Response to DNA vaccination in dogs with oral MM may be useful in development of plasmid DNA vaccination protocols for human patients with similar disease.

An excellent long-term survival rate may be achieved by treating soft-tissue sarcomas in dogs with resection followed by radiation. Amputation is not necessary for long-term control of soft-tissue sarcomas in limbs. Development of metastases and recurrence of local tumors after radiation treatment are associated with decreased survival rate. Acute and delayed radiation toxicosis was minimal with the protocol used in this study.

A fundamental problem in cancer drug development is that antitumor efficacy in preclinical cancer models does not translate faithfully to patient outcomes. Much of early cancer drug discovery is performed under in vitro conditions in cell-based models that poorly represent actual malignancies. To address this inconsistency, we have developed a technology platform called CIVO, which enables simultaneous assessment of up to eight drugs or drug combinations within a single solid tumor in vivo. The platform is currently designed for use in animal models of cancer and patients with superficial tumors but can be modified for investigation of deeper-seated malignancies. In xenograft lymphoma models, CIVO microinjection of well-characterized anticancer agents (vincristine, doxorubicin, mafosfamide, and prednisolone) induced spatially defined cellular changes around sites of drug exposure, specific to the known mechanisms of action of each drug. The observed localized responses predicted responses to systemically delivered drugs in animals. In pair-matched lymphoma models, CIVO correctly demonstrated tumor resistance to doxorubicin and vincristine and an unexpected enhanced sensitivity to mafosfamide in multidrug-resistant lymphomas compared with chemotherapy-naïve lymphomas. A CIVO-enabled in vivo screen of 97 approved oncology agents revealed a novel mTOR (mammalian target of rapamycin) pathway inhibitor that exhibits significantly increased tumor-killing activity in the drug-resistant setting compared with chemotherapy-naïve tumors. Finally, feasibility studies to assess the use of CIVO in human and canine patients demonstrated that microinjection of drugs is toxicity-sparing while inducing robust, easily tracked, drug-specific responses in autochthonous tumors, setting the stage for further application of this technology in clinical trials.

Surgery, chemotherapy, and irradiation have been used singly or in combination to treat dogs with cutaneous grade-2 mast cell tumors (MCT). However, optimal treatment has not been established. At The Animal Medical Center, 32 dogs with grade 2, stage 0 MCT received cobalt radiation treatment to a dose of 54 Gy; 94% had a disease-free interval of 1 year. The 2-,3-,4-, and 5-year disease-free intervals were 86%. Survival rates were 100% for 1 year and 96% for 2 to 5 years, with only 1 death caused by MCT. Primary site was not a prognostic factor for survival in this study. Minimal ast cell tumors (MCTs) are common in dogs, compris-M ing 7% to 21% of all cutaneous neoplasms.' The average age at diagnosis is 8.5 years, and Boxers, Boston Terriers, Bull Terriers, and Labrador Retrievers are reportedly at high risk.' Cutaneous MCTs can metastasize to the liver, spleen, kidney, and regional lymph nodes, as well as to other areas of the skin. MCTs of the inguinal, scrotal, or perineal regions have been reported to have a poorer prognosis than those on the trunk or extremities.'MCTs have been graded histologically by a number of different methods, and studies show that histologic grade is prognostically signifi~ant."~ In general, using the system devised by Patnaik et a],' grade 1 MCTs are considered to be well-differentiated tumors that have a good prognosis when treated with surgery alone. Grade 3 MCTs are anaplastic and infiltrative, with aggressive local and systemic behavior. Local treatments, such as surgery or radiation therapy (RT) alone, are not adequate for dogs with grade 3 tumors. Although less aggressive than grade 3 MCTs, grade 2 MCTs are not well-differentiated, and are locally infiltrative. Recurrence of grade 2 MCTs has been reported in 50% of dogs treated with surgery alone, with an approximate time to recurrence of 6 months in 1 r e p~r t .~.~ The reported 5-year survival time in 1 group of dogs with grade 2 MCTs treated by surgery alone was 44%.* Clinical stage has been found to have a marked effect on prognosis in dogs with MCTs. In fact, both disease-free interval (DFI) and survival rate decrease in dogs with advanced-stage disease.' Stage of disease also may dictate the best treatment options for dogs with MCT, since dogs with local or regional disease are best treated with localized therapy, such as surgery or RT, and dogs with infiltrative or metastatic disease might need systemic treatment, such as chemotherapy.