Outcome in dogs with advanced (stage 3b) anal sac gland carcinoma treated with surgery or hypofractionated radiation therapy

Stage 3b anal sac gland carcinoma (ASGC) can be life‐threatening. A surgical approach is not always possible or may be declined. Dogs with stage 3b ASGC treated with surgery or conformal radiation therapy (RT) with 8 × 3.8 Gy (total dose 30.4 Gy, over 2.5 weeks) were retrospectively evaluated. Patient characteristics, median progression‐free interval (PFI) and median survival time (MST) were compared. Twenty‐eight dogs were included; 15 underwent surgery, 13 underwent RT. At the time of presentation, 21% showed life‐threatening obstipation and 25% showed hypercalcaemia. PFI and MST for surgery cases were 159 days (95% CI: 135–184 days) and 182 days (95% CI: 146–218 days), both significantly lower than for RT cases with 347 days (95% CI: 240–454 days) and 447 days (95% CI: 222–672 days), (P = 0.01, P = 0.019). Surgery as well as RT led to a fast relief of symptoms. PFI and survival of surgical patients were significantly inferior to that of a comparable patient group treated with conformal hypofractionated RT.     

Genome-wide association study of swine farrowing traits. Part I: Genetic and genomic parameter estimates

The primary objective of this study was to determine genetic and genomic parameters among swine (Sus scrofa) farrowing traits. Genetic parameters were obtained using MTDFREML. Genomic parameters were obtained using GENSEL. Genetic and residual variances obtained from MTDFREML were used as priors for the Bayes C analysis of GENSEL. Farrowing traits included total number born (TNB), number born alive (NBA), number born dead (NBD), number stillborn (NSB), number of mummies (MUM), litter birth weight (LBW), and average piglet birth weight (ABW). Statistically significant heritabilities included TNB (0.09, P = 0.048), NBA (0.09, P = 0.041), LBW (0.20, P = 0.002), and ABW (0.26, P < 0.0001). Statistically significant genetic correlations included TNB-NBA (0.97, P < 0.0001), TNB-LBW (0.74, P < 0.0001), NBA-LBW (0.56, P < 0.0017), NSB-LBW (0.87, P < 0.0395), and LBW-ABW (0.63, P < 0.0002). Genetic parameters are similar to others found in the literature. The proportion of phenotypic variance explained by genomic markers (GP) generated by GENSEL was TNB (0.04), NBA (0.06), NBD (0.00), NSB (0.01), MUM (0.00), LBW (0.11), and ABW (0.31). Limited information is available in the literature about genomic parameters. Only the GP estimate for NSB is significantly lower than what has been published. The GP estimate for ABW is greater than the estimate for heritability found in this study. Other traits with significant heritability had GP estimates half the value of heritability. This research indicates that significant genetic markers will be found for TNB, NBA, LBW, and ABW that will have either immediate use in industry or provide a roadmap to further research with fine mapping or sequencing of areas of significance. Furthermore, these results indicate that genomic selection implemented at an early age would have similar annual progress as traditional selection, and could be incorporated along with traditional selection procedures to improve genetic progress of litter traits.     

Survival analysis of dogs with advanced primary lung carcinoma treated by metronomic cyclophosphamide,piroxicam and thalidomide

Unresectable or metastatic (advanced) primary pulmonary carcinoma (PPC) represents a therapeutic challenge where surgery may be contraindicated and the therapeutic role of maximum‐tolerated dose (MTD) chemotherapy remains uncertain. This study was undertaken to explore the impact of metronomic chemotherapy (MC) in dogs with advanced PPC. Previously untreated dogs with advanced (T3 or N1 or M1) PPC, with complete staging work‐up and follow‐up data, receiving MC (comprising low‐dose cyclophosphamide, piroxicam and thalidomide), surgery, MTD chemotherapy or no oncologic treatment were eligible for inclusion. For all patients, time to progression (TTP) and survival time (ST) were evaluated. Quality‐of‐life (QoL) was only evaluated in patients receiving MC. To assess QoL, owners of dogs receiving MC were asked to complete a questionnaire before and during treatment. Ninety‐one dogs were included: 25 received MC, 36 were treated with surgery, 11 with MTD chemotherapy and 19 received no treatment. QoL was improved in dogs receiving MC. Median TTP was significantly longer in patients receiving MC (172 days) than patients undergoing surgery (87 days), receiving MTD chemotherapy (22 days), or no oncologic treatment (20 days). Median ST was similarly longer in patients receiving MC (139 days) than those undergoing surgery (92 days), MTD chemotherapy (61 days) and no oncologic treatment (60 days). In dogs with advanced PPC, MC achieved a measurable clinical benefit without significant risk or toxicity. This makes MC a potential alternative to other recognized management approaches.     

Efficacy and side effects of radiation therapy in comparison with radiation therapy and temozolomide in the treatment of measurable canine malignant melanoma

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 radiation therapy (RT) and RT with post‐radiation temozolomide in dogs with chemotherapy‐naïve, measurable MM. RT consisted of 5 × 6 Gy fractions over 2.5 weeks. Dogs whose owners wished to pursue chemotherapy received adjuvant oral temozolomide (60 mg m^?2 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 coarse fractionated RT.     

Estimates of genetic parameters for kyphosis in two crossbred swine populations

Genetic parameters for degree of kyphosis were estimated from a Duroc-Landrace F(2) population (n = 316) and from a composite population (line C) composed of Duroc, Large White, and 2 sources of Landrace (n = 1,552). Live presentation did not indicate kyphosis in pigs or sows. Degree of kyphosis was measured by scoring the shape of the vertebral column of split carcasses on a scale from 0 (normal) to 3 (severe). Of the animals slaughtered, 75.6 and 68.9% were normal, 11.1 and 23.3% were mild, 11.1 and 6.2% were moderate, and 2.2 and 1.5% were severe in F(2) and line C, respectively. Fixed effects of age, sex, number of ribs, number of lumbar vertebrae, number of nipples, carcass length, and HCW were not significantly associated (P > 0.10) with kyphosis score when using linear models. Estimated heritabilities for kyphosis score were 0.30 and 0.32 in F(2) and line C, respectively, when using an animal model. Estimated genetic correlations between kyphosis score and number of ribs, number of lumbar vertebrae, number of nipples, carcass length, and HCW were 0.05, -0.13, 0.00, 0.05, and 0.03, respectively. Selection to decrease kyphosis should be effective and would not be expected to affect the number of ribs, lumbar vertebrae, nipples, or carcass length. In addition, selection for growth should not affect the incidence of kyphosis.     

Clinical assessment of repeated propofol-associated anesthesia in cats

OBJECTIVE: To assess the effects of repeated episodes of propofol-associated anesthesia on quality of recovery from anesthesia, clinical status, and erythrocyte physiology in cats. DESIGN: Original study. ANIMALS: 37 cats undergoing short-duration anesthesia for radiotherapy. PROCEDURES: Twice daily on 5 consecutive days, 13 cats with squamous cell carcinoma of the nasal planum (group 1) underwent anesthesia: first via administration of propofol or a midazolam (0.2 mg/kg [0.09 mg/lb])-propofol combination and then via administration of ketamine and midazolam each day (latter data were not analyzed). During a 19-day period, 24 cats with vaccine associated sarcoma (group 2) were anesthetized 12 times with propofol or a midazolam-propofol combination. Anesthesia was maintained with propofol in both groups. Hematologic analysis was performed before, during, and on completion of radiotherapy; changes in Hct and hemoglobin concentration between groups were compared. RESULTS: Mean duration of anesthesia was 8.1 minutes (range, 5 to 20 minutes); no adverse events were detected during recovery. Total dose of propofol administered did not differ between groups 1 (6.34 mg/kg [2.88 mg/lb]) and 2 (4.71 mg/kg [2.14 mg/lb]). Midazolam administration decreased the propofol dose by 26%. Overall decreases from baseline in Hct and hemoglobin concentration were not significantly different between the 2 groups, nor clinically important; however, compared with baseline, values in group 2 were significantly lower after 6 and 12 anesthetic episodes for both protocols. Heinz bodies were identified in low numbers in both groups during radiotherapy. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that repeated propofol-associated short-duration anesthesia does not lead to clinically relevant hematologic changes in cats undergoing short-duration radiotherapy.     

An Open‐label Phase 1 Dose‐escalation Clinical Trial of a Single Intravenous Administration of Gemcitabine in Dogs with Advanced Solid Tumors

Background

A broad range of gemcitabine dosages have been used in dogs.

Hypothesis/Objectives

To determine maximally tolerated dose (MTD), dose‐limiting toxicity (DLT), and preliminary antitumor activity of intravenous administration of gemcitabine in dogs with advanced solid tumors.

Animals

Twenty‐two client‐owned dogs.

Methods

Dogs with advanced cancer were prospectively enrolled in an open‐label Phase 1 study of gemcitabine. Gemcitabine was administered as a 30‐minute intravenous bolus starting at 800 mg/m², using escalation of 50 mg/m² increments with 3 dogs per dose level. MTD was established based on the number of dogs experiencing DLT assessed after 1 cycle. Treatment continued until disease progression or unacceptable toxicosis. Additional dogs were enrolled at MTD to better characterize tolerability, and to assess the extent and duration of gemcitabine excretion.

Results

Twenty‐two dogs were treated at 4 dose levels, ranging from 800 to 950 mg/m². Neutropenia was identified as DLT. MTD was 900 mg/m². DLT consisting of grade 4 febrile neutropenia was observed at 950 mg/m² in 2 dogs. There were no nonhematologic DLTs. Twenty dogs received multiple doses, and none had evidence of severe toxicosis from any of their subsequent treatments. At 900 mg/m², 2 complete and 5 partial responses were observed in dogs with measurable tumors. The amount of gemcitabine excreted in urine decreased over time, and was undetectable after the first 24 hours.

Conclusions and Clinical Importance

The recommended dose of gemcitabine for future Phase 2 studies is weekly 900 mg/m². In chemotherapy‐naïve dogs with advanced solid tumor this dose level merits further evaluation.     

Ki67 reactivity in nasal and periocular squamous cell carcinomas in cats treated with electron beam radiation therapy

Squamous cell carcinomas of sparsely haired skin are relatively common tumors in cats, and these tumors likely exhibit a rapid growth rate. Thus, we evaluated response and duration of response in relation to the Ki67 proliferative reactivity in such tumors. Seventeen cats with confirmed squamous cell carcinomas and treated with an accelerated, hypofractionated electron beam radiation protocol were included in the study. For all of them histologic grading, Ki67 reactivity, response, and disease-free interval (DFI) were evaluated. Response to therapy was excellent (94% complete response rate) with a median DFI of 414 days. Only moderate acute and few long-term adverse effects were seen. Cats with tumors with a low Ki67 reactivity had markedly shorter DFIs than cats with tumors with high Ki67 reactivity. We concluded that an accelerated, hypofractionated electron beam radiation therapy protocol is well suited for feline squamous cell carcinomas. The protocol appears especially efficacious in tumors with a high Ki67 reactivity.     

Dosimetric benefit of adaptive radiotherapy in the neoadjuvant management of canine and feline thymoma—An exploratory case series

While surgery is the treatment of choice for thymomas, complete excision is not possible in a significant proportion of cases. For these patients, radiotherapy can be used as neoadjunctive, post‐operative adjunctive or sole therapy. During radiotherapy, rapid biological clearance of tumour cells is often observed, requiring adaptation of the treatment plan. Adaptive radiation therapy (RT) is a dynamic process, whereby the treatment plan is altered throughout the treatment course due to changes in morphologic, functional or positioning changes. With the hypothesis, that individually adapted replanning will massively reduce the dose to organs at risk (OAR) in a fast‐changing environment such as a rapidly responding thymoma, the dosimetric impact of adaptive treatment planning in 5 patients with large thymoma was measured. In all patients rapid tumour‐shrinkage of the gross tumour volume was observed after 1 week of therapy, with a mean shrinkage of 31.0% ± 15.2%, or a tumour regression of 5.2% per day. In consequence, there was a considerable change in position of organs such as heart and lung, both of them moving cranially into the high dose area upon tumour regression. After mid‐therapy replanning, the dose to OAR was significantly reduced, with ?18.2% in the mean heart dose and ?27.9% in the V20 lung dose. Adaptive planning led to a significantly reduced radiation dose and hence protection of OAR for these patients. It can be concluded that adaptive replanning should be considered for canine and feline thymoma patients receiving fractionated RT.     

Cover Image,Volume 16, Issue 2

The cover image, by S. Dressel et al., is based on the Original Article Novel hyperthermia applicator system allows adaptive treatment planning: Preliminary clinical results in tumour‐bearing animals, DOI: 10.1111/vco.12340