Veterinary and comparative oncology最新文献

Fixed dose rate (FDR) gemcitabine offers pharmacokinetic advantages over bolus dosing, and there is evidence in human medicine that FDR gemcitabine is more effective than intravenous (IV) bolus. To date, literature describing gemcitabine use in dogs is limited to bolus administration. The goal of this study was to describe the tolerability and adverse event profile of a novel FDR gemcitabine protocol in tumour-bearing dogs. Thirty-nine dogs who received at least one infusion of FDR gemcitabine at 400 mg/m² IV over 2 h (3.3 mg/m²/min) were retrospectively evaluated. An average of 4 FDR gemcitabine doses (range, 1-15) were administered per dog. Sixteen dogs (41%) developed neutropenia (12 Grade 1, 1 Grade 2, 2 Grade 3, 1 Grade 4) and 5 dogs (13%) developed thrombocytopenia (3 Grade 1, 1 Grade 2, 1 Grade 3). Gastrointestinal adverse events were reported in 23 dogs (59%), and all were classified as Grade 1 or 2. Of the 35 dogs who had gross disease and adequate information available to assess response to treatment, 8 dogs (23%) achieved a partial response (PR), 11 dogs (31%) maintained stable disease (SD) and 16 dogs (46%) experienced disease progression. PR was documented in 5 out of 8 dogs (63%) with squamous cell carcinoma. This FDR gemcitabine protocol demonstrated manageable toxicity and a promising response rate in dogs. Further investigation is warranted to explore its potential role in treating canine tumours.

Elective neck dissection (END) and sentinel lymph node biopsy (SLNB) are suggested for nodal staging of canine head and neck malignancies (HNM). This study aims to compare the morbidity of END to SLNB. Seventy-six client-owned dogs with HNM that underwent END (n = 28) or SLNB (n = 48) in two institutions were retrospectively enrolled. Retrieved variables included data on signalment, lymph centre and lymph nodes, intra- and post-surgical complications (PSC) of lymphadenectomy, and histopathology results. The cumulative incidence of PSC at 30 days was estimated for END and SLNB and compared with Gray's test. The influence of variables on the incidence of complications was evaluated using univariate and multivariate models. No intraoperative complication occurred. The PSC were mostly mild. Seroma was the most frequent. The cumulative incidence of PSC of lymphadenectomy at 30 days was 47.4%, and they were severe in 14% of cases. The incidence of PSC was 25% for SLNB and 85.7% for END, and the difference was statistically significant (p < 0.001). Clinically enlarged nodes (p = 0.03), institution (p = 0.03), increasing number of resected nodes (p < 0.001) and of lymph centres (p < 0.001) predicted a higher incidence of PSC in the univariate model. In the multivariate analysis, only the type of node management (END vs. SLNB) remained significant. Although lymphadenectomy is a well-tolerated procedure in dogs with HNM, END was correlated with a higher risk of PSC compared to SLNB. Stratification of dogs by the risk of multiple nodal metastases is warranted to identify those who may still benefit from END despite a higher PSC risk.

Immune checkpoint inhibitors (ICIs) have emerged as a promising therapeutic strategy for canine oral malignant melanoma (OMM). However, only a subset of cases have shown clinical responses. Additionally, predictive biomarkers for the efficacy of ICIs in veterinary medicine are yet to be established. Tumour-infiltrating lymphocytes (TILs) are predictive biomarkers for ICI therapy in humans. In this study, we aimed to investigate the predictive utility of TILs for canine OMM treated with ICI therapy. Immunohistochemistry was performed on pre-treatment pathological tissues to detect cells positive for CD3 (pan-T cell marker), Granzyme B (cytotoxic T lymphocyte or natural killer cell marker) and Foxp3 (regulatory T cell marker). Further, we analysed the infiltration patterns of these cells and their prognostic utility for anti-programmed cell death ligand 1 (PD-L1) antibody therapy. There were variances in the infiltration levels of each TIL subset; further, we observed several TIL infiltration patterns in canine OMM. Survival analysis revealed that high infiltration of CD3⁺ and Granzyme B⁺ cells was significantly associated with prolonged progression-free survival and overall survival. Furthermore, the immune cell composition ratio, which reflected the balance between cytotoxic and regulatory cells, was significantly associated with survival time. These findings suggest that canine OMM exhibits immunological phenotypes analogous to those observed in human cancers. Taken together, the TIL profile holds significant potential as a prognostic biomarker for canine OMM treated with anti-PD-L1 antibody therapy.

Canine lymphoma is a heterogenous group of diseases. The most common subtype is diffuse large B cell lymphoma (DLBCL), though definitive diagnosis beyond non-indolent = multicentric B cell lymphoma is not often achieved in clinical practice as it requires histopathology. Most dogs respond well to standard-of-care multiagent chemotherapy (CHOP) but relapse and eventual CHOP-resistance is likely. Less commonly there is a lack of complete response to initial CHOP treatment. CHOP-resistant cases are treated with rescue chemotherapy protocols, of which many are published, but the most effective is unknown. In this systematic review we aimed to determine the most effective rescue chemotherapy protocol for dogs with multicentric non-indolent B cell lymphoma resistant to initial chemotherapy with a CHOP-based protocol. After initial screening, 65 full-text articles were reviewed. However, outcomes for the population of interest could not be identified in any, leaving our research question unanswered. Future publications of rescue treatment for canine lymphoma should report outcomes separately for groups of dogs where disease characteristics and prior treatment may affect outcome.

Advanced carcinomas in dogs present significant therapeutic challenges with limited treatment options and poor prognoses. Sorafenib, a multi-kinase inhibitor targeting RAF and receptor tyrosine kinases, has demonstrated antitumor activity and tolerability in preclinical veterinary studies; however, clinical data remain limited. This prospective, open-label cohort study evaluated the tolerability and clinical efficacy of oral sorafenib (6 mg/kg once daily) in 24 dogs with cytologically or histologically confirmed unresectable, recurrent, or metastatic carcinomas. Tumour response was assessed using RECIST criteria, and adverse events were graded according to VCOG-CTCAE v2.0. Stable disease at 1 month was observed in 14 of 18 evaluable dogs (77.8%), yielding an overall clinical benefit rate of 58.3%. Median time to progression and overall survival were 51 days (95% CI, 14-115) and 65 days (95% CI, 49-143), respectively. Dogs presenting with lameness (n = 7) showed significantly longer time to progression and overall survival than those without (p < 0.01). Adverse events occurred in 9 of 24 dogs (37.5%), primarily mild lameness (29%) and gastrointestinal signs. Weight gain at 1 month, observed in 66.7% of dogs, was significantly associated with clinical benefit (p = 0.005; OR = 45.0; 95% CI, 1.8-1127.7). Sorafenib was well tolerated and provided measurable clinical benefit in dogs with advanced carcinomas. Lameness may represent a prognostic biomarker, and weight gain may reflect a favourable clinical response. These findings support further investigation of sorafenib and other tyrosine kinase inhibitors in veterinary oncology.

Canine transmissible venereal tumour (CTVT) is the oldest naturally occurring transmissible cancer and serves as a unique comparative model for tumour-immune interactions. Unlike conventional neoplasms, CTVT is transmitted as an allograft between genetically distinct hosts, facing strong immune pressure while maintaining clonal persistence for millennia. This success reflects its remarkable ability to evade, adapt to, and remodel host immunity. CTVT modulates the tumour microenvironment through secretion of immunosuppressive cytokines such as TGF-β and IL-10, downregulation of MHC molecules, impaired dendritic cell differentiation, and disrupted apoptotic signalling. IL-8 further contributes by shifting the immune profile from Th1 to Th2 and inducing neutrophil extracellular traps (NETs), which promote antigen sequestration, angiogenesis, stromal remodelling, and dissemination. Immunometabolic reprogramming, including lactate-driven suppression of cytotoxic lymphocytes and NK cells, reinforces immune escape. Molecular pathways central to human oncology-such as STAT3, FGFR, PPAR-γ, and p53-remain underexplored in CTVT but may critically shape its immune dynamics. Recent findings indicate synonymous TP53 mutations associated with reduced p53 expression, partial apoptotic activation through caspase-9, and overexpression of BCL2, BAX, and MMP-9, highlighting imbalance between cell death regulation and extracellular matrix remodelling. The alternation between progressive and regressive phases provides a natural framework to study tumour immunoediting, tolerance, and long-term dormancy. Beyond its biological relevance, CTVT functions as a natural transplantation model in immunocompetent hosts and a platform for immunotherapeutic approaches, including dendritic cell-based vaccines. Altogether, the evolutionary longevity, genetic adaptability, and immune plasticity of CTVT underscore its value for comparative oncology and the development of novel immunotherapies.

In human medicine, transarterial embolisation (TAE) is widely used to manage inoperable tumours and intractable haemorrhages. However, its application in veterinary patients with oral tumours remains limited. Accordingly, we aimed to investigate the clinical utility of TAE using polyvinyl alcohol particles for the treatment of oral neoplasms in dogs and cats. We included 15 dogs and cats with oral neoplasia. The tumour types included squamous cell carcinoma (SCC), melanoma and chondrosarcoma. All patients underwent intra-arterial administration of carboplatin, followed by selective embolisation of the tumour-feeding arteries. There was a significant post-procedural improvement in clinical signs such as oral bleeding and anorexia (p < 0.05). Follow-up computed tomography imaging findings, which were available for 12 patients, demonstrated a significant tumour volume reduction of 50.66% (95% confidence interval: 10.46%-83.92%; p = 0.002). There were no major complications, with minor adverse events such as skin ulceration or transient pain being self-limiting. Among the 15 patients, 13 died during the study period, with survival times ranging from 60 to 499 days. Two patients were still alive at the time of analysis, at 305 and 406 days, respectively. When categorised by species and tumour type, dogs with SCC survived for 60-305 days, cats with SCC for 70-291 days, dogs with melanoma for 77-406 days and the two dogs with chondrosarcoma survived for 103 and 499 days, respectively. These findings suggest that TAE is a well-tolerated, minimally invasive treatment that can effectively reduce the tumour burden and clinical symptoms in veterinary patients with oral tumours.

Surgery is a common treatment for intracranial meningiomas in dogs, although the prognostic impact of the extent of resection (EOR) has not been systematically evaluated. This retrospective study identified prognostic factors associated with clinical outcomes in dogs that underwent surgery and early post-operative magnetic resonance imaging (epoMRI) to evaluate meningioma EOR. We hypothesised that gross total tumour resection (GTR) would result in longer progression free (PFS) and overall survival (OS), and superior post-operative seizure control and resolution of neurological dysfunction than subtotal resection (STR). Multivariable logistic regression was used to identify prognostic factors, and Kaplan-Meier analyses to compare survival outcomes. Forty-one dogs were included of which 24 (59%) had GTR and 17 (41%) had STR. GTR was associated with decreased rates of tumour progression (HR = 0.21; 95% CI, 0.09-0.42; p < 0.0001) and death (HR = 0.49; 95% CI, 0.14-0.69; p < 0.0001), and longer PFS (618 vs. 189 days, p < 0.0001) and OS (694 vs. 349 days, p < 0.0001) compared to STR. Higher tumour grade and increasing age negatively impacted PFS and OS, respectively. Seizure freedom was attained in a larger proportion of dogs with GTR (18/20 [90%]) than STR (4/13 [31%]; p < 0.001), but rates of improvement of neurological deficits were not different between groups. GTR resulted in durable clinical improvements and survivals in the absence of adjuvant treatments. EpoMRI to assess EOR should be routinely incorporated into management of canine meningiomas to inform outcome expectations, and to identify STR cases in which adjuvant therapies should be considered.

Radiation therapy (RT) has emerged as a promising non-surgical approach for treating canine adrenal tumours. This multi-institutional, retrospective study describes clinical outcomes for 21 dogs having been prescribed a course of hypofractionated image-guided intensity-modulated RT (IMRT) entailing delivery of 25-35 Gy total in 5 fractions given over 5-15 days for an adrenal tumour. Diagnoses were based on imaging (abdominal ultrasound or computed tomography) and biochemical testing. All dogs had unilateral or bilateral irregular adrenal masses with evidence of vessel compression or invasion. Adrenal masses were incidentally identified in 11 dogs. The clinical diagnoses included pheochromocytoma (n = 13, 61.9%), adrenocortical adenocarcinoma (n = 2, 9.5%) and unspecified (n = 6, 28.6%). Among the 16 dogs with available follow-up imaging, the rates of partial response and stable disease were 37.5% (6/16) and 62.5% (10/16), respectively. Mild gastrointestinal side effects related to RT were reported in four dogs (19%). Early death that could have been attributable to tumour or complications of treatment occurred in two dogs (9.5%) at 21 and 52 days post-RT; one presenting with acute vomiting, and the other presenting with vomiting, tremors, and shock before death. Of the 15 deceased dogs, 4 (26.7%) died due to tumour-related causes and 11 died due to unknown (n = 2) or unrelated (n = 9) causes. The median overall survival time was 377 days, with a median follow-up time of 458 days for censored patients (n = 6). The one- and two-year survival rates were 59.4% and 34.7%, respectively. These data build upon prior published reports, demonstrating that RT can be associated with prolonged survival in dogs with adrenal tumours. Hypofractionated IMRT appears to offer a potential survival benefit even in dogs with major vessel invasion or comorbidities. Future research should focus on identifying risk factors for early death and determining which patient populations are most likely to benefit from RT.

The cardiac-gated computed tomography (CT) scan reports of 12 dogs with right auricular appendage masses between 2018 and 2023 were reviewed to describe the use of cardiac-gated CT for assessment of right auricular appendage tumour location and extent and for staging. Imaging reports from thoracic radiographs, CT scans, abdominal ultrasound, and echocardiogram were evaluated for detection of a cardiac mass, mass location on the heart, and detection and location of suspected metastases. Surgery and necropsy reports were evaluated for definitive location of the cardiac mass. Descriptive statistics were performed. Cardiac-gated CT identified a mass that was confined to the right auricular appendage in seven dogs and involved additional cardiac structures in five dogs. Metastases were suspected on CT in 10 dogs. Surgery with the intent to remove the mass for cytoreduction was pursued in five dogs. Right auriculectomy was performed in four dogs. One dog whose mass was suspected to extend beyond the right auricular appendage on CT died during attempted surgical resection. Cardiac-gated CT helped guide clinical decision making by providing information about the location and extent of the mass to assess feasibility of surgical resection and also functioned as a sensitive staging test.