Veterinary and comparative oncology最新文献

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.

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.