Veterinary and comparative oncology最新文献

Glomerular filtration rate (GFR) predicts carboplatin clearance and myelotoxicity in humans and cats. This relationship is unknown in dogs. In canines, elevated serum symmetric dimethylarginine (SDMA) correlates with reduced GFR. This study prospectively evaluated whether dogs with elevated SDMA (> 14 μg/dL) are at increased risk of hematologic and gastrointestinal toxicity following carboplatin chemotherapy. Plasma samples were collected to determine if SDMA or other factors are significant determinants of carboplatin pharmacokinetics. Thirty client-owned dogs weighing > 15 kg with confirmed neoplasia were enrolled. Dogs received carboplatin intravenously (300 mg/m²). SDMA was measured on the day of treatment. Nonlinear mixed effects modelling was done to identify possible covariates affecting pharmacokinetic parameters. Adverse effects were monitored with weekly complete blood counts and owner assessment forms. Five dogs had elevated SDMA; four had significantly reduced carboplatin clearance (mean 93.9, range 76.1-116.8 mL/h/kg) compared with dogs with SDMA ≤ 14 μg/dL (mean 185.4, range 114.3-268.3 mL/h/kg, p < 0.001). Three dogs with elevated SDMA experienced grade 4 neutropenia; one was euthanized due to sepsis. Two additional dogs with elevated SDMA were euthanized 5- and 13-days post treatment due to severe gastrointestinal signs. Twenty-five dogs had SDMA ≤ 14 μg/dL: 10 had asymptomatic grade 3 or 4 neutropenia, 3 had grade 3 or 4 GI toxicity, and none died. Elevated SDMA was associated with decreased carboplatin clearance in dogs and predicted risk for treatment-related toxicity and death in our study population.

Dogs with intracranial tumours routinely receive radiotherapy, yet species-specific dose-volume constraints for normal brain tissue remain undefined. In human radiation oncology, exceeding certain brain dose-volume thresholds markedly increases the risk of radiation-induced injury (e.g., radionecrosis). Current veterinary practice often extrapolates human guidelines without validation in discrete species, creating a gap in evidence-based planning. This study aimed to identify brain dose-volume thresholds associated with overall survival (OS) in canine brain-tumour patients. We pooled data from two prospective randomised trials (n = 105 dogs) treated with 10 daily fractions of 4 Gy (total 40 Gy) for intracranial tumours at a single institution. Semi-automated scripting extracted multiple dose-volume metrics, including generalised equivalent uniform dose (gEUD), for the whole brain and brain minus gross tumour volume (Brain-GTV). An iterative Kaplan-Meier and Cox proportional hazards approach identified optimal dosimetric cutoffs, which were then adjusted for tumour volume and body weight via a regression residual method. A brain-volume-adjusted gEUD threshold was also derived to account for variation in brain size. Exposure to normal brain to doses around 30-40 Gy emerged as the strongest predictor of OS. Brain-GTV V32 Gy ≤ 13 cm³ was associated with longer OS (covariate-adjusted cutoff 13.4 cm³, HR = 1.74; p = 0.022, unadjusted optimal split 11.5 cm³, HR = 2.08; p = 0.001). Whole-brain gEUD > 30 Gy similarly predicted poorer survival (HR = 1.72; p = 0.034). Implementing a personalised gEUD ceiling increased 2-year sensitivity from 31% to 38% with only a three-point drop in specificity. In a 10 × 4 Gy canine intracranial radiotherapy model, limiting Brain-GTV V32 Gy to ≤ 13 cm³ and whole-brain gEUD to ≤ 30 Gy was associated with longer overall survival. A brain-volume-adjusted gEUD ceiling further refined risk prediction. These evidence-based thresholds provide actionable guidance for veterinary treatment planning, with the potential to improve outcomes in canine brain tumour therapy.

Mammary carcinomas are aggressive neoplasms and a significant cause of mortality in female cats. Despite surgical removal, feline mammary carcinoma (FMC) often recurs or metastasizes. Specific tumour biomarkers are necessary for early detection, prognosis and therapy selection. This study aims to identify candidate biomarkers for FMC by comparing tissue proteomic profiles among grades of 31 FMC cats and six normal mammary tissues (control) using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Candidate proteins identified by LC-MS/MS were validated by Western blotting and LC-MS/MS. Prognostic values of candidate proteins were evaluated using immunohistochemistry and survival analysis. Protein-chemotherapy drug interaction networks were also evaluated. Among the 268 differential proteins observed, dermatopontin (DPT) expression was significantly downregulated, while sorting nexin 5 (SNX5) expression was elevated in cancerous tissues compared to controls (p < 0.05). Immunohistochemistry results revealed a significant association of DPT and SNX5 with stages (DPT, p < 0.0001; SNX5, p = 0.046) and grades of FMC (DPT, p < 0.0001; SNX5, p = 0.04). Low DPT expression was associated with poor overall survival (p = 0.02), along with Stage 4 FMC (p = 0.0001), high mitotic count (p = 0.003) and the presence of lymphovascular invasion (p = 0.003). Moreover, protein-chemotherapy drug interaction showed a relationship of DPT with doxorubicin, lapatinib and neratinib. This study identified DPT and SNX5 as potential diagnostic and therapeutic targets for FMC, with DPT emerging as a promising prognostic biomarker.

Stereotactic body radiation therapy (SBRT) has become a non-invasive alternative option for canine adrenal tumours with high surgical risks; however, its clinical benefits and risks are still to be fully understood. The goal of this multi-institutional retrospective study was to describe the clinical outcome and safety of SBRT for the treatment of 21 dogs with adrenal tumours. Ten were suspected pheochromocytomas, two adenocarcinomas, and the diagnosis was unknown in nine dogs. Vascular invasion was present in 81% of cases (17/21). Thirteen dogs received 3 fractions of 6 to 11 Gy, 7 received 5 fractions of 6 to 9 Gy, and 1 received 4 fractions of 6 Gy. For the 20 patients with follow-up imaging, 9 (43%) had partial response, 10 (47%) stable disease, and 1 (5%) progressive disease. Progression-free survival was 16.8 months (95% CI: 3.4-23), and overall survival time was 16.8 months (95% CI: 3.7-23.7). Twelve patients (57%) experienced acute adverse events (AEs); of those, seven were gastrointestinal grade ≥ III, including one grade V. Late AEs were suspected in seven dogs (33%), including gastrointestinal grade V in four of them. A total of five dogs (24%) died from radiation-related toxicities. Although SBRT seems to be effective against adrenal tumours, it was associated with a high morbidity and mortality rate, suggesting that re-evaluation of radiation therapy protocols is necessary for maintaining patient safety.

Mammary tumours account for approximately 50% of the neoplasms in female dogs. Even conventionally accepted prognostic indicators often fail to reliably predict the clinical behaviour of these tumours, underscoring the need for more effective prognostic markers. Proteins of the LOX family are associated with tumour invasion and metastasis in several types of tumours. The purpose of this study was to characterise the immunohistochemical expression of LOX and LOXL2 in canine mammary carcinomas and to investigate their prognostic significance. Samples of mammary carcinomas from 80 female dogs with a minimum post-surgical follow-up of 180 days were analysed. Tumour samples were submitted to immunohistochemistry to detect LOX and LOXL2. Immunolabelling was evaluated based on scores for staining intensity and percentage of positive cells, and a combined score was used to classify each protein as having either 'low-' or 'high-expression'. The results were compared with histological types, mortality due to the disease and post-surgical survival. We found that negativity for LOXL2 expression was an indicator of higher risk of death due to the disease. Our results suggest that lysyl oxidases such as LOXL2 are potential prognostic markers in mammary carcinomas of dogs.

Melanocytic tumours (MT) occur in both humans and companion animals, presenting an opportunity for comparative oncology research. Thus, this study provides a comprehensive epidemiological analysis comparing MT in Portuguese dogs, cats and humans. Data were obtained from the Portuguese National Cancer Registry (RON) (2011-2021) and Vet-OncoNet (2020-2023), utilising standardised oncological classification systems (ICD-O-3.2 and Vet-ICD-O-canine-1). The results indicate that Melanoma was the most frequently diagnosed MT across all three species, while melanocytomas were common in dogs but rare in cats and humans. A higher incidence rate (IR) for MT was observed in dogs (IR = 16.1) compared to humans (IR = 8.1) and cats (IR = 6.3), and neutered dogs (10.8 years) were diagnosed at significantly older ages than intact ones (9.9 years). Shar-Peis (RR = 14.2, p < 0.001) had the highest RR compared to mixed-breed dogs, followed closely by Rhodesian Ridgebacks (RR = 12.2, p < 0.001) and Golden Retrievers (RR = 6.4, p < 0.001). Spatial analysis revealed significant clustering of MT cases in humans and dogs, with a strong geographical overlap (BLISA = 0.345, p < 0.001) in urban regions. This study provides the first epidemiological comparison of MT in these three species in Portugal, underscoring the sentinel role of companion animals in human oncology and the relevance of comparative oncology in translational cancer research.

Lymph node (LN) metastasis is a negative prognostic factor in canine mast cell tumours (MCTs). Flow cytometry (FC) can identify and quantify mast cells (MCs) in LNs. This tri-institutional prospective study aimed to evaluate the impact of previously reported MC cut-off values in sentinel LNs (SLNs) detected by FC on clinical outcomes in dogs with cutaneous or subcutaneous MCTs, and to determine a prognostically significant cut-off. Dogs with newly diagnosed, previously untreated, single MCT scheduled for primary tumour excision and sentinel lymphadenectomy were enrolled. The SLNs of enrolled dogs were analysed using cytology and FC after excision. MCs were quantified as a percentage using FC, and SLNs were cytologically and histologically classified according to the Krick and Weishaar systems, respectively. The influence of potential prognostic variables, including MCs cut-offs > 1.1% and > 4%, on tumour progression and tumour-specific survival (TSS) was evaluated using Cox regression and log-rank analysis. The optimal cut-off for predicting tumour-related death was determined via ROC curves. A total of 64 dogs were enrolled. Dogs with nodal MC infiltration exceeding 1.1% and 4% were 10 and 40 times more likely, respectively, to experience tumour progression. SLN MC infiltration > 4% and HN3 SLN (observed in 9 out of 64 dogs) were associated with shorter TSS (median, 327 versus not reached; p < 0.001). The optimal SLN cut-off for predicting tumour-related death was 16%. These findings suggest that previously established cut-offs may hold prognostic value. Additional studies performing in vivo sampling with a larger number of events are necessary to validate this proposed cut-off.

Canine multicentric lymphoma is a common cancer in dogs without evidence-based prevention measures. While breed accounts for part of lymphoma risk, environmental exposures might also contribute. Human non-Hodgkin lymphoma (NHL), which resembles canine lymphoma, is associated with exposures to volatile organic compounds (VOCs) and herbicides. Pet dogs are commonly exposed to these genotoxic chemicals, but it is unknown whether such exposures are associated with in vivo DNA damage as a potential contributor to lymphoma in dogs or whether early DNA damage can be detected before lymphoma diagnosis. The aims of this study were to determine whether DNA strand breaks or oxidised DNA residues precede a diagnosis of canine lymphoma and to assess whether DNA damage events correlate with estimated systemic exposures to the VOCs benzene, xylene and 1,3-butadiene or the herbicides 2,4-D and glyphosate. In a nested case-control study within the Golden Retriever Lifetime Study, we found increased DNA strand breaks in dogs with lymphoma compared to controls at the time of diagnosis (p = 0.004). We also found higher oxidised DNA residues both at the time of diagnosis (p = 0.02) and in the year prior to diagnosis (p = 0.03). DNA strand breaks across all dogs and time points were positively correlated with estimated aggregate blood VOC exposures and estimated plasma 2,4-D and glyphosate concentrations. These data indicate that detectable oxidative DNA damage may precede a diagnosis of canine lymphoma and support the hypothesis that VOC and herbicide exposures might contribute to DNA strand breaks in pet dogs.

This retrospective study evaluated a cyclical, hypofractionated palliative-intent radiotherapy protocol ('quad-shot', QS) in 81 dogs with sinonasal tumours treated between 2011 and 2023. The protocol consisted of a 'cycle' of four fractions of 3.25-4.0 Gy delivered over 48-72 h, repeated every 3-4 weeks, up to three cycles (maximum cumulative dose, 48 Gy). Most were treated with 3D conformal radiation therapy and a small number with a clinical setup. Carcinomas accounted for 78% of cases and tumours were modified Adams stage 1 (n = 5; 6%), 2 (n = 8; 10%), 3 (n = 29; 36%), 4 (n = 33; 41%) or unknown in n = 6 (7%). Ninety percent of patients received three full cycles to a total of 39-48 Gy, and 77% showed clinical improvement at presentation for Cycle 2 and 90% at presentation for Cycle 3. Median progression-free interval (PFI) was 207 days (95% CI: 124-290), and median overall survival time (OST) was 296 days (95% CI: 177-415). One-, two-, and 3-year survival rates were 40.6%, 17.2%, and 9.4%, respectively. Acute toxicity was generally mild, with conjunctivitis (33%), mucositis (7%), and radiodermatitis (6%) being the most frequent. Severe late toxicity was infrequent, but toxicities were considered likely under-reported. In the multivariable analysis, three QS cycles (vs. 1 or 2 cycles only) was a positive prognostic factor. The QS protocol resulted in improvements in nasal clinical signs, with survival outcomes comparable to other palliative radiation protocols. Toxicity was acceptable, despite the poor conformality of the radiation therapy in this population.

Hypofractionated radiotherapy (hRT) is often used to treat dogs with oral malignant melanoma (OMM); however, there is no consensus as to whether clinically uninvolved regional lymph nodes should be prophylactically irradiated. The objective of this retrospective study is to compare outcomes for dogs with OMM treated with hRT+/- elective nodal irradiation (ENI). Dogs with nonmetastatic OMM undergoing hRT+/- ENI with a prescription of ≥ 30 Gy were included. Survival statistics were evaluated with Kaplan-Meier curves and log-rank testing. Univariable and multivariable Cox proportional hazard models were used to assess how survival was impacted by the use of ENI, WHO T-stage, mitotic count, RT technique, and use of Oncept melanoma vaccine. Data from four institutions and 100 dogs (80 with ENI and 20 without) were included. In the ENI group, nodal and distant metastases were documented in 4 and 30 dogs, respectively. In the non-ENI group, nodal and distant metastases were documented in 6 and 4 dogs, respectively. There was no significant difference in the 1-year nodal or distant progression-free intervals (p = 0.174, and 0.563, respectively). The only variable maintaining significance on multivariable analysis was T-stage (overall progression-free survival, HR 1.393, p = 0.006; overall survival time, HR 1.426, p = 0.005; distant progression-free interval, HR 1.521, p = 0.033). ENI did not measurably alter the oncologic outcomes in this study population. Results should be interpreted cautiously given the lack of standardised staging/restaging and the heterogenous nature of this clinical population. Future investigations are needed to clarify the role of ENI in the treatment of canine OMM.