Corey F. Saba

Fibrosarcoma adjacent to the site of microchip implantation in a cat.

A 14-year-old spayed female domestic shorthair cat presented with an interscapular mass. A computed tomography scan, biopsy, and histological examination revealed a fibrosarcoma adjacent to a pet identification microchip. Because the cat was previously vaccinated at this site, it is not possible to establish definitive causation of the fibrosarcoma, but this is the first report of a tumor in the vicinity of a microchip in a cat. Microchip-associated tumors have been reported in rodents and dogs. Veterinarians should be aware that because inflammation may predispose felines to tumor formation, separation and observation of vaccination and implantation sites are indicated. Adherence to American Association of Feline Practitioners (AAFP) vaccination guidelines and monitoring of microchip implantation sites are recommended.

Masitinib demonstrates anti-proliferative and pro-apoptotic activity in primary and metastatic feline injection-site sarcoma cells

Dysregulation of platelet-derived growth factor receptor (PDGFR) may play a role in feline injection-site sarcoma (ISS) cell growth and viability. Masitinib, a tyrosine kinase inhibitor approved for treatment of canine mast cell tumours, is highly selective for the PDGFR signalling pathway and may offer a new therapeutic approach for this disease. The in vitro effects of masitinib on growth, apoptosis and PDGFR signalling in two novel ISS cell lines were investigated. PDGFR expression was confirmed by Western blot in cell lines derived from a primary ISS tumour (JB) and a corresponding, histologically confirmed ISS lung metastasis (JBLM). Masitinib inhibited cell growth and PDGFR phosphorylation in both cell lines. Higher drug concentrations were required to inhibit growth than to modulate ligand-induced autophosphorylation of PDGFR. These in vitro data suggest that masitinib displays activity against both primary and metastatic ISS cell line and may aid in the clinical management of ISS.

An Integrated Widefield Imaging and Spectroscopy System for Contrast-Enhanced, Image-Guided Resection of Tumors

Tumor recurrence following surgery is a common and unresolved medical problem of great importance since surgery is the most widely used treatment for solid-mass tumors worldwide. A contributing factor to tumor recurrence is the presence of residual tumor remaining at or near the surgical site following surgery. Goal: The primary objective of this study was to develop and evaluate an image-guided surgery system based on a near-infrared, handheld excitation source and spectrograph in combination with a widefield video imaging system. Methods: This system was designed to detect the fluorescence of near-infrared contrast agents and, in particular, indocyanine green (ICG). The imaging system was evaluated for its optical performance and ability to detect the presence of ICG in tumors in an ectopic murine tumor model as well as in spontaneous tumors arising in canines. Results: In both settings, an intravenous ICG infusion provided tumor contrast. In both the murine models and surgical specimens from canines, ICG preferentially accumulated in tumor tissue compared to surrounding normal tissue. The resulting contrast was sufficient to distinguish neoplasia from normal tissue; in the canine surgical specimens, the contrast was sufficient to permit identification of neoplasia on the marginal surface of the specimen. Conclusion: These results demonstrate a unique concept in image-guided surgery by combining local excitation and spectroscopy with widefield imaging. Significance: The ability to readily detect ICG in canines with spontaneous tumors in a clinical setting exemplifies the potential for further clinical translation; the promising results of detecting neoplasia on the marginal specimen surface underscore the clinical utility.

Mechlorethamine, procarbazine and prednisone for the treatment of resistant lymphoma in dogs.

Forty-one dogs with resistant lymphoma were treated with a modified MOPP (mechlorethamine, vincristine, procarbazine and prednisone) protocol (MPP [mechlorethamine, procarbazine and prednisone] administered on a 21-day cycle, shortened from the 28-day MOPP cycle). The overall response rate to MPP was 34% for a median of 56 days (95% confidence interval 30-238). Seventeen percent of dogs had a complete response for a median duration of 238 days, 17% had a partial response for a median of 56 days and 32% had stable disease for a median of 24 days. Histological grade or cell morphology on cytology was associated with response. Minimal toxicity was observed with the MPP protocol, suggesting that further dose intensification or addition of another chemotherapeutic agent would be possible.

Phase II Evaluation of VDC‐1101 in Canine Cutaneous T‐Cell Lymphoma

Background Canine cutaneous T‐cell lymphoma (CTCL) is an uncommon disease for which efficacious therapies are lacking. The novel anticancer nucleotide prodrug VDC‐1101 (formerly known as GS‐9219) has shown efficacy in dogs with multicentric lymphoma. One of the observed adverse effects with this drug was a skin change characterized by hair loss, erythema, and pruritus, implying delivery of VDC‐1101 to the skin. Hypothesis/Objectives The primary study objective was to identify the objective response rate (ORR) to VDC‐1101 in canine CTCL; secondary objectives included characterization of progression‐free survival (PFS) and adverse events (AEs). Animals Twelve dogs with chemotherapy‐naïve or relapsed, histologically and immunohistochemically confirmed CTCL. Methods Dogs received VDC‐1101 as a 30‐minute IV infusion once every 21 days. Prednisone (1 mg/kg PO q48h) was administered concurrently. Results In 11 evaluable patients, responses included 1 complete response (CR), 4 partial responses (PR), 2 stable disease (SD), and 4 progressive disease for an ORR of 45% and biologic response rate (CR/PR/SD) of 64%. The median PFS was 37.5 days (26 to >399 days), which includes 1 durable and ongoing CR (>1 year). Gastrointestinal and hematologic AEs were mild; no dogs developed grade 3 or 4 AEs. Three dogs developed dermatopathies and 1 of these dogs was removed from the study as a result of this AE. Conclusions and Clinical Importance VDC‐1101 has activity against canine CTCL and could provide another treatment option in a disease process with a poor prognosis.

Phase II clinical evaluation of lomustine chemotherapy for feline vaccine‐associated sarcoma

Treatment of feline vaccine-associated sarcoma (VAS) is challenging, in part due to the high likelihood of tumour recurrence despite aggressive local therapy. Lomustine is potentially an attractive agent to add to the current treatment armamentarium. In this de-escalating phase I/II prospective trial, 28 cats with measurable VAS were treated at target dosages of 38-60 mg m(-2) every 3 weeks until disease progression. The overall response rate was 25%, with a median progression-free survival and median duration of response of 60.5 and 82.5 days, respectively. Haematologic toxicity, specifically cumulative neutropenia, was significant, and dose reductions and treatment delays were common. Although these data support further investigation of lomustine for the treatment of VAS, safe, multidosing protocols must first be determined.

Changes in γ-H2AX expression in irradiated feline sarcoma cells: An indicator of double strand DNA breaks

Feline injection site sarcoma (ISS) is a highly invasive soft tissue tumor that is commonly treated with radiation. Cellular deoxyribonucleic acid (DNA) is the principal target for the biologic effects of radiation with cell killing correlating to the number of double stranded DNA breaks (DSBs). The objective of this study was to determine if radiation-induced damage to feline ISS cells could be detected using a commercially available DNA DSB detection kit. Feline ISS cells were irradiated and evaluated for extent of DSB induction with a γ-H2AX chemiluminescent kit; results were validated by Western Blot analysis. Irradiated cells showed a significant increase in double strand break induction compared to control cells, which was supported by Western Blot. DNA damage in feline sarcoma cells following single exposure of radiation can be indirectly detected using a commercially available mouse anti-human monoclonal antibody for γ-H2AX.

Indirect computed tomography lymphangiography with aqueous contrast for evaluation of sentinel lymph nodes in dogs with tumors of the head

Sentinel lymph node evaluation is widely used in human medicine to evaluate the first lymph node(s) to which a tumor drains. Sentinel lymph node biopsy allows avoidance of extensive lymphadenectomies in cases where the sentinel lymph node is negative for metastasis, thereby reducing patient morbidity. It has been shown that regional lymph nodes are not always the sentinel lymph node, thus identification and sampling of sentinel lymph nodes allows for more accurate staging, which is critical for treatment and prognostication in dogs with cancer. The objective of this prospective, pilot study was to determine if indirect computed tomography (CT) lymphangiography with aqueous contrast agent would successfully allow identification of sentinel lymph nodes in dogs with masses on the head. Eighteen dogs underwent CT lymphangiography. The sentinel lymph node was successfully identified within 3 min of contrast injection in 16 dogs (89%). Compression of lymphatic vessels from endotracheal tube ties and/or the patients own body weight delayed or prevented identification of sentinel lymph nodes in two dogs (11%). Computed tomography lymphangiography with aqueous contrast can be used successfully to rapidly identify sentinel lymph nodes in dogs with masses on the head.

Masitinib mesylate does not enhance sensitivity to radiation in three feline injection-site sarcoma cell lines under normal growth conditions ☆

Masitinib, a selective tyrosine kinase inhibitor, was investigated as a radiosensitizer in three primary feline injection-site sarcoma (ISS) cell lines. Sensitivity to masitinib was previously assessed via cell growth inhibition assays with mean IC50 values of 5.5-8.6μM. Clonogenic assays were performed to determine the effect of masitinib and radiation on cell survival. Single dose radiation (0-12Gy) experiments were carried out under normal growth conditions in control ISS cells and in cells incubated with 1 or 6μM masitinib for 72h prior to irradiation. Radiation administered either alone or in combination with masitinib induced a dose-dependent reduction in clonogenic survival. Survival from the combined masitinib and radiation treatment was not significantly different from that of radiation alone. Results suggest that masitinib does not directly enhance ISS cell radiosensitivity under normal in vitro conditions, although this does not preclude the utility of further investigations to assess sensitization properties under altered conditions.

Febrile neutropenia in cats treated with chemotherapy.

The purpose of this study was to describe the clinical presentation, potential causative agents, treatment and outcome of febrile neutropenia (FN) in chemotherapy-treated cats. Medical records from eight institutions were retrospectively reviewed. A total of 22 FN events in 20 cats were evaluated. Lymphoma was the most common cancer diagnosis; lomustine and vinca alkaloids were the most frequently implicated causative agents. Presenting clinical signs included decreased appetite, lethargy, vomiting and diarrhoea. Median body temperature and absolute neutrophil count at presentation were 104.1 °F; 40 °C (range: 103.1-105.1 °F; 39.5-40.6 °C) and 246 mL-1 (range: 0-1600 mL-1 ), respectively. Median number of days between chemotherapy administration and FN onset was 5 (range: 4-25 days). All but one cat were treated with intravenous fluids and broad spectrum antibiotics. Fevers resolved in all cases and absolute neutrophil counts returned to normal in 19 cats. Clinical presentation of cats with FN appears similar to that of dogs.