Solitary osseous plasmacytomas in dogs: 13 cases (2004-2019).

OBJECTIVES: To further characterise solitary osseous plasmacytoma in dogs, an extremely rare disease. To describe diagnosis, disease progression and treatment outcomes in dogs with solitary osseous plasmacytoma. MATERIALS AND METHODS: Retrospective review of dogs with solitary osseous plasmacytomas that were diagnosed and treated at a single institution from 2005 to 2019. Kaplan-Meier single group survival analysis was used to estimate median survival time and progression-free interval. RESULTS: Thirteen dogs met the inclusion criteria for the study, and of those, 11 were treated. The median age at diagnosis was 8 years (range 4 to 11). Most solitary osseous plasmacytomas occurred in the vertebrae (n=8). Other sites included the maxilla (n=2), the mandible (n=1), the tibia (n=1) and the carpus (n=1). The median survival time for all dogs with solitary osseous plasmacytoma was 912 days (range 5 to 2179), and the progression-free interval for treated dogs was 310 days (range 22 to 2179). Most dogs were treated with radiation therapy (n=10) with nine of 10 receiving a definitive, daily fractionated protocol and with five of ten having had neoadjuvant surgery. Seven dogs received chemotherapy, which was initiated after progressive disease in five dogs. The median survival time for dogs that completed radiation therapy (n=9) was 1166 days (range 545 to 2179). While five dogs developed lesions at other sites, no dogs progressed to multiple myeloma. CLINICAL SIGNIFICANCE: Canine solitary osseous plasmacytomas can be managed long term with appropriate local therapy. This observation reflects the biologic behaviour observed in humans.

Clinical Evaluation of Tavocept to Decrease Diuresis Time and Volume in Dogs with Bladder Cancer Receiving Cisplatin.

BACKGROUND: Transitional cell carcinoma is the most common bladder cancer of dogs. Cisplatin combined with piroxicam provides superior response rates, but unacceptable rates of nephrotoxicity. Tavocept is a chemoprotectant that has mitigated cisplatin toxicity and decreased the required infusion/diuresis volume in clinical trials in humans. HYPOTHESIS/OBJECTIVES: We hypothesized that Tavocept would decrease diuresis volume and time and facilitate safe administration of a cisplatin/piroxicam protocol to dogs with bladder cancer. Secondary objectives were to compare response rate and survival times to an historical comparator group treated without Tavocept. ANIMALS: Fourteen client-owned dogs were prospectively enrolled. METHODS: Tumor volume was measured by computed tomography at days 0, 42, and 84. Dogs received combination Tavocept/cisplatin with a shortened diuresis protocol. A total of 4 doses was planned, with concurrent administration of piroxicam. Serial biochemical analyses were evaluated for azotemia. RESULTS: A 90-minute infusion/diuresis time was used for all dogs. Three dogs (21%) had concurrent increases in serum creatinine (>2.0 mg/dL) and BUN (>42 mg/dL) concentrations; 2 of these dogs were isosthenuric. This frequency of nephrotoxicity is significantly less (P = 0.0406) than that of an historical control group treated without Tavocept. Overall response rate was 27%. Median survival time was comparable to historical controls (253 vs. 246 days). CONCLUSIONS AND CLINICAL IMPORTANCE: Tavocept decreased the required diuresis time with cisplatin from > 6 hours to 90 minutes, while also decreasing occurrence of azotemia. Survival time was comparable, but the response rate was inferior to an historical comparator group. Further evaluation in other tumors susceptible to platinum agents is warranted.

Programmed death ligand 1 is expressed in canine B cell lymphoma and downregulated by MEK inhibitors.

Programmed death ligand 1 (PD-L1) expression in antigen-presenting cells and tumors can inhibit T cell-mediated immunity. In this study, PD-L1 mRNA and protein expression was evaluated in canine B cell lymphoma (CLL17-71), large T-cell leukemia (CLGL-90), B cell leukemia (GL-1) and primitive leukocyte round cell neoplasia (CLL-1390). Variable PD-L1 mRNA and protein were observed in these cells with high endogenous expression present in CLL17-71 cells. PD-L1 protein was also observed in canine patient B cell lymphoma tissues using immunostaining. PD-L1 and signal transducer and activator of transcription 1 ( STAT1 ) mRNA expression were reduced in the presence of mitogen-activated protein kinase kinase 1.2 (MEK1/2) inhibitors RDEA119 and AZD6244 in CLL 17-71 cells. RDEA119 had similar effect on PD-L1 and STAT-1 in IFN-γ activated CLL-1390 cells. Overall, these results indicate that PD-L1 is expressed in canine B cell lymphoma. Its inhibition by MEK1/2 inhibitors suggests a possible treatment strategy using targeted drugs which likely could enhance antitumor immune response.

Integrative veterinary medical education and consensus guidelines for an integrative veterinary medicine curriculum within veterinary colleges.

Integrative veterinary medicine (IVM) describes the combination of complementary and alternative therapies with conventional care and is guided by the best available evidence. Veterinarians frequently encounter questions about complementary and alternative veterinary medicine (CAVM) in practice, and the general public has demonstrated increased interest in these areas for both human and animal health. Consequently, veterinary students should receive adequate exposure to the principles, theories, and current knowledge supporting or refuting such techniques. A proposed curriculum guideline would broadly introduce students to the objective evaluation of new veterinary treatments while increasing their preparation for responding to questions about IVM in clinical practice. Such a course should be evidence-based, unbiased, and unaffiliated with any particular CAVM advocacy or training group. All IVM courses require routine updating as new information becomes available. Controversies regarding IVM and CAVM must be addressed within the course and throughout the entire curriculum. Instructional honesty regarding the uncertainties in this emerging field is critical. Increased training of future veterinary professionals in IVM may produce an openness to new ideas that characterizes the scientific method and a willingness to pursue and incorporate evidence-based medicine in clinical practice with all therapies, including those presently regarded as integrative, complementary, or alternative.

Preclinical imaging and treatment of cancer: the use of animal models beyond rodents.

The development of novel radiopharmaceutical agents for imaging and therapy of neoplastic diseases relies on accurate and reproducible animal models. Rodent models are often used to demonstrate the proof-of-principle tracer and therapeutic agent development, but their small size can make tissue sampling challenging. The dosimetry of decay emissions in the much smaller rodent tumors do not model dosimetry in human tumors well. In addition, rodent models of cancer represent a simplified version of a very complex process. Spontaneous tumors are heterogenous and the response to intervention can be unpredictable; tumor cells can adopt alternate signaling pathways and modify their interaction with the microenvironment. These inconsistencies, while present in humans, are difficult to fully reproduce in a genetically-engineered rodent model. Companion animals, primarily dogs and cats, offer translational models that more accurately reflect the intricate nature of spontaneous neoplasia in humans. Their larger size facilitates tissue and blood sampling when needed, and allows radiopharmaceutical tracers to be studied on human-scale imaging systems to better mimic the clinical application of the agent. This article will review the growing body of literature surrounding the use of radiopharmaceutical agents for both imaging and therapy in companion dogs and cats. Previous investigations have been performed both for the advancement of routine, high-level veterinary care, and in the context of translational research from which the results of imaging and treatment can be readily applied to people. Studies utilizing the spontaneously occurring cancer model in companion animals involving positron emission tomography, radiotracers, dosimetry, theranostics, targeted radiopharmaceuticals, brachytherapy, and boron neutron capture therapy are discussed.

Vincristine-induced central neurotoxicity in a collie homozygous for the ABCB1Δ mutation.

A six-year-old, neutered, female collie was presented to an oncology specialty service after developing tetraparesis and self-mutilation that progressively worsened while receiving chemotherapy for lymphoma. Neurologic examination revealed ataxia, paresis and diminished conscious proprioception in all limbs with entire spinal reflexes. Magnetic resonance imaging of the brain and spinal cord was normal. Electromyography of the limbs ruled out a vincristine-induced peripheral neuropathy. Cerebrospinal fluid analysis and cerebrospinal fluid and serum testing for Neospora and Toxoplasma were normal. Results of MDR1 genotyping revealed that the dog was homozygous for the ABCB1-1Δ (MDR1) mutation. This clinical presentation strongly resembled the effects seen from inadvertent intrathecal administration of vincristine in humans. Dogs that are homozygous for the ABCB1-1Δ (MDR1) mutation should not receive standard dosages of chemotherapy drugs known to be eliminated by P-glycoprotein, the gene product of ABCB1. Testing for this mutation is strongly recommended before chemotherapy initiation for at-risk breeds.

Tolerability of metronomic administration of lomustine in dogs with cancer.

BACKGROUND: Metronomic chemotherapy with alkylating agents has been shown to suppress tumor angiogenesis and prevent tumor recurrence in some settings. The use of adjuvant lomustine (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea) administered in a metronomic fashion has not been evaluated in dogs. HYPOTHESIS: Oral metronomic administration of lomustine will be well tolerated in dogs with spontaneously occurring malignant neoplasms. ANIMALS: Eighty-one dogs with naturally occurring primary or metastatic tumors received metronomic administration of lomustine. METHODS: Dogs were enrolled prospectively after cytological or histological diagnosis of a tumor that was unresectable, incompletely resected, refractory to chemotherapy, or metastatic. Dogs received once daily lomustine (2.84 mg/m² PO). End points of the trial were clinical, hematologic, or biochemical evidence of toxicosis, tumor progression, or death. RESULTS: Starting dosage (median) was 2.84 mg/m² PO daily and treatment duration was 98 days (median, range, 1-770 days). The drug was discontinued in 22 dogs because of toxicoses. Toxicoses occurred in 13 dogs with gastrointestinal toxicosis, 4 dogs with thrombocytopenia, 3 dogs with increased alanine transaminase, 1 dog with neutropenia, and 1 dog with progressive azotemia. Eight dogs developed some degree of azotemia during treatment. Hepatotoxicosis was observed at a median of 265 days in 11 dogs. Thrombocytopenia was identified at a median of 432 days of administration. CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs with metastatic or terminal neoplasms without renal compromise, metronomic administration of lomustine was well tolerated. This can provide a treatment strategy for dogs that do not have other standard-care treatment options, and warrants evaluation in primary therapy.

A retrospective analysis of renal carcinoma in the horse.

BACKGROUND: Renal carcinoma is a rare tumor of horses. HYPOTHESIS: Presenting complaints and clinical signs of this disease are vague and early diagnosis increases survival time. ANIMALS: Data were collected from the medical records of 4 horses presented to Washington State University as well as the 23 previously published case reports of horses with renal carcinoma. METHODS: Retrospective study. RESULTS: Renal carcinoma affects horses of all ages with most cases observed in geldings and Thoroughbreds. The most common presenting complaints are nonspecific and usually do not occur until late in the course of the disease. Routine laboratory results generally are unremarkable with no evidence of renal dysfunction. Urine and peritoneal fluid analyses are consistently abnormal, but the changes usually are nonspecific. Rectal palpation often allows detection of an abnormal kidney or a mass in the area of the kidney. Renal ultrasound examination is the most rewarding imaging procedure, and when combined with renal biopsy, antemortem diagnosis can be achieved. Renal carcinoma is both locally invasive and metastatic, necessitating careful staging for metastasis using thoracic radiography and abdominal ultrasound examination. If the tumor is localized to 1 kidney, nephrectomy is the treatment of choice. No chemotherapy or radiation treatment for renal carcinoma has been reported in the horse. Median survival for this series of cases was 11 days (0 days-1 year). CONCLUSIONS AND CLINICAL IMPORTANCE: Prognosis is poor to grave.

Development of a two-antibody model for the evaluation of copper-64 radioimmunotherapy.

Copper-64 emits beta(+) and beta(-) particles suitable for positron emission tomography and radioimmunotherapy (RIT) of cancer. Copper-64-labelled antibodies have caused complete responses in laboratory animal RIT studies at far lower radiation doses than traditionally prescribed. The intracellular localization of copper radioisotopes may lead to cytotoxic effects by mechanisms beyond ionizing radiation damage. The purpose of this research was to develop a model using both internalizing and non-internalizing antibodies for direct comparison in future RIT studies using the same animal model of cancer. The monoclonal antibodies, cBR96 and cT84.66, were conjugated with N-hydroxysulfosuccinimidyl DOTA. All conjugates retained high immunoreactivity and labelled efficiently with (64)Cu with high specific activity and radiochemical purity. Twenty-four hour biodistributions determined in LS174T tumour-bearing nude mice demonstrated low organ and high tumour uptakes for both monoclonal antibodies. This model constitutes a promising system for elucidating whether internalization of (64)Cu is responsible for an enhanced tumour cytotoxicity in vivo.