The objective of this observational, descriptive, retrospective study was to report CT characteristics associated with fractures following stereotactic radiosurgery in canine patients with appendicular osteosarcoma. Medical records (1999 and 2012) of dogs that had a diagnosis of appendicular osteosarcoma and undergone stereotactic radiosurgery were reviewed. Dogs were included in the study if they had undergone stereotactic radiosurgery for an aggressive bone lesion with follow-up information regarding fracture status, toxicity, and date and cause of death. Computed tomography details, staging, chemotherapy, toxicity, fracture status and survival data were recorded. Overall median survival time (MST) and fracture rates of treated dogs were calculated. CT characteristics were evaluated for association with time to fracture. Forty-six dogs met inclusion criteria. The median overall survival time was 9.7 months (95% CI: 6.9-14.3 months). The fracture-free rates at 3, 6, and 9 months were 73%, 44%, and 38% (95% CI: 60-86%, 29-60%, and 22-54%), respectively. The region of bone affected was significantly associated with time to fracture. The median time to fracture was 4.2 months in dogs with subchondral bone involvement and 16.3 months in dogs without subchondral bone involvement (P-value = 0.027, log-rank test). Acute and late skin effects were present in 58% and 16% of patients, respectively. Findings demonstrated a need for improved patient selection for this procedure, which can be aided by CT-based prognostic factors to predict the likelihood of fracture.

High-grade canine mast cell tumours (HG-MCT) have a high rate of locoregional relapse. In this study, dogs with HG-MCT treated with radiation therapy (RT) were retrospectively evaluated to determine the benefit associated with treating the locoregional lymph nodes (LNs). Forty-two dogs were included. Variables assessed for association with overall survival (OS) and progression-free survival (PFS) included WHO stage, tumour location and size, LN irradiation (prophylactic, therapeutic or none), LN treatment (yes or no), LN status at RT (metastatic or nonmetastatic) and RT intent (definitive vs palliative). Lower-stage disease at irradiation was significantly associated with prolonged median PFS (425 vs 125 days for stage 0 vs 1-4), and OS (615 vs 314 days for stage 0 vs 1-4). Having any LN treatment and definitive RT were both significantly associated with prolonged OS. In order to evaluate the role of LN irradiation, dogs were divided into subgroups: (a) stage 0 at irradiation with no LN treatment (n = 14), (b) stage 0 at irradiation with prophylactic LN irradiation (n = 6), (c) stage 0 at irradiation but previously stage 2 (n = 5) and (d) stage >0 at irradiation (n = 17). Prophylactic LN irradiation significantly prolonged PFS (>2381 vs 197 days; group B vs A). Interestingly, dogs that were stage 2 and had LN treatment (C) had prolonged OS vs dogs with negative LNs and no LN treatment (A) (1908 vs 284 days; P = .012). This study confirms that prophylactic and therapeutic LN irradiation in dogs with HG-MCT is beneficial and improves outcome. K E Y W O R D S dogs, lymph nodes, lymphatic metastasis, mast cells, skin neoplasms

Stereotactic radiosurgery (SRS) is a relatively new therapeutic option in veterinary oncology. The role of this modality has not been extensively evaluated for the use in canine nasal tumors. The objective of this retrospective, observational study was to describe the clinical outcome and prognostic factors associated with survival times in a sample of canine patients treated with SRS for sinonasal tumors. Fifty-seven dogs with sinonasal tumors met inclusion criteria. Histologic diagnoses included sarcoma (SA) (n = 9), carcinoma (CA) (n = 40), osteosarcoma (OSA) (n = 7), and round cell (n = 1). Four of 57 cases were treated twice with SRS. For these, the median and mean doses delivered were 30Gy and 33Gy, respectively (range 18.75Gy-56Gy). Late effects occurred in 23 cases and ranged from grades I-III. The median overall survival time was 8.5 months. The median overall survival times in dogs with tumor type of CA, SA, and OSA were 10.4, 10.7, and 3.1 months, respectively. Dogs with the tumor type of OSA had shorter overall survival time than that in dogs with tumor type of CA and SA. Findings from this retrospective study indicated that SRS may be beneficial for canine patients with sinonasal tumors, however a controlled clinical trial would be needed to confirm this. Prospective studies are also needed to better define the role of SRS as palliative or curative, and to further investigate the risk of clinically significant toxicity.

Purpose/Objective(s) Imaging biomarkers of resistance to radiation therapy can inform and guide treatment management. Most studies so far have focused on assessing a single imaging biomarker. The goal of this study was to explore a number of different molecular imaging biomarkers as surrogates of resistance to radiation therapy. Methods and Materials Twenty-two canine patients with spontaneous sinonasal tumors were treated with accelerated hypofractionated radiation therapy, receiving either 10 fractions of 4.2 Gy or 10 fractions of 5.0 Gy to the GTV. Patients underwent FDG, FLT, and Cu-ATSM PET/CT imaging before therapy, and FLT and Cu-ATSM PET/CT imaging during therapy. In addition to traditional SUV measures (eg, maximum SUV), imaging metrics providing response and spatiotemporal information were extracted for each patient. Progression-free survival was assessed according to RECIST criteria. The prognostic value of each imaging biomarker was evaluated using univariable Cox proportional hazards regression. Multivariable analysis was also performed, but was restricted to two predictor variables due to the limited patient number. The best bivariable model was selected according to Pseudo R2. Results The following variables were significantly associated with poor clinical outcome following radiation therapy according to univariable analysis: tumor volume (P=0.011), midtreatment FLT SUVmean (P=0.018), and midtreatment FLT SUVmax (P=0.006). Large decreases in FLT SUVmean from pretreatment to midtreatment were associated with worse clinical outcome (P=0.013). In the bivariable model, the best two-variable combination for predicting poor outcome was high midtreatment FLT SUVmax (P=0.022) in combination with large FLT response from pretreatment to midtreatment (P=0.041). Conclusions In addition to tumor volume, pronounced tumor proliferative response quantified using FLT PET, especially when associated with high residual FLT PET at midtreatment, is a negative prognostic biomarker of outcome in canine tumors following radiation therapy. Neither FDG PET nor Cu-ATSM PET were predictive of outcome.

The purpose of our study was to compare setup variation in four degrees of freedom (vertical, longitudinal, lateral, and roll) between canine nasal tumor patients immobilized with a mattress and bite block, versus a mattress alone. Our secondary aim was to define a clinical target volume (CTV) to planning target volume (PTV) expansion margin based on our mean systematic error values associated with nasal tumor patients immobilized by a mattress and bite block. We evaluated six parameters for setup corrections: systematic error, random error, patient–patient variation in systematic errors, the magnitude of patient-specific random errors (root mean square [RMS]), distance error, and the variation of setup corrections from zero shift. The variations in all parameters were statistically smaller in the group immobilized by a mattress and bite block. The mean setup corrections in the mattress and bite block group ranged from 0.91 mm to 1.59 mm for the translational errors and 0.5°. Although most veterinary radiation facilities do not have access to Image-guided radiotherapy (IGRT), we identified a need for more rigid fixation, established the value of adding IGRT to veterinary radiation therapy, and define the CTV–PTV setup error margin for canine nasal tumor patients immobilized in a mattress and bite block.

Toceranib phosphate and piroxicam have individually demonstrated antineoplastic activity. Additionally, non-steroidal anti-inflammatory therapy is often warranted in aged cancer-bearing dogs for management of osteoarthritis comorbidity. As concurrent use may be warranted for a given individual and the adverse event (AE) profile for each can be overlapping (gastrointestinal), a phase I trial was performed in tumour-bearing (non-mast cell) dogs to establish the safety of the combination using a standard 3+3 cohort design. Five dose-escalating cohorts, up to and including approved label dosage for toceranib and standard dosage for piroxicam, were completed without observing a frequency of dose-limiting AEs necessitating cohort closure. Therefore, the combination of standard dosages of both drugs (toceranib, 3.25 mg kg(-1), every other day; piroxicam, 0.3 mg kg(-1) daily) is generally safe. Several antitumour responses were observed. As with single-agent toceranib, label-indicated treatment holidays and dose reductions (e.g. 2.5-2.75 mg kg(-1)) may occasionally be required owing to gastrointestinal events.

Stereotactic radiation therapy (SRT) has emerged as a convenient definitive treatment modality in veterinary medicine, but few studies exist evaluating outcome with treatment for canine nasal tumors, and no studies report the treatment of one single tumor histotype. This retrospective, observational study evaluates toxicity, response, and survival in 17 dogs with nasal carcinomas treated with SRT. Dogs received a median of 3000 centigray in three fractions via 6-MV linear accelerator. Eighty-eight percent of patients (n = 15) demonstrated clinical benefit. Of dogs with repeated CT imaging (n = 10), 60% (n = 6) achieved a partial response and 10% (n = 1) achieved a complete response. Median progression-free survival (PFS) was 359 days. Median survival time (MST) was 563 days. Among dogs evaluable for acute toxicity, 50% (n = 10) developed low grade toxicity (grade 1, n = 4; grade 2, n = 1). No patients developed grade 3 toxicity. 16 dogs (87%) evaluable over the long term developed signs consistent with possible late toxicity. The majority of late toxicities were mild (alopecia, hyperpigmentation, and leukotrichia n = 10; ocular discharge and keratoconjunctivitis sicca n = 5). Thirty-seven percent of patients (n = 6) developed seven possible grade 3 late toxicities (blindness, n = 3; fistula, n = 1; seizures, n = 3), which were difficult to distinguish from progressive disease in most patients. Of the prognostic factors evaluated (demographics, tumor stage, dosimetric data, epistaxis, facial deformity, clinical response, image-based response, nonsteroidal anti-inflammatory drugs, and chemotherapy), only clinical response was a positive prognostic factor on MST (P < .00). No factors were found to be significantly associated with PFS.

Kinetic parameter variability may be sensitive to kinetic model choice, kinetic model implementation or patient-specific effects. The purpose of this study was to assess their impact on the variability of dynamic contrast-enhanced computed tomography (DCE-CT) kinetic parameters. A total of 11 canine patients with sinonasal tumours received high signal-to-noise ratio, test-double retest DCE-CT scans. The variability for three distributed parameter (DP)-based models was assessed by analysis of variance. Mixed-effects modelling evaluated patient-specific effects. Inter-model variability (CV ) was comparable to or lower than intra-model variability (CV ) for blood flow (CV :[4-28%], CV :[28-31%]), fractional vascular volume (CV :[3-17%], CV :[16-19%]) and permeability-surface area product (CV :[5-12%], CV :[14-15%]). The kinetic models were significantly (P<0.05) impacted by patient characteristics for patient size, area underneath the curve of the artery and of the tumour. In conclusion, DP-based models demonstrated good agreement with similar differences between models and scans. However, high variability in the kinetic parameters and their sensitivity to patient size may limit certain quantitative applications.