Evaluation of bone marrow aspirates from multiple sites for staging of canine lymphoma and mast cell tumours

This prospective study evaluated the utility of bone marrow aspirates (BMAs) obtained from multiple sites for staging of canine lymphoma (LSA) and mast cell tumours (MCTs). Forty dogs (LSA, n = 24; MCTs, n = 16) were enrolled, but only 33 (82.5%) had diagnostic bone marrow (BM) aspirates obtained from two sites for inclusion in the study. Nineteen dogs with LSA were included, and 6 (31.6%) had BM involvement. Neoplastic lymphocytes were present in BM from both sites in all of these dogs. Fourteen dogs with MCTs were included, and 3 (21.4%) had BM involvement. Neoplastic mast cells were present at both sites in two dogs and at only one site in the third. These results indicate that BMAs from multiple sites may not be needed for accurate staging of canine LSA patients, but more studies evaluating the pattern of BM infiltration in dogs with high‐grade MCTs are warranted.     

OUTCOMES AND PROGNOSTIC FACTORS ASSOCIATED WITH CANINE SINONASAL TUMORS TREATED WITH CURATIVE INTENT CONE‐BASED STEREOTACTIC RADIOSURGERY (1999–2013)

Stereotactic radiosurgery (SRS) is a relatively new therapeutic option in veterinary oncology. The role of this modality has not been extensively evaluated for the use in canine nasal tumors. The objective of this retrospective, observational study was to describe the clinical outcome and prognostic factors associated with survival times in a sample of canine patients treated with SRS for sinonasal tumors. Fifty‐seven dogs with sinonasal tumors met inclusion criteria. Histologic diagnoses included sarcoma (SA) (n = 9), carcinoma (CA) (n = 40), osteosarcoma (OSA) (n = 7), and round cell (n = 1). Four of 57 cases were treated twice with SRS. For these, the median and mean doses delivered were 30Gy and 33Gy, respectively (range 18.75Gy–56Gy). Late effects occurred in 23 cases and ranged from grades I–III. The median overall survival time was 8.5 months. The median overall survival times in dogs with tumor type of CA, SA, and OSA were 10.4, 10.7, and 3.1 months, respectively. Dogs with the tumor type of OSA had shorter overall survival time than that in dogs with tumor type of CA and SA. Findings from this retrospective study indicated that SRS may be beneficial for canine patients with sinonasal tumors, however a controlled clinical trial would be needed to confirm this. Prospective studies are also needed to better define the role of SRS as palliative or curative, and to further investigate the risk of clinically significant toxicity.     

Cranial mediastinal carcinomas in nine dogs*

Nine dogs were diagnosed with cranial mediastinal carcinomas. Based on histological and immunohistochemical analysis, four dogs were diagnosed with ectopic follicular cell thyroid carcinomas, one dog with ectopic medullary cell thyroid carcinoma, two dogs with neuroendocrine carcinomas and two dogs with anaplastic carcinomas. Clinical signs and physical examination findings were associated with a space‐occupying mass, although one dog was diagnosed with functional hyperthyroidism. Surgical resection was attempted in eight dogs. The cranial mediastinal mass was invasive either into the heart or into the cranial vena cava in three dogs. Resection was complete in six dogs and unresectable in two dogs. All dogs survived surgery, but four dogs developed pulmonary thromboembolism and two dogs died of respiratory complications postoperatively. Adjunctive therapies included pre‐operative radiation therapy (n = 1) and postoperative chemotherapy (n = 3). Three dogs had metastasis at the time of diagnosis, but none developed metastasis following surgery. The overall median survival time was 243 days. Local invasion, pleural effusion and metastasis did not have a negative impact on survival time in this small case series.     

Non-coagulopathic spontaneous hemothorax in dogs

Objective: To determine the history, clinicopathologic findings, underlying causes, and outcomes for dogs with non‐coagulopathic spontaneous hemothorax. Design: Retrospective case series. Setting: University referral hospital. Animals: Sixteen client‐owned dogs. Interventions: The medical records database was searched for dogs with hemothorax. Dogs with trauma, secondary coagulopathy, recent thoracic surgery, or pericardial intervention were excluded. For the remaining dogs, signalment, clinical signs, clinicopathologic findings, radiographic findings, histopathologic findings, interventions, and outcome were recorded. Measurements and main results: The most common presenting signs were tachypnea (n=9) and lethargy (n=5), typically of <1‐week duration. The most common cause of non‐coagulopathic spontaneous hemothorax in dogs was neoplasia, which was diagnosed in 14 patients (88%). Identified malignancies included hemangiosarcoma (n=1), malignant mesothelioma (n=1), metastatic ovarian carcinoma (n=1), osteosarcoma (n=2), and pulmonary carcinoma (n=2). An intrathoracic mass was visualized in 7 other dogs; however, histopathology was not obtained. Pancreatitis and lung lobe torsion were each diagnosed in 1 dog, and survival was prolonged with both surviving at least 1 year post discharge. Only 6 of 14 dogs that were diagnosed with neoplasia were discharged from the hospital. For the 4 dogs with cancer with available outcome data, median survival time was 16 days (range 1–70 days). Two dogs were lost to follow‐up and had unknown survival times. Conclusions: The development of non‐coagulopathic spontaneous hemothorax warrants a high‐index suspicion for neoplasia, in particular thoracic wall neoplasia.     

Retrospective comparison of first‐line adjuvant anthracycline vs metronomic‐based chemotherapy protocols in the treatment of stage I and II canine splenic haemangiosarcoma

Splenectomy followed by adjuvant chemotherapy is commonly used to treat canine splenic haemangiosarcoma (HSA), although it is unclear if different treatment protocols may have a similar efficacy. The objective of this retrospective study was to assess outcome in dogs with stage I and II splenic HSA treated with either first‐line adjuvant anthracycline (AC) or metronomic (MC)‐based chemotherapy protocols, by comparing median time to progression (TTP) and median survival time (MST). Medical records of nine institutions were searched for dogs diagnosed with stage I and II splenic HSA that underwent adjuvant treatment with AC‐ or MC‐based protocols following splenectomy. Patients treated with MC following AC were included in an additional group (AMC). Ninety‐three dogs were included: 50 in the AC group, 23 in the AMC group and 20 in the MC group. The overall MST was 200 days (range 47‐3352) and the overall median TTP was 185 days (range 37‐1236). The median TTP of stage I dogs was significantly longer compared to stage II dogs (338 vs 151 days, respectively, P = .028). When adjusting for treatment type, the MST was 154 days for the AC group (range 47‐3352 days), 338 days for the AMC group (range 79‐1623 days) and 225 days for the MC group (range 57‐911 days). The difference in MST and median TTP was not found to be statistically significant between treatment groups. This study suggests that adjuvant MC in canine splenic HSA may result in a similar outcome when compared to other treatment protocols. Further studies are warranted to confirm these findings.     

Retrospective study evaluating the efficacy of stereotactic body radiation therapy for the treatment of confirmed or suspected primary pulmonary carcinomas in dogs

Canine primary pulmonary carcinomas (PCCs) are commonly treated with surgery with overall median survival times (MST) around a year; however, due to extent of disease, prognosis, or client preference, alternative treatments have been considered. Stereotactic body radiation therapy (SBRT) has been utilized in human cancer patients for local control of lung tumours as a surgical alternative. Twenty-one PCCs in 19 dogs that received SBRT for local control were retrospectively evaluated. Dogs were staged according to the canine lung carcinoma stage classification (CLCSC) system with three as Stage 1, five as Stage 2, three as Stage 3, and eight as Stage 4. Overall MST was 343 days with 38% of patients alive at 1 year. Stage did not significantly impact survival time (p = .72). Five (26%) dogs had lymphadenopathy and MST was not significantly different from dogs without lymphadenopathy (343 vs. 353 days; p = .54). Five out of 18 evaluable dogs (28%) experienced acute lung VRTOG effects and 2 of 12 dogs (17%) experienced late lung VRTOG effects. Median lung dose, V5, V20, and D30 to the lung did not correlate significantly with the development of adverse radiation events. Twelve dogs had follow-up imaging and the best response included a complete response (17%), partial response (42%), and stable disease (42%). Progressive disease was noted in seven dogs a median of 229 days after SBRT. SBRT was documented to be a safe and effective alternative to surgery and may have survival advantages for Stage 3 or 4 dogs according to the CLCSC.     

Identification of genomic alterations with clinical impact in canine splenic hemangiosarcoma

Canine hemangiosarcoma (HSA) is an aggressive cancer of endothelial cells with short survival times. Understanding the genomic landscape of HSA may aid in developing therapeutic strategies for dogs and may also inform therapies for the rare and aggressive human cancer angiosarcoma. The objectives of this study were to build a framework for leveraging real-world genomic and clinical data that could provide the foundation for precision medicine in veterinary oncology, and to determine the relationships between genomic and clinical features in canine splenic HSA. One hundred and nine dogs with primary splenic HSA treated by splenectomy that had tumour sequencing via the FidoCure® Precision Medicine Platform targeted sequencing panel were enrolled. Patient signalment, weight, metastasis at diagnosis and overall survival time were retrospectively evaluated. The incidence of genomic alterations in individual genes and their relationship to patient variables including outcome were assessed. Somatic mutations in TP53 (n = 44), NRAS (n = 20) and PIK3CA (n = 19) were most common. Survival was associated with presence of metastases at diagnosis and germline variants in SETD2 and NOTCH1. Age at diagnosis was associated with somatic NRAS mutations and breed. TP53 and PIK3CA somatic mutations were found in larger dogs, while germline SETD2 variants were found in smaller dogs. We identified both somatic mutations and germline variants associated with clinical variables including age, breed and overall survival. These genetic changes may be useful prognostic factors and provide insight into the genomic landscape of hemangiosarcoma.     

Abdominal ultrasonographic findings at diagnosis of osteosarcoma in dogs and association with treatment outcome

The purpose of this study was to describe abdominal ultrasonographic findings present at diagnosis of osteosarcoma (OSA) in dogs and to investigate for associations with treatment outcome. Medical records from 118 dogs diagnosed with OSA that had abdominal ultrasonography performed as part of their initial evaluation were reviewed. Fifty‐seven percent had ultrasonographic abnormalities identified. The organ with the highest frequency of ultrasonographic changes was the spleen. While most sonographic changes were considered to be either benign or of unknown clinical consequences, metastases were identified in three dogs (2.5%), two of which (1.7%) did not have other evidence of metastasis. Dogs with any ultrasonographic abnormality were less likely to receive definitive therapy (P = 0.005) and exhibited shorter survival, although the latter observation was not statistically significant (P = 0.071). However, the identification of lesions in either the liver (P = 0.021) or the kidney (P = 0.003) was statistically associated with shorter survival.     

Identification of occult micrometastases and isolated tumour cells within regional lymph nodes of previously diagnosed non‐metastatic (stage 0) canine carcinomas

Metastatic dissemination of carcinomas to lymph nodes impacts prognosis and treatment recommendations in human and veterinary medicine. Routine histopathologic evaluation of regional lymph nodes involves haematoxylin and eosin (H&E) staining to identify intra‐nodal neoplastic cells; however, identification of small volume metastases (micrometastases and individual tumour cells) may be missed without the aid of immunohistochemistry or additional step‐sections. The aim of this study was to identify occult carcinoma metastases in previously diagnosed non‐metastatic lymph nodes using step‐sections and pancytokeratin (panCK) immunohistochemistry. Samples from 20 regional lymph nodes diagnosed as non‐metastatic were serially sectioned and evaluated with panCK. Of these, 25% (n = 5) contained micrometastases (n = 1) or isolated tumour cells (n = 4). This study demonstrates the increased efficacy of serial step‐sections combined with panCK immunohistochemistry to identify small volume metastases in regional lymph nodes. The prognostic significance of micrometastases and isolated tumour cells in regional lymph nodes warrants further investigation in veterinary medicine.     

Evaluation of ifosfamide salvage therapy for metastatic canine osteosarcoma

A retrospective study was performed to assess toxicity and response rate of ifosfamide salvage treatment for dogs diagnosed with metastatic osteosarcoma (OSA). Dogs diagnosed with OSA and previously treated with standard chemotherapy were included in the study. Nineteen dogs met the inclusion criteria, and 17 dogs were evaluable for response. Ifosfamide doses ranged from 375 to 425 mg m^?2 (median dose 375 mg m^?2), with a median of two doses administered per dog (range 1–7 doses). The overall response to ifosfamide was 11.8% [complete response (CR) = 1/17, partial response (PR) = 1/17, stable disease (SD) = 2/17, progressive disease (PD) = 13/17]. Two dogs were hospitalized due to ifosfamide toxicosis. The median survival duration from the first dose of ifosfamide to death was 95 days. Ifosfamide was well tolerated, but minor anti‐tumour activity was observed.     

Three‐dimensional conformal radiation therapy alone or in combination with surgery for treatment of canine intracranial meningiomas

Treatment protocols, treatment planning methods and tumour types in studies evaluating radiotherapy for canine brain tumours have been varied. This case series retrospectively evaluated the outcome of definitive, three‐dimensional conformal radiation therapy (3D‐CRT) as either a sole modality or as an adjuvant to surgery in 31 dogs diagnosed with meningioma by histopathology (n = 10) or cross‐sectional imaging of the head (n = 21, assessed independently by two board certified radiologists). Prescribed dose ranged from 45 to 54 Gy in 2.5 to 3 Gy fractions. Median overall survival was 577 days (interquartile range = 272–829 days; range = 30–1942 days) when all deaths were considered and 906 days (interquartile range = 336–912 days; range = 101–1942 days) when only dogs dying due to meningioma were considered. No significant difference in survival time was detected for the defined clinical or imaging findings or between treatment with radiotherapy alone versus adjuvant radiotherapy, suggesting that 3D‐CRT may be a viable alternative to surgery.     

Prognostic impact of neoadjuvant aglepristone treatment in clinicopathological parameters of progesterone receptor‐positive canine mammary carcinomas

Neoadjuvant treatment of canine mammary carcinomas with the progesterone receptor (PR) antagonist aglepristone has a PR expression‐related inhibiting effect on proliferation index (PI). The aim of this study was to evaluate the effect of the treatment in the disease‐free period (DFP) and overall survival (OS) of canine mammary carcinomas. Fifty female dogs with mammary carcinomas were treated with aglepristone (n = 34) or oil vehicle (n = 16) before surgery (day 15). PR expression and PI were analysed by immunohistochemistry in samples taken at days 1 and 15. Epidemiological and clinicopathological data were assessed. DFP and OS data were retrieved every 4–6 months for at least 24 months after surgery. Aglepristone treatment increased DFP of animals bearing PR+ tumours with size smaller than 3 cm, complex and mixed tumours, with histologic grades I and II, and with PI ≤ 10%. Although further studies are necessary, current evidence points to treatment with aglepristone as useful for the management of canine mammary tumours.     

Analysis of outcome in dogs that undergo secondary amputation as an end‐point for managing complications related to limb salvage surgery for treatment of appendicular osteosarcoma

Appendicular osteosarcoma (OSA) remains a prevalent musculoskeletal cancer in dogs and definitive local control followed by adjuvant cytotoxic chemotherapy is considered the gold standard approach. Several studies support surgical limb salvage as a means of local control with similar outcomes compared with limb amputation. Complications are well described for limb salvage but little is known of dogs that undergo secondary amputation as a result of complications and outcomes specific to this group. A retrospective analysis of dogs in an institutional primary bone tumour registry was performed to identify dogs diagnosed with histologically confirmed OSA treated with surgical limb salvage with a technique that required an implant to reconstruct the osseous defect. A total of 192 dogs were identified with 31 dogs undergoing secondary amputation representing a limb preservation rate of 84%. A total of 111 dogs were analysed: 31 secondary amputation cases and 80 controls were selected for comparison. The most common reasons for secondary amputation were local recurrence (LR) and surgical site infection (SSI), with odds ratios of 3.6 and 1.7, respectively. Dogs that underwent secondary amputation had a significantly (P = .05) longer median disease specific survival time (ST) (604 days) compared with the control group (385 days). Dogs lived for a median of 205 days beyond secondary amputation and 97% had good functional outcome. Significant independent factors that positively influenced ST were secondary amputation, moderate SSI, severe SSI and age.     

Surgical treatment of mammary carcinomas in dogs with or without postoperative chemotherapy

This retrospective study identified prognostic factors associated with survival; and compared survival data in 94 canine mammary carcinoma (MCA) dogs treated with surgery (n = 58), or surgery and adjunct chemotherapy (n = 36), and a subset of dogs with poor prognostic factors. On multivariate analysis independent predictors of median survival time (MST) were clinical stage, lymphatic invasion (LI; present 179 days; none 1098 days), ulceration (present 118 days; none 443 days) and surgical margins (incomplete 70 days; complete 872 days). Complete surgical margins were associated with MST in dogs with stages 1–3 MCA (incomplete 68 days; complete 1098 days) and dogs with LI (incomplete 70 days; complete 347 days). There was no statistically significant improvement in MST in dogs with advanced disease (stage 4 or LI) treated with adjunctive chemotherapy (chemotherapy 228 days; none 194 days); although five dogs with complete surgical margins that received mitoxantrone and carboplatin had a mean survival of 1139 days.     

Safety evaluation of the canine osteosarcoma vaccine,live Listeria vector

Canine osteosarcoma (OSA) is an aggressive bone tumour in dogs. Standard‐of‐care treatment typically results in relatively short survival times; thus, alternative treatments are needed to confer a survival advantage. It has been shown that OSA is an immunogenic tumour, suggesting that immune modulation may result in superior outcomes. A cryopreserved, Listeria‐based OSA vaccine was recently developed and an initial study in dogs reported prolonged survival for patients receiving the vaccine in conjunction with standard‐of‐care. The goal of the current observational study was to report on the safety of the lyophilized formulation of this vaccine (the canine OSA vaccine, live Listeria vector [COV‐LLV]) in a group of dogs previously diagnosed with OSA. Forty‐nine (49) dogs received the COV‐LLV and were included for analysis. Adverse events (AEs) noted during and after vaccinations were recorded. The AEs observed were typically mild and self‐limiting, with nausea, lethargy and fever being most common. Four dogs (8%) cultured positive for Listeria (three infections including an amputation site abscess, septic stifle joint and bacterial cystitis; and one dog whose lungs cultured Listeria‐positive on necropsy within 24 hours of COV‐LLV administration). These cases join the previously reported Listeria‐positive thoracic abscess that developed in a canine following use of COV‐LLV. Although uncommon, it is important to realize this clinically significant AE is possible in patients treated with live therapeutic Listeria vaccines. As Listeria is zoonotic, caution is required not only for the patient receiving the vaccine, but also for the health care workers and family caring for the patient.     

Adjuvant therapy with carboplatin and pamidronate for canine appendicular osteosarcoma

Amputation and chemotherapy are the mainstay of treatment for canine appendicular osteosarcoma (OSA). In vitro studies have demonstrated anti‐tumour activity of pamidronate against canine OSA. The purpose of this study was to assess the safety of adding pamidronate to standard post‐operative carboplatin chemotherapy in 17 dogs with appendicular OSA treated with limb amputation. Median disease‐free interval (DFI) and median survival time (MST) were evaluated as secondary endpoints. Incidence of side effects and treatment outcomes were compared to 14 contemporary control patients treated with carboplatin alone. There were no identified side effects to the pamidronate treatment. The median DFI for the study group was 185 days compared to 172 days for the control group (P = 0.90). The MST of the study group was 311 days compared to 294 days for the control group (P = 0.89). Addition of pamidronate to carboplatin chemotherapy for the treatment of canine appendicular OSA is safe and does not impair efficacy of standard carboplatin treatment.     

Characterization of the biological behaviour of appendicular osteosarcoma in Rottweilers and a comparison with other breeds: a review of 258 dogs*

The purpose of this retrospective study was to compare Rottweilers diagnosed with osteosarcoma (OSA) with other breeds to determine whether Rottweilers experienced a more aggressive form of the disease. Two hundred and fifty‐eight dogs were evaluated (102 clinical and 156 necropsy cases). In the necropsy population, Rottweilers had a younger mean age at death (7.3 versus 9 years, P= 0.006). There were no significant differences between Rottweilers and other breeds in age at diagnosis, median disease‐free interval or survival time. However, Rottweilers were more likely to have metastasis to the brain (7 versus 0%, P= 0.03). These results suggest that OSA in Rottweilers may have a different biological behaviour, but this study did not confirm that these differences were associated with a worse outcome.     

WHOLE BODY COMPUTED TOMOGRAPHIC CHARACTERISTICS OF SKELETAL AND CARDIAC MUSCULAR METASTATIC NEOPLASIA IN DOGS AND CATS

Muscular metastatic neoplasia has been reported to be rare in domestic animals, however previous studies were based primarily on necropsy findings. The purpose of this retrospective study was to describe whole body computed tomography (CT) characteristics of confirmed muscular metastases in a cohort of dogs and cats presented for oncology evaluation. Medical records of 1201 oncology patients were reviewed. Included animals underwent pre and postcontrast whole body CT, and CT‐guided tru‐cut biopsy or fine needle aspiration of one or more metastatic lesions. Twenty‐one dogs and six cats met inclusion criteria, representing 2.08% of all canine oncology patients and 3.1% of all feline oncology patients. Mean age was 9.6 years. Postcontrast CT characteristics included well‐demarcated, oval‐to‐round lesions with varying enhancement patterns: ring enhancing (n = 16), heterogeneously enhancing (n = 8), or homogeneously enhancing (n = 5). Five animals showed concurrent and varying nodular patterns. In seven cases (five dogs and two cats), one single muscular nodule was observed. In 20 cases, two or more lesions were observed. In two cases, cardiac hypodense nodules were observed in the postcontrast CT, while appearing isodense in the precontrast study. Necropsy confirmed neoplasia in both of them. Locations of muscular metastases included epaxial/paraspinal muscles of the cervical, thoracic, and lumbar spine (n = 18), superficial muscles of the thoracic wall (n = 13), scapular/shoulder region (n = 3), hind limb (n = 3), and abdominal wall muscles (n = 1). Findings supported the use of pre and postcontrast whole body CT for oncologic staging in dogs and cats, especially for primary tumors characterized by a high metastatic rate.