the reirradiated site. Estimated survival time after reirradiation was 41% at 1 year. Favorable prognostic indicators were complete response at 2 months and location of tumor; animals with skin tumors had a favorable prognosis. The acute effects of reirradiation on normal tissues were acceptable, but 12% of the animals had severe delayed complications. Significant risk of complications after reirradiation was associated with squamous cell carcinoma (P = 0.015) and reirradiated field size greater than 30 cm2 (P = 0.056). When the interval between irradiations was greater than 5 months, the risk of complications was significantly (P = 0.022) lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroid carcinoma causing hyperthyroidism in cats: 14 cases (1981-1986).

The medical records of 14 hyperthyroid cats with thyroid carcinoma were analyzed retrospectively regarding historical, physical, laboratory, and thyroid scintiscan findings, treatment, and treatment outcome. Breed predilection was not detected, and older castrated male cats were most commonly affected. The most common clinical signs detected by owners were weight loss, polydipsia, polyuria, polyphagia, hyperactivity, and anorexia. Physical examination findings included tachycardia, palpable cervical mass, hyperactivity, cardiac murmur, and abnormal coat. Common abnormal laboratory findings were high serum thyroxine and triiodo-thyronine concentrations and high serum alanine transaminase, alkaline phosphatase, and aspartate transaminase activities. Azotemia, hyperphosphatemia, and hyperglycemia were noticed less frequently. The most common thyroid scintiscan findings were multiple nodular areas of high radionuclide uptake in the cervical region, thoracic inlet, and cranial mediastinum. The most common morphologic diagnosis was mixed compact and follicular carcinoma, with follicular and papillary carcinomas being less common. Most cats responded well to treatment of the thyroid tumor, with rapid resolution of the historical and physical examination findings. The most common necropsy findings were local tumor invasion, regional lymph node metastases, cardiomyopathy, and interstitial nephritis.

A multicompartmental model for iodide, thyroxine, and triiodothyronine metabolism in normal and spontaneously hyperthyroid cats.

A comprehensive multicompartmental kinetic model was developed to account for the distribution and metabolism of simultaneously injected radioactive iodide (iodide*), T3 (T3*), and T4 (T4*) in six normal and seven spontaneously hyperthyroid cats. Data from plasma samples (analyzed by HPLC), urine, feces, and thyroid accumulation were incorporated into the model. The submodels for iodide*, T3*, and T4* all included both a fast and a slow exchange compartment connecting with the plasma compartment. The best-fit iodide* model also included a delay compartment, presumed to be pooling of gastrosalivary secretions. This delay was 62% longer in the hyperthyroid cats than in the euthyroid cats. Unexpectedly, all of the exchange parameters for both T4 and T3 were significantly slowed in hyperthyroidism, possibly because the hyperthyroid cats were older. None of the plasma equivalent volumes of the exchange compartments of iodide*, T3*, or T4* was significantly different in the hyperthyroid cats, although the plasma equivalent volume of the fast T4 exchange compartments were reduced. Secretion of recycled T4* from the thyroid into the plasma T4* compartment was essential to model fit, but its quantity could not be uniquely identified in the absence of multiple thyroid data points. Thyroid secretion of T3* was not detectable. Comparing the fast and slow compartments, there was a shift of T4* deiodination into the fast exchange compartment in hyperthyroidism. Total body mean residence times (MRTs) of iodide* and T3* were not affected by hyperthyroidism, but mean T4* MRT was decreased 23%. Total fractional T4 to T3 conversion was unchanged in hyperthyroidism, although the amount of T3 produced by this route was increased nearly 5-fold because of higher concentrations of donor stable T4. Analysis of the data indicates that the increased overall T4* turnover (decreased MRT) in hyperthyroidism is due to increased losses through pathways other than T3 formation. Conjugation, with subsequent deiodination, is proposed as one possibly important pathway. Results of this multicompartmental analysis are compared with those of noncompartmental analysis of the same data and with results of similar model analyses in other species.

Predictive value of tracer studies for 131I treatment in hyperthyroid cats.

In 76 cats with hyperthyroidism, peak thyroidal radioiodine (131I) uptakes and effective half-lives were determined after administration of tracer and therapeutic activities of 131I. In 6 additional hyperthyroid cats, only peak thyroidal uptakes after administration of tracer and therapeutic activities of 131I were determined. Good correlation was found between peak thyroidal uptakes of tracer and therapeutic 131I; however, only fair correlation was observed between effective half-lives. In 79% of the cats, the effective half-life for therapeutic 131I was longer than that for tracer 131I. After administration of therapeutic activity of 131I, monoexponential and biphasic decay curves were observed in 51 and 16 cats, respectively. Using therapeutic kinetic data, radiation doses to the thyroid gland were calculated retrospectively on the basis of 2 methods for determining the activity of 131I administered: (1) actual administration of tracer-compensated activity and (2) hypothetic administration of uniform activity (3 mCi). Because of the good predictive ability of tracer kinetic data for the therapeutic kinetic data, the tracer-compensated radiation doses came significantly (P = 0.008) closer to the therapeutic goal than did the uniform-activity doses. In addition, the use of tracer kinetic information reduced the extent of the tendency for consistently high uniform-activity doses. A manual method for acquiring tracer kinetic data was developed and was an acceptable alternative to computerized techniques. Adoption of this method gives individuals and institutions with limited finances the opportunity to characterize the iodine kinetics in cats before proceeding with administration of therapeutic activities of 131I.

Management of pleural effusion secondary to metastatic adenocarcinoma in a dog.

A 4-year-old spayed Collie-type dog was evaluated for pleural effusion secondary to metastatic adenocarcinoma with no identifiable primary tumor. For 48 weeks, chemotherapy and thoracentesis palliated clinical signs associated with pleural effusion. At week 49, 5 mCi of chronic phosphate P32 (32P) suspension was injected into the right pleural space. Pleural effusion was not detected for 14 weeks after 32P administration (week 63). In week 64, 32P suspension was readministered by injecting 7.5 mCi into the right hemithorax and 2.5 mCi into the left. Pleural effusion was again detected 3 weeks later (week 67), and the dog was treated with additional chemotherapy. Death, at week 72, was caused by disseminated intravascular coagulopathy.

Serial determination of thyroxine concentrations in hyperthyroid cats.

Serum thyroxine (T4) concentrations of 10 hyperthyroid cats were measured at hourly intervals between 9 AM and 4 PM. In 5 cats, blood samples were obtained by jugular venipuncture; the remaining 5 cats had blood samples obtained from jugular catheters. Over the 7-hour period, a significant temporal (diurnal) variation was not identified in the serum T4 concentrations of the cats (P greater than 0.01). The lowest mean serum T4 concentration (9.1 micrograms/dl) was measured at 3 PM and was 14.2% less than the highest mean serum T4 concentration (10.6 micrograms/dl) measured at 9 AM. Though there were fluctuations in serum T4 concentrations during the 7-hour period, the differences were not systematic. The maximal variation in serum T4 concentrations over the 7-hour period averaged less than 21%. Despite the random variations during the 7-hour period, none of the measured serum T4 concentrations was in the normal range. Measurement of serum T4 concentration from randomly obtained blood samples was determined to be reliable for diagnosing feline hyperthyroidism.

Effect of sampling site on early kinetics of blood radioiodide and pertechnetate.

Radioiodide (I) and radiopertechnetate (TcO4) were sampled simultaneously from left ventricle, right atrium, and femoral vein early after intravenous injection to pentobarbital sodium-anesthetized cats. Concentrations of both tracers in femoral vein blood was lower than in left ventricular (arterial) blood, with rapid narrowing of the differences over 20 min and gradual approach to steady state. Right atrial blood concentrations were intermediate. When these data were fitted to three-compartment mamillary models, representing blood and tissue pools, compartment size and kinetics differed according to which sampling site was taken as representative of each cat's blood. We have developed a model incorporating subcompartmentalization of the blood with an exchange compartment connecting to the pulmonary circulation as well as compartments exchanging with peripheral sites. With the use of this model, all data sets fitted well. The pulmonary exchange compartment and a large rapid exchange compartment in the femoral vein drainage areas are essential to reconciling the differences among sampling sites.

Peripheral metabolism of thyroid hormones and iodide in healthy and hyperthyroid cats.

The metabolic clearance rate, volume of distribution, and fractional clearance rate of thyroxine (T4), triiodothyronine (T3), and iodide were calculated for 6 healthy and 7 hyperthyroid cats, using single-compartmental and noncompartmental methods of analysis. The mean T4 volume of distribution of the hyperthyroid cats was 32.0% less than that of the healthy cats; it was the only variable that was significantly different (P less than 0.05) between these 2 groups of cats. The mean fractional clearance rate of T4 in the hyperthyroid cats was 53.2% greater than that in the healthy cats, but this difference was not significant. Hyperthyroid cats had no significant differences in T3 or iodide kinetic variables when compared with those in healthy cats. Single-compartmental analysis significantly overestimated T4 kinetic variables of healthy cats and T4, T3, and iodide kinetic variables of hyperthyroid cats when compared with the noncompartmental method of analysis.

Intraoperative radiotherapy of carcinoma of the prostate gland in ten dogs.

Ten dogs with carcinoma of the prostate gland were treated with intraoperative orthovoltage radiotherapy (radiation therapy to surgically exposed tumors). Seven dogs had tumor growth confined to the prostate gland and urethra, and 3 dogs had carcinoma of the prostate gland and regional lymph node involvement. Total radiation doses delivered to the prostate gland of 9 dogs and the affected regional lymph nodes of 3 dogs, using orthovoltage x-rays, ranged from 20 to 30 Gy. Carcinoma of the prostate gland of one dog was intraoperatively irradiated to 15 Gy and was then given a boost of 40 Gy, using cobalt-60 teletherapy. Survival time ranged from 41 to 750 days after intraoperative radiotherapy. Median and mean survival times for all dogs were 114 and 196 days, respectively. The median survival time for 7 dogs with localized prostatic carcinoma was 180 days, which was longer, but not significantly longer (P = 0.09), than the median survival time of 80 days in 3 dogs having prostatic carcinoma and metastatic disease. Intraoperative radiotherapy was tolerated well and caused complete response in 5 dogs. However, surgical complications in 2 dogs, which had subtotal lymphadenectomy or prostatic biopsy performed concurrently at the time of irradiation, resulted ultimately in their deaths. The 2 other dogs with metastatic disease and 1 dog without metastatic disease also had poor response to treatment. Our results indicated that intraoperative radiotherapy is an effective treatment for localized prostatic carcinoma in the dog.