Outcome in dogs with advanced (stage 3b) anal sac gland carcinoma treated with surgery or hypofractionated radiation therapy.

Stage 3b anal sac gland carcinoma (ASGC) can be life-threatening. A surgical approach is not always possible or may be declined. Dogs with stage 3b ASGC treated with surgery or conformal radiation therapy (RT) with 8 × 3.8 Gy (total dose 30.4 Gy, over 2.5 weeks) were retrospectively evaluated. Patient characteristics, median progression-free interval (PFI) and median survival time (MST) were compared. Twenty-eight dogs were included; 15 underwent surgery, 13 underwent RT. At the time of presentation, 21% showed life-threatening obstipation and 25% showed hypercalcaemia. PFI and MST for surgery cases were 159 days (95% CI: 135-184 days) and 182 days (95% CI: 146-218 days), both significantly lower than for RT cases with 347 days (95% CI: 240-454 days) and 447 days (95% CI: 222-672 days), (P = 0.01, P = 0.019). Surgery as well as RT led to a fast relief of symptoms. PFI and survival of surgical patients were significantly inferior to that of a comparable patient group treated with conformal hypofractionated RT.

Efficacy and side effects of radiation therapy in comparison with radiation therapy and temozolomide in the treatment of measurable canine malignant melanoma.

Prognosis for unresectable canine malignant melanoma (MM) is typically poor, and therapeutic approaches remain largely palliative. A bi-institutional trial was conducted to compare efficacy and safety of radiation therapy (RT) and RT with post-radiation temozolomide in dogs with chemotherapy-naïve, measurable MM. RT consisted of 5 × 6 Gy fractions over 2.5 weeks. Dogs whose owners wished to pursue chemotherapy received adjuvant oral temozolomide (60 mg m-2 for 5 days every 28 days). Fifteen dogs were treated with RT only (Group 1) and 12 dogs subsequently received temozolomide (Group 2). Overall response rate was similar between Group 1 (86.7%) and Group 2 (81.1%). Median time to progression (TTP) was significantly longer in Group 2 (205 days) compared to Group 1 (110 days; p = 0.046). Survival time was not significantly different between groups. Both treatments were well tolerated. Post-radiation temozolomide has a good safety profile, and may improve TTP in MM when compared to coarse fractionated RT.

Immunohistochemical expression of cyclooxygenase-2 in normal, hyperplastic and neoplastic canine lymphoid tissues.

There is much interest in the potential use of selective inhibitors of cyclooxygenase (COX)-2 in combination with other cancer therapeutics. COX-2 is a key enzyme in prostaglandin synthesis and has been implicated in the pathogenesis of numerous canine and feline malignancies. There are few data on the potential role of COX-2 in the pathogenesis of canine lymphoma. The present study examined COX-2 expression in normal, hyperplastic and neoplastic canine lymphoid tissues. Immunohistochemical expression was evaluated in 12 samples of non-pathologically enlarged normal lymph nodes, 24 samples of hyperplastic lymph node and 44 samples of lymphoma (22 B-cell and 22 T-cell lymphomas). The labelling was scored semiquantitatively and a score of +2 or +3 was interpreted as overexpression. In hyperplastic lymph nodes only a few macrophages were COX-2-positive while six of the 44 lymphomas (13.6%; three B- and three T-cell lymphomas) overexpressed COX-2. These data provide a rationale for further investigation of COX-2 expression in canine lymphoma for prognostic, chemopreventive and chemotherapeutic purposes.

Concordance of c-kit mutational status in matched primary and metastatic cutaneous canine mast cell tumors at baseline.

BACKGROUND: Mutation analysis of proto-oncogene c-kit (c-kit) is advisable before starting treatment with tyrosine kinase inhibitors in dogs with mast cell tumor (MCT), including those with metastatic disease. Testing is usually performed on primary tumors, assuming that c-kit mutation status does not change in metastasis. HYPOTHESIS/OBJECTIVES: To give an insight into the mutational processes and to make a recommendation on the use of c-kit mutational analysis in the clinical setting. ANIMALS: Twenty-one client-owned dogs with metastatic MCT. METHODS: Dogs undergoing resection or biopsy for both primary and matched metastatic MCT were prospectively enrolled. Total RNA or DNA was extracted from primary MCT and corresponding metastases. Exons 8, 9, and 11 were amplified by PCR and sequenced. Genetic features between primary MCT and metastases were compared. Their correlation with clinicopathologic features was investigated. RESULTS: Concordance (mutated or wild-type) of mutational status, evaluable in 21 primary and matched metastatic (20 nodal and 1 splenic) MCTs, was 100%. Three new c-kit mutations were identified. No significant correlation was detected between c-kit mutation and clinicopathologic features. CONCLUSIONS AND CLINICAL IMPORTANCE: Proto-oncogene c-kit mutational status is conserved between any primary and its matched secondary tumor, suggesting that both can be used for c-kit mutational testing. Targeted therapies might be also used to treat metastatic disease.

Immunohistochemical expression of COX-2, mPGES and EP2 receptor in normal and reactive canine bone and in canine osteosarcoma.

Accumulating evidence suggests that cyclooxygenase (COX)-2 is involved in the pathogenesis of human and canine osteosarcoma. The aim of this study was to investigate the expression of COX-2 in normal, reactive and neoplastic canine bone and the events downstream to COX-2 that lead to prostaglandin E(2) (PGE(2)) production. COX-2, microsomal PGE(2) synthase-1 (mPGES-1) and the PGE(2) receptor (EP2) were assessed by immunohistochemistry in 12 samples of normal bone, 14 cases of fracture callus and 27 appendicular osteosarcomas. No immunoreactivity to COX-2, mPGES-1 or EP2 receptor was observed in normal bone. Fifty percent of reactive bone samples expressed COX-2 and 57% expressed mPGES-1 and EP2 receptor, although with weak labelling intensity. Ninety-three percent of osteosarcomas expressed COX-2, while mPGES-1 was expressed by 85% and EP2 receptor by 89% of the tumours. The data confirm that COX-2 is expressed at high level in osteosarcoma and support the use of COX-2 inhibitors to improve the response to chemotherapy. The possibility of blocking the EP2 or the selective inhibition of mPGES-1, rather than COX-2 activity, might decrease the incidence of adverse effects that occur due to the inhibition of prostanoids other than PGE(2).