Auranofin improves overall survival when combined with standard of care in a pilot study involving dogs with osteosarcoma.

Osteosarcoma is the most common paediatric primary bone malignancy. The major cause of death in osteosarcoma is drug-resistant pulmonary metastasis. Previous studies have shown that thioredoxin reductase 2 is a driver of metastasis in osteosarcoma and can be inhibited by auranofin (AF). Moreover, studies have shown that AF significantly reduces pulmonary metastases in xenotransplant models. Here, we describe a phase I/II study of AF in canine osteosarcoma, a well-recognized spontaneous model of human osteosarcoma. We performed a single-arm multicentre pilot study of AF in combination with standard of care (SOC) (amputation + carboplatin). We recruited 40 dogs to the trial and used a historical SOC-only control group (n = 26). Dogs >15 kg received 9 mg AF q3d PO and dogs <15 kg received 6 mg q3d. Follow-up occurred over at least a 3-year period. Auranofin plus SOC improved overall survival (OS) (P = .036) in all dogs treated. The improved outcome was attributable entirely to improved OS in male dogs (P = .009). At the time of writing, 10 dogs (25%) survive without measurable disease in the treatment group with survival times ranging between 806 and 1525 days. Our study shows that AF improves OS in male dogs when combined with SOC. Our findings have translational relevance for the management of canine and human osteosarcoma. Our data justify a larger multicentre phase 2 trial in dogs and a phase I/II trial in human patients with refractory disease at the time of initial surgery.

Cutaneous non-epitheliotropic T-cell lymphoma associated with a fracture site in a cat.

CASE SUMMARY: A 7-year-old male neutered domestic shorthair cat presented for investigation of a swelling over the right forelimb. Radiographs of the right forelimb revealed significant lysis and soft tissue swelling surrounding a previously implanted surgical plate, used to repair a fracture of the distal radius 5 years prior. The implant was removed, and a biopsy was collected. Histopathological analysis and immunohistochemistry diagnosed a non-epitheliotropic T-cell cutaneous lymphoma. Staging confirmed multiple regional lymph node involvement. The cat was started on a CHOP-based protocol (vincristine, doxorubicin, cyclophosphamide and prednisolone). At week 4, the disease progressed both locally and within the regional lymph nodes. The primary lesion became severely ulcerated and the cat was euthanased, 42 days post-diagnosis. RELEVANCE AND NOVEL INFORMATION: This is the first report of a cutaneous non-epitheliotropic lymphoma developing at the site of a previous traumatic fracture and metal implant. The cat's response to chemotherapy was poor and euthanasia was performed owing to progressive disease. More investigation is required to understand the role that malignant transformation could have at sites of chronic inflammation, bone fractures and surgical implants.

Polyostotic lymphoma with multiple pathological fractures in a six-month-old cat.

A 6-month-old female neutered domestic shorthair cat was examined for pain and swelling of the distal limbs. Swelling and malalignment of both carpi, dorsiflexion of the distal metatarsals and a mild, multicentric lymphadenopathy were detected on examination. Screening blood tests revealed a biclonal gammopathy, hypercalcemia and atypical leukocytes. Survey radiographs revealed lysis and proliferative changes within the physes. Multiple pathological physeal fractures were present, including the distal radii, metacarpal and metatarsal bones. No treatment was attempted and the patient was euthanased. Histopathology revealed infiltration by monomorphic round cells within the liver, spleen, kidney and bone marrow. Immunohistochemistry revealed strong reactivity to CD20. Clonality assays revealed clonal results for the B-cell loci, consistent with B-cell lymphoma. To the authors' knowledge this is the first report of polyostotic lymphoma with multiple pathological fractures in a cat. The predominantly distal distribution of osseous lesions is rarely reported in dogs and humans.