Stereotactic body radiation therapy for heart-base tumors in six dogs.

INTRODUCTION: Heart-base tumors are increasingly treated with radiotherapy, yet safety and efficacy are incompletely understood. This case series describes outcomes after stereotactic body radiation therapy (SBRT) for presumed chemodectoma. ANIMALS: Six pet dogs. METHODS: A retrospective study was performed, including dogs with a clinical diagnosis of chemodectoma and treatment with three-fraction SBRT (30 Gy total). RESULTS: Heart-base tumors, presumed or confirmed to be chemodectomas, were diagnosed via histopathology or imaging. Treatment was delivered with intensity modulation and cone-beam computed tomography-based image guidance, using a linear accelerator and robotic couchtop. Intrafraction respiratory motion was managed with either neuromuscular blockade and breath-holding (n = 3) or high-frequency jet ventilation (n = 3); mean total anesthesia times for each technique were 165 and 91 min per fraction, respectively. Four tumors were assessed after SBRT; tumor volume decreased by 30-76%. Possible treatment-related complications included cough, tachyarrhythmias, and congestive heart failure. Two dogs experienced sudden death 150 and 294 days after SBRT. Three dogs are alive 408-751 days after SBRT, and one dog died of unrelated disease 1,228 days after SBRT. CONCLUSIONS: This SBRT protocol resulted in rapid tumor volume reduction, and jet ventilation effectively reduced treatment delivery times. However, cardiac arrhythmias (presumably tumor or treatment associated) and sudden death were common after SBRT. Therefore, SBRT is a potentially useful treatment but may not be appropriate for dogs with incidentally diagnosed, slowly growing tumors, which are not causing cardiovascular disturbances. Longer follow-up and larger case numbers are needed to more completely define safety and impact of treatment on long-term survivability.

Linac-based stereotactic radiation therapy for canine non-lymphomatous nasal tumours: 29 cases (2013-2016).

Twenty-nine dogs were treated with linac-based stereotactic radiation therapy (SRT) for non-lymphomatous nasal tumours. Only dogs with a follow-up time >365 days were included in this retrospective analysis. No dogs had evidence of distant metastasis at diagnosis. Treatment was planned and a total of 30 Gy in 3 daily 10 Gy fractions was delivered using intensity-modulation, cone-beam CT-based image guidance and a robotic treatment couch. Clinical signs improved in all cases. Nineteen dogs had CT scans 3-4 months post-SRT and all had partial or complete tumour response. Minimal acute toxicities were detected. Clinically significant late toxicities included oronasal or nasocutaneous fistulas (N = 3) and biopsy-confirmed fungal rhinitis with no evidence of tumour progression (N = 2). The median progression-free survival (PFS) was 354 days, with 49% and 39% progression-free at 1 and 2 years post-SRT, respectively. The median survival time (ST) was 586 days, with 69% and 22% alive 1 and 2 years post-SRT, respectively. Neither the clinical parameters evaluated (modified Adams' stage, histopathology, presence of intracranial extension of the tumour) nor dosimetric data were predictive for PFS or ST. This SRT protocol appears to be well tolerated, and PFI and ST are comparable or superior to those reported in other definitive-intent radiotherapy protocols.

Pilot study to determine the feasibility of radiation therapy for dogs with right atrial masses and hemorrhagic pericardial effusion.

OBJECTIVES: To determine the short-term safety and biologic activity of radiation therapy (RT) for presumptive cardiac hemangiosarcoma in pet dogs. ANIMALS: Six dogs with echocardiographic evidence of a right atrial/auricular mass, and hemorrhagic pericardial effusion, were enrolled in a prospective, single-arm clinical trial. METHODS: A single fraction of 12 Gy was delivered using conformal external beam irradiation. Serum cardiac troponin I and plasma concentrations of vascular endothelial growth factor were quantified before, 4 and 24 h after RT. The frequency of required pericardiocenteses (quantified as the number of pericardiocenteses per week) before RT was compared to that after treatment. Overall survival time was determined. RESULTS: No treatment-related complications were observed. Pericardiocentesis was performed an average of 0.91 times per week before RT, and an average of 0.21 times per week after RT; this difference was statistically significant (p=0.03, as compared using a Wilcoxon signed-rank test of paired data). Pre- and post-treatment plasma vascular endothelial growth factor concentrations were not significantly different at any time point; there was a statistically significant (p=0.04; Friedman's test for non-parametric repeated measures) increase in cardiac troponin concentrations 4 h after irradiation. Median overall survival time was 79 days. CONCLUSIONS: In this population of dogs, RT was delivered without complication, and appears to have reduced the frequency of periacardial tamponade that necessitated pericardiocentesis. Serum cardiac troponin levels are altered after RT. RT alone, or in combination with chemotherapy, may provide clinical benefit to dogs with presumptive diagnoses of cardiac hemangiosarcoma.

Misadministration of radiation therapy in veterinary medicine: a case report and literature review.

Recent technical advancements in radiation therapy have allowed for improved targeting of tumours and sparing nearby normal tissues, while simultaneously decreasing the risk for medical errors by incorporating additional safety checks into electronic medical record keeping systems. The benefits of these new technologies, however, depends on their proper integration and use in the oncology clinic. Despite the advancement of technology for treatment delivery and medical record keeping, misadministration errors have a significant impact on patient care in veterinary oncology. The first part of this manuscript describes a medical incident that occurred at an academic veterinary referral hospital, in a dog receiving a combination of stereotactic radiation therapy and full-course intensity-modulated, image-guided radiation therapy. The second part of the report is a literature review, which explores misadministration errors and novel challenges which arise with the implementation of advancing technologies in veterinary radiation oncology.

Detection of synchronous primary tumours and previously undetected metastases in 736 dogs with neoplasia undergoing CT scans for diagnostic, staging and/or radiation treatment planning purposes.

The purpose of our study was to describe synchronous primary tumours and previously undetected metastases in 736 dogs with confirmed neoplasia in which computed tomography (CT) scans were performed for diagnostic, staging and/or radiation treatment planning purposes. All CTs were reviewed by a radiologist. Tumour-associated CT abnormalities were detected in 38/736 (5%), including confirmed or suspected synchronous primary neoplasms (n = 24), metastases of the primary tumour (n = 9) or both (n = 3). In lymph nodes (LN) that were considered abnormal on CT scan and were aspirated, 23% contained metastasis, and 6% of 'normal' appearing LN that were aspirated contained metastasis. Thorough evaluation of CTs and routine aspiration of regional LN are critical because results affect recommendations to perform additional staging tests and treatment for the primary and secondary tumour(s).

Detection of comorbidities and synchronous primary tumours via thoracic radiography and abdominal ultrasonography and their influence on treatment outcome in dogs with soft tissue sarcomas, primary brain tumours and intranasal tumours.

Canine soft tissue sarcomas (STS), primary brain tumours and intranasal tumours are commonly treated with radiotherapy (RT). Given the low metastatic potential of these tumours, recommendations regarding imaging tests as staging are variable among institutions. The purpose of our study was to describe thoracic radiographic and abdominal ultrasonographic findings in dogs with these neoplasms and to investigate association of abnormal findings with alterations in recommended treatment. Medical records from 101 dogs, each having thoracic radiographs and abdominal ultrasound performed as part of their staging, were reviewed. In 98 of 101 (97%), imaging abnormalities were detected, 27% of which were further investigated with fine needle aspiration cytology or biopsy. Nine percent of the detected abnormalities were considered serious comorbidities that altered treatment recommendations, including 3 (3%) which were confirmed as synchronous primary neoplasms. These findings may influence recommendations regarding the decision to perform thoracic radiographs and abdominal ultrasound prior to initiation of RT.

Prospective evaluation of biweekly streptozotocin in 19 dogs with insulinoma.

BACKGROUND: Administration of streptozotocin (STZ) at a 21-day interval has been described in dogs with stage II and III insulinoma. Myelosuppression was not observed, suggesting the possibility of increasing dose intensity by decreasing the interval between doses. OBJECTIVE: To describe the tolerability of a biweekly STZ protocol. A secondary objective was to describe the outcome of dogs treated with this protocol. ANIMALS: Nineteen dogs with residual local, metastatic, or recurrent insulinoma. METHODS: After surgery for insulinoma, or at the time of recurrence, dogs were treated with a previously described STZ and saline diuresis protocol. Treatments were administered every 14 days. All dogs received antiemetic treatment. Adverse events (AEs) were recorded and graded. Outcome endpoints assessed were progression-free survival (PFS) and survival. RESULTS: None of the dogs experienced neutropenia or thrombocytopenia. Mild to moderate gastrointestinal toxicity was the most common AE. Diabetes mellitus was observed in 8 dogs and, in 6, resulted in euthanasia or death. Two dogs developed nephrotoxicity manifested as Fanconi syndrome in 1 and nephrogenic diabetes insipidus in the other. Six dogs developed increased alanine amino transferase activity. Hypoglycemia at the end of the STZ infusion, resulted in collapse in 1 dog and a generalized seizure in another. The median overall PFS and survival time were 196 and 308 days, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Streptozotocin can be safely administered to dogs with insulinoma, but serious AEs are possible. Additional investigation is required to better define the role of STZ in managing dogs with insulinoma.

Immunohistochemical characterization of feline mast cell tumors.

Expression of histamine, serotonin, and KIT was evaluated in 61 archived feline mast cell tumors (MCTs) from the skin (n = 29), spleen (n = 17), and gastrointestinal (GI) tract (n = 15) using immunohistochemistry. Twenty-eight percent of cutaneous MCTs, 18% of splenic MCTs, and 53% of GI MCTs displayed histamine immunoreactivity. Serotonin immunoreactivity was detected in 3 GI and 1 cutaneous MCT. Sixty-nine percent of cutaneous MCTs, 35% of splenic MCTs, and 33% of GI MCTs were positive for KIT. Expression of these biogenic amines and KIT was less common than expected. Results of this study suggest heterogeneity in feline MCTs based on anatomic location. Further studies are needed to explain the significance of these differences.

Three-dimensional conformal versus non-graphic radiation treatment planning for apocrine gland adenocarcinoma of the anal sac in 18 dogs (2002-2007).

Differences in dose homogeneity and irradiated volumes of target and surrounding normal tissues between 3D conformal radiation treatment planning and simulated non-graphic manual treatment planning were evaluated in 18 dogs with apocrine gland adenocarcinoma of the anal sac. Overall, 3D conformal treatment planning resulted in more homogenous dose distribution to target tissues with lower hot spots and dose ranges. Dose homogeneity and guarantee of not under-dosing target tissues with 3D conformal planning came at the cost, however, of delivering greater mean doses of radiation and of irradiating greater volumes of surrounding normal tissue structures.

Mechlorethamine, procarbazine and prednisone for the treatment of resistant lymphoma in dogs.

Forty-one dogs with resistant lymphoma were treated with a modified MOPP (mechlorethamine, vincristine, procarbazine and prednisone) protocol (MPP [mechlorethamine, procarbazine and prednisone] administered on a 21-day cycle, shortened from the 28-day MOPP cycle). The overall response rate to MPP was 34% for a median of 56 days (95% confidence interval 30-238). Seventeen percent of dogs had a complete response for a median duration of 238 days, 17% had a partial response for a median of 56 days and 32% had stable disease for a median of 24 days. Histological grade or cell morphology on cytology was associated with response. Minimal toxicity was observed with the MPP protocol, suggesting that further dose intensification or addition of another chemotherapeutic agent would be possible.

Variation among pathologists in the histologic grading of canine cutaneous mast cell tumors with uniform use of a single grading reference.

Ten veterinary pathologists independently assigned histologic grades to the same 60 canine cutaneous mast cell tumors using the Patnaik classifications. The degree of agreement in grading among the pathologists was compared with the degree of agreement among the same pathologists in a previous study, in which each pathologist used the reference for grading that he/she uses routinely. Mean agreement improved significantly from 50.3% to 62.1% with uniform use of the Patnaik classifications (P = 0.00001), suggesting that there is value in uniform application of a single grading scheme for canine cutaneous mast cell tumors. Agreement among pathologists was still not 100%, suggesting that a more objective grading scheme should be developed and that other histologic indicators of prognosis should be investigated.

Lymphoma as a model for chronic illness: effects on adrenocortical function testing.

Many dogs with chronic illness have serum biochemical abnormalities consistent with hyperadrenocorticism (HAC). Lymphoma (LSA) is a chronic disease of dogs. The purpose of this study was to evaluate adrenocortical screening test results in dogs with LSA to evaluate their specificity. Criteria for inclusion in the study included a diagnosis of LSA, an expected survival time of 16-56 weeks, no glucocorticoid treatment beyond 4 weeks after the initiation of chemotherapy, no evidence of HAC, and owner consent. Post-ACTH stimulation plasma cortisol concentrations (PACs), urine cortisol : creatinine (UC : Cr) ratios, and maximal left adrenal width measurements were performed at the time of LSA diagnosis before the initiation of chemotherapy and at 16, 24, 32, 40, and 52 weeks or until the loss of remission or the development of another disease. Ten dogs met the criteria for inclusion. Forty-two PACs were performed; 1 abnormal, 2 borderline, and 39 normal values were detected. Thirty-five maximal left adrenal width measurements were obtained; 0 abnormal, 5 borderline, and 30 normal measurements were detected. Thirty-six UC : Cr ratios were obtained, with 26 abnormal, 4 borderline, and 6 normal values detected and 9 of 10 dogs having at least 1 abnormal value. These data suggest that in dogs with LSA, the UC : Cr ratio frequently is abnormal and may not be a specific test for HAC, or it may be the most sensitive test for increases in cortisol secretion due to chronic illness. Maximal left adrenal width measurements and PACs were almost always normal and may be more specific for HAC or less sensitive for demonstrating chronic increases in cortisol secretion.

Phase I evaluation of CCNU (lomustine) in tumor-bearing cats.

1-(2-Chloroethyl)3-cyclohexyl-1-nitrosourea (CCNU) is an alkylating agent in the nitrosourea subclass. A prospective evaluation of CCNU was done to determine the maximally tolerated dosage of CCNU in tumor-bearing cats. Response data were obtained when available. Twenty-five cats were treated with CCNU at a dosage of 50-60 mg/m3 body surface area. Complete hematologic data were available for 13 cats. Neutropenia was the acute dose-limiting toxicity. The median neutrophil count at the nadir was 1,000 cells/microL (mean, 2,433 cells/microL; range, 0-9,694 cells/microL). The time of neutrophil nadir was variable, occurring 7-28 days after treatment, and counts sometimes did not return to normal for up to 14 days after the nadir. Based on these findings, a 6-week dosing interval and weekly hematologic monitoring after the 1st treatment with CCNU are recommended. The nadir of the platelet count may occur 14-21 days after treatment. The median platelet count at the nadir was 43,500 cells/microL. No gastrointestinal, renal, or hepatic toxicities were observed after a single CCNU treatment, and additional studies to evaluate the potential for cumulative toxicity should be performed. Five cats with lymphoma and 1 cat with mast cell tumor had measurable responses to CCNU. Phase II studies to evaluate antitumor activity should be completed with a dosing regimen of 50-60 mg/m3 every 6 weeks.

Phenol poisoning in three dogs.

Three adult dogs were evaluated following oral administration of phenol by the owner. All three dogs experienced severe oral and gastric ulceration. Hematological abnormalities included neutropenia with the presence of toxic neutrophils, thrombocytopenia, and increased muscle enzymes. Endoscopic examination was performed, and biopsies yielded a diagnosis of gastric mucosal necrosis in two of the dogs. Following supportive care, the dogs recovered completely. Phenol is a caustic, highly poisonous derivative of coal tar. The dogs of this report were poisoned inadvertently by their owner who received misinformation concerning the use of this chemical via the Internet.

Thyroid function and serum hepatic enzyme activity in dogs after phenobarbital administration.

Phenobarbital is the drug of choice for control of canine epilepsy. Phenobarbital induces hepatic enzyme activity, can be hepatotoxic, and decreases serum thyroxine (T4) concentrations in some dogs. The duration of liver enzyme induction and T4 concentration decreases after discontinuation of phenobarbital is unknown. The purpose of this study was to characterize the changes in serum total T4 (TT4), free T4 (FT4), thyroid-stimulating hormone (TSH), cholesterol and albumin concentrations, and activities in serum of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) after discontinuation of long-term phenobarbital administration in normal dogs. Twelve normal dogs were administered phenobarbital at a dosage of approximately 4.4-6.6 mg/kg PO q12h for 27 weeks. Blood was collected for analysis before and after 27 weeks of phenobarbital administration and then weekly for 10 weeks after discontinuation of the drug. The dogs were clinically normal throughout the study period. Serum ALT and ALP activity and TSH and cholesterol concentrations were significantly higher than baseline at week 27. Serum T4 and FT4 were significantly lower. Serum albumin and GGT were not changed from baseline at week 27. Changes in estimate of thyroid function (TT4, FT4, TSH) persisted for 1-4 weeks after discontinuation of phenobarbital, whereas changes in hepatic enzyme activity (ALT, ALP) and cholesterol concentration resolved in 3-5 weeks. To avoid false positive results, it is recommended that thyroid testing be performed at least 4 weeks after discontinuation of phenobarbital administration. Elevated serum activity of hepatic enzymes 6-8 weeks after discontinuation of phenobarbital may indicate hepatic disease.