Cancer is the leading cause of death in dogs, yet there are no established screening paradigms for early detection. Liquid biopsy methods that interrogate cancer-derived genomic alterations in cell-free DNA in blood are being adopted for multi-cancer early detection in human medicine and are now available for veterinary use. The CANcer Detection in Dogs (CANDiD) study is an international, multi-center clinical study designed to validate the performance of a novel multi-cancer early detection “liquid biopsy” test developed for noninvasive detection and characterization of cancer in dogs using next-generation sequencing (NGS) of blood-derived DNA; study results are reported here. In total, 1,358 cancer-diagnosed and presumably cancer-free dogs were enrolled in the study, representing the range of breeds, weights, ages, and cancer types seen in routine clinical practice; 1,100 subjects met inclusion criteria for analysis and were used in the validation of the test. Overall, the liquid biopsy test demonstrated a 54.7% (95% CI: 49.3–60.0%) sensitivity and a 98.5% (95% CI: 97.0–99.3%) specificity. For three of the most aggressive canine cancers (lymphoma, hemangiosarcoma, osteosarcoma), the detection rate was 85.4% (95% CI: 78.4–90.9%); and for eight of the most common canine cancers (lymphoma, hemangiosarcoma, osteosarcoma, soft tissue sarcoma, mast cell tumor, mammary gland carcinoma, anal sac adenocarcinoma, malignant melanoma), the detection rate was 61.9% (95% CI: 55.3–68.1%). The test detected cancer signal in patients representing 30 distinct cancer types and provided a Cancer Signal Origin prediction for a subset of patients with hematological malignancies. Furthermore, the test accurately detected cancer signal in four presumably cancer-free subjects before the onset of clinical signs, further supporting the utility of liquid biopsy as an early detection test. Taken together, these findings demonstrate that NGS-based liquid biopsy can offer a novel option for noninvasive multi-cancer detection in dogs.

Genetic polymorphisms of various cytochromes P450 have recently been described and could be implicated in the individual susceptibility of alcoholics to ethanol-related diseases. Rsal and Dral polymorphisms of CYP2E1 and Mspl polymorphism of CYP1A1 were studied in 260 controls and 511 alcoholic patients, without any clinical symptoms (n = 202) or with various ethanol-related diseases (n = 309), such as liver cirrhosis (n = 110), esophageal cancer (n = 62), upper aerodigestive tract cancer (n = 96), and other miscellaneous diseases (n = 41). Frequencies of the mutated alleles were found to be 2.5% (Rsal), 7.9% (Dral), and 8.7% (Mspl) in controls; 4%, 14.1%, and 12% in alcoholics without clinical symptoms; and 3.1%, 12.5%, and 11.2% in alcoholics with ethanol-related diseases. The only significant difference was found in the Dral polymorphism, whose frequency was enhanced in alcoholics with (p < 0.05) or without ethanol-related diseases (p < 0.01) when compared with controls. No differences were found between alcoholics without clinical symptoms and alcoholics with cirrhosis, esophageal cancer, or upper aerodigestive tract cancer. However, in liver cirrhosis and in ethanol-related cancers, the rare Dral-C allele was three times less frequent in patients under the age of 45 than in older patients, suggesting a protective role for this allele. In conclusion, our data indicate that the aforementioned mutations do not play a critical role in the development of cirrhosis, esophageal cancer, or upper aerodigestive tract cancers in Caucasians.

Background Serum thymidine kinase 1 (sTK1) activity is closely correlated with DNA synthesis. Objectives Evaluate sTK1 activity as a biomarker for treatment response and early detection of relapse in dogs with lymphoma. Animals Ninety‐seven client‐owned dogs with naive or relapsed lymphoma and 23 healthy dogs. Methods Prospective study. Serum TK1 activity measured by refined ELISA‐based method (DiviTum assay, Biovica International) before treatment, at clinical response, and every 4 weeks until relapse or last follow‐up. Results Serum TK1 activity was ≤20 Du/L in 96% (22/23) of healthy dogs. Pretreatment sTK1 activity was >20 Du/L in 88% (85/97) dogs with lymphoma. At clinical response, sTK1 activity was significantly lower in dogs with complete (CR, n = 36) versus partial (PR, n = 29) response ( P < .0001). Sensitivity (Se) and specificity (Sp) of sTK1 activity for detecting nonfully responders were 76% and 100%, respectively, with cutoff of 119.5 Du/L (AUC, 0.90; 95%‐CI, 0.81‐0.98; P < .0001). In dogs with CR, a 5‐fold increase in sTK1 activity at a 4‐week interval predicted relapse at the subsequent 4‐week assessment with a Se 50% and Sp 94% (AUC, 0.72; 95%‐CI, 0.55‐0.90; P = .02). An increase of sTK1 activity (>2.7‐fold value measured at clinical response) predicted relapse at subsequent 4‐week assessment with a Se 61% and Sp 88% (AUC, 0.79; 95%‐CI, 0.64‐0.95; P = .004). Conclusions and Clinical Importance Monitoring sTK1 activity could help to detect complete responders and early disease progression in dogs with lymphoma.

This study shows that physiological heart murmurs may not be limited to growing dogs or specific breeds, as they were commonly encountered in this population of healthy young adult dogs.