Veterinary and comparative oncology最新文献

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.

The goal of this prospective, single-arm pilot study was to assess tolerability and clinical benefit for cats with histologically confirmed lymphocytic lymphoma/chronic inflammatory enteropathy complex (FLL/CIE) treated with low-dose abdominal cavity radiation therapy (RT; 8 Gy total dose administered in four 2 Gy fractions). No cats received steroids or chemotherapy prior to RT. Fourteen cats were enrolled and 13 completed the study. Eight cats had enteropathy-associated T cell lymphoma type II (FLL), and 6 cats had CIE (lymphoplasmacytic enteritis, 3 with concurrent eosinophilic enteritis). Nine of 13 cats (69%) had transient worsening of GI signs in the 1-3 weeks after RT, presumed secondary to RT and/or stress of travel/anaesthesia. Eight were managed as outpatients and one cat died after being syringe fed by the owner. Nine of the 12 remaining cats (75%; N = 6 with FLL and N = 3 with CIE) had a clinical benefit to treatment (resolution or improvement of GI signs as defined by owner surveys and body weight) that was sustained for > 340 days. Three cats experienced presumed or confirmed disease progression at 341, 465 and 449 days after RT and were treated with steroids. Six cats remained asymptomatic (N = 5) or stable (N = 1) at a median of 635 days after RT (range, 447-1014 days). Low-dose abdominal cavity RT could be considered for cats that cannot tolerate steroids and/or for owners that cannot pill cats routinely. Further optimisation of the protocol and use of RT as a rescue treatment for cats that fail traditional therapies are considerations for further study.

Spontaneous canine prostate cancer (PC) is widely considered a pertinent clinical model for the human disease. While over 95% of PC in men are adenocarcinomas, arising from prostatic glandular epithelium, it is increasingly recognised that many canine PC are of urothelial origin, arising within the prostatic urethra or ducts, or through invasion from a primary urinary bladder tumour. At diagnosis, canine prostatic tumours are often poorly differentiated and widely disseminated, masking the primary site and limiting the sensitivity of cellular biomarkers. Consequently, published studies of canine PC show varying representation of glandular versus urothelial tumours, yielding conflicting observations regarding their molecular pathogenesis and clinical behaviour. We characterised DNA sequence mutations and copy number aberrations in 31 canine PC, seeking evidence supporting relevance as a disease model. Only three tumours resembled adenocarcinomas. The remainder were either histologically consistent with urothelial carcinoma (n = 15), showed mixed glandular and urothelial morphology (n = 4), or were carcinomas of undetermined cell type (n = 9). BRAF V588E mutation was detected in 87% of tumours, including all three adenocarcinomas. Urinary bladder involvement was evident in 46% of cases, but none of the adenocarcinomas. Genome-wide DNA copy number instability was apparent throughout the cohort, with chromosome 36 gain significantly associated with urothelial tumours. Hallmark alterations of human PC, such as defects within PI3K and androgen receptor signalling pathways, were not detected. Improved molecular subclassification of canine PC is needed to direct selection of relevant cases for modelling the human disease and to ensure appropriate extrapolation between canine and human studies.

The fraction size in canine pelvic tumours has traditionally been limited to minimisze radiation toxicity. However, advancements in precision radiotherapy techniques have enabled the use of larger fraction sizes, thereby facilitating a reduction in the overall treatment course. This study assessed the radiation toxicity risks of a 10-fraction radiation protocol for canine prostatic carcinoma by calculating normal tissue complication probabilities (NTCPs). Computed tomography data from 22 dogs with prostatic carcinoma were analysed. The new protocol was designed to deliver 43 Gy in 10 fractions over 2 weeks (Monday-Friday), with a biologically effective dose similar to that of standard protocols. Compared to the standard 20-fraction protocol, the 10-fraction protocol demonstrated comparable toxicity risks in most organs except for some rectal endpoints and the urethra, while also offering advantages in treatment time and patient convenience. Nevertheless, under the 10-fraction protocol, the relatively high NTCPs for late rectal toxicities and the identification of patients at high risk of toxicity support the recognition of the rectum as a primary organ at risk in hypofractionated radiotherapy. Rectal toxicity risks were higher in patients with trigonal invasion, dorsal rectal displacement or rectal narrowing. Higher tumour length/L6 height and maximal tumour diameter/L6 height ratios were associated with increased rectal NTCPs. Relative tumour size indices effectively predicted patients at high risk for rectal toxicity. Cut-off values were identified for acute rectal toxicity (Grade ≥ 2; tumour height/pelvic inlet ratio: 0.62), rectal bleeding (Grade 2; tumour height/L6 height: 4.03) and proctitis (Grade 2; maximal tumour diameter/pelvic inlet ratio: 0.82). These findings highlight the importance of relative tumour size indices as predictive markers for rectal toxicity risk in the 10-fraction protocol. The results suggest that the 10-fraction, 43 Gy protocol may be safely applied when tumour size remains below specific thresholds.