Cancer detection in clinical practice and using blood-based liquid biopsy: A retrospective audit of over 350 dogs

Cancer detection in clinical practice and using blood-based liquid biopsy: A retrospective audit of over three hundred fifty dogs

Abbreviations: CANDID, CANcer Detection in Dogs; CLASSIC, Cancer Lifetime Assessment Screening Study in Canines; CSO, Cancel Signal Origin; IACUC, Institutional Animal Care and Use Committee; MCED, multicancer early detection; NGS, next-generation sequencing.

Abstract

Background: Guidelines-driven screening protocols for early cancer detection in dogs are lacking, and cancer often is detected at advanced stages.

Hypothesis/Objectives: To examine how cancer typically is detected in dogs and whether the addition of a next-generation sequencing-based "liquid biopsy" test to a wellness visit has the potential to enhance cancer detection.

Animals: Client-owned dogs with definitive cancer diagnoses enrolled in a clinical validation study for a novel blood-based multicancer early detection test.

Methods: Retrospective medical record review was performed to establish the history and presenting complaint that ultimately led to a definitive cancer diagnosis. Blood samples were subjected to DNA extraction, library preparation, and next-generation sequencing. Sequencing data were analyzed using an internally developed bioinformatics pipeline to detect genomic alterations associated with the presence of cancer.

Results: In an unselected cohort of three hundred fifty-nine cancer-diagnosed dogs, four percent of cases were detected during a wellness visit, eight percent were detected incidentally, and eighty-eight percent were detected after the owner reported clinical signs suggestive of cancer. Liquid biopsy detected disease in fifty-four point seven percent of patients, including thirty-two percent of dogs with early-stage cancer, forty-eight percent of preclinical dogs, and eighty-four percent of dogs with advanced-stage disease.

Conclusions/Clinical Importance: Most cases of cancer were diagnosed after the onset of clinical signs; only four percent of dogs had cancer detected using the current standard of care (i.e., wellness visit). Liquid biopsy has the potential to increase detection of cancer when added to a dog's wellness visit.

One INTRODUCTION |

The value of early cancer detection using routine screening protocols has been clearly established in people, with formal guidelines in place over the past few decades for multiple cancer types. As such, human medicine employs multiple screening modalities including traditional, site-specific approaches (e.g., mammography, colonoscopy), as well as newer site-agnostic approaches (e.g., blood-based multican- cer early detection testing) to increase the opportunity for early detection. In veterinary medicine, professional organizations recognize the importance of early cancer detection for optimal patient outcomes, but no formal screening guidelines currently exist, and cancer in dogs often is detected at advanced stages. The term "early cancer detection" can be conceptualized as detection of cancer at an early disease stage (i.e., "early-stage detection"), or detection of cancer before the onset of clinical signs (i.e., "preclinical detection"). Early-stage detection can occur regardless of the presence of clinical signs, and preclinical detection can occur regardless of formal disease stage.

The current standard of care for cancer detection in dogs is the annual or semiannual wellness visit, which typically consists of a history and thorough physical examination, and may include a minimum database (CBC, serum biochemistry panel, and urinalysis). Recently, a novel, blood-based cancer screening tool called liquid biopsy became clinically available for use in dogs. In short, this testing method employs next-generation sequencing technology to analyze fragments of cell-free DNA in a dog's blood to identify the presence of cancer-associated genomic alterations. Although this technology is hypothesized to increase the detection of cancer when added to a dog's wellness visit, the extent of this benefit has not yet been quantified.

The purpose of our study was two-fold. The first was to examine how cancer currently is detected in dogs. The second was to determine whether the addition of liquid biopsy to a dog's wellness visit could enhance the number and type of cancer cases detected, with particular focus on preclinical and early-stage cancer detection. To achieve these goals, a retrospective chart review was performed for a cohort of dogs with definitive diagnoses of cancer to determine the presenting complaint that ultimately led to the diagnosis of cancer in these patients, and then the percentage of cases detected by the current standard of care (wellness visit) was examined in relation to the detection rate of liquid biopsy.