Sequential low-dose rate half-body irradiation and chemotherapy for the treatment of canine multicentric lymphoma.

BACKGROUND: Sequential half-body irradiation (HBI) combined with chemotherapy is feasible in treating canine lymphoma, but prolonged interradiation intervals may affect efficacy. A 2-week interradiation interval is possible in most dogs receiving low-dose rate irradiation (LDRI) protocols at 6 Gy dose levels. HYPOTHESIS: LDRI incorporated into a cyclophosphamide, doxorubicin, vincritine, and prednisone (CHOP)-based chemotherapy protocol is effective for the treatment of lymphoma in dogs. ANIMALS: Thirty-eight client-owned animals diagnosed with multicentric lymphoma. METHODS: Retrospective study evaluating the efficacy and prognostic factors for the treatment of canine lymphoma with sequential HBI and chemotherapy. RESULTS: The median 1st remission was 410 days (95% confidence interval [CI] 241-803 days). The 1-, 2-, and 3-year 1st remission rates were 54, 42, and 31%. The median overall survival was 684 days (95% CI 334-1,223 days). The 1-, 2-, and 3-year survival rates were 66, 47, and 44%. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggest that treatment intensification by a 2-week interradiation treatment interval coupled with interradiation chemotherapy is an effective treatment for dogs with lymphoma.

Hyperthermic enhancement of rhodamine 123 cytotoxicity in B16 mouse melanoma cells in vitro.

The effect of elevated temperature on cytotoxicity of rhodamine 123 (R123) was tested in vitro on B16 mouse melanoma cells. Simultaneous 1-h exposure to R123 and hyperthermia (43 degrees C for 1 h) resulted in marked enhancement of R123 cytotoxicity. Thermal enhancement of R123 cytotoxicity occurred at temperatures as low as 38 degrees C. Heat treatment (43 degrees C for 1 h) given immediately before or after R123 exposure (37 degrees C for 1 h) yielded no significant increase in cytotoxicity over that expected for strict additivity. The effects of heat on two mechanisms reported to be associated with R123 cytotoxicity were evaluated: (a) target inactivation by R123; and (b) R123 intracellular accumulation. Hyperthermia caused an increased rate of target inactivation by R123 and also caused an increased net intracellular accumulation of R123. This indicates that at least two mechanisms are responsible for the synergistic cytotoxicity of R123 and hyperthermia.

Treatment of MRI-Diagnosed Trigeminal Peripheral Nerve Sheath Tumors by Stereotactic Radiotherapy in Dogs.

BACKGROUND: Stereotactic radiotherapy (SRT) is an emerging technique for treating tumors in animals. OBJECTIVES: To assess the outcome of dogs with suspected intracranial trigeminal nerve peripheral nerve sheath tumors (PNST) treated with SRT. ANIMALS: Eight dogs with presumptive PNST. METHODS: This was a retrospective study of dogs identified by searching UC Davis Veterinary Medical Teaching Hospital medical records for dogs treated with SRT for a presumed PNST. Presumptive diagnosis was based on magnetic resonance imaging. SRT was delivered in 3 dose fractions of 8 Gray (Gy) on consecutive days or every other day to a total dose of 24 Gy. RESULTS: Median disease-specific survival was 745 days (range: 99-1375 days, n = 6). No signs of acute adverse effects of radiation treatment were recorded. Late radiation effects versus tumor progression could not be confirmed histopathologically because of few animals undergoing necropsy. CONCLUSIONS AND CLINICAL IMPORTANCE: This study provides preliminary evidence that dogs with PNST benefit from SRT in terms of long-term survival. The treatment appears to be well tolerated and requires fewer anesthetic events for animals compared to full-course radiation.

Concurrent irradiation and intratumoral chemotherapy with cisplatin: a pilot study in dogs with spontaneous tumors.

PURPOSE: A preliminary study was undertaken to determine whether the addition of a collagen gel in the formulation of cisplatin for intratumoral administration of cisplatin affected platinum plasma concentrations. A second study was undertaken to determine the local effects of intratumoral administration of cisplatin mixed with collagen given concurrently with irradiation. METHODS AND MATERIALS: Twelve dogs with advanced stage tumors were administered a dose of 0.25 mg of cisplatin per kg of body weight intratumorally with or without collagen using a two-period crossover design. Twelve additional dogs received concurrent irradiation (48 Gy) delivered in 12 fractions over 4 weeks and intratumoral cisplatin chemotherapy given the first day of each week at a dose of 0.5 mg of cisplatin per cm3 of tissue. RESULTS: The cumulative cisplatin plasma concentrations varied over time from dog to dog, but the use of collagen in the formulation significantly reduced the systemic exposure of cisplatin. For the dogs given intratumoral cisplatin and irradiation, complete responses were observed in 10 dogs. Seven dogs had local recurrence. One dog had tumor recurrence in the radiochemotherapy field and six dogs had recurrence at the margin of the radiochemotherapy field, but within the irradiation field. Normal tissue reactions were similar in the radiochemotherapy field and in the margin treated with radiation only. Cumulative effect of repeated intratumoral administration on plasma concentration of cisplatin was not observed. CONCLUSIONS: These findings provide support for an extended investigation of this combined regimen. The lack of systemic toxicity associated with intratumoral administration of cisplatin mixed with collagen may allow a safe clinical evaluation of the interaction between cisplatin and radiation.

Analysis of the equine tumor suppressor gene p53 in the normal horse and in eight cutaneous squamous cell carcinomas.

Wild type equine p53 was amplified between exons 2 and 9 by the polymerase chain reaction using primers designed from conserved regions in other species. An 828 base pair region, corresponding to codons 25-313 of human p53, was sequenced in both directions. Human and equine amino acid sequences were 87% homologous in this region and 96% homologous in conserved domains II-V. Of eight equine cutaneous or mucocutaneous squamous cell carcinomas directly sequenced from exons 5-8, two had p53 point mutations resulting in single amino acid substitutions.

Tissue distribution of transdermal toremifene.

PURPOSE: Toremifene is an orally administered triphenylethylene derivative with antiestrogenic activity that is primarily used in the treatment of patients with metastatic breast cancer. The purpose of this study was to evaluate the therapeutic advantage of local (transdermal) administration of toremifene in several animal models. Local (subcutaneous and skin) versus systemic concentrations of toremifene were evaluated serially following transdermal application of the drug. With high local concentrations and minimal distribution to other organs via the circulation, topical toremifene may deliver maximal therapeutic effects to local tissue while avoiding the side effects seen with systemic therapy. METHODS: Three animal models (nude mice, baboons, and a horse) were used to examine topically administered toremifene for kinetic measurements. RESULTS: In nude mice implanted subcutaneously with MDA-MB-231 human breast tumors, topical toremifene (2.5 mg/day x 5 days) produced greater than 50-fold higher tumor concentrations compared with intraperitoneal (i.p.) administration (1.0 mg/day x 5 days). Systemic distribution in plasma, uterus, and liver was lower following topical than following i.p. administration. In nude mice inoculated subcutaneously with estrogen receptor-positive (ER +) MCF-7 human breast cancer cells, topical toremifene and 4-hydroxytoremifene (4-OH) prevented tumor growth in the presence of estradiol. In four nontumor-bearing baboons that were given transdermal toremifene, relatively high distribution of drug was noted in normal breast tissue and fat, compared with undetectable serum concentrations. Finally, a new topical formulation of toremifene (a gel preparation for human use, Orion-Farmos, Finland) achieved high local tumor toremifene concentrations in a horse melanoma, with minimal systemic distribution. CONCLUSIONS: Transdermal toremifene can achieve high local tissue concentrations with minimal systemic distribution.

Lymph node uptake of interstitially delivered particulate contrast media before and after irradiation in dogs.

RATIONALE AND OBJECTIVES: The authors' purpose was to assess the effects of ionizing radiation on the uptake and distribution of interstitially delivered particulate contrast medium in normal lymph nodes in dogs. MATERIALS AND METHODS: Two milliliters of an iodinated nanoparticle suspension (NC 67722 Sterile Suspension, 76 mg of iodine per milliliter) was injected subcutaneously or submucosally into nine normal adult beagle dogs. Targeted lymph node groups were evaluated with computed tomography (CT). Region-of-interest analysis was used to estimate volume, attenuation, and iodine concentration of the opacified nodes and nonopacified contralateral nodes on CT images obtained before and 24 hours after the injection. All right-sided and some left-sided lymph nodes were irradiated with 50 Gy in 25 fractions of 2 Gy per day, beginning 28-35 days after the CT examination. Contrast medium administration and quantitative CT imaging were performed again 3 months after irradiation. RESULTS: Contrast material uptake resulted in a twofold increase in node volume before irradiation (P < .0001). Mean attenuation of contrast-enhanced nodes increased to 230-330 HU from a precontrast enhancement value of 36.5 HU. After irradiation, opacified node volumes decreased to approximately 25%-50% of their preirradiation volumes (P < .02). Contrast material uptake decreased 10%-15% after irradiation but was not significantly less than preirradiation uptake. Qualitatively, no substantial difference in contrast material distribution existed between irradiated and nonirradiated nodes. CONCLUSION: An elective irradiation dose decreased lymph node size, but the imaging characteristics of opacification were not otherwise appreciably altered 3 months after irradiation.

In situ analysis of cellular proliferation in canine, feline and equine tumors by immunohistochemistry: a comparison of bromodeoxyuridine, proliferating cell nuclear antigen, and interchromatin-associated antigen immunostaining techniques.

Cell proliferation in canine, feline, and equine tumors was evaluated using immunohistochemical detection of in vitro 5-bromodeoxyuridine (BrdU) incorporation, proliferating cell nuclear antigen (PCNA), and interchromatin-associated antigen (p105). Ten tumors in each species were analyzed. The tumor proliferative fraction (PF) was defined as the percentage of labeled nuclei for 5,000 tumor nuclei counted. Immunoreactivity was observed with all techniques in all species. A good correlation was observed between the proliferative fractions measured with the BrdU (PFBrdU) and PCNA (PFPCNA) techniques (rs = 0.523, P = 0.0026). There was no correlation between the PFs measured with the BrdU (PFBrdU) and p105 (PFP105) techniques. Using the median values obtained from the different approaches as cutoff points to define slowly and rapidly proliferating tumors, there was an 80% agreement (P = 0.009) between PFBrdU and PFPCNA and no agreement between PFBrdU and PFP105. The results of this study indicate that both BrdU and PCNA labeling methods can be used reliably for identifying proliferating cells in animal tumors. In addition, PCNA could be used to replace the BrdU method to assess tumor proliferative fraction because it does not require pretreatment of tissues.

Iridium-192 interstitial brachytherapy for equine periocular tumours: treatment results and prognostic factors in 115 horses.

One hundred and fifteen horses with periocular tumours were treated with iridium-192 interstitial brachytherapy. Tumours included squamous cell carcinomas (n = 52) and sarcoids (n = 63). All horses were scheduled to receive 60 Gy (minimal tumour dose) given at a low dose rate (0.034 +/- 0.010 Gy/h). The mean and median follow-up times to last contact or death were 24 and 16 months, respectively. Chronic radiation reactions included palpebral fibrosis (10.4%), cataract (7.8%), keratitis and corneal ulceration (6.9%). Cosmetic changes included permanent epilation (21.7%) and hair dyspigmentation (78.3%). The one year progression-free survival (PFS) rates for sarcoids and carcinomas were 86.6% and 81.8% and the 5 year PFS rates were 74.0% and 63.5%, respectively. The horse age and sex, histopathological type, anatomical subsite and classification (WHO T1-3) were included in the analysis of prognostic factors. The only significant prognostic factor that independently affected PFS time was the WHO T-classification (P = 0.009, relative risk = 0.85). When compared to horses with T1 lesions, horses with T2 and T3 lesions had 1.8-fold and 3.4-fold increased risks, respectively, for tumour recurrence (relative excess risk). The one year PFS rates for T1, T2 and T3 lesions were 95.2%, 89.5% and 66.2%, respectively. The 5 year PFS rates were 72.2%, 74.0% and 53.1%, respectively. The results of this study indicate that irradiation is an effective treatment option for horses with T1-2 lesions and should be part of a combined treatment modality for horses with T3 lesions.

Equine basal cell tumors: 6 cases (1985-1999).

Basal cell tumors are rare benign tumors in horses. Over a 15-year period, 6 horses were diagnosed with basal cell tumors. The tumors were well-circumscribed. freely moveable, firm, raised papules, nodules, or masses that ranged from 0.6 to 5 cm in diameter. Five of the 6 tumors were ulcerated. Based on gross appearance, the tumors were diagnosed as sarcoids, and 1 was diagnosed as a melanoma. The range of age of affected horses was 6-26 years. The tumors were identified clinically 1 week to 3 years before excision. In 4 horses for which information was available, complete surgical excision was curative with no recurrence 4 months to 2 years after removal.

Prospective randomized comparison of intravenous versus subcutaneous administration of radioiodine for treatment of hyperthyroidism in cats.

One hundred twenty cats with hyperthyroidism were treated with radioiodine (131I); 60 cats were administered radioiodine SC, and 60 cats were administered radioiodine IV. Before treatment, radioactive tracer studies were performed on each cat to determine peak radioactive iodine uptake and effective half-life. These data were used to calculate the dose of radioiodine that would have to be given to each cat to deliver 150 Gy to the thyroid tissue. The 2 groups of cats were similar with regard to age, tracer study results, and radioiodine dose. Mean estimated thyroid mass was larger for cats treated IV, but mean serum thyroxine concentration was higher for cats treated SC. Route of administration did not affect thyroidal uptake of radioiodine. However, radiation exposure of personnel was significantly lower with SC administration than with IV administration, even when IV catheterization was performed Eighty-five percent of cats treated IV and 84% of cats treated SC were euthyroid 4 years after treatment. Six percent of the cats became hypothyroid after treatment. When compared with IV administration, SC administration of radioiodine appeared to be as effective for treatment of hyperthyroidism, safer to personnel, and less stressful to the cats.

Intratumoral administration of carboplatin for treatment of squamous cell carcinomas of the nasal plane in cats.

OBJECTIVE: To develop a slow-release carboplatin formulation for intratumoral administration to cats. DESIGN: Preliminary study to analyze pharmacokinetic effects of purified sesame oil in the carboplatin formulation for intratumoral administration, and a second study to evaluate the efficacy and toxicosis of intratumoral administration of carboplatin in purified sesame oil. ANIMALS: 23 cats with squamous cell carcinomas of the nasal plane. PROCEDURE: Eight cats with advanced-stage tumors were submitted to intratumoral administration of 100 mg of carboplatin/m2 of body surface area, with or without purified sesame oil, using a two-period, cross-over design. Fifteen additional cats were treated by intratumoral administration of carboplatin in purified sesame oil. Four weekly intratumoral chemotherapy injections of carboplatin in purified sesame oil at a dosage of 1.5 mg/cm3 of tissue were given. RESULTS: Purified sesame oil in the formulation significantly reduced systemic exposure to carboplatin and drug leakage from the sites of injection. Cumulative effects of repeated intratumoral administrations on plasma concentrations of carboplatin were not observed. Systemic toxicosis was not observed, and local toxicosis was minimal. Healing of ulcerated lesions was not compromised. Rates of complete clinical tumor clearance and complete response were 67 and 73.3%, respectively. Product-limit estimates of mean progression-free survival times was 16 +/- 3.3 months. The 1-year progression-free survival rate was 55.1 +/- 13%. Local recurrence was observed in 7 cats; 4 had marginal tumor recurrence, and 3 had in-field and marginal tumor recurrence. CONCLUSIONS: Intratumoral carboplatin chemotherapy is safe and effective for cats with squamous cell carcinoma of the nasal plane. Future studies to improve treatment efficacy could include evaluation of increased dose-intensity as well as combination of this modality with radiotherapy. CLINICAL RELEVANCE: Intratumoral administration of carboplatin in a water-sesame-oil emulsion was found to be a practical and effective new treatment for facial squamous cell carcinomas in cats.

Bovine papillomavirus DNA in neoplastic and nonneoplastic tissues obtained from horses with and without sarcoids in the western United States.

OBJECTIVE: To determine the incidence of bovine papillomavirus (BPV) type 1 or 2 in sarcoids and other samples of cutaneous tissues collected from horses in the western United States. ANIMALS: 55 horses with sarcoids and 12 horses without sarcoids. PROCEDURE: Tissue samples (tumor and normal skin from horses with sarcoids and normal skin, papillomas, and nonsarcoid cutaneous neoplasms from horses without sarcoids) were collected. Tissue samples were analyzed for BPV-1 or -2 DNA, using a polymerase chain reaction (PCR) and restriction fragment length polymorphism. The PCR products from 7 sarcoid-affected horses were sequenced to evaluate percentage homology with expected sequences for BPV-1 or-2. RESULTS: Most (94/96, 98%) sarcoids contained BPV DNA. Sixty-two percent of the tumors examined had restriction enzyme patterns consistent with BPV-2. Thirty-one of 49 (63%) samples of normal skin obtained from horses with sarcoids contained BPV DNA. All samples subsequently sequenced had 100% homology with the expected sequences for the specific viral type. All tissues from healthy horses, nonsarcoid neoplasms, and papillomas were negative for BPV DNA. CONCLUSIONS AND CLINICAL RELEVANCE: Bovine papillomaviral DNA was detected in essentially all sarcoids examined. There appears to be regional variation in the prevalence of viral types in these tumors. The fact that we detected viral DNA in normal skin samples from horses with sarcoids suggests the possibility of a latent viral phase. Viral latency may be 1 explanation for the high rate of recurrence following surgical excision of sarcoids.

Comparison of intratumoral administration of cisplatin versus bleomycin for treatment of periocular squamous cell carcinomas in horses.

OBJECTIVE: To compare therapeutic benefits of intratumoral administration of cisplatin and bleomycin for squamous cell carcinoma of the eyelids in horses. ANIMALS: 25 horses with 27 T2-stage periocular squamous cell carcinomas. PROCEDURE: Horses were treated 4 times at 2-week intervals with a slow-release formulation of cisplatin (1 mg/cm3 of tissue) or bleomycin (1 IU/cm3 of tissue). A two-stage design was used to minimize the sample size in each treatment arm. RESULTS: The local control rate at 1 year for lesions treated with cisplatin was 93 +/- 6%, and with bleomycin was 78 +/- 10%. Difference in local control duration between the 2 treatment groups was not significantly different. A high tumor proliferative fraction index value was associated with a higher local (infield) control rate, but also with a higher risk of marginal and regional recurrences. Tumors with a low proliferative fraction index value (< 28%) had 9.5-times higher (P = 0.0411) risk of recurrence than those with a high index value. Local acute reactions were similar in the 2 treatment groups, and chronic reactions were not observed. CONCLUSIONS: Cisplatin and bleomycin were effective anticancer agents for carcinoma of the eyelid in horses. Based on therapeutic benefit and treatment cost, cisplatin was found to be a better choice for intratumoral chemotherapy of eyelid carcinomas. CLINICAL RELEVANCE: Results of this study confirm the value of intratumoral chemotherapy, using cisplatin, for treatment of cutaneous squamous cell carcinomas in horses.

Expression of a transforming gene (E5) of bovine papillomavirus in sarcoids obtained from horses.

OBJECTIVE: To determine expression of a transforming gene (E5) of bovine papillomavirus in sarcoids, other tumors, and normal skin samples collected from horses with and without sarcoids. SAMPLE POPULATION: 23 sarcoids and 6 samples of normal skin obtained from 16 horses with sarcoids, 2 samples of normal skin and 2 papillomas obtained from horses without sarcoids, and 1 papilloma obtained from a cow. PROCEDURE: Protein was extracted from tissue samples collected from horses and incubated with agarose beads covalently coupled to Staphylococcus aureus protein A and an anti-E5 polyclonal antibody. Following incubation, proteins were eluted from the beads and electrophoresed on a 14% polyacrylamide gel and transferred to a polyvinylidene difluoride membrane. The E5 protein was detected by use of western blot analysis, using a chemiluminescence detection system. RESULTS: All 23 sarcoids had positive results for expression of E5 protein. Quantity of viral protein appeared to vary among sarcoids. All other tissues examined had negative results for E5 protein. Highest expression for E5 protein was observed in biologically aggressive fibroblastic variants of sarcoids, compared with expression in quiescent tumors. CONCLUSIONS AND CLINICAL RELEVANCE: This study documented that activation and expression of the E5 gene is evident in sarcoids obtained from horses. These data support the conclusion that infection with bovine papillomavirus is important in the initiation or progression of sarcoids in horses. Treatment strategies designed to increase immune recognition of virally infected cells are warranted.

Effects of glutamine supplementation of an amino acid-based purified diet on intestinal mucosal integrity in cats with methotrexate-induced enteritis.

OBJECTIVE: To determine effects of glutamine-supplemented and glutamine-free amino acid-based purified diets, compared with a dry expanded diet, on intestinal structure and function in a model that used cats with methotrexate-induced enteritis. ANIMALS: 18 adult specific-pathogen-free cats. PROCEDURE: 12 cats were given intragastric feedings of an amino acid-based purified diet supplemented with glutamine (7% [wt:wt]) or an isonitrogenous amount of glycine and alanine; 6 cats consumed a dry expanded diet. After 21 days, cats received methotrexate (MTX; 11 mg/kg of body weight, IV). Intestinal permeability testing was performed immediately before and 66 hours after MTX administration. Celiotomy was performed 72 hours after MTX administration for aseptic removal of mesenteric lymph nodes, collection of full-thickness intestinal biopsy specimens, determination of intestinal cellular proliferation, and collection of aortic and portal venous blood samples for determination of arteriovenous amino acid concentrations across the intestine. RESULTS: Administration of MTX was associated with severe enterotoxicosis manifested as diarrhea (8/12 cats), vomiting (12/12), and positive results for bacterial culture of mesenteric lymph nodes (12/12) in cats receiving the purified diets, independent of glutamine supplementation. Diet did not affect villus tip length and villus surface area in the small intestine or cellular proliferation. Administration of MTX was associated with significantly increased intestinal permeability, which was not attenuated by glutamine supplementation. CONCLUSIONS: Feeding of a glutamine-supplemented amino acid-based purified diet was unable to preserve intestinal function in cats with MTX-induced enteritis. CLINICAL RELEVANCE: Intestinal morphologic alterations correlate poorly with intestinal function as measured by means of bacterial translocation and intestinal permeability.

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)

Megavoltage irradiation of pituitary macrotumors in dogs with neurologic signs.

OBJECTIVE: To assess the efficacy and determine prognostic factors of megavoltage irradiation for pituitary macrotumors in dogs with neurologic signs. DESIGN: Prospective clinical trial. ANIMALS: 24 dogs with pituitary macrotumor syndrome; 19 ACTH-secreting and 5 clinically endocrine-inactive tumors. PROCEDURE: Dogs were treated with 48 Gy of radiation during 4 weeks on an alternate-day schedule of 4 Gy/fraction. Three (12.5%) dogs did not complete the planned treatment because of progression of neurologic signs. RESULTS: A significant correlation was found between relative tumor size (i.e., size of tumor relative to calvarium size) and severity of neurologic signs and between relative tumor size and remission of neurologic signs after irradiation. In dogs with pituitary-dependent hyperadrenocorticism, a significant correlation was found between relative tumor size and plasma endogenous ACTH concentrations. Prognostic factors that independently affected duration of remission of neurologic signs were relative tumor size and endocrine activity. The prognostic factor that independently affected overall survival time was severity of neurologic signs. Prognostic factors of duration of eucortisolism were not found. Use of a large field of irradiation was associated with substantial damage to brain tissue. CLINICAL IMPLICATIONS: Because radiation therapy was effective for treatment of tumors of small relative size in dogs, early treatment of pituitary tumors should improve prognosis. Further improvements may be obtained, using protocols in which higher total radiation doses and smaller radiation dose fractions are given. Irradiation was effective for long-term control of functional pituitary macrotumors and resulted in acceptably low complication rates when small fields of radiation were used.

Analysis of prognostic factors and patterns of failure in dogs with malignant oral tumors treated with megavoltage irradiation.

OBJECTIVE: To determine quality and duration of progression-free survival (PFS) time in dogs with malignant oral tumors after definitive megavoltage irradiation, to analyze prognostic factors for PFS time and patterns of failure, and to analyze the influence of tumor recurrence and development of metastasis on survival. DESIGN: Prospective clinical trial. ANIMALS: 105 dogs with squamous cell carcinoma, fibrosarcoma, or malignant melanoma of the oral cavity without evidence of metastasis. PROCEDURE: Dogs were treated with 48 Gy over 4 weeks on an alternate-day schedule of 4 Gy/fraction. Multivariate analysis was done by use of Cox's regression model to determine significant prognostic factors and by use of a competing risk model to determine the differential effects of prognostic factors on type of, and time to, failure. In 8% of the dogs, severe acute radiation reactions in the final week of treatment resulted in treatment discontinuation. In 7.6% of the dogs, chronic radiation reactions, including bone necrosis and fistula formation, developed. RESULTS: Prognostic factors that independently affected PFS time were histologic type and tumor T stage. Histologic type significantly influenced pattern of failure, but not time to failure, whereas clinical stage significantly influenced time to failure, but not type of failure. CLINICAL IMPLICATIONS: Irradiation was a safe and effective treatment of malignant oral tumors. Because the local efficacy of radiation was influenced only by tumor size, early treatment of oral tumors should improve the prognosis. In dogs without tumor recurrence, systemic metastases, rather than regional metastases, limited long-term survival after radiation therapy.

Perioperative intratumoral administration of cisplatin for treatment of cutaneous tumors in equidae.

Twenty-seven horses (and 1 mule) with 32 histologically confirmed cutaneous tumors were studied to evaluate the effects of intratumoral injection of cisplatin initiated at the time of surgery. As a result of surgery, 9 of the wounds were closed primarily (5 sarcoids, 4 carcinomas) and 23 were left open to granulate (16 sarcoids, 6 carcinomas, 1 hamartoma). Chemotherapy consisted of 4 treatment sessions of intratumoral injection of cisplatin in purified sesame oil at 2-week intervals. The first treatment session was administered intraoperatively. A controlled-release formulation of cisplatin in sesame oil was used to limit drug egress from the injection site. Dosage was 1 mg of cisplatin/cm3 of tissue. The mean relapse-free interval was 41 +/- 3.7 months. The estimates of overall relapse-free survival rates were 92 +/- 5% at 1 year and 77 +/- 11% at 4 years. Cisplatin-related local toxicosis was minimal and wound healing was not compromised. Intratumoral injection of cisplatin appears safe and effective when administered in the perioperative period for selected tumors in equidae.