Background: Feline nasal lymphoma (NLSA) is a condition for which no standard of care exists. Hypothesis: There is no difference in survival times of cats with NLSA treated with single or multimodality therapy. Animals: Records from 97 cats diagnosed with NLSA were examined. Methods: The purpose of this retrospective study was to compare the survival times of cats with NLSA treated with radiation therapy (RT) alone, chemotherapy alone, or RT 1 chemotherapy and identify potential prognostic variables that affected survival. Cats were grouped according to therapy: RT 1 chemotherapy (n 5 60), RT alone (n 5 19), or chemotherapy alone (n 5 18).Results: Survival was calculated with 2 methods. The 1st survival analysis (method A) included all cats, but counted only deaths caused by progressive NLSA. The median survival time (MST), regardless of therapy modality, was 536 days. The 2nd survival analysis (method B) also included all cats and counted all deaths, regardless of cause, as events. The overall MST calculated for all deaths was 172 days. A negative independent prognostic variable identified was anemia (P o .001), and positive independent prognostic variables were a complete response to therapy (P o .001) and total radiation dose 432 Gy (P 5 .03).Conclusions and Clinical Importance: There were no significant differences in survival times among the 3 treatment groups but these results suggest that the addition of higher doses of RT to a cat's treatment protocol may control local disease and therefore influence survival.

Dogs, with their breed-determined limited genetic background, are great models of human disease including cancer. Canine B-cell lymphoma and hemangiosarcoma are both malignancies of the hematologic system that are clinically and histologically similar to human B-cell non-Hodgkin lymphoma and angiosarcoma, respectively. Golden retrievers in the US show significantly elevated lifetime risk for both B-cell lymphoma (6%) and hemangiosarcoma (20%). We conducted genome-wide association studies for hemangiosarcoma and B-cell lymphoma, identifying two shared predisposing loci. The two associated loci are located on chromosome 5, and together contribute ~20% of the risk of developing these cancers. Genome-wide p-values for the top SNP of each locus are 4.6×10-7 and 2.7×10-6, respectively. Whole genome resequencing of nine cases and controls followed by genotyping and detailed analysis identified three shared and one B-cell lymphoma specific risk haplotypes within the two loci, but no coding changes were associated with the risk haplotypes. Gene expression analysis of B-cell lymphoma tumors revealed that carrying the risk haplotypes at the first locus is associated with down-regulation of several nearby genes including the proximal gene TRPC6, a transient receptor Ca2+-channel involved in T-cell activation, among other functions. The shared risk haplotype in the second locus overlaps the vesicle transport and release gene STX8. Carrying the shared risk haplotype is associated with gene expression changes of 100 genes enriched for pathways involved in immune cell activation. Thus, the predisposing germ-line mutations in B-cell lymphoma and hemangiosarcoma appear to be regulatory, and affect pathways involved in T-cell mediated immune response in the tumor. This suggests that the interaction between the immune system and malignant cells plays a common role in the tumorigenesis of these relatively different cancers.

Purpose:To test that prospective delivery of higher thermal dose is associated with longer tumor control duration. Experimental Design: 122 dogs with a heatable soft tissue sarcoma were randomized to receive a low (2-5 CEM43jCT90) or high (20-50 CEM43jCT90) thermal dose in combination with radiotherapy. Most dogs (90%) received four to six hyperthermia treatments over 5 weeks. Results: In the primary analysis, median (95% confidence interval) duration of local control in the low-dose group was1.2 (0.7-2.1) years versus1.9 (1.4-3.2) years in the high-dose group (log-rank P = 0.28). The probability (95% confidence interval) of tumor control at 1 year in the low-dose versus high-dose groups was 0.57 (0.43-0.70) versus 0.74 (0.62-0.86), respectively. Using multivariable procedure, thermal dose group (P = 0.023), total duration of heating (P = 0.008), tumor volume (P = 0.041), and tumor grade (P = 0.027) were significantly related to duration of local tumor control. When correcting for volume, grade, and duration of heating, dogs in the low-dose group were 2.3 times as likely to experience local failure. Conclusions: Thermal dose is directly related to local control duration in irradiated canine sarcomas. Longer heating being associated with shorter local tumor control was unexpected. However, the effect of thermal dose on tumor control was stronger than for heating duration. The heating duration effect is possibly mediated through deleterious effects on tumor oxygenation. These results are the first to show the value of prospectively controlled thermal dose in achieving local tumor control with thermoradiotherapy, and they establish a paradigm for prescribing thermoradiotherapy and writing a thermal prescription.

ABSTRACT:The efficiency of germ cell transplantation, the procedure of transferring germ cells from a donor male into the testes of recipient males, can be greatly increased by reduction of endogenous germ cells in recipient animals. To develop effective methods for suppression of endogenous spermatogenesis in potential pig and goat recipients, we either administered busulfan to pregnant sows or irradiated the testes of immature goats. Piglets from sows treated twice with busulfan (7.5 mg/kg) at days 98 and 108 of gestation showed reduced gonocyte numbers at 2, 4, and 8 weeks of age and reduced initiation of spermatogenesis at 16 weeks of age. For goats, groups of 3 kids at 1, 5, or 9.5 weeks of age received fractionated irradiation of the testes with 3 doses of 2 Gy on 3 consecutive days. At 2 months after irradiation, 5%-10% of seminiferous tubule cross sections contained pachytene spermatocytes, compared with 50%-100% in controls. At 3 months after irradiation, spermatozoa appeared in 20% of tubule cross sections in all treated goats and in 100% of tubules in control goats. By 6 months after irradiation, spermatogenesis had recovered in 60% of tubules in goats treated at 5 or 9.5 weeks of age but in only 29% of tubules after treatment at 1 week of age. Therefore, late gestation in utero treatment of pigs with low doses of busulfan and testicular irradiation of goats at 1 week of age will result in a reduction in the endogenous germ cell population that could facilitate donor cell colonization after germ cell transplantation.

Accurate assessments of therapeutic efficacy are confounded by intra-and intertumor heterogeneity. To address this issue we employed multispectral (MS) analysis using the apparent diffusion coefficient (ADC), T 2 , proton density (M 0 ), and k-means (KM) clustering algorithm to identify multiple compartments within both viable and necrotic tissue in a radiation-induced fibrosarcoma (RIF-1) tumor model receiving single-dose (1000 cGy) radiotherapy. Optimization of the KM method was achieved through histological validation by hematoxylin-eosin (H&E) staining and hypoxia-inducible factor-1␣ (HIF-1␣) immunohistochemistry. The optimum KM method was determined to be a two-feature (ADC, T 2 ) and four-cluster (two clusters each of viable tissue and necrosis) segmentation. KM volume estimates for both viable (r ‫؍‬ 0.94, P < 0.01) and necrotic (r ‫؍‬ 0.69, P ‫؍‬ 0.07) tissue were highly correlated with their H&E counterparts. HIF-1␣ immunohistochemistry showed that the intensity of HIF-1␣ expression tended to be concentrated in perinecrotic regions, supporting the subdivision of the viable tissue into well-oxygenated and hypoxic regions. Since both necrosis and hypoxia have been implicated in poor treatment response and reduced patient survival, the ability to quantify the degree of necrosis and the severity of hypoxia with this method may aid in the planning and modification of treatment regimens. Magn Reson Med 57:501-512, 2007.