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

• Published in: PloS one 2022-01, Vol.17 (4), p.e0266623
• Main Authors: Andi Flory, Kristina M Kruglyak, John A Tynan, Lisa M McLennan, Jill M Rafalko, Patrick Christian Fiaux, Gilberto E Hernandez, Francesco Marass, Prachi Nakashe, Carlos A Ruiz-Perez, Donna M Fath, Thuy Jennings, Rita Motalli-Pepio, Kate Wotrang, Angela L McCleary-Wheeler, Susan Lana, Brenda Phillips, Brian K Flesner, Nicole F Leibman, Tracy LaDue, Chelsea D Tripp, Brenda L Coomber, J Paul Woods, Mairin Miller, Sean W Aiken, Amber Wolf-Ringwall, Antonella Borgatti, Kathleen Kraska, Christopher B Thomson, Alane Kosanovich Cahalane, Rebecca L Murray, William C Kisseberth, Maria A Camps-Palau, Franck Floch, Claire Beaudu-Lange, Aurélia Klajer-Peres, Olivier Keravel, Luc-André Fribourg-Blanc, Pascale Chicha Mazetier, Angelo Marco, Molly B McLeod, Erin Portillo, Terry S Clark, Scott Judd, C Kirk Feinberg, Marie Benitez, Candace Runyan, Lindsey Hackett, Scott Lafey, Danielle Richardson, Sarah Vineyard, Mary Tefend Campbell, Nilesh Dharajiya, Taylor J Jensen, Dirk van den Boom, Luis A Diaz, Daniel S Grosu, Arthur Polk, Kalle Marsal, Susan Cho Hicks, Katherine M Lytle, Lauren Holtvoigt, Jason Chibuk, Ilya Chorny, Dana W Y Tsui
• Format: Article
• Language: English
• ISSN: 1932-6203
• DOI: 10.1371/journal.pone.0266623

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.