Clinical outcome in 94 cases of dermal haemangiosarcoma in dogs treated with surgical excision: 1993-2007*

Canine dermal haemangiosarcoma (HSA) is believed to have a better prognosis compared to HSA in other organs, but outcome has only been reported in a small number of dogs. The purpose of this study was to assess outcome and prognostic factors in a larger cohort of dogs with dermal HSA. Clinical data was collected retrospectively for 94 dogs and histopathology was reviewed in 53 dogs. Median overall survival time was 987 days. Dogs of predisposed breed with ventral location and histologic solar changes had longer survivals. Loco-regional recurrence occurred in 72/94 (77%) dogs. Predisposed breeds with ventral location and multiple masses were more likely to develop recurrence. Non-predisposed breeds with invasive tumours were more likely to develop metastasis. Results suggest that dogs with solar-induced dermal HSA may have high recurrence rates, but prolonged survivals. Dogs with non-solar tumours may be at increased risk for metastasis and shorter survival.     

Outcomes and prognostic variables associated with primary abdominal visceral soft tissue sarcomas in dogs: A Veterinary Society of Surgical Oncology retrospective study

Primary abdominal visceral soft tissue sarcomas (STSs) are rare tumours in dogs with little information available on outcomes. The goal of this retrospective, multi‐institutional study was to describe the common tumour types, location and prognostic factors associated with primary abdominal visceral STSs. Medical records were searched for dogs with primary abdominal visceral STSs at six institutions and were retrospectively reviewed. Tumours were graded using the previously described grading scheme for STSs of the skin and subcutis when information in the histopathology report contained adequate details. Forty‐two dogs were included in the study. Five dogs had grade I tumours, 11 had grade II and 15 had grade III tumours. The most common tumour type was leiomyosarcoma (38.1%). The most common tumour locations were the spleen (47.6%) and small intestine (23.8%). The local recurrence rate was low (4.7%). Metastasis was present at the time of surgery in 23.8%, and the overall metastatic rate was 40.4%. Mitotic index of ≥9 was associated with significantly shorter survival time (MST 269 days) compared with a mitotic index of <9 (MST not reached). The MST for grade I STSs was not reached, was 589 days for grade II and 158 days for grade III. Dogs with grade III tumours were more likely to develop metastatic disease. Neither location of the primary tumour nor the histologic subtype was associated with survival time. Histologic grading of abdominal visceral STSs using the previously described scheme is prognostic and should be provided on histopathology reports.     

Frameless stereotactic radiosurgery for the treatment of primary intracranial tumours in dogs

Stereotactic radiosurgery (SRS) is a procedure that delivers a single large radiation dose to a well‐defined target. Here, we describe a frameless SRS technique suitable for intracranial targets in canines. Medical records of dogs diagnosed with a primary intracranial tumour by imaging or histopathology that underwent SRS were retrospectively reviewed. Frameless SRS was used successfully to treat tumours in 51 dogs with a variety of head sizes and shapes. Tumours diagnosed included 38 meningiomas, 4 pituitary tumours, 4 trigeminal nerve tumours, 3 gliomas, 1 histiocytic sarcoma and 1 choroid plexus tumour. Median survival time was 399 days for all tumours and for dogs with meningiomas; cause‐specific survival was 493 days for both cohorts. Acute grade III central nervous system toxicity (altered mentation) occurred in two dogs. Frameless SRS resulted in survival times comparable to conventional radiation therapy, but with fewer acute adverse effects and only a single anaesthetic episode required for therapy.     

Role of monocyte recruitment in hemangiosarcoma metastasis in dogs

Canine hemangiosarcoma (HSA) is a highly malignant tumour associated with short survival times because of early and widespread metastasis. In humans and rodents, monocytes play key roles in promoting tumour metastasis through stimulating tumour cell extravasation, seeding, growth and angiogenesis. Therefore, we investigated the potential association between monocyte infiltration and tumour metastasis in HSA and other common canine tumours. Immunohistochemistry was used to quantify CD18⁺ monocytes within metastases. We found that HSA metastases had significantly greater numbers of CD18⁺ monocytes compared with metastases from other tumour types. HSA cells were the highest producers of the monocyte chemokine CCL2, and stimulated canine monocyte migration in a CCL2 dependent manner. These results are consistent with the hypothesis that overexpression of CCL2 and recruitment of large numbers of monocytes may explain in part the aggressive metastatic nature of canine HSA. Thus, therapies designed to block monocyte recruitment may be an effective adjuvant strategy for suppressing HSA metastasis in dogs.     

Comparative aspects and clinical outcomes of canine renal hemangiosarcoma

BACKGROUND: Hemangiosarcoma (HSA) is a common solid tumor of the spleen, heart, and skin of dogs. Renal HSA represents an uncommon anatomic variant, with little reported about its biologic behavior and clinical outcome. HYPOTHESIS: That renal HSA is associated with longer survival than other visceral forms of HSA. ANIMALS: 14 dogs with renal HSA. METHODS: Medical records from 1999 to 2004 were searched for dogs with histopathologically confirmed renal HSA, and data relevant to clinical signs, treatments, and outcomes were abstracted. RESULTS: Clinical signs were nonspecific, and the median duration of clinical signs before diagnosis was 60 days. Two dogs presented in cardiovascular collapse secondary to hemoperitoneum. Common hematologic and biochemical abnormalities were anemia (9/14), hematuria (7/14), and proteinuria (7/14). One dog had pulmonary metastasis at diagnosis. All dogs had evidence of a renal mass visualized by abdominal radiography (14/14), ultrasound (9/14), or both. All dogs underwent nephrectomy, and 4/14 dogs also received adjunctive chemotherapy. Median survival time of all dogs was 278 days (range 0-1,005 days), and dogs with hemoperitoneum had significantly shorter survival times than dogs without hemoperitoneum (62 days versus 286 days, P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: These results indicate that hemoperitoneum and distant metastasis at diagnosis appear to occur less frequently in dogs with renal HSA compared with other visceral forms of HSA. Furthermore, dogs with renal HSA have protracted disease progression, with improved 1-year survival rates and longer median survival time compared to dogs with splenic, cardiac, and retroperitoneal HSA.     

Masitinib mesylate for metastatic and non‐resectable canine cutaneous mast cell tumours

Masitinib mesylate is a tyrosine kinase inhibitor approved for the treatment of gross, non‐metastatic grade II and III canine mast cell tumours (MCTs). This study evaluated the use of masitinib as a frontline and rescue agent for metastatic and non‐metastatic canine MCTs. Identification of toxicities and prognostic factors in these dogs was of secondary interest. Twenty‐six dogs were included in this study. The overall response rate to masitinib was 50%. The median survival time for dogs that responded to masitinib was 630 days versus 137 days for dogs that did not respond (P = 0.0033). Toxicity was recorded in 61.5% of treated dogs, but the majority of adverse events were mild and self‐limiting. Response to masitinib, not tumour grade, stage or location, was the most significant prognostic factor for survival in dogs with MCTs.     

Prognostic significance of specific magnetic resonance imaging features in canine nasal tumours treated by radiotherapy

Objectives : To investigate the prognostic significance of the magnetic resonance (MR) findings of meningeal hyperintensity of the olfactory bulbs and tumour extension into the caudal nasal recess (CNR) in dogs with nasal tumours treated by radiotherapy. Methods : MR images of 41 dogs with nasal tumours treated with radiotherapy were reviewed. The occurrence of neurological signs and survival of patients with and without meningeal hyperintensity of the olfactory bulbs and tumour extension into the CNR were analysed together with possible confounding factors including intracranial extension and patient age. Results : There was no significant association between the presence of meningeal hyperintensity or CNR involvement and the occurrence of neurological signs. Although there was a tendency towards shorter survival in dogs with tumour extension into the CNR, multivariable analysis showed no significant difference in survival between dogs with/without CNR involvement, meningeal hyperintensity or intracranial tumour extension (P=0·12, 0·50 and 0·57, respectively). Clinical Significance : In dogs with nasal tumours treated with radiotherapy, tumour extension into the cranium is not necessarily associated with shorter survival in patients without neurological signs at time of diagnosis. Although a definite influence of CNR involvement on case outcome could not be demonstrated, studies with a larger population are warranted.     

Chlorambucil and prednisolone chemotherapy for dogs with inoperable mast cell tumours: 21 cases

O bjectives : To evaluate the response of measurable canine mast cell tumours unsuitable for other treatment modalities to a chemotherapy protocol comprising chlorambucil and prednisolone.
M ethods : Dogs bearing measurable mast cell tumours, unsuitable for treatment by surgery or radiotherapy, were treated with orally administered prednisolone and chlorambucil, and their responses assessed.
R esults : Twenty-one dogs were enrolled in the study; 13 had intermediate-grade mast cell tumour, six were high grade and two were diagnosed by cytology alone. Eight dogs had multiple tumours and 13 dogs had single tumours, and six dogs had lymph node metastases and no dogs had visceral metastases detected. Three dogs achieved complete remission, five achieved partial remission (overall response rate 38 per cent), nine had static disease and four dogs had progressive disease. Median progression-free interval for the eight responders was 533 days, and median survival time for all dogs in the study was 140 days. Progression-free interval and median survival time were not influenced by the age, sex, weight or neutering status of the patient, by the grade or stage of the tumour or whether the patient had single or multiple tumours. No toxicity was detected.
C linical S ignificance : Response and survival rates of inoperable canine MCT to chlorambucil and prednisolone are comparable to previously described protocols, with no apparent toxicity.     

Biological behaviour of canine mandibular osteosarcoma. A retrospective study of 50 cases (1999–2007)

The purpose of this retrospective study was to describe the biological behaviour of canine mandibular osteosarcoma (OSA) and to examine factors for their impact on metastasis‐free interval (MFI) and survival time (ST). Records from dogs treated with mandibulectomy for OSA (1999–2007) were reviewed. Archived tumour samples were evaluated for mitotic index (MI) and tumour grade. Fifty dogs were included, 21 received chemotherapy. Twenty‐nine dogs (58%) developed metastatic disease. The median MFI was 627 days, and median ST was 525 days. In univariate analysis MI > 40 was prognostic for decreased MFI and ST. Grade also influenced MFI and ST, with 5/21 (24%) dogs with grade II/III tumours metastasis‐free at one year versus 16/22 (72%) dogs with grade I tumours (P = 0.002); and 5/21 (24%) dogs with grade II/III tumours alive versus 17/22 (77%) dogs with grade I tumours (P = 0.001). In multivariate analysis, histological grade and adjuvant chemotherapy were prognostic for MFI and ST.     

Continuous low-dose oral chemotherapy for adjuvant therapy of splenic hemangiosarcoma in dogs

BACKGROUND: Hemangiosarcoma (HSA) is a highly metastatic and often rapidly fatal tumor in dogs. At present, conventional adjuvant chemotherapy provides only a modest survival benefit for treated dogs. Continuous oral administration of low-dose chemotherapy (LDC) has been suggested as an alternative to conventional chemotherapy protocols. Therefore, we evaluated the safety and effectiveness of LDC using a combination of cyclophosphamide, etoposide, and piroxicam as adjuvant therapy for dogs with stage II HSA. HYPOTHESIS: We hypothesized that oral adjuvant therapy with LDC could be safely administered to dogs with HSA and that survival times would be comparable to those attained with conventional doxorubicin (DOX) chemotherapy. ANIMALS: Nine dogs with stage II splenic HSA were enrolled in the LDC study. Treatment outcomes were also evaluated retrospectively for 24 dogs with stage II splenic HSA treated with DOX chemotherapy. METHODS: Nine dogs with stage II splenic HSA were treated with LDC over a 6-month period. Adverse effects and treatment outcomes were determined. The pharmacokinetics of orally administered etoposide were determined in 3 dogs. Overall survival times and disease-free intervals were compared between the 9 LDC-treated dogs and 24 DOX-treated dogs. RESULTS: Dogs treated with LDC did not develop severe adverse effects, and long-term treatment over 6 months was well-tolerated. Oral administration of etoposide resulted in detectable plasma concentrations that peaked between 30 and 60 minutes after dosing. Both the median overall survival time and the median disease-free interval in dogs treated with LDC were 178 days. By comparison, the overall survival time and disease-free interval in dogs treated with DOX were 133 and 126 days, respectively. CONCLUSIONS: Continuous orally administered LDC may be an effective alternative to conventional high-dose chemotherapy for adjuvant therapy of dogs with HSA.     

Canine intranasal tumours treated with alternating carboplatin and doxorubin in conjunction with oral piroxicam: 29 cases

Few veterinary studies have evaluated the response to chemotherapy treatment of canine intranasal tumours, while many have focused on the efficacy of radiation therapy. Given the higher costs and limited access to radiation therapy, alternative treatment options are needed. The study describes a cohort of dogs with histologically confirmed intranasal tumours treated with chemotherapy as a sole therapy. This retrospective study was conducted using data from the Melbourne Veterinary Specialist Centre (MVSC) database between 2004 and 2017. Dogs with a histologically confirmed intranasal tumour who received chemotherapy treatment were included. Signalment, presenting signs, tumour type, chemotherapy details, adverse events (AEs) and survival times were reviewed. Twenty‐nine dogs met the inclusion criteria. Overall median survival time for dogs in the study was 234 days (range 12‐1698 days). Median survival for dogs with adenocarcinoma or carcinoma (n = 12) was 280 days, transitional cell carcinoma (n = 6) 163 days, squamous cell carcinoma, anaplastic carcinoma or undifferentiated carcinoma (n = 7) 59 days and all sarcomas (n = 4) 448 days. Adverse events were reported following 28% of treatments and 69% of dogs experienced at least one AE. Twenty four per cent of all dogs experienced grade 3 or 4 toxicities. The chemotherapy protocol was generally well tolerated. The study suggests potential benefit in the use of chemotherapy for dogs with adenocarcinoma, carcinoma and sarcoma.     

PCNA and grade in 13 canine oral squamous cell carcinomas: association with prognosis

This study evaluated the prognosis factors of age, tumour size, anatomic location, histological grade and proliferating cell nuclear antigen (PCNA) expression in 13 dogs with oral squamous cell carcinoma (OSCC) with bone invasion and without signs of lymph node or distant metastasis. All animals were treated with radical excision performed with at least 1 cm margin, based on computed tomography images. In the 2‐year follow‐up, median disease‐free survival was 138 days for dogs with grade 3 tumours and was not reached for those with grade 2 tumours. Grade 3 tumours and PCNA labelling index ≥65% were related with a shorter disease‐free survival time and consequently poor prognosis (p = 0.003 and p = 0.034, respectively). Mean PCNA labelling index was significantly higher in recurrent cases (p = 0.011). Histological grade and PCNA expression may be important prognosis factors in canine OSCC.     

Palliative radiotherapy as treatment for non-resectable soft tissue sarcomas in the dog – a report of 15 cases

Fifteen dogs with various non‐resectable soft tissue sarcomas were treated with a palliative protocol of Cobalt⁶⁰ radiation. Twelve (80%) of the 15 tumours were fibrosarcomas and haemangiopericytomas. Total tumour radiation dose was 24 Gy, given in three 8 Gy fractions, on days 0, 7, 21 or weekly. Thirteen tumours (87%) responded with stable disease; median time to progression and median survival time were 263 and 332 days, respectively. Radiation toxicity was negligible. The survival and local control with this palliative protocol are almost comparable with curative intent primary radiotherapy.     

Retrospective evaluation of canine heart base tumours treated with toceranib phosphate (Palladia): 2011‐2018

Heart base tumours (HBT) occur commonly in older, brachycephalic dogs. A presumptive diagnosis is made based on location and appearance of the tumour via echocardiogram. Effective treatment options are limited to surgery (when feasible) or radiation therapy. Benefit of medical management is presently unknown. The goal of this retrospective study was to assess the efficacy and tolerability of toceranib phosphate for dogs with HBT. Twenty‐eight dogs with histologically, cytologically confirmed or presumed HBT were evaluated retrospectively. Twenty‐seven dogs were treated with single agent toceranib. One dog received combination therapy with concurrent metronomic chemotherapy. This dog was not included in response or survival analysis. Factors assessed included clinical signs, hematologic/biochemical parameters and response to treatment. For the 27 dogs receiving single agent toceranib, an overall response rate of 10% was found. Overall median survival time was 823 days (range, 68‐1190 days). The overall response rate for the dogs presenting with metastasis was 28.5%, with a median survival time of 532 days (range, 77‐679 days). This was not significantly different than the median survival time of 796 days for dogs who did not present with metastasis. Of the dogs displaying clinical signs at the time of diagnosis, 90% had improvement and 81% had complete resolution of signs after starting toceranib. Toxicity was seen in 54% of dogs with gastrointestinal distress as the most common toxicity but dose reductions were infrequent required. Results demonstrate that toceranib phosphate is a well‐tolerated and effective treatment for inoperable canine heart base tumours including dogs with advanced or metastatic disease.     

Response of dogs with functional pituitary macroadenomas and macrocarcinomas to radiation

A prospective study was conducted to assess the use of radiation therapy for treatment of dogs with large, functional pituitary tumours and pituitary-dependent hyperadrenocorticism. Four dogs received only pituitary irradiation, whereas two dogs received irradiation and concurrent mitotane treatment. Effects of radiation therapy on tumour size and function were assessed by sequential CT scans, ACTH assays and ACTH stimulation tests. Reduction in tumour size and resolution of neurological abnormalities occurred in all dogs. The mean and median survival time following irradiation for dogs in this report was 740 days and 743 days, respectively. Atnecropsy, a pituitary chromophobe adenoma was detected in three dogs, and a pituitary carcinoma in one dog; necropsy was not carried out on two dogs. Pituitary hypersecretion of ACTH persisted for at     

Electrochemotherapy in treatment of canine oral non‐tonsillar squamous cell carcinoma. A case series report

Non‐tonsillar squamous cell carcinoma (ntSCC) is a common and locally aggressive oral tumour in dogs. The treatments of choice are currently surgery and radiotherapy. Electrochemotherapy (ECT) is a local ablative anti‐tumour technique using electric pulses to enhance the intracellular diffusion of cytotoxic drugs. The aim was to retrospectively evaluate the outcome of patients with oral ntSCC treated with ECT. Twelve dogs with ntSCC were retrospectively enrolled. ECT was combined with IV bleomycin (15 000 UI/m²) alone in 11 cases and post‐surgery in 1. Parameters considered were: tumour site and size, electroporation parameters, response rate (complete remission [CR], partial remission [PR]), median survival time (MST), recurrence rate (RR), median disease‐free interval (DFI) and treatment toxicity (6‐point scale). Median tumour size was 1.65 cm (range 0.3‐8.0 cm) and the response rate was 90.9% (10/11; 8 CR and 2 PR). Two dogs underwent a second ECT. MST for dogs dead with tumour (n = 2) was 110 days and for dogs dead without tumour (n = 3) was 831 days. Among five surviving dogs, one experienced tumour recurrence and four were in CR. Results from two dogs were analysed separately. Overall RR was 27.3%. DFI and MST for dogs with recurrence were 50 and 115 days, respectively. Treatment toxicity was very low. We noticed that all dogs with tumours smaller than 1‐2 cm achieved CR without recurrence suggesting a favourable prognosis when using ECT. ECT for canine ntSCC could be considered a valid treatment option especially for smaller tumours, but a larger caseload would be needed to confirm this statement.     

Evaluation of a novel tumor vaccine in dogs with hemangiosarcoma

BACKGROUND: Hemangiosarcoma (HSA) is a highly metastatic and often rapidly fatal tumor of dogs. At present, adjuvant chemotherapy is the only proven effective treatment for dogs with HSA, though the benefits from chemotherapy are modest. Administration of immunotherapy together with chemotherapy has also been reported to improve survival in dogs with HSA. Therefore, we evaluated safety and immunologic responses to a novel tumor vaccine administered together with doxorubicin chemotherapy in dogs with different stages of HSA. HYPOTHESIS: That tumor vaccination could be safely and effectively combined with doxorubicin chemotherapy for treatment of dogs with HSA. ANIMALS: Twenty-eight dogs with various stages of HSA were enrolled in the study. METHODS: The HSA vaccine was prepared with lysates of allogeneic canine HSA cell lines mixed with an adjuvant composed of liposome-DNA complexes. Dogs received a series of 8 immunizations administered over a 22-week period, and most also received chemotherapy. Clinical adverse effects were noted, immune responses were measured by enzyme-linked immunosorbent assay (ELISA) and flow cytometry, and survival times were calculated. RESULTS: The most common adverse effects observed in vaccinated dogs also treated with doxorubicin chemotherapy were diarrhea and anorexia. Vaccinated dogs were found to mount strong humoral immune responses against a control antigen and, most dogs also mounted antibody responses against canine HSA cells. Thirteen dogs with stage II splenic HSA that received the tumor vaccine plus doxorubicin chemotherapy had an overall median survival time of 182 days. CONCLUSIONS: We conclude that an allogeneic tumor lysate vaccine is safe in dogs with HSA and can elicit humoral immune responses in dogs that are receiving concurrent doxorubicin chemotherapy.     

Retrospective outcome evaluation for dogs with surgically excised,solitary Kiupel high‐grade,cutaneous mast cell tumours

Published outcomes for dogs with specifically high‐grade mast cell tumours (MCTs), controlled for clinical stage, are few. Clinical outcomes for 49 dogs with Kiupel high‐grade, clinical stage I, cutaneous MCTs were evaluated. Median survival time (MST) was 1046 days; 1 and 2‐year survival rates were 79.3% and 72.9%, respectively. At study end 24 dogs had died, 23 dogs were alive (median follow‐up 980 days) and 2 dogs were lost to follow‐up. Death was considered MCT‐related in 14 of 20 dogs with a known cause of death. Local tumour recurrence developed in nine dogs (18.4%); regional lymph node metastasis occurred in six dogs (12.2%); and a new MCT developed in 15 dogs (30.1%). Tumour location, histologic margin size and use of chemotherapy did not affect MST; increasing mitotic count (P = .001) and increasing tumour diameter (P = .024) were independently negatively prognostic. Six dogs that developed lymph node metastasis after surgery had worse MST (451 days) than 42 dogs that did not develop metastasis (1645 days); (P < .001). Our study suggests that dogs with local surgical control of clinical stage I histologically high Kiupel grade cutaneous MCT may have a long survival time; especially those with smaller tumours and a lower mitotic count. Our results suggest that evaluation of staging information and mitotic count may be equally helpful as histologic grading when making a prognosis; and highlight the importance of not relying on histologic grade alone when predicting survival for dogs with MCT.     

Deionised water as an adjunct to surgery for the treatment of canine cutaneous mast cell tumours

Medical records of 55 dogs with a diagnosis of cutaneous mast cell tumour were reviewed. Twenty-seven of the dogs were treated with surgery plus deionised water and the remaining 28 with surgery alone. A survival analysis was performed to determine whether deionised water, as an adjunct to surgery for cutaneous mast cell tumour, affected survival time or time to tumour recurrence. Dogs in which mast cell tumour recurred had a significantly shorter survival time compared with dogs with no recurrence (P=0.05), regardless of the method of treatment. A significant negative association between tumour recurrence and method of treatment (P=0.0097) and clinical stage (P=0.0223) was observed. Dogs treated with surgery and deionised water had a significantly shorter time to recurrence of their mast cell tumour (P=0.0113). Based on these results, deionised water does not appear to be beneficial in prolonging survival time or time to tumour recurrence for dogs with cutaneous mast cell tumours.     

Cytological lymph node evaluation in dogs with mast cell tumours: association with grade and survival*

The purpose of this retrospective cohort study is to describe the association of cytological assessment of lymph node metastasis with survival and tumour grade in dogs with mast cell tumours. Regional lymph node aspirates of 152 dogs diagnosed with a mast cell tumour were reviewed and classified according to specific cytological criteria for staging. 97 dogs (63.8%) had stage I tumours, and 55 (36.2%) had stage II tumours. Stage II dogs had a significantly shorter survival time than dogs with stage I disease (0.8 and 6.2 years, respectively; P < 0.0001). Dogs with grade III mast cell tumours were more likely to have stage II disease (P = 0.004). These results suggest that cytological evaluation of lymph nodes in dogs with mast cell tumours provides useful and valuable clinical information, and the results correlate with tumour grade and outcome thus providing a practical and non‐invasive method for staging.