Tumor Grade and Mitotic Count Are Prognostic for Dogs with Cutaneous Mast Cell Tumors Treated with Surgery and Adjuvant or Neoadjuvant Vinblastine Chemotherapy.

OBJECTIVE: Canine cutaneous mast cell tumors (cMCTs) have variable rates of recurrence and metastasis. We evaluated how various prognostic factors affect survival, recurrence, and metastasis in dogs with cMCT who underwent surgery and vinblastine chemotherapy. ANIMALS: 90 dogs with cMCT treated with surgery and vinblastine at a veterinary referral institution were included. METHODS: Medical records were retrospectively reviewed. Prognostic factors were evaluated. RESULTS: Most dogs (94%) had grade 2 or 3 cMCTs. Neoadjuvant vinblastine was used in 18 dogs, and none progressed locally before surgery. The use of neoadjuvant vinblastine was associated with a higher chance of local recurrence (p = 0.03) but not survival. Shorter survival times were found for tumors that were high-grade (p < 0.001), grade 3 (p < 0.001), or a MC of >5 (p < 0.001). Dogs with grade 2 tumors that were low-grade lived longer than those with high-grade tumors (p < 0.001). Histologic tumor-free margins and the ability to achieve local tumor control were not associated with outcome. CLINICAL RELEVANCE: Both grading systems and MC were prognostic for survival in this population of dogs, supporting the need for the standard reporting of histopathologic findings. Neoadjuvant chemotherapy can be effective in downsizing cMCTs but does not influence survival. These findings are consistent with previous publications, showing the benefits of a more modern population of patients, surgical treatments, and histopathologic assessments.

The use of sniffer dogs for early detection of cancer: a One Health approach.

This review, which is part of the "Currents in One Health" series, describes and evaluates the current research on the utilization of trained medical scent detection, aka "sniffer" dogs for the detection of diseases, with particular emphasis on neoplasia, both within human and veterinary patients. A recent study by the authors that used sniffer dogs to detect differences in saliva from dogs diagnosed with various neoplastic processes compared with healthy control dogs is described. The concept of One Health is explored by the description of previous studies that have utilized sniffer dogs in the detection of human neoplasia (focusing on lung, prostate, and breast cancer) and veterinary neoplasia and demonstrating that further research in this arena can benefit multiple species. Future avenues of research and utilization of these findings are outlined. The companion Currents in One Health by Ungar et al, JAVMA, January 2024, addresses the use of sniffer dogs to detect human COVID-19 infections.

A One Health perspective: COVID-sniffing dogs can be effective and efficient as public health guardians.

Scent-detection dogs have been used for decades to locate drugs, explosives, toxic waste, and more. Scent dogs have been trained to alert for seizures and hypoglycemia, locate cadavers, and screen for viruses, bacterial infections, and numerous cancers. These capable dogs warrant a more significant role in public health protection. The purpose of this preliminary study was to determine whether dogs could be trained to accurately identify coronavirus disease 2019 (COVID-19) infections in humans. In previously published studies, dogs were trained to identify the scent of COVID-19 in inert samples with high sensitivity and specificity. In this study, 2 dogs were trained to identify the scent in live individuals (vs inert samples, as used in previous studies), a faster and more efficient screening method. These dogs tested out at 94% to 96% positive and negative agreement compared to PCR testing. These results recommend the use of scent dogs for public health applications and warrant investigation for other applications beyond COVID-19. This study is included as part of the Currents in One Health series. A partner article by Pellin et al, AJVR, January 2024, describes and evaluates the current research on the utilization of trained scent-detection dogs for the detection of disease within human and veterinary patients.

Clinical outcomes in cats with renal carcinoma undergoing nephrectomy: A retrospective study.

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.

Trained dogs can accurately discriminate between scents of saliva samples from dogs with cancer versus healthy controls.

OBJECTIVE: To determine whether dogs can be trained to utilize olfaction to differentiate between saliva samples from dogs with cancer and those from healthy control dogs. SAMPLE: Canine patient saliva samples were collected (October 2020 to July 2022) from 139 dogs diagnosed with malignant tumors and from 161 healthy dogs (control samples) for use during training and testing of the dog detection team. Samples from canine patients were collected prior to treatment with radiation therapy or chemotherapy. PROCEDURES: Six pet dogs (mean ± SD age, 5.4 ± 1.9 years) were trained for odor discrimination between healthy control and malignant tumor samples. Training of the dogs, using a reward-based positive reinforcement method, took place 1 to 3 times per week for a period of 6 months (January to June 2022). After training was complete, a subset of samples not utilized during the training sessions were selected for use during odor discrimination testing of the dog team. RESULTS: The trained dogs could accurately distinguish between samples from cancer patients versus control dogs with a mean sensitivity of 90% and mean specificity of 98%, and with mean positive and negative predictive values of 95%. CLINICAL RELEVANCE: This study serves as preliminary evidence that dogs can be trained to detect differences in scent between saliva samples from cancer and normal patients. Further studies should expand upon these results with a larger sample, varied tumor types, use of non-cancer diseases as controls, and exploration of this technique in feline patients.

Tonsillar carcinoma in dogs: Treatment outcome and potential prognostic factors in 123 cases.

BACKGROUND: Tonsillar carcinomas are rarely reported in dogs. Information on outcome after treatment is sparse and prognosis is guarded to poor. HYPOTHESIS/OBJECTIVES: Assess treatment outcome and potential prognostic factors in a population of dogs with cytological or histopathological diagnosis of tonsillar carcinoma. ANIMALS: A total of 123 client-owned dogs with diagnosis of tonsillar carcinoma confirmed by cytology or histopathology. METHODS: Retrospective, multi-institutional study. Medical records of 12 institutions were reviewed from 2012 to 2021. RESULTS: Treatment included surgery, chemotherapy (conventional, tyrosine kinase inhibitors or metronomic chemotherapy), radiotherapy, nonsteroidal anti-inflammatory drugs (NSAIDs) or a combination of these. Surgery was performed in 68 cases, chemotherapy was administered in association with NSAIDs in 64 cases, NSAIDs were used alone in 14 cases and in association with surgery in 21 cases, whereas radiotherapy was used alone or in combination with surgery or chemotherapy in 20 cases. Overall survival time (OST) was 126 days (95% confidence interval [CI], 88-164). Significantly longer survival (P < .001) was seen in dogs without evidence of metastatic disease (median survival time, 381 days; 95% CI, 116-646). Other significant positive prognostic factors included absence of clinicals signs at presentation, surgery (tonsillectomy), use of adjuvant chemotherapy and use of NSAIDs. CONCLUSION AND CLINICAL IMPORTANCE: Asymptomatic dogs, those treated with surgery, those that received adjuvant chemotherapy, and those that received NSAIDs may have a better prognosis than previously expected, but overall survival remains short for dogs with tonsillar carcinoma.

The Use of Oncept Melanoma Vaccine in Veterinary Patients: A Review of the Literature.

The Oncept melanoma vaccine is xenogeneic DNA vaccine targeting tyrosinase. It is USDA approved for treatment of stage II to III canine oral melanoma and is also used off-label for melanomas arising in other locations and in other species. While the vaccine appears safe, the published data is mixed as to whether it provides a survival benefit, and the use of the vaccine is somewhat controversial in the veterinary oncology community. In this paper, the published literature describing the use of Oncept is reviewed and evaluated.

Outcome in dogs with curative-intent treatment of localized primary pulmonary histiocytic sarcoma.

Primary pulmonary histiocytic sarcoma (PHS) is a rare form of dendritic cell or macrophage neoplasia originating within the pulmonary parenchyma. There is limited literature describing prognosis in dogs with PHS receiving curative-intent treatment consisting of surgical excision and adjuvant chemotherapy. The primary objective of this study was to report outcomes in dogs with localized PHS treated with standardized local and systemic therapy. A secondary objective was to identify prognostic factors in this population. A multi-institutional retrospective study was performed and medical records including all surgical and histopathologic reports were retrospectively reviewed. For inclusion, dogs were required to have confirmed localized PHS and they must have undergone curative-intent surgery with resection of all gross primary tumour and enlarged tracheobronchial lymph nodes; additionally, they must have received curative-intent treatment with adjuvant single-agent CCNU chemotherapy. Twenty-seven dogs from six veterinary teaching hospitals and five private practices treated from 2008-2019 were included. The overall median survival time was 432 days. Higher CCNU dose was demonstrated to have a negative impact on survival on univariate, but not multivariable, analysis. Factors that were not found to be associated with survival on univariate analysis included body weight, breed, clinical signs at the time of diagnosis, hypoalbuminaemia, tumour size, lung lobe affected, lymph node metastasis, surgical margins and CCNU dose reductions. This study supports a favourable prognosis for dogs diagnosed with localized PHS treated with curative-intent surgery in addition to adjuvant CCNU chemotherapy and suggests that multimodal treatment may be advisable to attempt to prolong survival.

Low dose meloxicam is safe and tolerable when combined with toceranib phosphate in cancer-bearing cats.

OBJECTIVES: Non-steroidal anti-inflammatory drugs (NSAIDs) are infrequently utilized in cats due to concern for renal compromise; however, recent studies demonstrate tolerability of low dose meloxicam. Toceranib phosphate is used to treat several feline cancers and is well tolerated. This study aimed to determine the tolerability and adverse event profile of combined toceranib and low dose meloxicam in cancer-bearing cats. Secondary goals involved assessing anticancer tumor efficacy and impact upon quality of life and analgesia. METHODS: Cats with any cancer not involving the kidneys were eligible. The study adopted a conventional 3 + 3 dose escalation design. Toceranib was administered every other day at a standard dose with meloxicam administered in an escalating fashion in subsequent cohorts, at a starting dose of 0.01 mg/kg on opposite days to toceranib, up to a maximum of 0.02 mg/kg daily, based upon previous safety studies. Laboratory work, blood pressure, tumor measurements, pain score and client-completed quality-of-life surveys were recorded every 2-4 weeks during the 12-week study period. RESULTS: Twenty-one cats were enrolled. When combined with toceranib, a meloxicam dose of 0.02 mg/kg q24h was safe and well tolerated, with no cats being withdrawn due to adverse events from the drug combination. The majority of cats demonstrated clinical benefit with stable to mildly improved tumor measurements, quality of life and pain scores. CONCLUSIONS AND RELEVANCE: Low dose meloxicam combined with toceranib is safe and well tolerated in cancer-bearing cats. Continued patient recruitment and data collection are needed to determine the maximum tolerated dose of meloxicam. The results of our study will guide further phase II/III trials.

Feline cutaneous lymphoma: an evaluation of disease presentation and factors affecting response to treatment.

OBJECTIVES: The primary goal of this study was to characterize the clinical presentation of feline cutaneous lymphoma. The secondary aims included determining if treatment or initial response to treatment affected the overall survival of patients, and understanding if disease characteristics such as immunophenotype, cell size or the presence of epitheliotropism influenced response to treatment. METHODS: Veterinary medical oncologists at four academic veterinary teaching hospitals submitted cases of feline patients with cutaneous lymphoma diagnosed by histopathology or cytology. Signalment, feline leukemia virus (FeLV)/feline immunodeficiency virus (FIV) status, physical examination findings, clinical signs, diagnostic tests, therapy, response and outcome, and necropsy findings, when available, were recorded. RESULTS: Forty-one patients were identified and described. The majority of patients were domestic shorthair cats (n = 29). The median age at diagnosis was 12.3 years. Males were over-represented in the population (n = 30). In the majority of patients (n = 33), the FIV/FeLV status was unknown. Twenty patients were fully staged. Thirty-four patients were treated with a variety of modalities, including surgery, radiation, single-agent or combination chemotherapy, or prednisolone only. In multiple patients, surgery or radiation was combined with a systemic therapy. Of 34 patients treated with some form of therapy, 20 responded (achieving either a partial response or complete remission). CONCLUSIONS AND RELEVANCE: Clinical signs and physical examination findings varied among patients. Response to therapy appeared to be associated with survival (P = 0.0025); however, this population was highly censored. Immunophenotype, cell size and the presence of epitheliotropism did not influence treatment response. Results were limited by small numbers of patients, heterogeneous disease manifestations and treatment protocols. Further studies are necessary to evaluate the effect of specific treatment modalities and disease subtype on prognosis.

Evaluation of neutrophilia as a prognostic factor in dogs with multicentric lymphoma treated with a cyclophosphamide, doxorubicin, vincristine, and prednisone-based chemotherapy protocol.

OBJECTIVE: To determine whether, in dogs with naïve multicentric lymphoma, neutrophilia at the time of initial diagnosis was associated with progression-free survival time (PFST) or overall response rate (ie, percentage of dogs with a complete or partial remission) and whether the initial neutrophil-to-lymphocyte ratio was associated with PFST. ANIMALS: 30 dogs with multicentric lymphoma and neutrophilia (including 16 treated with a cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP]-based protocol) and 37 historical control dogs without neutrophilia treated with a CHOP-based protocol. PROCEDURES: Medical records were reviewed, and PFSTs and responses were documented. RESULTS: Median PFST for the 16 dogs with neutrophilia treated with a CHOP-based protocol (70 days; range, 0 to 296 days) was significantly shorter than that for the 37 control dogs without neutrophilia (184.5 days; range, 23 to 503 days), and the overall response rate for dogs with neutrophilia (12/16 [75%]) was significantly lower than the rate for dogs without neutrophilia (36/37 [97%]). However, when all dogs in the study and control populations were considered together, the neutrophil-to-lymphocyte ratio at the time of diagnosis was not significantly associated with PFST. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that neutrophilia at the time of initial diagnosis may suggest a poorer prognosis in dogs with multicentric lymphoma. Prospective investigation into the role of neutrophils in the peripheral circulation and tumor microenvironment of cancer-bearing patients is warranted.

Cutaneous and subcutaneous metastasis of appendicular osteosarcoma in dogs: 20 cases.

BACKGROUND: Metastasis of appendicular osteosarcoma is most common to the lungs and is generally considered a terminal event in dogs. Behavior and prognosis associated with cutaneous or subcutaneous metastases (CSM) is poorly defined. OBJECTIVE: Describe the population and gather prognostic information regarding appendicular osteosarcoma with CSM in dogs. ANIMALS: Twenty dogs with appendicular osteosarcoma and CSM. METHODS: Retrospective case series. Medical records were searched to identify dogs diagnosed with appendicular osteosarcoma that developed CSM. Demographic data, order of metastatic events, and CSM clinical features were evaluated. Kaplan-Meier survival curves were constructed and log-rank tests were used to compare survival between groups of dogs. RESULTS: In 19 dogs (95%), CSM was an incidental finding. Seventeen dogs (85%) developed pulmonary metastasis, and 1 dog (5%) developed bone metastasis. No other metastatic sites were detected before euthanasia. The median CSM-free interval and CSM survival time were 160 days (range: 0-542 days) and 55 days (range: 5-336 days), respectively. The median CSM survival time was significantly longer for dogs treated with surgery and chemotherapy (94 days) or chemotherapy only (64 days) than for dogs that did not receive these treatments (11 days) (P = .002 and P = .03, respectively). No other factors were associated with survival after diagnosis of CSM. CONCLUSION AND CLINICAL IMPORTANCE: The skin or subcutaneous tissue can be the first osteosarcoma metastatic site detected. After CSM diagnosis, the prognosis is grave with median survival <2 months. Although this finding could have been biased by case selection, treatment with surgery and chemotherapy may improve outcome.

A comparison of 12- and 19-week CHOP protocols using non-randomized, contemporaneous controls.

This study is a concurrent comparison of two versions of CHOP protocols, a 19-week CHOP and a comparatively overall dose-intense 12-week CHOP. The 12-week protocol was designed to be 58% more dose intense than the 19-week protocol for both doxorubicin and cyclophosphamide; however, it was 21% less dose intense for vincristine (VCR). Forty-seven dogs were included for evaluation, and the characteristics of each population were similar. For dogs receiving the 19-week CHOP protocol, 89.5% experienced a complete response, with a median progression-free survival (PFS) of 245 days and median overall survival (OS) of 347 days. For dogs receiving the 12-week CHOP protocol, 89.3% experienced a complete response, with a median PFS of 141 days and median OS of 229 days. When evaluated by Log-rank analysis, the difference of PFS (P = 0.047) and OS (P = 0.013) between the groups were statistically significant. In summary, these data suggest that despite overall increased dose-intensity, dogs receiving treatment with a 12-week CHOP protocol experience less durable remission than our standard 19-week protocol in this population. Additional prospective investigation will be required to explore the implication that VCR dose intensity and/or shorter overall temporal drug exposure in this protocol may result in diminished efficacy.

Treatment of feline gastrointestinal small-cell lymphoma with chlorambucil and glucocorticoids.

Gastrointestinal (GI) lymphoma is the most frequently diagnosed form of lymphoma in the cat and is categorized into two distinct forms based on the size of neoplastic lymphocytes. Treatments for both large- and small-cell GI lymphoma have been described previously; however, multiple chemotherapy protocols were used, a minimal amount of histopathological characterization was provided, and, in most studies, the majority of diagnoses were obtained via endoscopic pinch biopsies. Twenty-eight cats (24 with full-thickness intestinal biopsies) were diagnosed with small-cell GI lymphoma and treated with a combination of chlorambucil and glucocorticoids. The majority of cases were strongly CD3+, and many displayed epitheliotropism. The overall clinical response rate was 96%, with a median clinical remission duration of 786 days. Follow-up identified seven cats with relapsed disease-all of which were treated with a rescue protocol of cyclophosphamide and glucocorticoids; the response rate was 100%, and four of the 28 cats were diagnosed with a second malignancy.