2.1 Spontaneous Canine Tumor Models

All dogs studied and proposed for study are companion pets that have been referred from regional veterinarians. Owners must consent to the study parameters, follow-up schedule, and a post mortem examination for the patient. Inclusion in the study requires the dog be healthy (no serious medical condition or metastatic disease), have an appropriate biopsy-based diagnosis and CT scan of the tumor site. In this report we include six canine patients; two oral melanoma, three oral amelioblastomas and one non-oral carcinomas. During a 14-day treatment regimen; the dogs received hypofractionated radiation (6 x 6 Gy) and/or magnetic nanoparticle hyperthermia (2 X 43°C / 45 minutes) and/or an immunogenic-VLP (2 x 200 μg). Two tumors received all three therapeutic modalities, one tumor received radiation and hyperthermia, two tumors received radiation and VLP, and three treatments included only mNP hyperthermia. In brief, acanthomatous amelioblastomas (AA) are locally aggressive tumors that arise from periodontal epithelium. Acanthomatous amelioblastomas invade bone and recur following excisional surgery or other therapies, mandibulectomy or hemi-mandibulectomy are the only curative therapies. Oral melanoma is a common and lethal cancer in dogs. Untreated dogs rarely live more than 6-months post diagnosis. Surgery and/or radiation can extend post treatment to 12–18 months. The other tumors treated in this series are invasive carcinomas of the digit and breast. Both tumor types have the potential to be metastatic and rapidly fatal unless treated early with highly aggressive surgery and/or radiation. [28 – 31] The radiation-hyperthermia - immunomodulation study is designed t o monitor tumor response and multiple immune parameters (tumor biopsies and at multiple immune cell, hematology and cytokine markers) over time following treatment. The length of survival and time to metastasis is a critical endpoint for us, however it is the not primary endpoint of this study. Our canine treatments consist of 6 x 6 Gy radiation treatments and 4 x 200 ug intra-tumoral VLP treatments. The treatments are given concurrently, every other day for two weeks. Tumor biopsies and blood samples are taken, before treatment, one week into treatment, immediately following treatment, one week following treatment and at 2 – 4 week intervals thereafter for the first six months post therapy. Dogs are intubated and under surgical plane anesthesia (with continuous intravenous access) for all procedures. All procedures are approved by the Dartmouth College Institutional Animal Care and Use Committee (IACUC) and adhere to all USDA, AAALAC, and institutional guidelines.