Frameless stereotactic radiosurgery for the treatment of primary intracranial tumours in dogs

Stereotactic radiosurgery (SRS) is a procedure that delivers a single large radiation dose to a well‐defined target. Here, we describe a frameless SRS technique suitable for intracranial targets in canines. Medical records of dogs diagnosed with a primary intracranial tumour by imaging or histopathology that underwent SRS were retrospectively reviewed. Frameless SRS was used successfully to treat tumours in 51 dogs with a variety of head sizes and shapes. Tumours diagnosed included 38 meningiomas, 4 pituitary tumours, 4 trigeminal nerve tumours, 3 gliomas, 1 histiocytic sarcoma and 1 choroid plexus tumour. Median survival time was 399 days for all tumours and for dogs with meningiomas; cause‐specific survival was 493 days for both cohorts. Acute grade III central nervous system toxicity (altered mentation) occurred in two dogs. Frameless SRS resulted in survival times comparable to conventional radiation therapy, but with fewer acute adverse effects and only a single anaesthetic episode required for therapy.     

A complication probability planning study to predict the safety of a new protocol for intracranial tumour radiotherapy in dogs

Technical advances make it possible to deliver radiation therapy for canine intracranial tumours in fewer fractions, under the assumption of equivalent tumour control. With the aim of estimating the late toxicity risk profile for various tumour sizes and locations, the present paper evaluates the normal tissue complication probability (NTCP) values for the intracranial organs at risk. By making isoeffect calculations, a new 10‐fraction radiation protocol was developed with the same tumour control probability (TCP) as a currently used 20‐fraction standard protocol, and complication risk profiles for brain, brainstem and optic chiasm were modelled using a representative population of 64 dogs with brain tumours. For >59% of cases, the new 10‐fraction protocol yielded an acceptable, low risk estimate of late toxicity (<10%). Our calculations suggest that it may be safe to treat small to intermediate‐sized tumours that are neither located near the optic chiasm nor at the brainstem with 10 daily fractions of 4.35 Gy.     

Outcome of definitive fractionated radiation followed by exenteration of the nasal cavity in dogs with sinonasal neoplasia: 16 cases

Local control is a major challenge in treating canine nasal tumours. Surgical cytoreduction prior to radiation therapy has not been shown to offer a survival advantage. Only one study has previously evaluated the outcome when surgery is performed after radiation, which demonstrated an improved survival time compared with radiation alone. The purpose of this study was to investigate the outcome of surgery after definitive radiation on survival times in dogs with sinonasal tumours. Medical records were retrospectively reviewed for dogs with nasal tumours that received definitive radiation followed by surgery. Information obtained from medical record review included signalment, diagnosis, treatment and outcome. The median survival time was 457 days. No long‐term side effects were observed. These findings suggest that exenteration of the nasal cavity following definitive radiation for treatment of dogs with nasal tumours is well‐tolerated and provides a similar survival duration to previous reports of radiation alone.     

Configuration of pathologic fractures in dogs with osteosarcoma following stereotactic body radiation therapy: A retrospective analysis

For some cases of canine appendicular osteosarcoma (OSA), limb-sparing treatment options are often desired, one of which is stereotactic body radiation therapy (SBRT). A major complication of SBRT is fracture of the irradiated bone at the site of treatment. The present study evaluated 127 appendicular OSA sites in 122 dogs treated with SBRT to identify the most common pathologic fracture locations and configurations. A total of 50 tumours experienced a pathologic fracture, and 38 had imaging sufficient to identify fracture configuration. The distal tibia was more likely to develop a fracture than other sites. Multiple types of fracture configuration (transverse, oblique, spiral and comminuted) were observed. The distal radius was significantly more likely to develop a transverse fracture than other sites. Documentation of fracture location and configuration leads to the identification of the forces contributing to fracture occurrence, since each configuration is a result of different forces acting on each affected bone. Such knowledge is imperative for the development of new approaches to diminish the occurrence of pathologic fractures.     

Successful use of prednisolone and radiation therapy in a dog with intracranial histiocytic sarcoma

The ideal treatment for intracranial histiocytic sarcoma (HS) remains unclear. Herein, we report a case of intracranial HS that was successfully treated using prednisolone and radiation therapy. The patient was a 9-year-old spayed female Pembroke Welsh Corgi that presented with epileptic seizures. Magnetic resonance imaging revealed a contrast-enhancing mass adjacent to the right piriform lobe. Prednisolone administration (1 mg/kg/day) decreased the lesion size. Additional palliative radiation therapy (total dose, 37 Gy) resulted in complete disappearance of the lesion. However, on day 164, the dog’s neurological signs deteriorated, and she was euthanized. Necropsy revealed an intracranial metastasis of HS via the cerebrospinal fluid without any extracranial metastasis. Nonetheless, combined prednisolone and radiation therapy might be effective in treating intracranial HS.     

Treatment of canine oral papillary squamous cell carcinoma using definitive‐intent radiation as a monotherapy—a case series

Canine oral papillary squamous cell carcinoma (COPSCC) is a rare neoplasm and although locally invasive it carries a favourable prognosis following wide surgical excision. Radiotherapy has been reported to be effective as an adjunct treatment to surgery. However, limited information is available on the role of radiotherapy as single treatment. This single‐institution retrospective study describes a series of 10 dogs diagnosed with macroscopic COPSCC that were treated with definitive‐intent radiotherapy (DRT) as a monotherapy. These dogs had a median age of 4 years (range: 0.4‐9.6 years). The tumour was located in the rostral oral cavity in all cases with a median tumour size of 2.5 cm (range: 0.8‐6.8 cm). No local or distant metastases were identified. All dogs were treated with electron beam DRT (>32Gy, 10‐16 daily fractions of 3.2Gy). The median follow‐up time was 961 days (range: 333‐3.498 days) with nine dogs achieving a complete response and one dog a partial response. The dog with the partial response developed disease progression at 228 days after initiation of radiotherapy. Two dogs died from non‐tumour‐related causes. The remaining seven dogs were still alive and in complete remission at the time of last follow‐up. Median progression‐free survival time and median survival time were not reached. DRT was generally well tolerated, but all dogs experienced self‐limiting acute radiation mucositis (grade 2‐3) and/or dermatitis (grade 1). No late radiation toxicity was observed. Macroscopic COPSCC appears to be a radiosensitive tumour that can be successfully treated with DRT eliminating the need for aggressive surgery in advanced cases.     

A possible role of coarse fractionated radiotherapy in the management of gingival squamous cell carcinoma in dogs: A retrospective study of 21 cases from two referral centers in the UK

Surgery with or without the addition of radiotherapy is the treatment of choice for canine oral squamous cell carcinoma (SCC). Fractionated radiotherapy alone is also effective in the long-term control of the disease, however coarse fractionated radiotherapy (CF-RT) for gingival SCC has not been extensively reported. The aim of this study was to describe side effects, clinical response, and median survival time (MST) of dogs with gingival SCC treated with CF-RT in the palliative and adjuvant setting. Twenty-one cases from two referral centres in the UK treated with CF-RT for gingival SCC between July 2013 and June 2019 were retrospectively evaluated. Of the 21 dogs, 11 developed mild acute adverse effects. Oral mucositis was the most common radiation induced toxicity. Three dogs developed chronic severe adverse effects (oro-nasal fistula, bone necrosis and gum recession). Overall clinical response rate was 77% in dogs receiving palliative treatment with MST of 365 days (60–1,095 days). MST was not reached for dogs treated in the adjuvant setting with a mean of 466 days (121–730 days). In cases of advanced gross disease CF-RT might have a role in short term palliation of clinical signs. However, it carries a significant risk of late toxicity for cases with unexpectedly long survival times and further investigations are required to identify an optimal CF-RT protocol. Randomized controlled trials are needed to confirm the role of CF-RT as adjuvant treatment of incompletely resected gingival SCC.     

Curative-intent radiation therapy as a treatment modality for appendicular and axial osteosarcoma: a preliminary retrospective evaluation of 14 dogs with the disease

Canine osteosarcoma is a common bone malignancy associated with aggressive local disease and rapid metastasis. Current local therapeutic modalities do not provide curative‐intent options for dogs with significant orthopaedic or neurologic disease, dogs which are denied amputation or dogs with non‐resectable lesions. The goals of this retrospective study included the evaluation of local control, survival, and time to the development of metastases in 14 dogs treated with curative‐intent radiation therapy and chemotherapy. Median local disease control was 202 days (79–777). Median survival was 209 days (79–781). Median time to metastasis was 314 days (7–645). No significant correlation was found between the outcome and pre‐treatment alkaline phosphatase levels, radiographic appearance, tumour site, radiation dose or chemotherapeutics administered. In these dogs, full‐course radiation therapy in conjunction with chemotherapy was not found to yield equivalent results to the standard of care options.     

High-dose-rate brachytherapy for intranasal tumours in dogs: results of a pilot study

This prospective study describes the feasibility and toxicity of ¹⁹²Iridium high‐dose‐rate (HDR) brachytherapy as an alternative strategy for the treatment of canine intranasal tumours. Fifteen dogs with malignant intranasal tumours were treated twice weekly using a hypofractionated protocol with eight fractions, 5 Gy per fraction, resulting in a total dose of 40 Gy. Acute and chronic adverse side‐effects appeared to be rare. Only 7% of the acute side‐effects and 5% of the chronic were classified as severe (grade 3). Eight dogs showed clinical complete remission, and five dogs had partial remission, with a resolution of tumour‐related symptoms. Magnetic resonance imaging showed a reduced tumour mass in 12 cases. Median survival time was 17 months (range 4–48 months), with four dogs (three without disease) still alive. Median time to recurrence of these dogs was 14 months. In nine dogs, progression or recurrence of the tumour was the cause of death. This study suggests that HDR brachytherapy is feasible and well tolerated.     

Pregabalin alleviates clinical signs of syringomyelia-related central neuropathic pain in Cavalier King Charles Spaniel dogs: a randomized controlled trial

ObjectiveWe aimed to assess the efficacy and benefit-risk profile of pregabalin (PGN) to reduce the clinical signs of central neuropathic pain (CNeP) as reflected by scratching episodes in dogs with symptomatic syringomyelia (SM).Study designRandomized, double-blind, placebo-controlled crossover study.AnimalsA total of 12 client-owned Cavalier King Charles Spaniels (age, 1.1–7.4 years, bodyweight, 8.2–10.8 kg) with magnetic resonance imaging-confirmed SM and clinical signs of CNeP.MethodsDogs were randomized to either PGN 150 mg or placebo for 25 days, followed by 48 hour washout period before crossover to the alternate phase of 25 days. The primary outcome was defined as number of scratching events during 10 minutes of video-recorded physical activity. Treatment effect was estimated using a generalized estimation equation model. Benefit-risk and quality of life assessments were obtained through owner interviews focusing on potential adverse events.ResultsThe treatment effect estimate was an 84% (95% confidence interval = 75–89%) reduction in mean number of scratching events relative to baseline compared with placebo (p < 0.0001). Owner-assessed satisfactory quality of life was status quo and rated as ‘good’ or ‘could not be better’ in six/11 dogs and improved in four/11 dogs. The most prevalent adverse events were increased appetite in nine/12 dogs and transient ataxia in nine/12 dogs. There was one dog withdrawn by the owner 7 days after crossover to PGN owing to persistent ataxia. No dogs needed rescue analgesia during the trial.Conclusions and clinical relevancePGN is superior to placebo in the reduction of clinical signs of SM-related CNeP in dogs. At a dose range of 13–19 mg kg^–1 orally twice daily, the encountered adverse events were acceptable to all but one owner.     

Phase I lead‐in and subsequent randomized trial assessing safety and modulation of regulatory T cell numbers following a maximally tolerated dose doxorubicin and metronomic dose cyclophosphamide combination chemotherapy protocol in tumour‐bearing dogs

Maximally tolerated dose (MTD) and metronomic dose chemotherapeutic approaches alter the immune system and the angiogenic process in different yet potentially complementary ways. A combination of MTD doxorubicin (MTD‐DOX) and metronomic cyclophosphamide (mCTX) protocol was evaluated for safety and effect on circulating regulatory T (Treg) cells. We found that mCTX can be safely administered with MTD‐DOX in tumour‐bearing dogs. Both combination DOX/mCTX and single‐agent DOX resulted in significant depletions of circulating lymphocytes throughout the chemotherapy cycle without apparent selectivity for Tregs. The indiscriminant lymphocyte depletions were similar between dogs randomized to receive DOX and dogs randomized to receive DOX/mCTX, suggesting this effect is because of DOX alone. These findings may have implications as to the therapeutic benefit (or lack thereof) of concurrent combination MTD and metronomic protocols. Future investigations are required to determine the effects and indeed the efficacy of concurrent versus sequential applications of MTD and metronomic chemotherapy protocols.     

Comparison of cyclosporine A with methylprednisolone for treatment of canine atopic dermatitis: a parallel,blinded, randomized controlled trial

Abstract The objective of this multicentre, parallel, blinded, randomized controlled study was to evaluate the efficacy and the safety of cyclosporine (CsA group, 117 dogs) in comparison with methylprednisolone (MP group, 59 dogs) in the treatment of atopic dermatitis for 4 months. Mean induction dose of both drugs (5 mg/kg CsA, 0.75 mg/kg MP) was tapered over time according to the clinical response. At the end of the study, the mean estimated percentage reduction from baseline (confidence interval) of lesion scores was 52% (44–59) and 45% (35–56), and the reduction in pruritus score was 36% (27–43) and 33% (23–43) in dogs in the CsA and MP groups, respectively. These percentages were not significantly different between groups. A significantly better overall assessment of efficacy was obtained in the CsA-treated dogs (76 vs. 63% responses excellent or good in the CsA compared with MP group). CsA-treated dogs presented a higher frequency of gastrointestinal disorders, mainly vomiting, but MP dogs tended to be more susceptible to infections. There was no remarkable change over baseline of the haematological and biochemical parameters in the two groups.     

Comparison of the sedative effects of intranasal or intramuscular dexmedetomidine at low doses in healthy dogs: a randomized clinical trial

ObjectiveTo compare the sedative effects of dexmedetomidine administered either intranasally or intramuscularly to healthy dogs.Study designProspective, randomized, blinded, clinical trial.AnimalsA group of 16 client-owned healthy dogs.MethodsDogs were randomly allocated to one of two groups that were administered dexmedetomidine 5 μg kg^–1 via either the intranasal route (IN_Dex), through a mucosal atomization device in one nostril, or the intramuscular route (IM_Dex), into the epaxial muscles. Ease of intranasal administration, sedation score, onset of sedation, cardiopulmonary variables, mechanical nociceptive thresholds (MNTs) and response to venous catheterization were recorded at 0 (baseline), 5, 10, 15, 20, 25, 30, 35, 40 and 45 minutes, following drug administration. Data were compared with the one-way anova, Mann-Whitney U test, and chi-square test, where appropriate.ResultsGroups were not different for age, sex, weight, body condition score or temperament. Sedation scores, MNTs and response to intravenous catheter placement were not different when dexmedetomidine was administered by either route (p = 0.691; p = 0.630 and p = 0.435, respectively). Onset of sedation was not different between groups IN_Dex and IM_Dex reaching a score of 4.2 ± 0.9 and 5.5 ± 1.2 at 9 ± 5 and 8 ± 4 minutes, respectively (p = 0.467). The highest sedation score was achieved at 30 and 35 minutes and sedation scores were 9.7 ± 2.0 and 9.5 ± 2.3 in groups IN_Dex and IM_Dex, respectively (p = 0.799). Respiratory rate was higher in group IN_Dex (p = 0.014), while there were no differences between routes in heart rate (p = 0.275), systolic (p = 0.957), diastolic (p = 0.837) or mean arterial pressure (p = 0.921).Conclusions and clinical relevanceIntranasal administration of dexmedetomidine at 5 μg kg^–1 provides effective sedation in healthy dogs.     

Effect of leukoreduction on inflammation in critically ill dogs receiving red blood cell transfusions: A randomized blinded controlled clinical trial

BackgroundPrestorage leukoreduction of red blood cell (RBC) bags prevents accumulation of pro‐inflammatory mediators and experimentally attenuates post‐transfusion inflammation in healthy dogs. However, the effect of leukoreduction on post‐transfusion inflammation in critically ill dogs is unclear.HypothesisDogs transfused with leukoreduced (LR) RBC will have lower concentrations of leukocytes, interleukin (IL)‐6, IL‐8, monocyte chemoattractant protein‐1 (MCP‐1), and C‐reactive protein (CRP) within 24 hours of post‐transfusion compared to dogs transfused with nonleukoreduced (NLR) RBC.AnimalsSixty‐one RBC‐transfused dogs (LR = 34, NLR = 27).MethodsRandomized, blinded, controlled preliminary clinical trial. Blood bag processing was randomized to create identically appearing LR and NLR bags. Group allocation occurred with transfusion of the oldest compatible RBC bag. Blood samples were collected pretransfusion and at 8 and 24 hours post‐transfusion for leukocyte count, IL‐6, IL‐8, MCP‐1, and CRP. Data were analyzed on an intention‐to‐treat basis using linear mixed effects models. Significance was set at P < .05.ResultsNo significant differences were found between groups in concentrations of leukocytes (P = .93), IL‐6 (P = .99), IL‐8 (P = .75), MCP‐1 (P = .69), or CRP (P = .18) over time. Eleven LR dogs (32%) and 4 NLR dogs (15%) were euthanized in the hospital (P = .14). No natural deaths occurred.Conclusions and Clinical ImportanceNo differences in inflammation biomarker concentrations were detected over time between dogs transfused with LR or NLR RBC, but heterogeneity likely hampered the ability to detect a difference with this sample size. The novel randomization and enrollment protocol was successfully implemented across 2 participating institutions and will be easily scaled up for a future multicenter clinical trial.