Novel genomic prognostic biomarkers for dogs with cancer.

BACKGROUND: Growing evidence from dogs and humans supports the abundance of mutation-based biomarkers in tumors of dogs. Increasing the use of clinical genomic diagnostic testing now provides another powerful data source for biomarker discovery. HYPOTHESIS: Analyzed clinical outcomes in dogs with cancer profiled using SearchLight DNA, a cancer gene panel for dogs, to identify mutations with prognostic value. ANIMALS: A total of 127 cases of cancer in dogs were analyzed using SearchLight DNA and for which clinical outcome information was available. METHODS: Clinical data points were collected by medical record review. Variables including mutated genes, mutations, signalment, and treatment were fitted using Cox proportional hazard models to identify factors associated with progression-free survival (PFS). The log-rank test was used to compare PFS between patients receiving and not receiving targeted treatment before first progression. RESULTS: Combined genomic and outcomes analysis identified 336 unique mutations in 89 genes across 26 cancer types. Mutations in 6 genes (CCND1, CCND3, SMARCB1, FANCG, CDKN2A/B, and MSH6) were significantly associated with shorter PFS. Dogs that received targeted treatment before first progression (n = 45) experienced significantly longer PFS compared with those that did not (n = 82, P = .01). This significance held true for 29 dogs that received genomically informed targeted treatment compared with those that did not (P = .05). CONCLUSION AND CLINICAL IMPORTANCE: We identified novel mutations with prognostic value and demonstrate the benefit of targeted treatment across multiple cancer types. These results provide clinical evidence of the potential for genomics and precision medicine in dogs with cancer.

Discharge summaries provided to owners of pets newly diagnosed with cancer exceed recommended readability levels.

OBJECTIVE: To analyze the readability of discharge summaries distributed to owners of pets newly diagnosed with cancer. SAMPLE: 118 discharge summaries provided to pet owners following initial consultation. PROCEDURES: A database search identified records of new patients that had been presented to the North Carolina State Veterinary Hospital medical oncology service between June 2017 and January 2019. Owner-directed portions of the summaries provided at the time of discharge were copied and pasted into a document and stripped of all identifying information. Readability of summaries was assessed with the use of 2 previously established readability calculators: the Flesch-Kincaid Grade Level (FKGL) and Flesch Reading Ease (FRE) tests. RESULTS: Mean ± SD FKGL was 11.9 ± 1.1 (median, 11.9; range, 8.6 to 15.5; target ≤ 6), and the mean ± SD FRE score was 43 ± 5.9 (median, 42.7; range, 25.5 to 58.1; target ≥ 60). There were no significant differences in FKGL or FRE scores among discharge summaries for patients with the 4 most common tumor types diagnosed or the described treatment options. Ninety-three percent (110/118) of summaries were scored as difficult or very difficult to read. CLINICAL RELEVANCE: Owner-directed written information regarding a diagnosis of cancer at a single teaching hospital exceeded readability levels recommended by the American Medical Association and NIH and was above the average reading level of most US adults. Efforts to improve readability are an important component of promoting relationship-centered care and may improve owner compliance and patient outcomes.

Veterinary Clinical Ethics and Patient Care Dilemmas.

Veterinary ethical dilemmas are common, complex, and unavoidable. Creating a transparent and deliberate approach to ethical issues empowers the entire veterinary team and reduces stress associated with these dilemmas. This article discusses ethical considerations and principles and propose use of the 4Es model and core communication skills to address ethical dilemmas in veterinary practice. It reviews literature defining ethical issues in practice and provides case examples to show the application of our proposed methods. The goal is to provide veterinary professionals with an approach they can use to frame and address their own ethical decisions.

Survival time for dogs with previously untreated, peripheral nodal, intermediate- or large-cell lymphoma treated with prednisone alone: the Canine Lymphoma Steroid Only trial.

OBJECTIVE: To evaluate survival times for dogs with previously untreated, peripheral nodal, intermediate- or large-cell lymphoma treated with prednisone alone. ANIMALS: 109 client-owned dogs recruited from 15 institutions in the United States. PROCEDURES: Dogs were treated with prednisone at a dosage of 40 mg/m2, PO, once daily for 7 days and at a dosage of 20 mg/m2, PO, once daily thereafter. Quality of life (QOL) was assessed by owners with a visual analog scale when treatment was started (day 0), 1 and 2 weeks after treatment was started, and every 4 weeks thereafter. The primary outcome of interest was survival time as determined by the Kaplan-Meier method. Factors potentially associated with survival time were examined. RESULTS: Median overall survival time was 50 days (95% CI, 41 to 59 days). Factors associated with survival time included substage (a vs b) and immunophenotype (B cell vs T cell). Owner-assigned QOL scores on days 0 and 14 were significantly positively correlated with survival time. When QOL score was dichotomized, dogs with day 0 or day 14 QOL scores ≥ 50 had significantly longer survival times, compared with dogs with day 0 or day 14 QOL scores < 50. No variables were predictive of long-term (> 120 days) survival. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that survival times were short for dogs with previously untreated, peripheral nodal, intermediate- or large-cell lymphoma treated with prednisone alone. Owner-perceived QOL and clinician-assigned substage were both associated with survival time. Findings provide potentially important information for clinicians to discuss with owners of dogs with lymphoma at the time treatment decisions are made.

Value, Limitations, and Recommendations for Grading of Canine Cutaneous Mast Cell Tumors: A Consensus of the Oncology-Pathology Working Group.

One of the primary objectives of the Oncology Pathology Working Group (OPWG), a joint initiative of the Veterinary Cancer Society and the American College of Veterinary Pathologists, is for oncologists and pathologists to collaboratively generate consensus documents to standardize aspects and provide guidelines for oncologic pathology. Consensus is established through review of relevant peer-reviewed literature relative to a subgroup's particular focus. In this article, the authors provide a critical review of the current literature for grading of canine cutaneous mast cell tumors, suggest guidelines for reporting, and provide recommendations for its clinical interpretation. The article mainly focuses on histologic grading, but relevant information on mitotic count and cytological grading are also discussed. This document represents the opinions of the working group and the authors but does not constitute a formal endorsement by the American College of Veterinary Pathologists or the Veterinary Cancer Society.

Lymphoid leukemia in five bearded dragons (Pogona vitticeps).

CASE DESCRIPTION: 2 male and 3 female adult bearded dragons (Pogona vitticeps) were evaluated at the North Carolina State University College of Veterinary Medicine's Exotic Animal Medicine Service between September 2018 and October 2019 because of severe lymphocytosis. CLINICAL FINDINGS: All 5 bearded dragons had nonspecific clinical signs, including lethargy, poor appetite, ocular discharge, and weight loss. Clinicopathologic testing revealed extremely high lymphocyte counts with morphological findings consistent with lymphocytic leukemia. TREATMENT AND OUTCOME: All 5 patients were treated with lomustine, prednisolone, and antimicrobials. In addition, 1 or 2 doses of L-asparaginase were administered when the drug was available. Partial remission was achieved in all 5 patients. One patient, after disease progression was documented, was treated with cyclophosphamide and achieved a second partial remission. One of the 5 patients was still alive and continuing to receive chemotherapy at the time of final follow-up 244 days after the initial diagnosis. Survival times (ie, times from initial diagnosis to euthanasia) for the other 4 patients were 57, 157, 330, and 416 days. CLINICAL RELEVANCE: The present report represented the first description of lomustine as a primary chemotherapeutic agent for the treatment of lymphocytic leukemia in bearded dragons and provided information on response to treatment, adverse effects, and survival times.

Prognostic and predictive significance of KIT protein expression and c-kit gene mutation in canine cutaneous mast cell tumours: A consensus of the Oncology-Pathology Working Group.

One of the primary objectives of the Oncology-Pathology Working Group (OPWG), a joint initiative of the Veterinary Cancer Society and the American College of Veterinary Pathologists, is for oncologists and pathologists to collaboratively generate consensus documents to standardize aspects of and provide guidelines for oncologic pathology. Consensus is established through critical review of peer-reviewed literature relevant to a subgroup's particular focus. Subsequent acceptance and approval of the document by the OPWG membership at large establishes consensus. The intent of this publication is to help educate practitioners and pathologists on the value of diagnostics related to the KIT receptor tyrosine kinase for canine cutaneous mast cell tumours and to provide a guide for the use of these tests in veterinary medicine. This document represents the opinions of the OPWG and the authors and does not constitute a formal endorsement by the American College of Veterinary Pathologists or the Veterinary Cancer Society.

Evaluation of the Tolerability of Combination Chemotherapy with Mitoxantrone and Dacarbazine in Dogs with Lymphoma.

Combination chemotherapy can be an effective option for treating resistant lymphoma in dogs. This retrospective study examined the tolerability and efficacy of the combination of 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (dacarbazine) (DTIC) in a population of dogs with lymphoma resistant to a doxorubicin-containing chemotherapy protocol. Mitoxantrone was administered at 5 mg/m2 IV over 10 min followed by DTIC at 600 mg/m2 IV over 5 hr, every 3 wk. All dogs were treated with prophylactic trimethoprim-sulfadiazine and metoclopramide. The frequency of grade 4 neutropenia was 18%, and 5% of dogs were hospitalized from sepsis. Gastrointestinal toxicity was uncommon. The overall response rate was 34% (15 of 44; 95% confidence interval 20-48%) for a median duration of 97 days (range 24-636 days, 95% confidence interval 44-150 days). Fourteen of 15 dogs who received mitoxantrone and DTIC as first rescue responded to treatment. Dogs who achieved complete remission to their initial L-asparaginase, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy protocol were more likely to respond to mitoxantrone and DTIC (23 versus 11%, P = .035). The combination of mitoxantrone and DTIC is a safe treatment option for resistant lymphoma in dogs.

Dogs with acute myeloid leukemia or lymphoid neoplasms (large cell lymphoma or acute lymphoblastic leukemia) may have indistinguishable mediastinal masses on radiographs.

Acute myeloid leukemia is an uncommon hematopoietic neoplasm of dogs that should be differentiated from lymphoid neoplasms, such as lymphoma, because of different treatment protocols and a worse prognosis. Thoracic radiography is performed frequently in dogs with suspected hematopoietic neoplasia, and detecting a mediastinal mass often prioritizes lymphoma as the most likely diagnosis. However, we have observed a mediastinal mass in several dogs with acute myeloid leukemia and hypothesized that (1) the frequency of a mediastinal mass was higher and (2) the size of the mass was larger in dogs with acute myeloid leukemia compared to dogs with lymphoid neoplasms. In this analytical study (observational, retrospective, and cross-sectional), the sample population included 238 dogs with hematopoietic neoplasia. These dogs were divided into lymphoid (large cell lymphoma, acute lymphoblastic leukemia) and myeloid groups based on standard phenotyping tests. A mediastinal mass was detected during thoracic radiography in 73/218 (33%) and nine of 20 (45%) dogs in the lymphoid and myeloid groups (P = 0.21), respectively. The median size ratio of mediastinal mass to cardiac silhouette was 0.20 and 0.23 in the lymphoid and myeloid groups (P = 0.96), respectively. Additionally, we observed normal thoracic radiographs in 111/218 (51%) dogs in the lymphoid group and nine of 20 (45%) dogs in the myeloid group. In conclusion, acute myeloid leukemia should be considered when a mediastinal mass is detected during radiography in dogs with suspected hematopoietic neoplasia-but the presence or size of a mediastinal mass does not differentiate between myeloid and lymphoid neoplasms.

Tolerability of lomustine in combination with cyclophosphamide in dogs with lymphoma.

This retrospective study describes toxicity associated with a protocol of lomustine (CCNU) and cyclophosphamide (CTX) in dogs with lymphoma. CCNU was administered per os (PO) at a targeted dosage of 60 mg/m(2) body surface area on day 0, CTX was administered PO at a targeted dosage of 250 mg/m(2) divided over days 0 through 4, and all dogs received prophylactic antibiotics. Ninety treatments were given to the 57 dogs included in the study. Neutropenia was the principal toxic effect, and the overall frequency of grade 4 neutropenia after the first treatment of CCNU/CTX was 30% (95% confidence interval, 19-43%). The mean body weight of dogs with grade 4 neutropenia (19.7 kg ± 13.4 kg) was significantly less than the mean body weight of dogs that did not develop grade 4 neutropenia (31.7 kg ± 12.4 kg; P = .005). One dog (3%) developed hematologic changes suggestive of hepatotoxicity. No dogs had evidence of either renal toxicity or hemorrhagic cystitis. Adverse gastrointestinal effects were uncommon. On the basis of the findings reported herein, a dose of 60 mg/m(2) of CCNU combined with 250 mg/m(2) of CTX (divided over 5 days) q 4 wk is tolerable in tumor-bearing dogs.