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Tumor volume is controversially discussed as a prognostic factor in dogs treated with radiation therapy for sinonasal tumors. Dogs’ body sizes vary widely and relative rather than absolute tumor volume might provide better prognostic information. Our hypothesis was that relative rather than absolute tumor volume (gross tumor volume, GTV) influences time to progression (TTP) and that a larger tumor volume is correlated with a higher tumor stage. We retrospectively investigated possible correlations of initial GTV to weight, body surface area (BSA), nasal cavity size and the tumor stage in 49 dogs with sinonasal tumors. Here, also presumed sinonasal tumors, esthesioneuroblastomas and histologically benign tumors were included. The possible impact of absolute and relative GTV on response and outcome were assessed according to imaging findings in 34 dogs with available follow-up computed tomographies (CTs) after definitive-intent radiation therapy with either a regular (10x4.2 Gy) or a simultaneously- integrated boost protocol (SIB; GTV boosted to 10x4.83 Gy). In contrast to absolute GTV (p<0.001), the relative GTVs were not correlated with dogs’ body sizes. Absolute GTV, GTV relative to weight and BSA were not associated with TTP based on CT imaging. However, GTV relative to nasal cavity showed a prognostic influence with a hazard ratio of 10.97 (95%CI:1.25–96.06). When looking at GTV relative to nasal cavity, stage 3 and 4 tumors were significantly larger than stage 1 and 2 tumors (p = 0.005). Our results suggest that GTV relative to nasal cavity could be prognostic for TTP and a larger tumor volume relative to nasal cavity is correlated with a higher tumor stage.

Intensity modulated radiation therapy (IMRT) introduced marked changes to cancer treatment in animals by reducing dose to organs at risk (OAR). As the next technological step, volumetric modulated arc therapy (VMAT) has advantages (increased degrees-of-freedom, faster delivery) compared to fixed-field IMRT. Our objective was to investigate a possible advantage of VMAT over IMRT in terms of lower OAR doses in advanced-disease sinonasal tumors in dogs treated with simultaneously-integrated boost radiotherapy. A retrospective, analytical, observational study design was applied using 10 pre-existing computed tomography datasets on dogs with stage 4 sinonasal tumors. Each dataset was planned with both, 5-field IMRT and 2 arc VMAT with 10x4.83 Gy to the gross tumor volume and 10x4.2 Gy to the planning target volume. Adequate target dose coverage and normal tissue complication probability of brain ≤5% was required. Dose constraints aspired to were D60 <15 Gy for eyes, D2 <35.4 Gy for corneae, and Dmean <20 Gy for lacrimal glands. OAR dose was statistically significantly higher in IMRT plans than in VMAT plans. Median eye D60% was 18.5 Gy (interquartile range (IQR) 17.5) versus 16.1 Gy (IQR 7.4) (p = 0.007), median lacrimal gland dose 21.8 Gy (IQR 20.5) versus 18.6 Gy (IQR 7.0) (p = 0.013), and median cornea D2% 45.5 Gy (IQR 6.8) versus 39.9 Gy (IQR 10.0) (p<0.005) for IMRT versus VMAT plans, respectively. Constraints were met in 21/40 eyes, 7/40 corneae, and 24/40 lacrimal glands. Median delivery time was significantly longer for IMRT plans than for VMAT plans (p<0.01). Based on these results, VMAT plans were found to be superior in sparing doses to eyes, lacrimal glands, corneae. However, not all ocular OAR constraints could be met while ensuring adequate dose coverage and restricting brain toxicity risk for both planning techniques.

OBJECTIVE: Aims were to investigate sensitivity of various human and canine cancer cell lines to hyperthermia and the influence of particular treatment conditions, and to analyze the DNA-damage response and mode of cell death in cell line radiosensitized by hyperthermia. Additionally, we were interested in the involvement of HSP70 in radiosensitization. METHODS: Radiosensitization by hyperthermia was determined in a panel of human and canine cancer cell lines using clonogenic cell survival assay, as well as levels of heat shock proteins (HSPs) using immunoblotting. The influence of the hyperthermia-radiotherapy time gap, different temperatures and the order of treatments on clonogenicity of hyperthermia-sensitive A549 cells was investigated. Additionally, DNA damage and cell death were assessed by Comet assay and an apoptosis/necrosis assay. Further we induced transient knockdown in A549 cells to test HSP70's involvement in radiosensitization. RESULTS: Out of eight cell lines tested, only two (A549 and Abrams) showed significant decrease in clonogenic cell survival when pre-treated with hyperthermia at 42°C. Strong induction of HSP70 upon thermoradiotherapy (HT-RT) treatment was found in all cell lines. Transient knockdown of HSP70 in A549 cells did not result in decrease of clonogenic cell survival in response to HT-RT. CONCLUSION: Tumor cell-type, temperature and order of treatment play an important role in radiosensitization by hyperthermia. However, hyperthermia has limited potency to radiosensitize canine cancer cells grown in a 2D cell culture setting presented here. DNA damage and apoptosis/necrosis did not increase upon combined treatment and cytosolic levels of HSP70 appear not to play critical role in the radiosensitization of A549 cells.

Fitting canine cancer incidences through a conventional regression model assumes constant statistical relationships across the study area in estimating the model coefficients. However, it is often more realistic to consider that these relationships may vary over space. Such a condition, known as spatial non-stationarity, implies that the model coefficients need to be estimated locally. In these kinds of local models, the geographic scale, or spatial extent, employed for coefficient estimation may also have a pervasive influence. This is because important variations in the local model coefficients across geographic scales may impact the understanding of local relationships. In this study, we fitted canine cancer incidences across Swiss municipal units through multiple regional models. We computed diagnostic summaries across the different regional models, and contrasted them with the diagnostics of the conventional regression model, using value-by-alpha maps and scalograms. The results of this comparative assessment enabled us to identify variations in the goodness-of-fit and coefficient estimates. We detected spatially non-stationary relationships, in particular, for the variables related to biological risk factors. These variations in the model coefficients were more important at small geographic scales, making a case for the need to model canine cancer incidences locally in contrast to more conventional global approaches. However, we contend that prior to undertaking local modeling efforts, a deeper understanding of the effects of geographic scale is needed to better characterize and identify local model relationships.