Veterinary and comparative oncology最新文献

Intracranial gliomas are the second most common brain tumour in dogs. Radiation therapy provides a minimally invasive treatment option for this tumour type. Earlier publications reporting on the use of non-modulated radiation therapy suggested a poor prognosis for dogs with glioma, with median survival times ranging between 4 and 6 months; more recent literature utilizing stereotactic radiation therapy (SRT) demonstrates that the prognosis for canine gliomas may be more promising, with survival times closer to 12 months. A single institution retrospective study was performed between 2010 and 2020 investigating the outcomes of dogs with biopsy-confirmed glioma or a presumptive diagnosis of intra-cranial glioma based on MRI characteristics that were treated with SRT. Twenty-three client-owned dogs were included. Brachycephalic breeds were overrepresented, totalling 13 dogs (57%). SRT protocols included 16 Gy single fraction (n = 1, 4%), 18 Gy single fraction (n = 1, 4%), 24 Gy in 3 daily fractions (n = 20, 91%), or 27 Gy in four daily fractions (n = 1, 4%). Twenty-one dogs (91%) had improvement of their presenting clinical signs following SRT. Median overall survival time (MST) was 349 days (95% CI, 162-584). Median disease specific survival time was 413 days (95% CI, 217-717). When SRT is incorporated into the management plan for dogs with confirmed or presumed intracranial glioma, a median survival time of approximately 12 months may be achievable.

Adrenalectomies for canine adrenal tumours are associated with peri-operative morbidity and mortality. Objectives of this study included assessing the prognostic value of tumour- or surgery-related variables in predicting peri-operative mortality and overall survival in dogs undergoing adrenalectomies for primary adrenal tumours as well as pre-treatment with phenoxybenzamine on survival to discharge with pheochromocytomas specifically. A multi-institutional retrospective cohort study was performed across nine institutions. Electronic medical record searches identified 302 dogs which met the inclusion criteria. Data collected included dog-related, tumour-related, treatment-related, surgery-related, and outcome variables. Univariate and multivariable logistic regression and cox proportional hazards models were used to identify variables associated with death prior to discharge and tumour-related survival. Overall, 87% of dogs survived to discharge with a tumour-related survival time of 3.96 years. Post-operative complications were reported in 25%. Increased surgical time (p = 0.002) and pre-surgical medical treatment other than phenoxybenzamine (p = 0.024) were significantly associated with increased peri-operative mortality while ureteronephrectomy (p = 0.021), post-operative pancreatitis (p = 0.025), and post-operative aspiration pneumonia (p < 0.001) were significantly associated with decreased overall survival. Phenoxybenzamine pretreatment had no effect on peri-operative mortality. Thirty-seven of 45 (82%) dogs with pheochromocytomas not pretreated survived to discharge, and 50 of 59 (85%) dogs with pheochromocytomas pretreated with phenoxybenzamine survived to discharge (p = 0.730). This study provides information on risk factors for death prior to discharge and tumour-related survival that may help guide clinical management and owner expectations. In addition, the study findings challenge the previously reported benefit of phenoxybenzamine for pretreatment of dogs undergoing adrenalectomies for pheochromocytomas.

Renal carcinomas (RC) are uncommonly encountered in feline medicine. Limited information regarding clinical presentation and postoperative outcomes is available. The purpose of this multi-institutional, retrospective study was to describe the presenting features and clinical outcomes of cats with RC undergoing nephrectomy. Thirty-six client-owned cats were included. Medical records from participating institutions were searched to identify cats that had a histopathologic diagnosis of RC and underwent nephrectomy from January 2001 to October 2021. The most common presenting complaints were weight loss (36.1%) and hyporexia (30.6%). Based on preoperative imaging and intraoperative findings, eight cats had suspected metastasis at the time of surgery (22.2%). Twenty-eight cats survived to discharge (77.8%). Median progression free interval (PFI) could not be determined, as only six cats developed suspected recurrence (16.7%) and seven cats developed suspected metastasis (19.4%). The all-cause median survival time (MST) was 203 days (95% confidence interval [CI]: 84, 1379 days). When cases that died prior to discharge were excluded, MST increased to 1217 days (95% CI: 127, 1641 days). One-year, two-year, and three-year survival rates were all 40.4%. Neither renal tumour histologic subtype nor the presence of preoperative azotemia, anaemia, erythrocytosis, haematuria, or suspected metastasis at diagnosis were found to influence survival. For cats surviving to discharge, prolonged survival times were possible. Further studies are necessary to elucidate other potential prognostic factors, the utility of postoperative adjuvant treatment, and to identify cats at-risk of mortality in the perioperative period.

Haemangiosarcoma is a relatively common malignant tumour in dogs, and one of the primary outcomes of interest for the Golden Retriever Lifetime Study. This study collects longitudinal data and samples from a cohort of golden retrievers, with the aim of identification of nutritional, genetic, environmental, lifestyle and reproductive risk factors for cancers and other important diseases in dogs. This analysis describes the accumulating data and samples, which are available for use by researchers to fulfil the study's objectives. As of September 2022, 233/3044 dogs enrolled in the study had been diagnosed with haemangiosarcoma (7.65%), with an incidence rate of 1.10 cases per 100 dog-years. Visceral haemangiosarcoma was the most common, affecting 211/3044 study dogs (6.9%). One hundred and twenty eight visceral haemangiosarcoma diagnoses specified the presence of splenic tumours (60.7%) and 119 specified the presence of cardiac tumours (56.4%). The probability of remaining without a haemangiosarcoma diagnosis declined from 100% from approximately 4 years of age, to a 12 year probability of 91.1% in intact females (95% CI 84.4%-98.3%), 60.7% in neutered females (95% CI 41.6%-88.6%), 72.9% in intact males (95% CI 62.9%-84.6%) and 70.0% in neutered males (95% CI 53.4%-92.0%). The 1 year survival probability for visceral haemangiosarcoma was 1.42% (95% CI 0.37%-5.47%); for cutaneous haemangiosarcoma, it was 84.6% (95% CI 67.1%-99.99%). The accumulated data and samples are a considerable resource for further investigation of canine haemangiosarcoma and have a potential role in translational medicine.

The accrual of cancer mutation data and related functional and clinical associations have revolutionised human oncology, enabling the advancement of precision medicine and biomarker-guided clinical management. The catalogue of cancer mutations is also growing in canine cancers. However, without direct high-powered functional data in dogs, it remains challenging to interpret and utilise them in research and clinical settings. It is well-recognised that canine and human cancers share genetic, molecular and phenotypic similarities. Therefore, leveraging the massive wealth of human mutation data may help advance canine oncology. Here, we present a structured analysis of sequence conservation and conversion of human mutations to the canine genome through a 'caninisation' process. We applied this analysis to COSMIC, the Catalogue of Somatic Mutations in Cancer, the most prominent human cancer mutation database. For the project's initial phase, we focused on the subset of the COSMIC data corresponding to Cancer Gene Census (CGC) genes. A total of 670 canine orthologs were found for 721 CGC genes. In these genes, 365 K unique mutations across 160 tumour types were converted successfully to canine coordinates. We identified shared putative cancer-driving mutations, including pathogenic and hotspot mutations and mutations bearing similar biomarker associations with diagnostic, prognostic and therapeutic utility. Thus, this structured caninisation of human cancer mutations facilitates the interpretation and annotation of canine mutations and helps bridge the knowledge gap to enable canine precision medicine.

Palliative-intent radiation therapy can alleviate pain and clinical signs in dogs with cancer, but optimal fractionation scheme is unknown. The objective of this retrospective case series is to evaluate clinical benefit, objective response, adverse effects, and outcomes in 108 dogs with macroscopic solid tumours treated with a cyclical "QUAD" hypofractionated palliative-intent radiation therapy protocol. Median QUAD dose was 14 Gy (14-16 Gy). Median total dose was 28 Gy (14-48 Gy). Clinical benefit rate was 93%, with median onset of subjective palliation 21 days after the first QUAD, lasting a median of 134 days. Tumour volumetric objective response was assessed with CT prior to the third QUAD in 36 dogs, with stable disease in 24 dogs (67%) and partial response in 9 dogs (25%). Sinonasal and oral were the most common tumour locations in 32 and 30 dogs, respectively. Median progression-free survival was 153 days (95% CI 114-200). Median overall survival was 212 days (95% CI 152-259). Number of QUAD cycles completed, clinical benefit achieved, anti-inflammatory received, total radiation dose, time to maximum clinical benefit, and response duration were positively associated with progression-free and overall survival. Acute toxicities were observed in 15 dogs (14%) with 3 high-grade (grade 3) toxicities (3%). Low-grade (grade 1 and 2) late skin and ocular toxicities were observed in 31 dogs (29%), predominantly leukotrichia, alopecia, keratoconjunctivitis sicca, and cataracts. This report demonstrates that QUAD radiation is an alternative protocol to be considered for palliation of dogs with inoperable or advanced stage solid tumours.

Subcutaneous mast cell tumours (SC MCTs) can display a different biological behaviour in dogs when compared to their cutaneous counterpart. There is a paucity of information with regards to the outcome of dogs with SC MCTs treated with surgery and/or receiving adjuvant chemotherapy. The aim of this study was to retrospectively review the outcome of dogs with surgically excised SC MCTs undergoing adjuvant treatment or not. A secondary aim was to assess prognostic factors in the same group. Fifty-two cases were included. Recurrence rate was 15% and 63% of evaluated lymph nodes were consistent with early or overt metastasis. Median survival time (range 83-1357 days) and median time to progression (range 14-1357 days) were not reached. Factors predictive of shorter overall survival time included increasing age (HR 1.29, 95% CI 1.06-1.55, p = .0092), presence of clinical signs at presentation (HR 10.44, 95% CI 2.69-40.52, p = .0007), mitotic count >4 (HR 8.69, 95% CI 2.55-29.55, p = 0.0005), presence of multinucleation (HR 4.21, 95% CI 1.35-13.18, p = .0135), use of neoadjuvant and adjuvant chemotherapy (HR 7.16, 95% CI 1.26-40.73, p = .0266). The same factors, together with increasing tumour dimensions, were predictive for shorter progression-free survival (PFS), including increasing age (p = .0012), presence of clinical signs at presentation (p = .0045), increasing tumour dimensions (p = .0004), MC > 4 (p = .0004), presence of multinucleation (p = .0282), use of neoadjuvant and adjuvant chemotherapy (p = .0485). No variables remained significant for overall survival using multivariate analysis. There was a longer survival in cases where chemotherapy was not required (HR 0.14, 95% CI 0.03-0.68, p = .0148), and this variable remained significant for PFS on multivariate analysis (HR 0.13, 95% CI 0.02-0.76, p = .02). In conclusion, our study suggests that dogs with SC MCTs, in the absence of negative prognostic factors, may have a prolonged survival when treated with surgery alone. Further studies are needed to clarify the role of adjuvant treatment for biologically aggressive SC MCTs in dogs.

The ratio of κ light chains to λ light chains (κ:λ) in serum is used as a biomarker of immunoglobulin secreting neoplasia in humans but has not been evaluated in dogs. A mass-spectrometry based method for determining the canine serum κ:λ was developed and used to evaluate samples from control dogs, dogs with an infectious aetiology, dogs with secretory plasma cell tumours (sPCT) and dogs with non-secretory B cell neoplasia. A human-targeted immunoturbidometric κ:λ assay and immunofixation using antisera targeting human κ light chain or λ light chain was also performed on all samples. Using whole serum samples, the MS-based κ:λ method identified 5 sPCT as κ-predominant (mean κ:λ = 3.307) and 5 sPCT as λ-predominant (mean κ:λ = 0.023) and documented differences between these groups and all other groups (p < 0.05 for all). The infectious aetiology group had a lower mean κ:λ ratio (mean κ:λ = 0.069) than control samples (mean κ:λ = 0.103, p = 0.035). Similar results were obtained when samples were enriched for proteins between 10 and 50 kDa using size exclusion chromatography, except for the statistical difference between the control and infectious aetiology group. All λ-predominant cases had only anti-human λ light chain labelling by immunofixation. Three κ-predominant cases had only anti-human κ-light chain labelling and the remaining two cases did not label with either antisera by immunofixation. The immunoturbidometric method had high analytical CV% (λ light chain CV = 13%, κ light chain CV = 50%), was unable to measure light chains in 20.5% of samples and did not distinguish groups. The data suggests that the human-targeted immunoturbidometric method would not be diagnostically useful and that the MS-derived serum κ:λ may be a useful biomarker of canine immunoglobulin secretory neoplasia which may have the ability to distinguish neoplasia from infectious causes of immunoglobulin secretion.

In this study we undertook a comprehensive analysis of a Pet Tumour Registry of the Canary Archipelago (PTR-CA) in Spain to investigate the epidemiology of canine cutaneous round cell tumours. From a database of 2526 tumours collected from 2003 to 2020, we conducted a longitudinal analysis of the main trends in diagnosis, age, multiplicity and anatomical distribution as well as a case-control study comparing these cases with the contemporaneous canine population of the Canary Archipelago to analyse breed distribution. In line with former studies, we found histiocytomas mostly affect young dogs (2, IQR 1-5) and mast cell tumours affect middle-to-old dogs (8, IQR 6-10) with grade 1 affecting at younger ages (6.5, IQR 6-8) than both grade 2 (8, IQR 6-10 years) and grade 3 (9, IQR 7-11). Histiocytomas and plasmacytomas showed a similar anatomical distribution appearing mainly on the face, head and neck regions while mast cell tumours occur mainly on limbs and trunk. Higher risk for mast cell tumours and histiocytomas were found for Bulldog-related breeds such as Boxer (OR_MCT  = 23.61, CI95%: 19.12-29.15, OR_HCT  = 10.17, CI95%: 6.60-15.67), Boston Terrier (OR_MCT 19.47, CI95%: 7.73-49.05, OR_HCT 32.61, CI95%: 11.81-90.07) and Pug (OR_MCT 8.10, CI95%: 5.92-11.07, OR_HCT 7.87, CI95%: 4.66-13.28) while Chihuahua dogs showed significantly less risk (OR_MCT 0.18, CI95%: 0.09-0.33, OR_HCT 0.41, CI95%: 0.21-0.78). Notably, the Canarian Mastiff, a local breed, had a low risk of suffering from a mast cell tumour which raises the question of whether this relates to a genetic peculiarity of this breed or some husbandry and environmental factor.