The biological behavior of MCTs is highly variable and improvements in understanding of the natural history and prognostic indicators as well as the indications for multimodal therapy, will further result in better outcomes in canine patients with MCT. PATHOGENESIS OF MCTsThe aetiology of MCTs is unknown but, as with most neoplasms is probably multi-factorial, and the well- Mutations of c-kit, characterized by internal tandem duplications, produce a constitutively activated KIT protein in the absence of ligands 35,49,58 that leads to extracellular signal-regulated kinase phosphorylation. 58 Little is known about the consequences of these mutations. However, c-kit mutations and aberrant KIT protein localization are associated with increased expression of Ki67 and argyrophilic nucleolar organizing regions (AgNORs), both of which are markers of increased cellular proliferation. 47 Moreover, in vitro testing of drugs targeting the KIT tyrosine kinase receptor demonstrated inhibition of proliferation of canine MCT cell lines and primary neoplastic MCs, associated with cell-cycle arrest and apoptosis. 59 Despite these findings, no genetic defects in c-kit are identified in more than 60% of canineMCTs. This suggests that, mutations in this gene are associated with the development or progression of some MCTs, but mutations in other genes are likely to be involved in the initiation and progression of most canine MCTs.
Thirty-seven cases of histiocytic-like sarcomas (HLSs) in flat-coated retriever dogs were evaluated retrospectively. This tumour accounted for 36% of the malignant tumours seen in this breed during the study period. The median age at presentation was 8.2 years. Thirty-four dogs presented with a swelling or mass in a muscle group or surrounding a joint. The remaining three presented for rib (1), cutaneous (1) or primary splenic origin (1). A high rate of metastasis to local lymph nodes (45%), thorax (20%) and abdominal organs (20% confirmed) was seen. Overall metastastic rate by the time of death was 70%. The median survival for all dogs was 123 days. The most significant prognostic indicator was presence of distant metastasis at the time of diagnosis with median survival of 68 or 200 days, with or without metastasis, respectively. Chemotherapy and radiation therapy significantly improved survival. Dogs given chemotherapy survived a median of 185 versus 34 days for dogs that were not (P = 0.0008). Dogs treated with radiation survived a median of 182 versus 60 days for those that were not (P = 0.0282). Dogs receiving only palliative therapy survived a median of 17 versus 167 days in dogs receiving any kind of radiation, chemotherapy, surgery or combinations. A set protocol of radiation and CCNU (RTCCNU) induced minimal toxicity and provided a median survival of 208 versus 68 days for all other dogs. While this tumour carries a poor long-term prognosis in flat-coated retrievers, it is reasonable to treat these dogs for palliation of signs and extension of life.
Locoregional lymph nodes are routinely examined in order to define the spatial extent of neoplastic disease. As draining patterns of certain tumor types can be divergent from expected anatomical distribution, it is critical to sample the lymph nodes truly representing the draining area. The aim of this bicenter prospective pilot study was to describe the technique of computed tomographic (CT)-lymphography for primary draining lymph node mapping in tumor staging in dogs. Forty-five dogs with macro- or microscopic tumors in specified localizations were evaluated. Depending on body weight, 0.8-2 ml contrast agent (iohexol) was injected into four quadrants around the tumor, and CT-images were obtained at 1, 3, 6, 9, and 12 minutes post-injection. Attenuation of chosen regions of interest (Hounsfield units (HU)) and patterns of enhancement were assessed for 284 lymph nodes in the precontrast study with median HUs of 31.1 (Interquartile range (IQR) = 18.4) and for 275 in the intravenous postcontrast study with 104.3 HU (IQR = 31.2) (paired Wilcoxon test, P < 0.001). In the CT-lymphography study, 45 primary draining lymph nodes with a significantly higher median HU value of 348.5 (IQR = 591.4) (one-sample t-test, P < 0.001) were identified. Primary draining lymph nodes were found to be clearly visible after 1-3 minutes after local injection, often concurrent with a good visibility of the lymphatic vessel system. The herein described technique of peritumorally injected CT-contrast agent followed by subsequent CT-lymphography for primary draining lymph node mapping works well in a majority of cases in all investigated sites and warrants further validation for different tumor entities.
Radiation therapy is the treatment of choice for many primary canine brain tumors. The radiation dose tolerated by surrounding healthy brain tissue can be a limiting factor for radiation treatment and total dose as well as fractionation schedules, and volume effects may play a role in the outcome of patients undergoing radiation therapy. The purpose of this retrospective study was to evaluate the efficacy of radiation therapy in dogs with brain tumors that showed signs of neurologic disease. Forty-six dogs with brain tumors were included in the analysis. In 34 dogs, computer-generated treatment plans were available, and dose-volume data could be obtained. The totally prescribed radiation therapy doses ranged from 35 to 52.5 Gy (mean = 40.9 [SD +/- 2.91) applied in 2.5- to 4-Gy fractions (mean = 3.2). The median overall survival time calculated for deaths attributable to worsening of neurologic signs was 1,174 days (95% confidence interval [CI], 693-1,655 days). Assuming that all deaths were due to disease or treatment consequences, the median survival time was 699 days (95% CI, 589-809 days). No prognostic clinical factors such as the location or size of the tumor or neurologic signs at presentation were identified. With computerized treatment planning and accurate positioning, high doses of radiation (> 80% of the total dose) could be limited to mean relative brain volumes of 35.3% (+/- 12.6). These small volumes may decrease the probability of severe late effects such as infarction or necrosis. In this study, very few immediate or early delayed adverse effects and no late effects were noted, and quality of life was good to excellent.
We retrospectively evaluated predictive prognostic factors in 73 cats with vaccine-associated sarcoma given postsurgical curative (n=46, most with clean margins) or coarse fractionated radiotherapy (n=27, most with either macroscopic disease or dirty margins). The former animals displayed a median survival of 43 months and a median progression free interval (PFI) of 37 months, the latter reached a median survival of 24 months and a median PFI of 10 months. In cats undergoing coarse fractionated therapy, factors predictive of a better outcome included lack of visible mass (n=10) as opposed to macroscopic disease (n=17, survival: 30 vs. 7 months, P=0.025; PFI: 20 vs. 4 months, P=0.01), adjuvant chemotherapy for gross disease (n=5/17, survival: 29 vs. 5 months, P=0.04) and a smaller number of surgeries preceding radiation therapy (Coeff=0.41, P=0.03). The Ki67-index was not predictive for survival. We concluded that postsurgical curative and coarse fractionated radiotherapy are both effective legitimate options for managing vaccine-associated sarcomas. months and a median PFI of 10 months. In cats undergoing coarse fractionated therapy,
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