Adjuvant electrochemotherapy after debulking in canine bone osteosarcoma infiltration.

Osteosarcoma is a bone cancer considered rare to humans, but common in dogs. Dogs and humans share genetic homology and environmental risk factors. Improving the treatment of osteosarcoma in dogs could also be relevant to improve procedures in humans. Traditional treatments of osteosarcoma involve surgery and chemotherapy. Such treatments are commonly aggressive and not possible for many patients. Electrochemotherapy emerges as a minimally invasive, effective, and safe treatment alternative. Electrochemotherapy combines applications of high-intensity electric fields during short periods with anti-cancer drugs to improve its medicine cytotoxicity. Analyzing the electric field distribution, as well as electric current density, are essential to electrochemotherapy success. This paper brings the first case of a canine osteosarcoma treatment performed with bleomycin and electrochemotherapy. We performed in silico studies with finite element method software to observe the electric field distribution. In silico experiments help to verify possibilities and limitations of treating bone destruction and macro or micro tumor infiltrations around the primary tumor mass. Results show that both needle or plate electrodes are feasible to remove the tumor even with invasion into the bone. Plate electrodes perform well in treating micro infiltrations when associated with conductive gel and direct contact between electrode and bone (without soft tissues). Needle electrodes are effective in treating tumor infiltration on external cortical bone. Multiple applications are needed to cover all cranium layers with sufficient electric field intensity. Electrochemotherapy protocol with needle or plate electrodes does not present sufficient electric current density capable of affecting brain tissue, even in cases of bone destruction.

Metastasized Leydig cell tumor in a dog.

We present the clinical findings, diagnosis and treatment of an 11-year old intact male Fox Terrier with a malignant Leydig cell tumor of the right testicle, which metastasized to the skeletal musculature of the left hind limb. The primary tumor and the metastasis were resected with narrow margins. The dog was treated with metronomic chemotherapy using thalidomid and dyclophosphamide. Local recurrence at the site of the metastasis and a pulmonary metastasis were present 30 months after surgery. The dog was euthanized.

Postoperative adjuvant combination therapy with doxorubicin and noncytotoxic suramin in dogs with appendicular osteosarcoma.

Although conventional treatment of dogs with osteosarcoma (OSA) by amputation and chemotherapy results in reported survival times (STs) of 262-413 days, no major improvements in STs have occurred in the past 2 decades. Suramin is a polysulfonated napthylurea, which at noncytotoxic concentrations in vitro, increases tumor sensitivity to chemotherapy, including doxorubicin. The study authors evaluated the combination of noncytotoxic suramin and doxorubicin after amputation in dogs with OSA. The hypothesis was that treatment of dogs with appendicular OSA with amputation, adjuvant doxorubicin, and noncytotoxic suramin would be well tolerated and result in STs at least comparable to those of doxorubicin alone. Forty-seven dogs received 6.75 mg/kg of suramin IV followed by 30 mg/m(2) of doxorubicin IV 4 hr later. Treatment was repeated q 2 wk for five doses. The median disease free time (DFI) was 203 days (range, 42-1,580+ days) and the median ST for all dogs was 369 days (range, 92-1,616+ days). There was no statistical difference in ST and DFI between greyhounds and nonngreyhounds. Adjuvant doxorubicin and noncytotoxic suramin was well tolerated in dogs with OSA following amputation. Additional studies are needed to determine if this combination treatment protocol provides additional clinical benefit compared with doxorubicin alone.

Splenic stromal sarcomas in dogs: Outcome and clinicopathological prognostic factors in 32 cases.

Due to the low frequency and the changes in diagnostic techniques and terminology during the last few years, only little clinical information is available on splenic stromal sarcoma (SSS). This multi-institutional study aimed at gathering clinical cases of SSS in dogs and investigates their clinical behaviour, as well as analyse possible clinicopathological prognostic factors, including the use of adjuvant therapy. Dogs with a histologically confirmed SSS that underwent splenectomy were retrospectively included. To be included in the study, either FFPE tissue blocks or multiple tissue sections had to be available for histopathologic and immunohistochemical revision. Clinical and pathological variables, along with adjuvant therapy data, were collected. Cumulative incidence of metastatic disease was analysed through univariate and bivariate analyses. The impact of adjuvant chemotherapy on metastasis incidence and survival was assessed, considering an estimated propensity score. A total of 32 dogs were included. Among them, 22 developed metastases with an incidence of 37.5%, 59.38%, and 65.94% at 6, 12, and 24 months, respectively. Univariate analysis identified mitotic count, total scoring, and necrosis as prognostic factors. In bivariate analysis, mitotic count remained prognostic. The administration of adjuvant chemotherapy did not have an impact on metastasis incidence or survival time. The study found that dogs with SSSs are at high risk of metastasis, although a small subgroup may experience longer survival after splenectomy. Mitotic count was the only variable having a reliable prognostic impact. Adjuvant chemotherapy did not appear to decrease the incidence of metastasis or prolong survival in these dogs.

Clinical outcome of 42 dogs with scapular tumors treated by scapulectomy: a Veterinary Society of Surgical Oncology (VSSO) retrospective study (1995-2010).

OBJECTIVE: To report signalment, clinical signs, preoperative staging tests, histologic diagnosis, surgical, and oncologic outcomes including postoperative limb use, in dogs with scapular tumors treated by scapulectomy. STUDY DESIGN: Retrospective case series ANIMALS: Dogs (n = 42) with scapular tumors. METHODS: Medical records (1995-2010) from 6 hospitals were searched for dogs with scapular tumors treated by scapulectomy. Data retrieved were: signalment, weight, percentage of scapula removed, histologic diagnosis, postoperative limb use, adjunctive therapy, disease free interval (DFI), and survival time (ST). Individual variables were modeled with a Cox proportional hazard model accounting for censoring to determine risk factors for decreased DFI and ST. For categorical variables, Kaplan-Meier survival plots as well as mean and median survival times (MSTs) were calculated. RESULTS: Subtotal scapulectomy was performed in 18 dogs (42.9%). Osteosarcoma (OSA) was diagnosed in 27 dogs (64.3%). Limb use was evaluated immediately after surgery in 41 dogs. Information on limb use at other times (1, 2, 3, and >3 months) postoperatively was also available for some dogs and was good to excellent overall. Only adjunctive chemotherapy had a positive significant effect on DFI (P = .00011) and ST (P = .0003). CONCLUSION: Canine scapular tumors can be treated effectively by scapulectomy and limb use is fair to excellent for most dogs. OSA was the most common scapular tumor. Overall prognosis for scapular OSA is similar to appendicular OSA at other sites and use of adjunctive chemotherapy prolonged the overall DFI and MST.

Doxorubicin and deracoxib adjuvant therapy for canine splenic hemangiosarcoma: a pilot study.

Canine hemangiosarcoma (HSA) is a highly malignant tumor for which standard chemotherapy has done little to substantially improve survival. Cyclooxygenase-2 (Cox-2) plays a role in the formation, growth, and metastasis of tumors and inhibitors have demonstrated therapeutic benefit with certain canine cancers. In this prospective study, 21 dogs received adjuvant therapy combining the selective Cox-2 inhibitor deracoxib with doxorubicin, following splenectomy for HSA. The combination was well-tolerated with only low-grade gastrointestinal and hematologic toxicities noted. An overall median survival of 150 days (range; 21 to 1506 days) was noted. Although there was no significant difference in survival based upon stage of disease, dogs with stage III HSA (n = 11) had a median survival of 149 days, which appears to be longer than previously reported. Further studies are warranted to evaluate the potential benefit of Cox-2 inhibitors in the treatment of canine HSA.

Traitement adjuvant à la doxorubicine et au déracoxib pour l'angiosarcome splénique canin : étude pilote. L'angiosarcome canin est une tumeur hautement maligne pour laquelle la chimiothérapie standard a peu fait pour améliorer substantiellement la survie. La cyclooxygénase-2 (Cox-2) joue un rôle dans la formation, la croissance et la métastase des tumeurs et des inhibiteurs ont démontré des bienfaits thérapeutiques pour certains cancers canins. Dans cette étude prospective, 21 chiens ont reçu un traitement adjuvant combinant l'inhibiteur de la Cox-2 sélectif déracoxib avec la doxorubicine, après la splénectomie pour l'angiosarcome. La combinaison a été bien tolérée et seulement des toxicités gastro-intestinales et hématologiques de faible intensité ont été signalées. Une survie médiane globale de 150 jours (écart de 21 à 1506 jours) a été signalée. Même s'il n'y a pas eu de différence significative dans la survie si l'on se base sur le stade de la maladie, les chiens avec un angiosarcome de stade III (n = 11) ont eu une survie médiane de 149 jours, ce qui semble plus long que ce qui avait déjà été signalé. De nouvelles études sont justifiées afin d'évaluer le bienfait potentiel des inhibiteurs de la Cox-2 pour le traitement de l'angiosarcome canin.(Traduit par Isabelle Vallières).

Retrospective analysis of outcome and prognostic factors of subcutaneous mast cell tumours in dogs undergoing surgery with or without adjuvant treatment.

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.

Timely adjuvant chemotherapy improves outcome in dogs with non-metastatic splenic hemangiosarcoma undergoing splenectomy.

Timely delivery of adjuvant chemotherapy has been shown to be advantageous in many human cancers and canine osteosarcoma. Adjuvant chemotherapy has been shown to improve outcome for canine splenic hemangiosarcoma. The aim of this retrospective study was to investigate whether timely adjuvant chemotherapy administration resulted in better outcome in dogs with non-metastatic splenic hemangiosarcoma undergoing splenectomy. Medical records were searched for dogs with non-metastatic, splenic hemangiosarcoma that received splenectomy and adjuvant chemotherapy. The number of days from surgery to the first chemotherapy dose (StoC) was evaluated to identify the cut-off value associated with the best survival advantage. StoC and other possible prognostic factors were tested for influence on time to metastasis (TTM) and overall survival (OS). Seventy dogs were included. Median StoC was 20 days (range: 4-70). The time interval associated with the greatest survival benefit was 21 days. Median TTM and OS of dogs with StoC ≤ 21 days were significantly longer than those with StoC >21 days (TTM: 163 vs. 118 days, p = .001; OS: 238 vs. 146 days, p < .001). On multivariable analysis, StoC >21 days was the only variable significantly associated with increased risk of tumour progression (HR 2.1, p = .010) and death (HR 2.3; p = .008). Starting adjuvant chemotherapy within 21 days of surgery may be associated with a survival benefit in dogs with non-metastatic splenic hemangiosarcoma, possibly due to the early targeting of newly recruited metastatic cells after surgery.

Chemotherapy and radiation therapy in 4 dogs with muscle-invasive transitional cell carcinoma of the urinary tract.

Four dogs with T(2)N(0)M(0) transitional cell carcinoma of the lower urinary tract underwent multimodal treatment consisting of neoadjuvant chemotherapy, external-beam radiotherapy, and adjuvant chemotherapy. No significant toxicity was documented. All dogs showed clinical improvement and reduction of tumor volume based on computed tomography (CT).

RésuméChimiothérapie et radiothérapie comme traitement pour carcinomes à cellules transitionnelles urothéliaux avec infiltration du muscle dans 4 chiens. Quatre chiens avec des carcinomes à cellules transitionnelles du bas tractus urinaire (TNM) ont été traités avec une approche multimodale consistent en chimiothérapie néodjuvante, radiothérapie externe et chimiothérapie adjuvante. Nous n'avons pas observé une toxicité signifiante. Tous les chiens ont répondu à ce traitement multimodale, défini comme amélioration des symptômes cliniques et réduction des dimensions de la tumeur, indiqué au scanner.(Traduit par Julia Buchholz).

Treatment with DAV for advanced-stage hemangiosarcoma in dogs.

Hemangiosarcoma (HSA) is an aggressive disease that is fairly common in the dog. The authors evaluated a doxorubicin, dacarbazine, and vincristine (DAV) combination protocol in dogs with nonresectable stage II and stage III HSA. Twenty-four dogs were enrolled in this prospective, phase 2 study. Doxorubicin and dacarbazine were administered on day 1 while vincristine was administered on days 8 and 15. The protocol was repeated every 21 days for a maximum of six cycles or until disease progression. Toxicity and efficacy were assessed by clinical and laboratory evaluation and by questionnaires completed by the owners. Of the 24 included dogs, 19 were evaluable for response. The response rate (including five complete responses and four partial responses) was 47.4%. Median time to tumor progression was 101 days and median overall survival was 125 days. Significant toxicities were noted, including 41 high-grade hematologic and 12 high-grade gastrointestinal toxic events. Five dogs discontinued treatment due to chemotherapy-related toxicities, but no treatment-related deaths occurred. Multivariate analysis identified patient age (relative risk [RR], 2.3, P=0.049) to be negatively associated with time to progression whereas dacarbazine dose reductions (RR, 0.06, P=0.031) were positively associated with time to progression. Dacarbazine dose reduction was the sole factor positively associated with overall survival (RR, 0.28, P=0.015). In conclusion, the DAV combination appears to offer clinical responses and may prolong survival in dogs with advanced-stage HSA.

Timing of adjuvant chemotherapy after limb amputation and effect on outcome in dogs with appendicular osteosarcoma without distant metastases.

OBJECTIVE: To determine an optimal time interval between amputation and initiation of adjuvant chemotherapy (TIamp-chemo) in dogs with appendicular osteosarcoma without distant metastases and whether TIamp-chemo was associated with outcome. ANIMALS: 168 client-owned dogs treated at 9 veterinary oncology centers. PROCEDURES: Data were collected from the dogs' medical records concerning potential prognostic variables and outcomes. Dogs were grouped as to whether they received chemotherapy within 3, 5, 7, 10, 15, 20, 30, or > 30 days after amputation of the affected limb. Analyses were performed to identify variables associated with time to tumor progression and survival time after limb amputation and to determine an optimal TIamp-chemo. RESULTS: Median TIamp-chemo was 14 days (range, 1 to 210 days). Median time to tumor progression for dogs with a TIamp-chemo ≤ 5 days (375 days; 95% CI, 162 to 588 days) was significantly longer than that for dogs with a TIamp-chemo > 5 days (202 days; 95% CI, 146 to 257 days). Median overall survival time for dogs with a TIamp-chemo ≤ 5 days (445 days; 95% CI, 345 to 545 days) was significantly longer than that for dogs with a TIamp-chemo > 5 days (239 days; 95% CI, 186 to 291 days). CONCLUSIONS AND CLINICAL RELEVANCE: Findings indicated that early (within 5 days) initiation of adjuvant chemotherapy after limb amputation was associated with a significant and clinically relevant survival benefit for dogs with appendicular osteosarcoma without distant metastases. These results suggested that the timing of chemotherapy may be an important prognostic variable.

Metastatic feline mammary cancer: prognostic factors, outcome and comparison of different treatment modalities - a retrospective multicentre study.

OBJECTIVES: Although feline mammary carcinomas (FMCs) are highly metastatic, the literature and treatment options pertaining to advanced tumours are scarce. This study aimed to investigate the clinical outcome of metastatic FMC with or without adjuvant treatment. METHODS: The medical records of 73 cats with metastatic FMC (stage IV) were reviewed and included in this study. Metastatic disease was detected by distinct imaging techniques (radiography, ultrasound and CT) and confirmed by cytology and/or histopathology. Cats with adjuvant chemotherapy treatment (n = 34) were divided into three groups: group 1 (n = 9) cats receiving maximum tolerated dose chemotherapy; group 2 (n = 15) cats receiving metronomic chemotherapy; and group 3 (n = 10) cats treated with toceranib phosphate. The study endpoints were time to progression (TTP) and tumour-specific survival (TSS). Treatment-related toxicity was evaluated according to the Veterinary Co-operative Oncology Group's Common Terminology Criteria for Adverse Events version 1.1 (VCOG-CTCAE). RESULTS: Overall mean TTP and TSS were 23 and 44 days, respectively. Cats with clinical signs at the time of diagnosis had a lower TSS (14 days) than asymptomatic cats (128 days; P <0.001). Cats with pleural effusion had a lower TSS (16 days) than cats without (P <0.001). Median TSS was 58, 75 and 63 days in groups 1, 2 and 3, respectively (P = 0.197). Toxicity was observed in 66.7%, 20% and 30% of cats in groups 1, 2 and 3, respectively. CONCLUSIONS AND RELEVANCE: To the best of our knowledge, this study includes the highest number of patients with metastatic FMC assessed. Despite the overall poor prognosis, some cats survived >6 months, indicating that adjuvant treatment may be an option to consider in metastatic disease. More studies are warranted for better understanding and management of stage IV patients.

Adjuvant doxorubicin vs metronomic cyclophosphamide and meloxicam vs surgery alone for cats with mammary carcinomas: A retrospective study of 137 cases.

This study aims to evaluate the efficacy and side effects of low dose cyclophosphamide chemotherapy plus meloxicam as an adjuvant treatment, compared with high dose doxorubicin or surgery alone in cats with mammary carcinoma. Medical records of 228 female cats treated for mammary carcinoma between 2008 and 2018, were reviewed in eight veterinary institutions. Only cats with complete tumour staging and radical mastectomy were included in the study. One hundred and thirty-seven cats were divided into three treatment groups: group 1 (n = 80) cats treated with surgery, group 2 (n = 34) cats that had surgery and adjuvant treatment with doxorubicin, and group 3 (n = 23) cats with surgery and adjuvant treatment with low dose metronomic cyclophosphamide and meloxicam. The study endpoints were disease free interval (DFI) and overall survival (OS). Toxicity was evaluated according to the VCOG-CTCAE criteria. The median DFI was 270, 226 and 372 days in groups 1, 2 and 3, respectively. The median OS was 338 (group 1), 421 (group 2) and 430 (group 3) days. The differences between groups were not significant (DFI P = .280 and OS P = .186). Toxicity was observed in 52.9% (n = 18) of cats in group 2 and 39.1% (n = 9) of cats in group 3, with mild to moderate intensity. Differences were not significant (P = .306). In conclusion, adjuvant chemotherapy treatment did not improve survival and the overall benefit remains unproven. Randomized prospective trials are necessary to clarify the effectiveness of adjuvant chemotherapy treatment for feline mammary carcinomas.

Clinical outcomes in dogs with localized splenic histiocytic sarcoma treated with splenectomy with or without adjuvant chemotherapy.

BACKGROUND: Localized splenic histiocytic sarcoma (HS) in dogs is a poorly understood disease, and could have longer survival times than disseminated or hemophagocytic HS. Understanding the clinical behavior of localized splenic HS can refine treatment recommendations. OBJECTIVE: To describe the clinical characteristics and outcomes of dogs with localized splenic HS. ANIMALS: Fourteen client-owned dogs with histologically confirmed splenic HS that received splenectomy. METHODS: Multi-institutional retrospective case series-medical records of dogs with splenic HS were reviewed. Dog signalment, clinicopathologic data, primary and adjuvant treatments, and outcomes were obtained. Survival data were calculated using Kaplan-Meier analysis. Dog variables such as age, weight, platelet counts were reported using descriptive statistics. The Cox proportional hazards regression method was used to determine whether potential risk factors (weight, age, albumin level, hematocrit, and platelet count) were associated with PFI. RESULTS: Median survival time for the dogs in this study was 427 days. Twelve dogs received adjuvant lomustine-based chemotherapy. Five dogs (35.7%) were suspected or confirmed to have developed metastatic disease. Eleven dogs died of disease, 1 dog died of unrelated cause, and 2 dogs were alive at final follow-up. CONCLUSIONS AND CLINICAL SIGNIFICANCE: Histiocytic sarcoma in dogs can manifest as a localized form in the spleen. Dogs with localized splenic HS treated with surgery ± chemotherapy can experience survival times over a year.

Combination of bleomycin and cisplatin as adjuvant electrochemotherapy protocol for the treatment of incompletely excised feline injection-site sarcomas: A retrospective study.

Background: fFeline injection-site sarcomas (FISSs) are mesenchymal tumors that can occur in cats after injections of different medical agents and are easily prone to recurrence. Aim: The aims of this study were to report treatment outcomes for cats with feline injection-site sarcomas (FISSs) treated with both bleomycin and cisplatin, per adjuvant electrochemotherapy (ECT) protocol. Methods: The medical records of cats with a diagnosis of FISS that were treated with ECT using both bleomycin and cisplatin were retrospectively evaluated. A total of 27 cats were available for statistical evaluation of their response. The cats received intravenous 20 mg/m2 bleomycin, and the tumor bed and margins were infiltrated with cisplatin at the dose of 0.5 mg/cm2. Then, the trains of permeabilizing biphasic electric pulses lasting 50 + 50 µseconds each were delivered in bursts of 1,300 V/cm using caliper electrodes under sedation. A second session was performed 2 weeks later. Results: Side effects were limited to local inflammation in three cats. Three cats developed local tumor recurrence at days 180, 180, and 545 after surgery, two cats developed recurrence and metastases at 100 and 505 days after surgery, and two cats experienced distant metastases. A median time to recurrence could not be calculated as over 80% of the study population remained disease free or were censored due to death from other causes. Mean survival time was 985 days, and median cumulative survival for all cases was 1,000 days. Conclusion: When compared to historical controls, the results of this study demonstrate the superior rates of tumor-free survival and disease-free interval. This adjuvant therapy could be a useful addition to the current options for FISS in consideration of its efficacy, limited toxicity, and ease of administration.

Outcome comparison between radiation therapy and surgery as primary treatment for dogs with periarticular histiocytic sarcoma: An Italian Society of Veterinary Oncology study.

Localized histiocytic sarcoma may occur as a primary lesion in periarticular tissues of large appendicular joints. Treatment options for the primary lesion include radical surgical excision, radiation therapy (RT), or both, in combination with chemotherapy for potential systemic metastases. In an effort to better characterize the time to progression (TTP) following surgical vs non-surgical approaches for periarticular histiocytic sarcoma (PAHS), a contemporary European population of affected dogs was retrospectively surveyed. Medical records were queried for newly-diagnosed PAHS cases undergoing surgery (predominantly limb amputation) or RT followed by systemic chemotherapy. Of 49 dogs, 34 underwent RT and 15 underwent surgery. All dogs received adjuvant chemotherapy. There was no statistically significant difference in TTP or overall survival between groups. The median TTP was 336 days for the operated dogs and 217 days for the irradiated dogs (P = .117). The median overall survival time was 398 days for the operated dogs and 240 days for the irradiated dogs (P = .142). On multi-variable analysis, the variables significantly associated with an increased risk of both tumour progression and tumour-related death were regional lymph node and distant metastasis at admission. Survival and local control rates following RT may be comparable to radical resection. These data may better inform shared decision-making processes between multi-disciplinary care providers and owners.

Impact of repeated cycles of EGF bispecific angiotoxin (eBAT) administered at a reduced interval from doxorubicin chemotherapy in dogs with splenic haemangiosarcoma.

We previously reported that eBAT, an EGF-targeted angiotoxin, was safe and it improved the overall survival for dogs with splenic haemangiosarcoma when added to the standard of care in a single cycle of three administrations in the minimal residual disease setting. Our objective for the SRCBST-2 trial was to assess whether increased dosing through multiple cycles of eBAT would be well tolerated and would further enhance the benefits of eBAT. Eligibility was expanded to dogs with stage 3 haemangiosarcoma, provided that gross lesions could be surgically excised. The interval between eBAT and the start of chemotherapy was reduced, and the experimental therapy was expanded to three cycles, each administered at the biologically active dose (50 µg/kg) on a Monday/Wednesday/Friday schedule following splenectomy, and scheduled 1 week prior to the first, second and fifth doxorubicin chemotherapy. Twenty-five dogs were enrolled; six experienced acute hypotension with two requiring hospitalization. Self-limiting elevation of ALT was observed in one dog. A statistically significant survival benefit was not seen in this study in eBAT-treated dogs compared with a Contemporary comparison group of dogs with stages 1-3 haemangiosarcoma treated with standard of care alone. Our results indicate that repeated dosing cycles of eBAT starting 1 week prior to doxorubicin chemotherapy led to greater toxicity and reduced efficacy compared with a single cycle given between surgery and a delayed start of chemotherapy. Further work is needed to understand the precise mechanisms of action of eBAT in order to optimize its clinical benefits in the treatment of canine haemangiosarcoma and other tumours. IACUC Protocols 1110A06186 and 1507-32804A.

Adjuvant intraperitoneal ceftriaxone in the treatment of septic peritonitis in horses.

BACKGROUND: Intraperitoneal administration of ceftriaxone maintains therapeutic abdominal concentrations for 24 hours in healthy horses. Therefore, it is a possible treatment for septic peritonitis. The aim of this study was to evaluate the efficacy of ceftriaxone as an adjuvant treatment in horses with septic peritonitis. METHODS: Twenty-six horses with clinical signs, sonography and/or laboratory findings of septic peritonitis were included. Peritoneal fluid was collected for microbiological culture and in vitro microbial sensitivity profile assessment. Daily intraperitoneal administration of ceftriaxone (25 mg/kg) was initiated with supportive and systemic antimicrobial treatment. The animals were divided into three groups: group 1-gastrointestinal tract injuries and abdominal surgery (excluding perforations/ruptures); group 2-not related to changes in the gastrointestinal tract; group 3-secondary to intestinal rupture and/or faeces contamination. RESULTS: The mean success rate of the treatment was 77 per cent (20/26 animals), with success rates of 84.6 per cent in group 1; 87.5 per cent, group 2; and 40 per cent, group 3. CONCLUSIONS: This is the first study to report adjuvant intraperitoneal treatment ceftriaxone for septic peritonitis in horses and indicates that this treatment can successfully treat septic peritonitis in horses.

Adjuvant medical therapy provides no therapeutic benefit in the treatment of dogs with low-grade mast cell tumours and early nodal metastasis undergoing surgery.

Lymph node (LN) metastasis is a negative prognostic factor in dogs with cutaneous mast cell tumours (cMCTs). While elective lymphadenectomy of metastatic LNs improves outcome, the benefit of adjuvant medical therapy in dogs with early metastatic (HN2) LNs is debated. The aim of this retrospective multicentre study was to evaluate the therapeutic benefit of adjuvant medical therapy following surgical removal of the primary low-grade cMCT (Patnaik grade 1-2 and Kiupel low-grade) and lymphadenectomy of HN2 LNs by analysing survival rates and patterns of recurrence. Seventy-three dogs were included: 42 received adjuvant medical treatment (chemotherapy and/or kinase inhibitors), and 31 did not. The median follow-up time for medically treated dogs was 619 days: two experienced local recurrence, three nodal relapse and four distant relapse. For dogs undergoing surgery only, the median follow-up time was 545 days. None of them experienced local recurrence, nodal, or distant relapse. Time to progression was significantly shorter in dogs receiving adjuvant medical treatment (P = .021). A similar tendency was observed for overall survival (P = .056). The current study shows that dogs with low-grade cMCTs, that undergo surgical excision of the primary tumour and elective lymphadenectomy of the HN2 regional LN harbour a good prognosis. The use of adjuvant medical treatment in these dogs does not seem to provide any benefit in terms of progression and survival.

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.