ABSTRACT
Palliative chemotherapy options for dogs with macroscopic non-osseous mesenchymal tumours are limited. The purpose of this study was to assess the response rate of these tumours to carboplatin chemotherapy. Medical records of 28 dogs treated with carboplatin for macroscopic mesenchymal neoplasia between 1990 and 2022 were retrospectively reviewed. Sixteen dogs with soft tissue sarcoma and 12 dogs with haemangiosarcoma were included. Responses observed included one complete response and three partial responses, for an overall response rate of 14.2% (4/28) and median time to progression of 42 days (range 21-259 days). Responses were only seen in patients with haemangiosarcoma, for a response rate of 33.3% (4/12) and median time to progression for responders of 103 days (range 39-252 days). Median time to progression for dogs with metastatic disease was similar to those with only local disease (distant median: 44 days; local median: 23 days, p = 0.56). Dogs with chemotherapy-naïve disease were compared to dogs having received previous chemotherapy treatment and had a median time to progression of 75 days and 40.5 days respectively (p = 0.13). Twenty-two dogs experienced 48 adverse events, with most being grade 1 or 2 (79%). Carboplatin was well tolerated, with variable macroscopic anti-tumour activity and short response duration. Carboplatin may be an acceptable rescue option for dogs with macroscopic haemangiosarcoma, especially those patients that cannot receive doxorubicin.
Subject(s)
Antineoplastic Agents , Dog Diseases , Hemangiosarcoma , Humans , Dogs , Animals , Carboplatin/adverse effects , Antineoplastic Agents/adverse effects , Hemangiosarcoma/veterinary , Retrospective Studies , Dog Diseases/pathology , Treatment Outcome , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
Canine mast cell tumors (MCTs) have highly variable clinical behavior, and predicting outcomes in individual dogs remains challenging. Many studies combine dogs with varying tumor grades, clinical stage, or treatments, confounding those results. The purpose of this retrospective study was to determine outcome and prognostic factors in a specific subset of dogs with high-grade, stage 2, cutaneous MCTs treated with adequate local control via surgery with or without radiation therapy and adjuvant cytotoxic chemotherapy. Seventeen dogs met the inclusion criteria, and the median survival time was 259 days. Development of local recurrence, tumor location, and presence of ulceration were all associated with shorter survival times. Tumor size, mitotic count, chemotherapy protocol, lymph node classification, and radiation therapy were not significantly associated with outcome. In this study, a specific population of dogs characterized by high-grade MCTs with local lymph node metastasis who received aggressive local and systemic therapy had a median survival of about 8.5 mo. Dogs with ulcerated tumors, recurrent tumors, or tumors located on the head had a worse outcome despite aggressive therapy. These results may serve as a basis of comparison for future research exploring alternative treatment combinations in this specific population of dogs.
Subject(s)
Dog Diseases , Dogs , Animals , Dog Diseases/therapy , Mast Cells , Retrospective Studies , Aggression , Antineoplastic Combined Chemotherapy ProtocolsABSTRACT
Renal carcinomas (RC) are uncommonly encountered in feline medicine. Limited information regarding clinical presentation and postoperative outcomes is available. The purpose of this multi-institutional, retrospective study was to describe the presenting features and clinical outcomes of cats with RC undergoing nephrectomy. Thirty-six client-owned cats were included. Medical records from participating institutions were searched to identify cats that had a histopathologic diagnosis of RC and underwent nephrectomy from January 2001 to October 2021. The most common presenting complaints were weight loss (36.1%) and hyporexia (30.6%). Based on preoperative imaging and intraoperative findings, eight cats had suspected metastasis at the time of surgery (22.2%). Twenty-eight cats survived to discharge (77.8%). Median progression free interval (PFI) could not be determined, as only six cats developed suspected recurrence (16.7%) and seven cats developed suspected metastasis (19.4%). The all-cause median survival time (MST) was 203 days (95% confidence interval [CI]: 84, 1379 days). When cases that died prior to discharge were excluded, MST increased to 1217 days (95% CI: 127, 1641 days). One-year, two-year, and three-year survival rates were all 40.4%. Neither renal tumour histologic subtype nor the presence of preoperative azotemia, anaemia, erythrocytosis, haematuria, or suspected metastasis at diagnosis were found to influence survival. For cats surviving to discharge, prolonged survival times were possible. Further studies are necessary to elucidate other potential prognostic factors, the utility of postoperative adjuvant treatment, and to identify cats at-risk of mortality in the perioperative period.
Subject(s)
Carcinoma, Renal Cell , Cat Diseases , Kidney Neoplasms , Cats , Animals , Carcinoma, Renal Cell/surgery , Carcinoma, Renal Cell/veterinary , Retrospective Studies , Treatment Outcome , Nephrectomy/veterinary , Kidney Neoplasms/surgery , Kidney Neoplasms/veterinary , Cat Diseases/surgeryABSTRACT
Cyclophosphamide (CP) is an alkylating agent commonly included in multi-drug treatment protocols for canine cancer. As a prodrug, CP requires hepatic metabolism for activation to the intermediate compound 4-hydroxycyclophosphamide (4-OHCP) which then spontaneously forms alkylating phosphoramide mustard. CP is frequently administered in a fractionated manner, with the total dose given over multiple days. CP is reported to cause auto-induction of metabolism in humans, with faster CP clearance and relatively increased 4-OHCP formation following fractionated versus bolus dosing, however canine pharmacokinetic studies of CP dose fractionation are lacking. The study objective was to evaluate the pharmacokinetics of fractionated oral CP dosing at a dose of 200-250 mg/m2 over 3 to 4 days in a prospectively identified population of cancer-bearing dogs. Plasma concentrations of CP and 4-OHCP were measured by ultra-high performance liquid chromatography tandem-mass spectrometry in eight dogs following the first and last doses to assess for auto-induction of CP metabolism. No significant difference in the rate of CP elimination between first and last doses were detected (0.73 ± 0.46 vs. 1.22 ± 0.5 h-1 ; p = .125). Additionally, no significant difference in dose-normalized 4-OHCP exposure was identified between first and last doses (5.9 ± 2.1 vs. 7.9 ± 6.4 h × ng/ml; p = .936). These results suggest that fractionated dosing may not increase exposure to the active metabolite of CP in dogs as it does in humans. As such, standard bolus dosing and fractionated dosing may be equivalent in terms of bio-activation of CP in dogs administered a dose of 200-250 mg/m2 .
Subject(s)
Dog Diseases , Lymphoma, Non-Hodgkin , Neoplasms , Humans , Dogs , Animals , Dog Diseases/drug therapy , Cyclophosphamide , Neoplasms/veterinary , Lymphoma, Non-Hodgkin/veterinary , Area Under CurveABSTRACT
OBJECTIVE: To establish the pharmacokinetics of a single 2-mg oral dose of chlorambucil in cats with indolent lymphoproliferative malignancies. ANIMALS: 24 client-owned cats. PROCEDURES: Cats were assigned to 1 of 4 groups, with each group having a total of 3 sample collection time points over 12 hours after receiving a single 2-mg oral dose of chlorambucil. Each time point combined to generate 6 full patient plasma chlorambucil concentration-time curves from the 24 cats. Chlorambucil treatment was continued every other day and a single, variably timed sample collection was obtained on day 14. Population parameter estimates were obtained by nonlinear mixed-effects modeling. Covariates investigated included age, sex, baseline serum cobalamin, study location, weight, and body condition score. RESULTS: Chlorambucil administered orally to cats was found to have a peak plasma concentration of approximately 170 ng/mL (SE, 31.1 ng/mL), percent coefficient of variation (%CV) of 18.4% within 15 minutes, and a terminal half-life of 1.8 hours (SE, 0.21 hour; %CV, 12.4). At the 4-hour mark, a smaller secondary peak in plasma chlorambucil was found. Day 14 samples were similar to those of the initial dose. No covariates showed a significant effect in the population model. CLINICAL RELEVANCE: In these cats, chlorambucil at a 2-mg dose administered every other day undergoes rapid gastrointestinal absorption and plasma clearance with no drug accumulation between doses. These data are critical to inform future work investigating the association of chlorambucil drug exposure with adverse events and outcome of cats with lymphoproliferative diseases.
Subject(s)
Cat Diseases , Neoplasms , Cats , Animals , Chlorambucil/therapeutic use , Kinetics , Area Under Curve , Gastrointestinal Absorption , Neoplasms/veterinary , Administration, OralABSTRACT
PURPOSE: Although recombinant human interleukin-15 (rhIL-15) has generated much excitement as an immunotherapeutic agent for cancer, activity in human clinical trials has been modest to date, in part due to the risks of toxicity with significant dose escalation. Since pulmonary metastases are a major site of distant failure in human and dog cancers, we sought to investigate inhaled rhIL-15 in dogs with naturally occurring lung metastases from osteosarcoma (OSA) or melanoma. We hypothesized a favorable benefit/risk profile given the concentrated delivery to the lungs with decreased systemic exposure. EXPERIMENTAL DESIGN: We performed a phase I trial of inhaled rhIL-15 in dogs with gross pulmonary metastases using a traditional 3+3 cohort design. A starting dose of 10 µg twice daily × 14 days was used based on human, non-human primate, and murine studies. Safety, dose-limiting toxicities (DLT), and maximum tolerated dose (MTD) were the primary objectives, while response rates, progression-free and overall survival (OS), and pharmacokinetic and immune correlative analyses were secondary. RESULTS: From October 2018 to December 2020, we enrolled 21 dogs with 18 dogs reaching the 28-day response assessment to be evaluable. At dose level 5 (70 µg), we observed two DLTs, thereby establishing 50 µg twice daily × 14 days as the MTD and recommended phase 2 dose. Among 18 evaluable dogs, we observed one complete response >1 year, one partial response with resolution of multiple target lesions, and five stable disease for an overall clinical benefit rate of 39%. Plasma rhIL-15 quantitation revealed detectable and sustained rhIL-15 concentrations between 1-hour and 6 hour postnebulization. Decreased pretreatment lymphocyte counts were significantly associated with clinical benefit. Cytotoxicity assays of banked peripheral blood mononuclear cells revealed significant increases in peak cytotoxicity against canine melanoma and OSA targets that correlated with OS. CONCLUSIONS: In this first-in-dog clinical trial of inhaled rhIL-15 in dogs with advanced metastatic disease, we observed promising clinical activity when administered as a monotherapy for only 14 days. These data have significant clinical and biological implications for both dogs and humans with refractory lung metastases and support exploration of combinatorial therapies using inhaled rhIL-15.
Subject(s)
Bone Neoplasms , Lung Neoplasms , Melanoma , Osteosarcoma , Animals , Dogs , Humans , Mice , Bone Neoplasms/drug therapy , Bone Neoplasms/veterinary , Interleukin-15/therapeutic use , Leukocytes, Mononuclear/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/veterinary , Melanoma/drug therapy , Melanoma/pathology , Melanoma/veterinary , Osteosarcoma/drug therapy , Osteosarcoma/veterinaryABSTRACT
Visceral leiomyosarcoma is well described in dogs, but information about non-visceral locations and prevalence is lacking. The diagnosis of leiomyosarcoma is challenging without a gold standard, and often includes the use of immunohistochemical (IHC) stains. We used defined histopathologic patterns, histochemical staining, and IHC staining for smooth muscle actin (SMA), desmin, and laminin to characterize suspected non-visceral leiomyosarcoma in dogs at a single academic institution. In a retrospective search, we identified 24 dogs with a definitive or suspected histologic diagnosis of leiomyosarcoma in a non-visceral location. Histopathology results and clinical details were obtained. Biopsy sections were reviewed by a single pathologist using standardized histologic criteria, including light microscopic appearance, immunohistochemistry (more than two-thirds of neoplastic cells labeled with SMA and desmin or laminin), and histochemical staining (minimal-to-mild matrix deposition by Masson trichrome). Of the 24 cases of possible non-visceral leiomyosarcomas, 4 were consistent with a definitive diagnosis of non-visceral leiomyosarcoma (3) or leiomyoma (1) based on the established criteria. Only the leiomyoma had more than two-thirds of neoplastic cells label with all 3 markers; all 3 leiomyosarcomas had more than two-thirds of neoplastic cells label with SMA and laminin. Our data highlight the uncommon nature of non-visceral leiomyosarcoma and the importance of IHC for their diagnosis. A definitive diagnosis could not be made based on SMA alone, and desmin was not useful in this cohort. Further studies are needed to clarify the histopathologic, IHC, and clinical features of canine non-visceral SMA-positive mesenchymal tumors.
Subject(s)
Dog Diseases , Leiomyoma , Leiomyosarcoma , Animals , Desmin , Dog Diseases/diagnosis , Dogs , Humans , Laminin , Leiomyoma/diagnosis , Leiomyoma/pathology , Leiomyoma/ultrastructure , Leiomyoma/veterinary , Leiomyosarcoma/diagnosis , Leiomyosarcoma/veterinary , Retrospective StudiesABSTRACT
Primary pulmonary histiocytic sarcoma (PHS) is a rare form of dendritic cell or macrophage neoplasia originating within the pulmonary parenchyma. There is limited literature describing prognosis in dogs with PHS receiving curative-intent treatment consisting of surgical excision and adjuvant chemotherapy. The primary objective of this study was to report outcomes in dogs with localized PHS treated with standardized local and systemic therapy. A secondary objective was to identify prognostic factors in this population. A multi-institutional retrospective study was performed and medical records including all surgical and histopathologic reports were retrospectively reviewed. For inclusion, dogs were required to have confirmed localized PHS and they must have undergone curative-intent surgery with resection of all gross primary tumour and enlarged tracheobronchial lymph nodes; additionally, they must have received curative-intent treatment with adjuvant single-agent CCNU chemotherapy. Twenty-seven dogs from six veterinary teaching hospitals and five private practices treated from 2008-2019 were included. The overall median survival time was 432 days. Higher CCNU dose was demonstrated to have a negative impact on survival on univariate, but not multivariable, analysis. Factors that were not found to be associated with survival on univariate analysis included body weight, breed, clinical signs at the time of diagnosis, hypoalbuminaemia, tumour size, lung lobe affected, lymph node metastasis, surgical margins and CCNU dose reductions. This study supports a favourable prognosis for dogs diagnosed with localized PHS treated with curative-intent surgery in addition to adjuvant CCNU chemotherapy and suggests that multimodal treatment may be advisable to attempt to prolong survival.
Subject(s)
Dog Diseases , Histiocytic Sarcoma , Lung Neoplasms , Animals , Dog Diseases/drug therapy , Dog Diseases/pathology , Dogs , Histiocytic Sarcoma/drug therapy , Histiocytic Sarcoma/veterinary , Lomustine/therapeutic use , Lung/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/veterinary , Retrospective Studies , Treatment OutcomeABSTRACT
OBJECTIVE: To describe the procedure of prostatic artery embolization (PAE) in dogs with prostatic carcinoma and to evaluate the short-term outcome for treated dogs. ANIMALS: 20 client-owned dogs with prostatic carcinomas between May 2014 and July 2017. PROCEDURES: In this prospective cohort study, dogs with carcinoma of the prostate underwent PAE with fluoroscopic guidance. Before and after PAE, dogs underwent CT and ultrasonographic examinations of the prostate, and each owner completed a questionnaire about the dog's clinical signs. Results for before versus after PAE were compared. RESULTS: Prostatic artery embolization was successfully performed in all 20 dogs. Tenesmus, stranguria, and lethargy were significantly less common 30 days after PAE (n = 2, 1, and 0 dogs, respectively), compared with before PAE (9, 10, and 6 dogs, respectively). Median prostatic volume was significantly less 30 days after PAE (14.8 cm3; range, 0.4 to 48.1 cm3; interquartile [25th to 75th percentile] range, 6.7 to 19.5 cm3), compared with before PAE (21.7 cm3; range, 2.9 to 77.7 cm3; interquartile range, 11.0 to 35.1 cm3). All dogs had a reduction in prostatic volume after PAE, with a median prostatic volume loss of 39.4% (95% CI, 20.3% to 59.3%). CONCLUSIONS AND CLINICAL RELEVANCE: Prostatic artery embolization was associated with decreased prostate volume and improved clinical signs in this cohort. The short-term response to PAE appears promising, and evaluation of the long-term impact on survival time is needed.
Subject(s)
Carcinoma , Dog Diseases , Embolization, Therapeutic , Prostatic Hyperplasia , Animals , Arteries , Carcinoma/veterinary , Dog Diseases/diagnostic imaging , Dog Diseases/therapy , Dogs , Embolization, Therapeutic/veterinary , Male , Prospective Studies , Prostatic Hyperplasia/therapy , Prostatic Hyperplasia/veterinary , Treatment OutcomeABSTRACT
Zoledronic acid (ZOL) is an intravenous bisphosphonate indicated for the use of hypercalcemia of malignancy and management of bony metastases. Its therapeutic effect lies in the targeting of malignant osteoclasts; however, administration can be associated with renal toxicity. The objective of this retrospective study was to evaluate the frequency and severity of acute kidney injury (AKI) following ZOL administration in a cohort of cancer-bearing dogs. A pharmacy search was conducted to identify dogs that received a dose of ZOL between June 2016 and July 2019. Inclusion criteria included baseline and post-treatment chemistry panels. Medical records were reviewed to obtain clinical data including signalment, dose, dosage, number of treatments administered, and changes in renal function. Forty-four dogs met the inclusion criteria. Median number of doses administered was three [interquartile range (IQR), 2-5]. The median highest creatinine value occurred after a median of one dose (IQR, 1-2 doses) compared with the median highest value of blood urea nitrogen, phosphorus, and potassium, which occurred after a median of two doses (IQR, 1-3). Six (13.6%) dogs developed an AKI, and one dog (2.3%) had progression of an existing azotemia after treatment with ZOL was initiated. Two dogs (4.5%) had ZOL treatment discontinued secondary to development of azotemia. Use of concurrent administration of non-steroidal anti-inflammatory drugs or anesthesia did not significantly increase the risk of AKI in this cohort of dogs. Acute kidney injury is observed infrequently in cancer-bearing dogs treated with ZOL and is generally mild to moderate in severity; discontinuation of ZOL due to AKI is uncommon.
ABSTRACT
Tumour stage has been demonstrated to have prognostic significance in canine oral malignant melanoma (OMM). Various evaluation techniques of positron emission tomography/computed tomography (PET/CT) have been reported for staging of head-and-neck tumours in people, but canine-specific data are limited, and reports for CT accuracy have been variable. In this prospective study, the head/neck of client-owned dogs with cytologically or histologically diagnosed OMM were imaged with 18 Fluorine-fluorodeoxyglucose (18 F-FDG) PET/ CT. Bilateral mandibular lymphadenectomy was performed for histopathologic assessment. Two evaluation techniques for CT and PET were applied by four independent observers. CT evaluation utilized both a standardized grading scheme and a subjective clinical interpretation. PET evaluation was first performed solely on 18 F-FDG-uptake in lymph nodes compared to background on a truncated scan excluding the oral cavity. Subsequently, the entire head/neck scan and standardized uptake value (SUV) measurements were available. Receiver operating characteristic analysis was performed with histopathology as gold standard. Twelve dogs completed the study and metastatic OMM was identified in six mandibular lymph nodes from five dogs. Of the CT-interpretation techniques, use of clinical grading performed best (sensitivity = 83% and specificity = 94%). Both PET techniques resulted in 100% sensitivity, but primary tumour site evaluation and use of SUV increased specificity from 78% to 94%. The SUVmax cut-point, 3.3, led to 100% sensitivity and 83% specificity. In this population of dogs, PET appeared to be highly sensitive but at risk of being less specific without use of appropriate parameters and thresholds.
Subject(s)
Dog Diseases , Melanoma , Mouth Neoplasms/veterinary , Positron Emission Tomography Computed Tomography , Animals , Dog Diseases/diagnostic imaging , Dogs , Fluorodeoxyglucose F18 , Lymph Nodes/diagnostic imaging , Lymphatic Metastasis/diagnostic imaging , Melanoma/diagnostic imaging , Melanoma/veterinary , Mouth Neoplasms/diagnostic imaging , Positron Emission Tomography Computed Tomography/veterinary , Prospective Studies , Radiopharmaceuticals , Sensitivity and Specificity , Skin Neoplasms , Melanoma, Cutaneous MalignantABSTRACT
BACKGROUND: Azotemia occurs in cats administered doxorubicin, but risk factors have not been explored. OBJECTIVE: To determine incidence of progressive increases in serum creatinine concentration in cats with cancer receiving doxorubicin in single or multiagent chemotherapy protocols and associated risk factors. ANIMALS: Seventy cats with cancer receiving doxorubicin. METHODS: A retrospective study (2007-2017) of cats with indices of kidney function recorded before and after doxorubicin administration was reviewed. Cats diagnosed with kidney injury because of known etiologies other than possible doxorubicin toxicosis were excluded. Variables were compared to identify risk factors. RESULTS: Mean age (±SD) was 10.9 years (±3.2). Cancer types included lymphoma (n = 36), sarcoma (n = 19) and carcinoma (n = 14). Chronic kidney disease was present in 29/70 (41%) cats before receiving doxorubicin. Of 70 cats, 24 (34%) developed an increase in serum creatinine concentration ≥0.3 mg/dL and 10 (14%) had an increase ≥50% from baseline. Mean time to increases in serum creatinine concentration ≥0.3 mg/dL from first administration of doxorubicin was 119.3 days (±89.7), with mean 2.8 (±1.2) doses administered. Neutropenia or anemia during chemotherapy and number of radiation therapy treatments under general anesthesia were risk factors for increases in serum creatinine concentration (P < .05). Cats receiving single agent doxorubicin had a higher likelihood of an increase in serum creatinine concentration ≥0.3 mg/dL from baseline than cats receiving CHOP-based chemotherapy protocols (OR 20.0, 95% CI 2.9-100). CONCLUSIONS AND CLINICAL IMPORTANCE: Progressive increases in serum creatinine concentration from baseline were common in cats receiving doxorubicin and associated risk factors were identified.
Subject(s)
Cat Diseases , Neoplasms , Animals , Cat Diseases/chemically induced , Cats , Creatinine , Doxorubicin/adverse effects , Neoplasms/drug therapy , Neoplasms/veterinary , Retrospective Studies , Risk FactorsABSTRACT
Squamous cell carcinoma (SCC) is a frequently recognized dermal tumour in dogs and has been described as a common pathology induced by solar ultraviolet radiation exposure. Little has been published about this neoplasm with regard to clinical features and outcome in dogs. This retrospective study included 193 dogs from a single institution histopathologically diagnosed with SCC of the dermis. Thirty-eight percent of all dogs had documented histopathologic actinic change. The overall median survival time was 1004 days, with the population demonstrating actinic change associated with a significantly longer survival time (median 1359 days, range 16-3530 days) compared to dogs without actinic change (median 680 days, range 16-3066 days) and this achieved significance on multivariate analysis (hazard ratio 0.42, 95% confidence interval 0.193-0.930, P = 0.032). These data demonstrate increased survival of dogs with SCC demonstrating actinic change over those with non-actinic SCCs, and purports long-term survival for these animals. Dogs received a variety of treatment approaches as a retrospective study, and future prospective studies will be necessary to investigate whether adjunct therapies such as radiation or chemotherapy offer improvement in survival for dermal SCC in the dog.
Subject(s)
Carcinoma, Squamous Cell/veterinary , Dog Diseases/pathology , Keratosis, Actinic/veterinary , Skin Neoplasms/veterinary , Animals , California , Carcinoma, Squamous Cell/etiology , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Comorbidity , Dog Diseases/etiology , Dog Diseases/therapy , Dogs , Female , Keratosis, Actinic/etiology , Keratosis, Actinic/pathology , Male , Multivariate Analysis , Proportional Hazards Models , Retrospective Studies , Schools, Veterinary , Skin Neoplasms/etiology , Skin Neoplasms/pathology , Skin Neoplasms/therapy , Survival , Treatment Outcome , Ultraviolet Rays/adverse effectsABSTRACT
Immunotherapeutic strategies have shown promise for the treatment of canine osteosarcoma (cOSA). Very little is known about the immune microenvironment within cOSA, however, limiting our ability to identify potential immune targets and biomarkers of therapeutic response. We therefore prospectively assessed the disease-free interval (DFI) and overall survival time (ST) of 30 dogs with cOSA treated with amputation and six doses of adjuvant carboplatin. We then quantified lymphocytic (CD3+, FOXP3+) and macrophage (CD204+) infiltrates within the primary tumours of this cohort using immunohistochemistry, and evaluated their association with outcome. Overall, the median DFI and ST were 392 and 455 days, respectively. The median number of CD3+ and FOXP3+ infiltrates were 45.8 cells/mm2 (4.6-607.6 cells/mm2 ) and 8.5 mm2 (0-163.1 cells/mm2 ), respectively. The median area of CD204+ macrophages was 4.7% (1.3%-23.3%), and dogs with tumours containing greater than 4.7% CD204+ macrophages experienced a significantly longer DFI (P = 0.016). Interestingly, a significantly lower percentage of CD204+ macrophages was detected in cOSA arising from the proximal humerus compared to other appendicular bone locations (P = 0.016). Lymphocytic infiltrates did not appear to correlate with outcome in cOSA. Overall, our findings suggest that macrophages may play a role in inhibiting cOSA progression, as has been suggested in human osteosarcoma.
Subject(s)
Bone Neoplasms/veterinary , Dog Diseases/pathology , Lymphocytes/pathology , Macrophages/pathology , Osteosarcoma/veterinary , Animals , Bone Neoplasms/pathology , Dogs , Female , Humans , Male , Osteosarcoma/pathologyABSTRACT
BACKGROUND: A doxorubicin (DOX)-based chemotherapy protocol, CHOP, is the most effective treatment for canine high-grade B-cell lymphoma; however, the cost and time requirements associated with this protocol are not feasible for many pet owners. An alternative treatment option is the use of DOX, the most effective drug, in combination with prednisone. Prior studies with single-agent DOX included dogs with T-cell lymphoma, a known negative prognostic factor, which may have resulted in shorter reported survival times than if dogs with B-cell lymphoma were analyzed separately. The purpose of this study was to evaluate the outcome of dogs with high-grade B-cell lymphoma when treated with DOX and prednisone with or without L-asparaginase (L-ASP). Identification of prognostic factors was of secondary interest. RESULTS: Thirty-three dogs were included in the study; 31 dogs were evaluable for response with an overall response rate of 84%. The median progression free survival (PFS) and overall survival (OS) were 147 days and 182 days, respectively. The one-year survival fraction was 23%. No variable other than protocol completion was found to be significant for either PFS or OS including historical prognostic factors such as substage, thrombocytopenia, and body weight. CONCLUSIONS: Dogs with high-grade B-cell lymphoma treated with DOX and prednisone with or without L-ASP have similar response rates, PFS, and OS to prior studies that did not differentiate between lymphoma immunophenotype. This protocol is not a replacement for CHOP; however, it is an alternative if time and cost are factors, while providing therapeutic benefit greater than prednisone alone.
Subject(s)
Antibiotics, Antineoplastic/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Dog Diseases/drug therapy , Doxorubicin/therapeutic use , Lymphoma, B-Cell/veterinary , Prednisone/therapeutic use , Animals , Antibiotics, Antineoplastic/administration & dosage , Antineoplastic Agents, Hormonal/administration & dosage , Dog Diseases/mortality , Dogs , Drug Therapy, Combination/veterinary , Female , Kaplan-Meier Estimate , Lymphoma, B-Cell/drug therapy , Lymphoma, B-Cell/mortality , Male , Retrospective Studies , Treatment OutcomeABSTRACT
Curcumin has well-established anti-cancer properties in vitro, however, its therapeutic potential has been hindered by its poor bioavailability. Lipocurc is a proprietary liposome-encapsulated curcumin formulation that enables intravenous delivery and has been shown to reach its highest concentration within lung tissue. The goal of this study was to characterize the anti-cancer and anti-angiogenic activity of Lipocurc in vitro, in addition to evaluating Lipocurc infusions in dogs with naturally occurring cancer. We therefore evaluated the effect of Lipocurc, relative to free curcumin, on the viability of canine osteosarcoma, melanoma and mammary carcinoma cell lines, as well as the ability of Lipocurc to inhibit endothelial cell viability, migration and tube formation. We also undertook a pilot clinical trial consisting of four weekly 8-hour Lipocurc infusions in 10 cancer-bearing dogs. Tumour cell proliferation was inhibited by curcumin at concentrations exceeding those achievable in the lung tissue of dogs. Similarly, equivalent high concentrations of Lipocurc and curcumin also inhibited endothelial cell viability, migration and tube formation. Four out of six dogs completing planned infusions of Lipocurc experienced stable disease; however, no radiographic responses were detected.
Subject(s)
Antineoplastic Agents/therapeutic use , Curcumin/therapeutic use , Dog Diseases/drug therapy , Liposomes/therapeutic use , Neoplasms/veterinary , Animals , Antineoplastic Agents/administration & dosage , Cell Line, Tumor , Cell Movement/drug effects , Curcumin/administration & dosage , Dogs , Female , Inhibitory Concentration 50 , Liposomes/administration & dosage , Male , Neoplasms/drug therapy , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/veterinaryABSTRACT
OBJECTIVE To determine survival time and metastatic rate for dogs with early-stage anal sac adenocarcinoma (ASACA) treated with surgery alone and assess whether specific clinical, pathological, or immunohistochemical factors were predictive of outcome for those dogs. DESIGN Retrospective case series. ANIMALS 34 dogs with early-stage, nonmetastatic ASACA that were treated with surgery only. PROCEDURES Medical record databases of 2 referral hospitals were searched to identify dogs examined between 2002 and 2013 that had a diagnosis of nonmetastatic ASACA that was < 3.2 cm at its largest diameter. Only dogs that received surgical treatment alone were included in the study. For each dog, information extracted from the medical record included signalment, clinical and diagnostic test findings, tumor characteristics, and outcome. When available, archived tumor specimens were histologically reviewed and tumor characteristics were described; Ki-67 and E-cadherin expressions were evaluated by use of immunohistochemical methods. Clinical, pathological, and immunohistochemical factors were assessed for associations with survival time and tumor recurrence and metastasis rates. RESULTS Median survival time was 1,237 days. Seven dogs had tumor recurrence and 9 dogs developed metastatic disease at a median of 354 and 589 days, respectively, after primary tumor removal. Cellular pleomorphism was positively associated with development of metastatic disease. No other factors evaluated were associated with outcome. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated dogs with early-stage nonmetastatic ASACA generally had a favorable outcome following surgical removal of the primary tumor alone. Routine rectal examination may be a simple and useful method for detection of dogs with early-stage ASACA.
Subject(s)
Adenocarcinoma/veterinary , Anal Gland Neoplasms/surgery , Neoplasm Recurrence, Local/veterinary , Adenocarcinoma/surgery , Anal Gland Neoplasms/mortality , Anal Gland Neoplasms/pathology , Animals , Cadherins/metabolism , California , Dogs , Female , Immunohistochemistry/veterinary , Ki-67 Antigen/metabolism , Male , Neoplasm Recurrence, Local/surgery , Pathology, Clinical , Prognosis , Records/veterinary , Retrospective Studies , Survival Analysis , Treatment OutcomeABSTRACT
OBJECTIVE To evaluate potential associations between surgical approach and complication rate, progression-free survival time, and disease-specific survival time in cats with mammary adenocarcinoma. DESIGN Retrospective case series. ANIMALS 107 client-owned cats. PROCEDURES Medical records of cats that underwent surgical excision of mammary adenocarcinoma by means of a unilateral or bilateral (staged or single-session) mastectomy at 9 hospitals between 1991 and 2014 were reviewed. Relevant clinicopathologic data and details of surgical and adjuvant treatments were recorded. Outcome data were obtained, including postoperative complications, progression-free survival time, and disease-specific survival time. RESULTS Complications occurred in 12 of 61 (19.7%) cats treated with unilateral mastectomy, 5 of 14 (35.7%) cats treated with staged bilateral mastectomy, and 13 of 32 (40.6%) cats treated with single-session bilateral mastectomy. Complications were significantly more likely to occur in cats undergoing bilateral versus unilateral mastectomy. Median progression-free survival time was longer for cats treated with bilateral mastectomy (542 days) than for cats treated with unilateral mastectomy (289 days). Significant risk factors for disease progression included unilateral mastectomy, tumor ulceration, lymph node metastasis, and tumors arising in the fourth mammary gland. Significant risk factors for disease-specific death included lymph node metastasis and development of regional or distant metastasis. Among cats that did not develop metastasis, unilateral mastectomy was a significant risk factor for disease-specific death. Treatment with chemotherapy was associated with a significantly decreased risk of disease-specific death. CONCLUSIONS AND CLINICAL RELEVANCE Results supported bilateral mastectomy for the treatment of mammary adenocarcinoma in cats to improve progression-free and disease-specific survival time. Performing bilateral mastectomy in a staged fashion may help to decrease the complication rate.
Subject(s)
Adenocarcinoma/veterinary , Cat Diseases/surgery , Mammary Neoplasms, Animal/surgery , Mastectomy/veterinary , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Animals , Cat Diseases/pathology , Cats , Female , Mammary Neoplasms, Animal/pathology , Mastectomy/methods , Neoplasm Recurrence, Local/veterinary , Progression-Free Survival , Retrospective StudiesABSTRACT
The molecular mechanisms of acquisition of chemotherapy resistance in canine lymphoma have not been elucidated. The aim of the present study was to identify novel molecular mechanisms of chemotherapy resistance by a comprehensive analysis of changes in gene expression profiles (GEPs). Tumor samples were obtained from 10 dogs with lymphoma at chemotherapy sensitive and chemotherapy resistant phases. During chemotherapy resistance, the expression of genes associated with immune responses and inflammatory reactions was decreased compared to chemotherapy sensitive phases. In addition, 11 genes, with significant changes in expression (P<0.05), were extracted from seven dogs with chemotherapy resistant lymphoma. Further studies are needed to investigate the associations of these changes in GEPs with the acquisition of chemotherapy resistance in canine lymphoma.
Subject(s)
Dog Diseases/genetics , Drug Resistance, Neoplasm , Lymphoma, B-Cell/veterinary , Animals , Antineoplastic Agents/therapeutic use , Dog Diseases/drug therapy , Dogs , Female , Lymphoma, B-Cell/drug therapy , Lymphoma, B-Cell/genetics , Male , TranscriptomeABSTRACT
Fasting reduces gastrointestinal cellular proliferation rates through G1 cycle blockade and can promote cellular protection of normal but not cancer cells through altered cell signaling including down-regulation of insulin-like growth factor 1 (IGF-1). Consequently, the purpose of this study was to determine the effects of fasting on delayed-type chemotherapy-induced nausea and vomiting in dogs receiving doxorubicin. This prospective randomized crossover study involved intended administration of two doses of doxorubicin. Cancer-bearing dogs were randomized to be fasted for 24 hours beginning at 6 P.M. the night before the first or second doxorubicin administration, and all treatments were administered within an hour before or after 12 P.M. Dogs were fed normally before the alternate dose. Circulating IGF-1 concentrations were determined from serum samples obtained immediately before each doxorubicin treatment. Data from 35 doses were available from 20 dogs enrolled. Dogs that were fasted exhibited a significantly lower incidence of vomiting, when compared to fed dogs (10% compared to 67%, P = .020). Furthermore, among the 15 dogs that completed crossover dosing, vomiting was abrogated in four of five dogs that experienced doxorubicin-induced vomiting when fed normally (P = .050). No differences in other gastrointestinal, constitutional, or bone marrow toxicities or serum IGF-1 levels were observed.