Detection of Age-Related Somatic Alterations in Canine Blood Using Next-Generation Sequencing-Based Liquid Biopsy: An Analysis of over 4800 Dogs

Kruglyak, Kristina M.; O'Kell, Allison L; Cohen, Todd A.; Marshall, Maggie A.; Ruiz-Pérez, Carlos A.; Marass, Francesco; Tynan, John A.; Hicks, Susan C.; Lytle, Katherine M.; Phelps-Dunn, Ashley; Brandstetter, Gina; Warren, Chelsea D.; DiMarzio, Lauren R.; Rosentel, Michelle C.; Wong, Lilian K.; McLennan, Lisa; Rafalko, Jill; Grosu, Daniel S.; Chibuk, Jason; Chorny, Ilya; McCleary‐Wheeler, Angela L.; Flory, Andi; Tsui, Dana

doi:10.3390/vetsci10070455

Cited by 4 publications

(1 citation statement)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5 Referred to as "NGS-based liquid biopsy", this test was clinically validated to detect 30 different cancer types, with a low false positive rate, in the CANcer Detection in Dogs (CANDiD) study. 6 Since 2021, the test has been used clinically in thousands of dogs 7 , with the majority of samples submitted for screening of high-risk dogs with no current suspicion of cancer. 8 A separate study, involving a subset of subjects from the CANDiD study, showed that NGS-based liquid biopsy has the ability to detect cancer preclinically, as well as at an early disease stage, making it a promising tool to increase early cancer detection when added to a wellness visit.…”

Section: Introductionmentioning

confidence: 99%

Study Design and Interim Analysis of the Cancer Lifetime Assessment Screening Study in Canines (CLASSiC): The First Prospective Cancer Screening Study in Dogs Using Next-Generation Sequencing-Based Liquid Biopsy

Flory,

Gray,

McLennan

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

OBJECTIVE The Cancer Lifetime Assessment Screening Study in Canines (CLASSiC) is a prospective, longitudinal cancer screening study, in which enrolled dogs are screened for cancer with physical exams and next-generation sequencing-based liquid biopsy testing on a serial basis. The goals of the first interim analysis, presented here, are to assess the benefits of using the OncoK9® liquid biopsy test as a cancer screening tool in a prospective clinical setting, and to demonstrate test performance for cancer detection, including preclinical detection. SUBJECTS 726 presumably cancer-free client-owned dogs were prospectively enrolled in the study across 24 clinical sites in the US and Canada. Most subjects were at high risk of cancer at the time of enrollment based on age and/or breed. 419 dogs that were enrolled for at least one year and had at least two cancer screening study visits, or that had received a definitive or presumptive diagnosis of cancer up to the time of the interim analysis, were included in the analysis. METHODS Clinical data and a blood sample were collected at each study visit (once or twice per year and when cancer was clinically suspected). Cell-free DNA extracted from plasma was tested by OncoK9® using next-generation sequencing (NGS) technology. RESULTS 417 dogs were eligible for inclusion in the interim analysis and had classifiable outcomes, with a mean on-study duration of 422 days. Of these, 51 dogs were newly diagnosed with cancer (37 definitive, 14 presumptive), translating to a 12% (51/417) observed incidence over the study period; the liver, skin, bone, heart, spleen, lung, and lymph node(s) were the most common anatomic locations for disease. The prospectively observed sensitivity (detection rate) of the test was 56.9% (95% CI: 42.3-70.4%) with a specificity of 98.9% (95% CI: 97.0-99.6%). The prospectively observed positive predictive value was 87.9% (95% CI: 70.9-96.0%) and the negative predictive value was 94.3% (95% CI: 91.3-96.3%). NGS-based liquid biopsy doubled the overall number of cancer cases detected in this study population (from 25 to 51); remarkably, the detection rate for preclinical cancer was increased 4.6-fold from 12% (6/51) by routine care alone to 55% (28/51) by combining routine care with OncoK9® testing. CLINICAL RELEVANCE CLASSiC is the first study to prospectively document the incidence of cancer in a predominantly high-risk canine population, and to prospectively demonstrate that the addition of NGS-based cancer screening to regularly scheduled wellness visits has the potential to substantially increase preclinical cancer detection in this population.

show abstract

Section: Introductionmentioning

confidence: 99%

Study Design and Interim Analysis of the Cancer Lifetime Assessment Screening Study in Canines (CLASSiC): The First Prospective Cancer Screening Study in Dogs Using Next-Generation Sequencing-Based Liquid Biopsy

Flory,

Gray,

McLennan

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Standardized bone marrow assessment, risk variables, and survival in dogs with myelodysplastic syndrome and acute myeloid leukemia

Meredith,

Beeler-Marfisi,

Berke

et al. 2024

Vet Pathol

View full text Add to dashboard Cite

Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are heterogeneous neoplasms of hematopoietic stem cells that are challenging to diagnose, differentiate, and prognosticate. Cytogenetic and mutational analyses are useful in humans but unavailable for dogs, where diagnosis and classification still rely largely on hematologic and morphologic assessment. The objectives of this study were to apply a classification scheme to myeloid neoplasms and to assess outcome in relation to predictor variables. Keyword search of a laboratory database, application of sequential exclusion criteria, and consensus from 3 reviewers yielded 70 cases of myeloid neoplasia with hematology results, and cytologic (11), histologic (14), or both (45) types of marrow specimens. Based on blast percentage and morphology, 42 cases were classified as MDS and 28 as AML. Dogs with MDS had significantly lower body weights, hemoglobin concentrations and blood blasts, and higher red blood cell size variability and platelet numbers than dogs with AML. Estimates of median survival using Kaplan-Meier curves for dogs with MDS and AML were 384 and 6 days, respectively ( P < .001). The instantaneous risk of death for dogs with MDS was approximately 5× lower than that of dogs with AML. Significant predictor variables of survival were body weight, white blood cell count, platelet count, and percent blood blasts ( P < .05). Hazard ratios (HRs) derived from best-fitting Cox regression models were 1.043, 0.998, and 1.061 for increased neutrophils, decreased platelets, and increased blood blasts, respectively. Findings from this study suggest that hematologic and morphologic variables are useful to predict outcomes in myeloid neoplasia.

show abstract

Proof-of-concept evaluation of next-generation sequencing-based liquid biopsy for non-invasive cancer detection in cats

Ruiz-Perez,

Nakashe,

Marshall

et al. 2024

Front. Vet. Sci.

View full text Add to dashboard Cite

This proof-of-concept evaluation demonstrates that next-generation sequencing-based liquid biopsy can detect genomic alterations in the blood of cats with cancer and the absence of such alterations in the blood of presumably cancer-free cats. Two cats with cytologically confirmed lymphoma and nine presumably cancer-free cats were included in this analysis. Whole blood was collected from each subject and samples were subjected to DNA extraction, library preparation, and next-generation sequencing. Both cancer-diagnosed subjects had somatic copy number variants (a “cancer signal”) identified in cell-free DNA, suggesting the current presence of cancer in these subjects. All nine presumably cancer-free subjects had unremarkable genomic profiles, suggesting the absence of cancer in these subjects. Liquid biopsy using next-generation sequencing of cell-free DNA allows for blood-based detection of cancer-associated genomic alterations in cats. Such technology has the potential to offer considerable utility in veterinary medicine, particularly for the non-invasive prioritization of small cell intestinal lymphoma versus inflammatory bowel disease in cats with gastrointestinal signs. This study lays the foundation for future studies to fully validate this type of testing for use in clinical practice.

show abstract

Detection of Age-Related Somatic Alterations in Canine Blood Using Next-Generation Sequencing-Based Liquid Biopsy: An Analysis of over 4800 Dogs

Cited by 4 publications

References 12 publications

Study Design and Interim Analysis of the Cancer Lifetime Assessment Screening Study in Canines (CLASSiC): The First Prospective Cancer Screening Study in Dogs Using Next-Generation Sequencing-Based Liquid Biopsy

Study Design and Interim Analysis of the Cancer Lifetime Assessment Screening Study in Canines (CLASSiC): The First Prospective Cancer Screening Study in Dogs Using Next-Generation Sequencing-Based Liquid Biopsy

Standardized bone marrow assessment, risk variables, and survival in dogs with myelodysplastic syndrome and acute myeloid leukemia

Proof-of-concept evaluation of next-generation sequencing-based liquid biopsy for non-invasive cancer detection in cats

Contact Info

Product

Resources

About