Response-based modification of CHOP chemotherapy for canine B-cell lymphoma.

Despite high initial response rates, a subset of dogs with B-cell lymphoma responds less robustly to CHOP-based chemotherapy and experiences shorter survival. One hundred and four dogs with nodal B-cell lymphoma were treated with a response-based CHOP (RBCHOP) protocol modified based on response to individual drugs during the first chemotherapy cycle. Dogs achieving complete (CR) or partial response (PR) at week 3, following treatment with vincristine and cyclophosphamide, received RBCHOP 1 (n = 72), a protocol sequentially rotating vincristine, cyclophosphamide, and doxorubicin. Dogs without a detectable response at week 3 that subsequently achieved CR or PR following treatment with doxorubicin received RBCHOP 2 (n = 14), in which four doses of doxorubicin were given consecutively followed by vincristine and cyclophosphamide. Dogs that failed to respond at week 3 and then to doxorubicin at week 5 assessment were offered rescue chemotherapy (RBCHOP 3, n = 18). Median progression free survival (PFS) and overall survival time (OST) were similar between RBCHOP 1 (PFS 210 days, OST 354 days) and RBCHOP 2 (PFS 220 days, OST 456 days), but significantly shorter for RBCHOP 3 (PFS 34 days, OST 80.5 days, P < 0.001). No presenting signalment nor hematologic variable differentiated patient cohort, however, dogs in RBCHOP 2 and RBCHOP 3 were more likely to have a lymphocytosis at diagnosis (P = 0.02 and 0.04, respectively). Protocol modification based on response during the first cycle resulted in similar toxicity profiles and outcomes to previously published variants of CHOP, and prognosis remained poor for dogs failing to respond during the first treatment cycle.

Efficacy and toxicity of mustargen, vincristine, procarbazine and prednisone (MOPP) for the treatment of relapsed or resistant lymphoma in cats.

OBJECTIVES: The aims of this study were to evaluate the safety of mustargen, vincristine, procarbazine and prednisone (MOPP) chemotherapy in the treatment of relapsed or refractory feline lymphoma, and to determine the overall response rate and median remission time with this protocol. METHODS: The medical records of 38 cats with relapsed or refractory lymphoma treated with MOPP chemotherapy at three institutions (University of Pennsylvania, the Animal Medical Center, and VCA Western Veterinary Specialist and Emergency Centre) were examined. Information evaluated included patient signalment, feline immunodeficiency virus/feline leukemia virus status, anatomic location(s) of lymphoma, prior protocols (type and number), MOPP doses, MOPP response, remission duration, hematologic and biochemical parameters, and owner-reported adverse effects. RESULTS: Overall, 70.3% of cats responded to MOPP chemotherapy. Among the responders, the median remission duration was 166 days. The most common adverse effects were neutropenia and gastrointestinal upset, which were reported in 18.4% of cats. In 55.3% of cats, no adverse effects were reported. In total, 30.8% of responders continued to respond 6 months following the initiation of MOPP, and 15.4% maintained a response 1 year after starting MOPP. CONCLUSIONS AND RELEVANCE: MOPP is a safe protocol for the treatment of relapsed or refractory feline lymphoma, with a promising overall response rate and median remission time.

Outcomes in 40 cats with discrete intermediate- or large-cell gastrointestinal lymphoma masses treated with surgical mass resection (2005-2015).

OBJECTIVE: To report outcomes in cats with discrete intermediate- and large-cell gastrointestinal (GI) lymphoma masses after surgical resection. STUDY DESIGN: Retrospective clinical case series. ANIMALS: Forty client-owned cats in which intermediate- or large-cell GI lymphoma was diagnosed. METHODS: Records of 40 cats in which discrete intermediate- or large-cell GI lymphoma masses were diagnosed between 2005 and 2015 were reviewed. Cats were included if they survived curative intent surgery and had a known outcome for at least two weeks. Postoperative death was permitted. Data collected included anatomic site, surgical margins, lymphoma subtype, chemotherapy use, and postoperative and long-term outcome (beyond two weeks). RESULTS: Affected sites consisted of small intestines (n = 23), large intestines (n = 9), and stomach (n = 8). Thirty-six of 40 cats survived to discharge, and 31 cats were alive at suture removal. Median long-term follow-up of 22 cats was 111 days (range, 16-1407). Cats that survived to suture removal had a median survival time (MST) of 185 days (95% confidence interval: 72-465). Cats with large intestinal masses lived longer than those with small intestinal or gastric masses whether all cats (MST, 675, 64, 96 days, respectively; P = .03) or only those surviving to suture removal were considered. Complete surgical resection (n = 20) was positively associated with survival (370 vs 83 days, P = .016). CONCLUSION: Most cats in this population survived the perioperative period, with MST similar to those reported historically with medical management. CLINICAL SIGNIFICANCE: Surgical resection may be a reasonable consideration in cats with solitary lymphoma, particularly those with large intestinal masses.

Palliative radiation therapy for solid tumors in dogs: 103 cases (2007-2011).

OBJECTIVE: To evaluate the clinical response, adverse effects, and outcomes associated with palliative radiation therapy (PRT) in dogs with various solid tumor types at various body locations. DESIGN: Retrospective case series. ANIMALS: 103 dogs with solid tumors. PROCEDURES: Medical records for dogs with solid tumors treated with PRT between July 2007 and January 2011 at a veterinary teaching hospital were reviewed. Data collected included signalment, tumor type and location, initial staging results, PRT protocol, other tumor-specific treatments, patient and tumor response, outcome, and acute and chronic adverse effects. Median progression-free survival time, median survival time (MST), and other descriptive statistics were calculated. RESULTS: Types of tumors treated included carcinoma, sarcoma, melanoma, primary bone tumor, mast cell tumor, and ameloblastoma. For all dogs, the overall tumor and clinical response rates to PRT were 75% and 77%, respectively, and the MST was 134 days, but those responses varied substantially among tumor types. Dogs that developed a positive clinical response or maintained stable disease after PRT had a significantly longer MST than did dogs with progressive disease. Tumor location was not significantly associated with median progression-free survival time or MST. Most dogs tolerated the PRT well. Acute and chronic adverse effects were observed in 57 and 8 dogs, respectively, but were generally self-limiting. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that dogs with various types of solid tumors that received PRT had objective beneficial responses and an improvement in quality of life that was positively associated with survival time.

Outcome and toxicity assessment of feline small cell lymphoma: 56 cases (2000-2010).

Feline small cell lymphoma is associated with greater response to treatment and survival when compared to large cell lymphoma. Treatment-associated toxicity, response to rescue chemotherapy and prognostic factors are largely unknown. This retrospective study was performed to identify treatment-associated toxicity, response to rescue chemotherapy and treatment outcome for cats diagnosed with small cell lymphoma of various anatomic locations. Medical records from 56 cats were evaluated. All cats were treated with glucocorticoid and chlorambucil with discontinuation of treatment recommended at 1 year if complete clinical response was documented. Chemotherapy toxicity was uncommon (33.9%) and generally mild. Grade III or IV hepatotoxicity was documented in 10.7% of patients. Overall response rate was 85.7% with glucocorticoid and chlorambucil. Median progression-free survival was 1078 days. Overall response rate for rescue chemotherapy was 59%. Reintroduction of prednisone and chlorambucil was associated with significantly longer survival than prednisone and lomustine (>1500 vs. 492 days, P = 0.01). Median overall survival times for cats with lymphoma of the gastrointestinal tract was not significantly different from those with extra-intestinal disease locations (1148 vs. 1375 days, P = 0.23). Median overall survival was 1317 days. Toxicity, other than hepatotoxicity was mild. Rescue chemotherapy with re-introduction of glucocorticoids and chlorambucil was most successful. Discontinuation of glucocorticoid and chlorambucil with subsequent reintroduction as rescue chemotherapy appears to be just as effective as continued administration in cats.

Prevalence of regional and distant metastasis in cats with advanced oral squamous cell carcinoma: 49 cases (2005-2011).

The objective of this study was to evaluate the prevalence of regional and distant metastasis in cats with advanced oral squamous cell carcinoma (SCC) in a retrospective case series. Forty-nine cats with cytologically- or histopathologically-confirmed oral SCC presented to the Matthew J Ryan Veterinary Hospital of the University of Pennsylvania. History, clinical and laboratory results, diagnostic imaging findings and survival times were obtained from the medical records of patients who received diagnostic evaluation for metastasis. The prevalence of metastasis was assessed by means of mandibular lymph node cytology and three-view thoracic radiography. The prevalence of mandibular lymph node metastasis was 31% (15/49). Evidence of possible thoracic metastasis was seen in 10% (5/49) of cases. Of the patients with mandibular lymph node metastasis, 53% (8/15) were maxillary, 27% mandibular (4/15), 13% sublingual (2/15) and 7% caudal pharyngeal (1/15). Pulmonary metastasis was seen in three mandibular, one maxillary and one sublingual mass. Forty-one patients died or were euthanased owing to progression of local disease, and seven patients were lost to follow-up. The prevalence of regional metastasis in this study was more common than most previously reported studies, while the rate of pulmonary metastasis was higher than has previously been published. Although significant conclusions cannot be drawn, control of the primary tumor, regardless of tumor size at diagnosis, appears to be an important factor in improving survival time, and therefore treatment of metastasis may be important in those cases where long-term control of the primary tumor is possible.

Polyamine inhibitors for treatment of feline oral squamous cell carcinoma: a proof-of-concept study.

This study assessed proof-of-concept for use of polyamine inhibitor 2-diluoromethylornithine (DFMO) as a treatment for oral squamous cell carcinoma (SCC) in client-owned cats. Polyamine levels in tumor tissue and normal oral mucosa were quantified before and after treatment. DFMO was administered orally to 14 client-owned cats with histologically confirmed oral SCC. Patients were monitored for gastrointestinal, dermatologic, auditory, hematological, and biochemical abnormalities. Total polyamine levels in tumor tissue decreased after treatment, as did the specific polyamine putrescine in both tumor tissue and normal mucosa. Ototoxicity was observed in 5 of 6 cats receiving pre- and post-treatment brainstem auditory evoked potential tests. Subclinical thrombocytopenia was observed in 6 of 14 cats. One cat showed mild post-anesthetic tremors that resolved without treatment. Oral administration of DFMO at doses used in this study resulted in significantly decreased tumor polyamine levels without life-threatening clinical or hematological toxicities. Further studies are warranted to explore pathophysiology of polyamine biochemistry and use of polyamine inhibitors in treatment of cats with oral SCC.

Lymphoma in cats treated with a weekly cyclophosphamide-, vincristine-, and prednisone-based protocol: 114 cases (1998-2008).

OBJECTIVE: To evaluate the clinical response rate, progression-free survival time, overall survival time, and possible prognostic factors associated with a cyclophosphamide-, vincristine-, and prednisone (COP)-based chemotherapy protocol in cats with lymphoma. DESIGN: Retrospective case series. ANIMALS: 114 cats with lymphoma. PROCEDURES: Medical records of cats receiving a weekly COP-based chemotherapy protocol from 1998 to 2008 at the Matthew J. Ryan Veterinary Hospital of the University of Pennsylvania were evaluated for information regarding signalment, anatomic site of involvement, cell morphology, treatment, and outcome. Retroviral status, baseline weight, substage, anatomic location, dose delays, dose reductions, and response to treatment were evaluated for prognostic importance. RESULTS: The majority of cases (94 [82.4%]) were substage b, and the most common anatomic site was the gastrointestinal tract (57 [50%]). Clinical response rate after the first chemotherapy cycle was 47.4%. Response to treatment was significantly associated with progression-free survival time and overall survival time, whereas substage was significantly associated with progression-free survival time. The median progression-free survival time and overall survival time were 65.5 and 108 days, respectively. Compared with nonresponders, responders had significantly longer median progression-free survival time (364 vs 31 days) and median overall survival time (591 vs 73 days). CONCLUSIONS AND CLINICAL RELEVANCE: Clinical response after 1 cycle of COP-based chemotherapy was predictive for progression-free survival time and overall survival time in cats with lymphoma; therefore, response after 1 cycle of chemotherapy could be used to guide decisions about further treatment. No new prognostic factors were identified.

Evaluation of Clostridium novyi-NT spores in dogs with naturally occurring tumors.

OBJECTIVE: To establish the maximum tolerated dose of Clostridium novyi-NT spores in tumor-bearing dogs and evaluate spore germination within tumors and tumor response. ANIMALS: 6 client-owned dogs. PROCEDURES: A standard dose-escalation study was planned, with maximum tolerated dose defined as the highest dose at which 0 or 1 of 6 dogs had dose-limiting toxicoses (DLT). Dogs received 1 dose of C. novyi-NT spores i.v.. Toxicoses were graded and interventions performed according to specific guidelines. Grade 3 or higher toxicosis or any toxicosis combination that substantially affected patient status was considered DLT. Clinical response was measured by use of response evaluation criteria in solid tumors at 28 days. RESULTS: The first 2 dogs had DLT. The dose was decreased. Two of the next 4 dogs had DLT; therefore, dose administration was stopped because the study endpoint had been reached. The most common toxicosis was fever (n = 6 dogs). Two dogs developed abscesses (1 within a nasal carcinoma and 1 splenic abscess) attributable to C. novyi-NT infection; both required surgical intervention. Clostridium novyi-NT was cultured from 1 of 6 tumors. Five dogs were available for response assessment (4 had stable disease; 1 had progressive disease). CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that C. novyi-NT can germinate within tumors of dogs. Toxicosis, although common and sometimes severe, was manageable with treatment. Further studies in dogs with superficial tumors may allow for continued dose escalation and provide information for use in clinical trials in veterinary and human oncology.

CT features of pleural masses and nodules.

Pleural space masses and nodules are rarely described on computed tomography (CT) in veterinary medicine and have only been described in patients with neoplasia. Our purpose was to describe the CT findings and diagnoses in seven patients with pleural masses and nodules. Two patients had broad-based, plaque-like pleural masses, both of which were due to neoplasia (primary pleural carcinoma, metastatic thymoma). Two patients had well-defined pleural nodules and nodular pleural thickening, one of which had mesothelial hypertrophy, and another of which had metastatic hemangiosarcoma. Three patients had ill-defined pleural nodules to nodular pleural thickening, one of which had metastatic pulmonary carcinoma, while the other two had bacterial infection with mesothelial proliferation (n = 2), fibrinous pleuritis (n = 1), and severe mediastinal pleuritis/mediastinitis (n = 2). Five of the seven patients had focal, multifocal or diffuse smooth, and/or irregular pleural thickening. Five of seven patients had pleural effusion, and postcontrast CT was useful in several patients for delineating the pleural lesions from the effusion. All patients except one had additional lesions identified on CT besides those in the pleural space. CT is useful in identifying and characterizing pleural space lesions and could be used to guide further diagnostic procedures such as thoracoscopy or exploratory thoracotomy. Both neoplastic and nonneoplastic diseases should be considered in the differential diagnoses for pleural space masses and nodules found on CT.

Prognostic significance of weight changes during treatment of feline lymphoma.

The study purpose was to determine the prognostic significance of weight changes during feline lymphoma treatment. A secondary purpose was to compare weight changes according to baseline body weight, cell type and location. Records of 209 cats treated for lymphoma with chemotherapy from 1995 to 2007 were evaluated. Signalment, cell type, lymphoma location, baseline body weight, weight during treatment, and outcome information were collected. Lymphoma specific survival (LSS) was compared according to baseline weight and weight changes during treatment. Weight change over time was compared according to cell type (small versus large), location (gastrointestinal versus non-gastrointestinal) and baseline weight. Cats with large cell lymphoma that lost ≥ 5% body weight at 1 month had significantly shorter LSS than those that gained or had stable weight (P = 0.004). Percentage weight change over time differed significantly according to baseline weight group. These findings demonstrate the prognostic importance of weight loss in feline large cell lymphoma.

Perioperative complications after full-thickness gastrointestinal surgery in cats with alimentary lymphoma.

OBJECTIVE: To determine perioperative risk factors for complications that occur before hospital discharge after gastrointestinal (GI) surgery in cats with alimentary lymphosarcoma (LSA). STUDY DESIGN: Case series. ANIMALS: Cats (n=70) with a histopathologically confirmed diagnosis of alimentary LSA that had full-thickness GI surgery. METHODS: Medical record data (February 1996-March 2009) from 3 academic referral centers were reviewed. Retrieved data included signalment, preoperative clinical signs and laboratory findings, perioperative medications administered, type and location of GI surgery performed and outcome until hospital discharge. RESULTS: In 38 surgeries, intestinal resection and anastomosis was performed. Gastrotomy and/or enterotomy was performed in 53 surgeries. A preoperative serum albumin concentration <2.5 g/dL was recorded for 11 cases. There was no clinical evidence of postoperative leakage from any biopsy or anastomosis site. Postoperative complications that occurred before hospital discharge included: anorexia or decreased appetite (n=8), hyperthermia (3), pancreatitis (1) and constipation (1). CONCLUSIONS: Cats with alimentary LSA do not appear to be at high risk of postoperative dehiscence after full-thickness GI surgery.