Clinical validation of a next-generation sequencing-based multi-cancer early detection "liquid biopsy" blood test in over 1,000 dogs using an independent testing set: The CANcer Detection in Dogs (CANDiD) study.

Autor: Flory A; PetDx, La Jolla, California, United States of America.; Veterinary Specialty Hospital of San Diego, San Diego, California, United States of America.; Veterinary Specialty Hospital of North County, San Marcos, California, United States of America., Kruglyak KM; PetDx, La Jolla, California, United States of America., Tynan JA; PetDx, La Jolla, California, United States of America., McLennan LM; PetDx, La Jolla, California, United States of America., Rafalko JM; PetDx, La Jolla, California, United States of America., Fiaux PC; PetDx, La Jolla, California, United States of America., Hernandez GE; PetDx, La Jolla, California, United States of America., Marass F; PetDx, La Jolla, California, United States of America., Nakashe P; PetDx, La Jolla, California, United States of America., Ruiz-Perez CA; PetDx, La Jolla, California, United States of America., Fath DM; PetDx, La Jolla, California, United States of America., Jennings T; PetDx, La Jolla, California, United States of America., Motalli-Pepio R; PetDx, La Jolla, California, United States of America., Wotrang K; PetDx, La Jolla, California, United States of America., McCleary-Wheeler AL; PetDx, La Jolla, California, United States of America.; Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, Missouri, United States of America., Lana S; Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado, United States of America., Phillips B; Veterinary Specialty Hospital of San Diego, San Diego, California, United States of America., Flesner BK; Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, Missouri, United States of America.; Department of Clinical Science and Advanced Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America., Leibman NF; The Animal Medical Center, New York, New York, United States of America., LaDue T; Southeast Veterinary Oncology and Internal Medicine, Orange Park, Florida, United States of America., Tripp CD; Bridge Animal Referral Center, Edmonds, Washington, United States of America., Coomber BL; Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada., Woods JP; Institute for Comparative Cancer Investigation at the Mona Campbell Centre for Animal Cancer, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada., Miller M; Veterinary Specialty Hospital of North County, San Marcos, California, United States of America., Aiken SW; Veterinary Specialty Hospital of San Diego, San Diego, California, United States of America., Wolf-Ringwall A; Department of Veterinary Clinical Sciences, University of Minnesota, College of Veterinary Medicine, Saint Paul, Minnesota, United States of America., Borgatti A; Department of Veterinary Clinical Sciences, University of Minnesota, College of Veterinary Medicine, Saint Paul, Minnesota, United States of America., Kraska K; Veterinary Specialty Hospital of San Diego, San Diego, California, United States of America., Thomson CB; Veterinary Specialty Hospital of North County, San Marcos, California, United States of America., Kosanovich Cahalane A; Veterinary Specialty Hospital of Hong Kong, Wan Chai, Hong Kong., Murray RL; Bridge Animal Referral Center, Edmonds, Washington, United States of America., Kisseberth WC; Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, United States of America., Camps-Palau MA; The Animal Medical Center, New York, New York, United States of America., Floch F; Oncovet, Villeneuve-D'ascq, France.; AniCura TRIOVet, Rennes, France., Beaudu-Lange C; Clinique Vétérinaire de la Pierre Bleue, Pipriac, France., Klajer-Peres A; Eiffelvet, Paris, France., Keravel O; Eiffelvet, Paris, France., Fribourg-Blanc LA; Clinique Vétérinaire SeineVet, Rouen, France., Mazetier PC; Clinique Vétérinaire Mazetier, Argenteuil, France., Marco A; Governor Animal Clinic, Inc., San Diego, California, United States of America., McLeod MB; City Paws Home Health, Columbus, Ohio, United States of America., Portillo E; VCA Valley Oak Veterinary Center, Chico, California, United States of America., Clark TS; VCA Metroplex Animal Hospital, Irving, Texas, United States of America., Judd S; Prices Creek Veterinary Services, Lewisburg, Ohio, United States of America., Feinberg CK; Governor Animal Clinic, Inc., San Diego, California, United States of America., Benitez M; Governor Animal Clinic, Inc., San Diego, California, United States of America., Runyan C; Carlsbad Animal Hospital, Carlsbad, California, United States of America., Hackett L; Oceanside Veterinary Hospital, Oceanside, California, United States of America., Lafey S; Amici Pet Hospital of Little Italy, San Diego, California, United States of America., Richardson D; Institute for Comparative Cancer Investigation at the Mona Campbell Centre for Animal Cancer, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada., Vineyard S; Colony Veterinary Hospital, San Diego, California, United States of America., Tefend Campbell M; Carriage Hills Animal Hospital, Montgomery, Alabama, United States of America., Dharajiya N; Healthbit.ai Inc., San Diego, California, United States of America.; Advisor to PetDx, La Jolla, California, United States of America., Jensen TJ; Laboratory Corporation of America, Durham, North Carolina, United States of America.; Advisor to PetDx, La Jolla, California, United States of America., van den Boom D; Advisor to PetDx, La Jolla, California, United States of America., Diaz LA Jr; Advisor to PetDx, La Jolla, California, United States of America.; Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America., Grosu DS; PetDx, La Jolla, California, United States of America., Polk A; PetDx, La Jolla, California, United States of America., Marsal K; PetDx, La Jolla, California, United States of America., Hicks SC; PetDx, La Jolla, California, United States of America., Lytle KM; PetDx, La Jolla, California, United States of America., Holtvoigt L; PetDx, La Jolla, California, United States of America., Chibuk J; PetDx, La Jolla, California, United States of America., Chorny I; PetDx, La Jolla, California, United States of America., Tsui DWY; PetDx, La Jolla, California, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2022 Apr 26; Vol. 17 (4), pp. e0266623. Date of Electronic Publication: 2022 Apr 26 (Print Publication: 2022).
DOI: 10.1371/journal.pone.0266623
Abstrakt: 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.
Competing Interests: AF, KMK, JAT, LMM, JMR, PCF, GEH, FM, PN, CAR-P, DMF, TJ, RM-P, KW, ALM-W, DSG, AP, KM, SCH, KML, LH, JC, IC, and DWYT are employed by or affiliated with PetDx; and receive compensation from PetDx and/or hold vested or unvested equity in PetDx. Drs. Flesner and Leibman are members of the PetDx clinical advisory board and receive compensation and equity. Dr. Borgatti has ownership interest (including patents) in a patent entitled “Reduction of EGFR therapeutic toxicity” filed by the University of Minnesota Office of Technology Commercialization. Drs. Cahalane, Phillips, and Aiken are investors in PetDx. Drs. Jensen, van den Boom, Dharajiya, and Diaz are advisors for PetDx and hold vested or unvested equity in PetDx. Drs. Chorny, Kruglyak, Grosu, Marass, Ruiz-Perez and Tsui hold pending patent applications related to technology described in this work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Databáze: MEDLINE
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