Katherine A. Skorupski

Long‐term survival in dogs with localized histiocytic sarcoma treated with CCNU as an adjuvant to local therapy*

Histiocytic sarcoma (HS) is associated with a poor prognosis owing to the presence of metastasis at the time of diagnosis in most dogs. Improved outcome has been reported in several dogs with localized HS following local therapy, however, distant metastasis occurs in 70-91% of dogs suggesting that adjuvant systemic therapy is necessary. The purpose of this retrospective study was to describe clinical characteristics and outcome in dogs with localized HS treated with aggressive local therapy plus adjuvant CCNU chemotherapy. Data from 16 dogs were evaluated. The median disease-free interval was 243 days. Two dogs had local recurrence and eight dogs developed metastatic disease with a median time to relapse of 201 days in these 10 dogs. The median survival time for all 16 dogs was 568 days. These results support the recommendation for aggressive local therapy combined with adjuvant CCNU chemotherapy in dogs with localized HS.

CHOP chemotherapy for the treatment of canine multicentric T-cell lymphoma

Dogs with multicentric T-cell lymphoma are commonly treated with CHOP chemotherapy protocols that include cyclophosphamide, doxorubicin, vincristine and prednisone. The purpose of this study was to evaluate the use of CHOP chemotherapy for dogs with multicentric T-cell lymphoma. Identification of prognostic factors in this specific subset of dogs was of secondary interest. Twenty-three out of 24 dogs responded to CHOP chemotherapy and these dogs remained on the protocol for a median of 146 days. No variable was associated with progression free survival (PFS) including stage, substage, hypercalcemia or radiographic evidence of a cranial mediastinal mass. The median overall survival time (OST) for all dogs was 235 days. Dogs that were thrombocytopenic at presentation experienced a significantly longer OST (323 versus 212 days, P=0.01).

Temporal changes in characteristics of injection-site sarcomas in cats: 392 cases (1990–2006)

OBJECTIVE To evaluate changes in characteristics of feline injection-site sarcomas (ISSs) from 1990 through 2006. DESIGN Retrospective case series. ANIMALS 392 cats with a histologic diagnosis of soft tissue sarcoma, osteosarcoma, or chondrosarcoma at potential injection sites. PROCEDURES Classification and anatomic location of tumors and signalment of affected cats were compared between ISSs diagnosed before and after publication of the Vaccine Associated Feline Sarcoma Task Force vaccination recommendations in 1996. RESULTS From before to after publication of the vaccination recommendations, proportions of ISSs significantly decreased in the interscapular (53.4% to 39.5%) and right and left thoracic (10.2% to 3.6% and 9.1% to 1.3%, respectively) regions. On the other hand, proportions of ISSs significantly increased in the right thoracic limb (1.1% to 9.5%) and the combined regions of the right pelvic limb with right lateral aspect of the abdomen (12.5% to 25.0%) and the left pelvic limb with left lateral aspect of the abdomen (11.4% to 13.8%). Patterns of tumor classification and signalment did not change. CONCLUSIONS AND CLINICAL RELEVANCE Despite publication of the vaccination recommendations, a high proportion of tumors still developed in the interscapular region. There was also an increase in lateral abdominal ISSs, which are more difficult to treat and are likely attributable to aberrant placement of injections intended for the pelvic limbs. Veterinarians are complying with vaccination recommendations to some extent, but they need to focus on administering vaccines as distally as possible on a limb to allow for complete surgical margins if amputation of a limb is required.

Prospective Randomized Clinical Trial Assessing the Efficacy of Denamarin for Prevention of CCNU-Induced Hepatopathy in Tumor-Bearing Dogs

BACKGROUND Increases in liver enzymes occur in up to 86% of dogs receiving CCNU and can result in treatment delay or early discontinuation of treatment. Denamarin contains S-adenosylmethionine and silybin, both of which have been investigated as treatments for various liver diseases. HYPOTHESIS Dogs on CCNU receiving Denamarin have lower alanine aminotransferase (ALT) activity than dogs not receiving Denamarin. Dogs on Denamarin are less likely to require treatment delay because of hepatopathy and are more likely to complete their prescribed course of CCNU. ANIMALS Dogs with lymphoma, mast cell tumor, or histiocytic sarcoma that were prescribed CCNU with or without corticosteroids and with normal ALT activity were eligible for enrollment. METHODS Dogs were prospectively randomized to receive either concurrent Denamarin during CCNU chemotherapy or to receive CCNU alone. Liver-specific laboratory tests were run before each dose of CCNU. RESULTS Increased liver enzyme activity occurred in 84% of dogs receiving CCNU alone and in 68% of dogs on concurrent Denamarin. Dogs receiving CCNU alone had significantly greater increases in ALT, aspartate aminotransferase, alkaline phosphatase, and bilirubin and a significantly greater decrease in serum cholesterol concentrations than dogs receiving concurrent Denamarin. Dogs receiving CCNU alone were significantly more likely to have treatment delayed or discontinued because of increased ALT activity. CONCLUSIONS Increased liver enzyme activity occurs commonly in dogs receiving CCNU chemotherapy. These results support the use of concurrent Denamarin to minimize increased liver enzyme activity in dogs receiving CCNU chemotherapy. Denamarin treatment also increases the likelihood of dogs completing a prescribed CCNU course.

Carboplatin versus alternating carboplatin and doxorubicin for the adjuvant treatment of canine appendicular osteosarcoma: a randomized, phase III trial

Despite numerous published studies describing adjuvant chemotherapy for canine appendicular osteosarcoma, there is no consensus as to the optimal chemotherapy protocol. The purpose of this study was to determine whether either of two protocols would be associated with longer disease-free interval (DFI) in dogs with appendicular osteosarcoma following amputation. Dogs with histologically confirmed appendicular osteosarcoma that were free of gross metastases and underwent amputation were eligible for enrollment. Dogs were randomized to receive either six doses of carboplatin or three doses each of carboplatin and doxorubicin on an alternating schedule. Fifty dogs were included. Dogs receiving carboplatin alone had a significantly longer DFI (425 versus 135 days) than dogs receiving alternating carboplatin and doxorubicin (P = 0.04). Toxicity was similar between groups. These results suggest that six doses of carboplatin may be associated superior DFI when compared to six total doses of carboplatin and doxorubicin.

Clinical and Pharmacokinetic Characteristics of Intracavitary Administration of Pegylated Liposomal Encapsulated Doxorubicin in Dogs with Splenic Hemangiosarcoma

BACKGROUND Canine splenic hemangiosarcoma (HSA) is a fatal malignancy, and most affected dogs die within a few months of diagnosis. Most dogs present with signs from tumor rupture, resulting in hemoabdomen and intra-abdominal dissemination. The abdomen is also the main site of disease recurrence. HYPOTHESIS Intraperitoneal (IP) administration of doxorubicin will delay or prevent intra-abdominal tumor recurrence and prolong survival in dogs with HSA. ANIMALS Fourteen dogs with splenic HSA. METHODS A prospective, unmasked, uncontrolled clinical trial. After staging of disease status and splenectomy, pegylated liposomal encapsulated doxorubicin was administered intraperitoneally (1 mg/kg body weight) every 3 weeks for 4 cycles. All dogs were monitored for recurrence of HSA. Samples of plasma and abdominal fluid were collected for measurement of doxorubicin concentration and pharmacokinetic analysis. Nonlinear mixed-effect modeling was used to describe the pharmacokinetics of liposomal doxorubicin administered IP. RESULTS All 14 dogs died, 12 because of HSA and 2 from other causes. Postmortem examination was performed on 12 dogs. All 12 dogs died because of HSA-related causes and had hepatic metastases and hemoabdomen. The IP-treated dogs had fewer serosal, mesenteric, and omental metastases than historical controls treated with systemic doxorubicin. Results of the postmortem examination and pharmacokinetic analysis confirmed that IP delivery of doxorubicin resulted in an effective drug concentration with a clearance comparable with that after i.v. delivery. CONCLUSIONS AND CLINICAL IMPORTANCE IP pegylated liposomal encapsulated doxorubicin administration did not prevent intraabdominal recurrence of HSA in dogs.

ULTRASONOGRAPHY OF INTESTINAL MAST CELL TUMORS IN THE CAT

The sonographic features of intestinal mast cell tumors (MCT) were reviewed in 14 cats. The mean age was 13.4 ± 2.5 years. There were 16 focal intestinal tumors and one diffuse submucosal infiltrate. The most common pattern was focal, hypoechoic wall thickening that was noncircumferential and eccentric (9/16 tumors) or circumferential, asymmetric, and eccentric (5/16 tumors). Nine of the cats had lesions in the jejunum or duodenum, four were at the ileocecocolic junction, and one cat had a colonic mass. Six MCTs had altered but not loss of wall layering, and the most commonly affected layer on ultrasound examination was the muscularis propria. Nine cats had enlarged abdominal lymph nodes, and seven were due to metastatic disease. Metastatic disease was not routinely detected by ultrasound in the liver (1/4 cats) or the spleen (0/3 cats). Concurrent small cell (T cell) lymphoma was present in four of 14 cats (29%).

Outcome in dogs with surgically resected oral fibrosarcoma (1997-2008).

Oral fibrosarcoma (FSA) is a common oral tumour in dogs, and historically reported survival times after surgical excision range from 7.0 to 12.2 months with local recurrence rates of 32-57%. The purpose of this retrospective study was to report outcome in a cohort of dogs with oral FSA treated with surgical excision with or without adjuvant radiation therapy. Twenty-nine dogs with a histological diagnosis of FSA arising from the oral cavity that underwent surgical resection of their oral FSA were included in this study. Twenty-one dogs were treated with surgical excision alone and eight dogs with both surgery and radiation therapy. The median progression-free interval was >653 days. The median survival time was 743 days. The 1- and 2-year survival rates were 87.7 and 57.8%, respectively. Seven (24.1%) dogs developed local recurrence. Seven dogs (24.1%) developed metastasis.

Randomized Phase III Trial of Piroxicam in Combination with Mitoxantrone or Carboplatin for First-Line Treatment of Urogenital Tract Transitional Cell Carcinoma in Dogs

Background Reported response rates of transitional cell carcinoma (TCC) in dogs to piroxicam in combination with either mitoxantrone or carboplatin are similar; however, it is unknown whether either drug might provide superior duration of response. Hypothesis/Objectives To determine if the progression‐free interval (PFI) of dogs with TCC treated with mitoxantrone and piroxicam was different than that of dogs receiving carboplatin and piroxicam. The hypothesis was that the efficacy of mitoxantrone is no different from carboplatin. Animals Fifty dogs with TCC without azotemia. Methods Prospective open‐label phase III randomized study. Either mitoxantrone or carboplatin was administered every 3 weeks concurrently with piroxicam with restaging at 6‐week intervals. Twenty‐four dogs received carboplatin and 26 received mitoxantrone. Results Response was not different between groups (P = .56). None of the dogs showed complete response. In the mitoxantrone group, there were 2 (8%) partial responses (PR) and 18 (69%) dogs with stable disease (SD). In the carboplatin group, there were 3 PR (13%) and 13 (54%) dogs with SD. The PFI was not significantly different between groups (mitoxantrone = 106 days; carboplatin = 73.5 days; P = .62; hazard ratio 0.86; 95% confidence interval 0.47–1.56). Dogs with prostatic involvement experienced a shorter survival (median, 109 days) compared to dogs with urethral, trigonal, or apically located tumors; this difference was significant (median 300, 190, and 645 days, respectively; P = .005). Conclusions and Clinical Importance This study did not detect a different in outcome in dogs with TCC treated with either mitoxantrone or carboplatin in combination with piroxicam.

Clinical Characteristics and Outcome in Dogs with Splenic Marginal Zone Lymphoma

BACKGROUND Splenic marginal zone lymphoma (MZL) is a form of indolent B-cell lymphoma that is not well characterized in dogs. HYPOTHESIS/OBJECTIVES The purpose of this study was to describe clinical characteristics and outcome in dogs with splenic MZL confirmed by histopathology, immunophenotyping, and molecular clonality assessment. We hypothesized that affected dogs would have prolonged survival time with splenectomy alone. ANIMALS Thirty-four dogs were included. Twenty-nine dogs were diagnosed after splenectomy, and 5 dogs were diagnosed at necropsy. METHODS Pathology records were searched for dogs with histologically confirmed splenic MZL. Clinical and outcome data were retrospectively collected by medical record review, and prognostic factors were evaluated. Histopathology was reviewed by a board-certified pathologist, and tissue sections were subjected to immunophenotyping and molecular clonality assessment by PCR. RESULTS Immunohistochemistry confirmed a B-cell phenotype for all dogs. Molecular clonality assessment was performed in 33 of 34 dogs, of which 24 had clonal rearrangement of immunoglobulin (Ig) loci, 3 had pseudoclonal rearrangement, and 6 had polyclonal rearrangement. The overall median survival time (MST) for the 29 dogs that underwent splenectomy was 383 days. The MST for 14 of 29 asymptomatic dogs that underwent splenectomy for MZL was 1,153 days as compared to 309 days for 15/29 dogs with clinical signs referable to splenic MZL (P = .018). Lymph node involvement, hemoabdomen, anemia, chemotherapy, and concurrent malignancy did not affect survival outcome. CONCLUSIONS AND CLINICAL IMPORTANCE Dogs diagnosed with splenic MZL can have prolonged survival with splenectomy alone, without the use of adjuvant chemotherapy. Asymptomatic dogs may have a better survival outcome.