Contrast-enhanced ultrasound was used to study focal and multifocal lesions of the spleen in 26 dogs and two cats affected by 11 benign and 18 malignant splenic diseases. A second-generation microbubble contrast medium (Sonovue) was injected into the cephalic vein and enhancement patterns were subjectively described and time intensity curves calculated. Final diagnosis was obtained by histopathologic examination after splenectomy (n=19) or by needle aspiration and sonographic follow-up after 4 and 8 weeks (n=9). Contrast-enhanced ultrasound parameters, improving the characterization between benign and malignant lesions, were established. The most useful criterion was the hypoechogenicity of the lesion in the wash-out phase combined with the presence of tortuous feeding vessels, which was observed in association with malignancy. All malignant lesions were hypoechoic to the surrounding spleen 30s after starting the contrast medium injection. Lymphosarcoma and hemangiosarcoma had characteristic perfusion patterns. Lymphosarcoma had rapid time to peak and early wash-out phase with a honeycomb pattern during the wash-out. Hemangiosarcomas were large nonperfused masses in all phases surrounded by hypervascular splenic parenchyma. Benign lesions except one hematoma and a benign histiocytoma had the same perfusion pattern as the surrounding spleen. Ultrasonographic and contrast-enhanced ultrasound findings of an accessory spleen are reported. Contrast-enhanced ultrasound can improve the characterization of focal or multifocal lesions of the spleen.

Purpose: Active immunotherapy is a promising antitumoral strategy; however its use in combination with chemotherapy in dogs with large B-cell lymphoma (DLBCL) remains largely untested. Heat shock proteins (HSP) bind the small peptides they chaperone (HSPPC), allowing for immunization of the host against a large repertoire of tumor-associated antigens. Hydroxylapatite vehicles HSPPCs and acts as an immunologic adjuvant. The aim of this study was to show that an autologous vaccine with hydroxylapatite and tumor-derived HSPPCs is safe and therapeutically effective in dogs with DLBCL.Experimental Design: Nineteen dogs with naturally occurring DLBCL were entered into a prospective randomized placebo-controlled double-blinded trial of HSPPCs-hydroxylapatite plus chemotherapy versus chemotherapy alone. Endpoints included time to progression (TTP), lymphoma-specific survival (LSS), and incidence of toxicoses.Results: Median first TTP after randomization to the vaccine arm was 304 days versus 41 days for the control arm (P ¼ 0.0004). There was also a statistically significant difference in duration of second remission between the two groups (P ¼ 0.02). Median LSS was 505 days for the vaccinated dogs versus 159 days for the unvaccinated dogs (P ¼ 0.0018). Six vaccinated dogs achieved molecular remission, as shown by clonal immunoglobulin H (IgH) rearrangement. Toxicoses were comparable between the two treatment arms.Conclusions: The results of this trial demonstrate that the autologous vaccine tested here is safe and efficacious in prolonging TTP and LSS in dogs with DLBCL when used in combination with dose-intense chemotherapy. On the basis of these results, additional evaluation of this novel therapeutic strategy is warranted in human DLBCL. Clin Cancer Res; 20(3); 668-77. Ó2013 AACR.

Prognosis for unresectable canine malignant melanoma (MM) is typically poor, and therapeutic approaches remain largely palliative. A bi-institutional trial was conducted to compare efficacy and safety of radiotherapy (RT) and RT with post-radiation temozolomide in dogs with chemotherapy-naïve, measurable MM. RT consisted of 5x6 Gy fractions over 2.5 weeks. Dogs whose owners wished to pursue chemotherapy received adjuvant oral temozolomide (60 mg/m2 for 5 days every 28 days). Fifteen dogs were treated with RT only (Group 1) and 12 dogs subsequently received temozolomide (Group 2). Overall response rate was similar between Group 1 (86.7%) and Group 2 (81.1%). Median time to progression (TTP) was significantly longer in Group 2 (205 days) compared to Group 1 (110 days; p=0.046). Survival time was not significantly different between groups. Both treatments were well tolerated. Post-radiation temozolomide has a good safety profile, and may improve TTP in MM when compared to conventionally fractionated RT.

In helical hydro-computed tomography (helical hydro-CT), water is used as a neutral luminal contrast medium together with intravenous iodine contrast medium for the diagnosis and staging of human gastric neoplasia. We evaluated the feasibility of helical hydro-CT in 11 healthy animals (nine dogs and two cats). Adequate uniform gastric distension was obtained with 30 ml water/kg body weight. Fourteen client-owned dogs and four cats with suspected or diagnosed gastric neoplasia then underwent helical hydro-CT followed by intravenous contrast medium administration. Focal thickening with moderate contrast enhancement was found in 10 dogs and 3 cats. The extent of the lesion was assessed easily in all these patients. Three dogs and one cat had a normal stomach wall. One dog had multifocal thickening of the antrum but no histopathologic diagnosis was made. Helical hydro-CT, followed by intravenous contrast medium administration, is a simple technique for assessing the stomach wall.

Wide surgical resection or a marginal/incomplete resection followed by full-course radiation therapy is the current standard of care for canine soft tissue sarcoma. The purpose of this retrospective, descriptive, bi-institutional study was to determine the effectiveness and toxicity of a hypofractionated 5 × 6 Gy protocol on macroscopic canine soft tissue sarcoma in terms of progression-free interval (PFI) and overall survival (OS), and to identify prognostic factors for patient outcome. Dogs with macroscopic soft tissue sarcoma irradiated with 5 × 6 Gy were eligible for the study. Progression-free interval and OS were compared with respect to different tumor and patient characteristics by the Kaplan-Meier method and multivariable Cox regression analysis. Fifty dogs with macroscopic disease were included. All dogs received the same radiation therapy protocol; part of the group (n = 20) received postradiation metronomic chemotherapy. Median PFI for all cases was 419 days (95% confidence interval (CI): 287-551) and median OS was 513 days (95% CI: 368-658). Dogs with tumors on the limbs had significantly longer PFI and OS, compared with head or trunk. Increasing tumor burden decreased OS. The addition of metronomic chemotherapy yielded a significantly longer OS (757 days (95% CI: 570-944) compared with dogs that did not receive systemic treatment (286 days (95% CI: 0-518), (P = 0.023)), but did not influence progression-free interval. Toxicity was low throughout all treatments. The 5 × 6 Gy radiation therapy protocol was well tolerated and provided long PFI and OS in dogs with macroscopic soft tissue sarcoma.

Carcinomas represent two-thirds of canine nasosinal neoplasms. Although radiation therapy (RT) is the standard of care, the incidence of local recurrence following treatment is high. Cyclooxygenase-isoform-2 (COX-2) is expressed in 71-95% of canine nasal carcinomas and has been implicated in tumor growth and angiogenesis. Accordingly, COX-2 inhibition seems rational to improve outcome. Dogs with histologically confirmed, previously untreated nasal carcinomas were randomized to receive the combination of a selective COX-2 inhibitor (firocoxib) and palliative RT (Group 1) or RT and placebo (Group 2). Patients were regularly monitored with blood tests, urinalysis, and computed tomography. Pet owners were asked to complete monthly a quality-of-life questionnaire. Twenty-four dogs were prospectively enrolled. According to Adams modified system, there were five stage 1, five stage 2, three stage 3, and 11 stage 4 tumors. Two dogs had metastases to regional lymph nodes. Median progression-free interval and overall survival were 228 and 335 days in Group 1 (n = 12) and 234 and 244 days in Group 2 (n = 12). These differences were not statistically significant. The involvement of regional lymph nodes was significantly associated with progression-free interval and overall survival (P = 0.004). Quality of life was significantly improved in Group 1 (P = 0.008). In particular, a significant difference was observed for activity and appetite. Although not providing a significant enhancement of progression-free interval and overall survival, firocoxib in combination with RT is safe and improved life quality in dogs with nasal carcinomas.

Unresectable nodular and diffuse hepatocellular carcinoma (HCC) have a poor prognosis with limited treatment options. Systemic traditional chemotherapy has been only rarely reported, with unsatisfactory results. The aim of this prospective, non-randomized, non-blinded, single center clinical trial was to investigate safety profile, objective response rate, time to progression and overall survival of sorafenib in comparison with metronomic chemotherapy (MC) consisting of thalidomide, piroxicam and cyclophosphamide in dogs with advanced, unresectable HCC. Between December 2011 and June 2017, 13 dogs were enrolled: seven received sorafenib, and six were treated with MC. Median time to progression was 363 days (95% CI, 191–535) in dogs treated with sorafenib versus 27 days (95% CI, 0–68) in dogs treated with MC (p = 0.044). Median overall survival was 361 days (95% CI, 0–909) in dogs receiving sorafenib, while 32 days (95% CI, 0–235) in those receiving MC (p = 0.079). Sorafenib seems to be a good candidate for the treatment of dogs with advanced HCC, due to a benefit in disease control and an acceptable safety profile, offering a good basis on which new randomized prospective clinical trials should be undertaken to compare the efficacy and drawback of sorafenib versus MC or traditional chemotherapy.

Recently, a multimodal approach to oral squamous cell carcinoma (SCC) in cats, combining medical treatment and accelerated radiation therapy, showed a substantial outcome improvement in a small pilot study. Herein we retrospectively review 51 cats with unresectable, histologically confirmed oral SCC and a complete initial staging work‐up: cats in group A (n = 24) received medical anti‐angiogenic treatment consisting of bleomycin, piroxicam and thalidomide, cats in group B (n = 27) received the anti‐angiogenic treatment and concurrent accelerated hypofractionated radiation therapy with 48Gy delivered in 10 fractions. Overall median progression‐free interval (PFI) was poor with 70 days (95% CI: 48;93). In the irradiated cats (group B), however, PFI was significantly longer with 179 days (95% CI: 58;301) days, vs 30 days (95% CI: 23;38) in medically only treated cats (P < .001). Overall median overall survival (OS) was 89 days (95% CI: 55;124), again significantly longer in the irradiated cats (group B) with 136 (95% CI: 40;233) vs 38 days (95% CI: 23;54) (P < .001). In 8 of the 27 (29.6%) cats in group B, however, severe toxicity (grade 3) occurred. Neither onset nor severity of toxicity could be associated with any of the tested variables, including anatomic site, tumour size, clinical stage and duration of neoadjuvant medical treatment. Given the potential severe acute effects and the impact on quality of life after chemo‐radiotherapy, owners must be clearly informed about the risks of treatment. With the overall poor outcome and high occurrence of acute toxicity, we cannot recommend the use of this accelerated radiation protocol combined with anti‐angiogenic therapy for oral SCC in cats.