Dataset Information

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.

ABSTRACT: 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.

SUBMITTER: Flory A

PROVIDER: S-EPMC9041869 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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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.

Flory Andi A Kruglyak Kristina M KM Tynan John A JA McLennan Lisa M LM Rafalko Jill M JM Fiaux Patrick Christian PC Hernandez Gilberto E GE Marass Francesco F Nakashe Prachi P Ruiz-Perez Carlos A CA Fath Donna M DM Jennings Thuy T Motalli-Pepio Rita R Wotrang Kate K McCleary-Wheeler Angela L AL Lana Susan S Phillips Brenda B Flesner Brian K BK Leibman Nicole F NF LaDue Tracy T Tripp Chelsea D CD Coomber Brenda L BL Woods J Paul JP Miller Mairin M Aiken Sean W SW Wolf-Ringwall Amber A Borgatti Antonella A Kraska Kathleen K Thomson Christopher B CB Kosanovich Cahalane Alane A Murray Rebecca L RL Kisseberth William C WC Camps-Palau Maria A MA Floch Franck F Beaudu-Lange Claire C Klajer-Peres Aurélia A Keravel Olivier O Fribourg-Blanc Luc-André LA Mazetier Pascale Chicha PC Marco Angelo A McLeod Molly B MB Portillo Erin E Clark Terry S TS Judd Scott S Feinberg C Kirk CK Benitez Marie M Runyan Candace C Hackett Lindsey L Lafey Scott S Richardson Danielle D Vineyard Sarah S Tefend Campbell Mary M Dharajiya Nilesh N Jensen Taylor J TJ van den Boom Dirk D Diaz Luis A LA Grosu Daniel S DS Polk Arthur A Marsal Kalle K Hicks Susan Cho SC Lytle Katherine M KM Holtvoigt Lauren L Chibuk Jason J Chorny Ilya I Tsui Dana W Y DWY

PloS one 20220426 4

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 "li ...[more]

PMID: 35471999

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Project description:BackgroundA rapid, low-cost blood test that can be applied to reliably detect multiple different cancer types would be transformational.MethodsIn this large-scale discovery study (n = 2092 patients) we applied the Dxcover® Cancer Liquid Biopsy to examine eight different cancers. The test uses Fourier transform infrared (FTIR) spectroscopy and machine-learning algorithms to detect cancer.ResultsArea under the receiver operating characteristic curve (ROC) values were calculated for eight cancer types versus symptomatic non-cancer controls: brain (0.90), breast (0.76), colorectal (0.91), kidney (0.91), lung (0.91), ovarian (0.86), pancreatic (0.84) and prostate (0.86). We assessed the test performance when all eight cancer types were pooled to classify 'any cancer' against non-cancer patients. The cancer versus asymptomatic non-cancer classification detected 64% of Stage I cancers when specificity was 99% (overall sensitivity 57%). When tuned for higher sensitivity, this model identified 99% of Stage I cancers (with specificity 59%).ConclusionsThis spectroscopic blood test can effectively detect early-stage disease and can be fine-tuned to maximise either sensitivity or specificity depending on the requirements from different healthcare systems and cancer diagnostic pathways. This low-cost strategy could facilitate the requisite earlier diagnosis, when cancer treatment can be more effective, or less toxic.Statement of translational relevanceThe earlier diagnosis of cancer is of paramount importance to improve patient survival. Current liquid biopsies are mainly focused on single tumour-derived biomarkers, which limits test sensitivity, especially for early-stage cancers that do not shed enough genetic material. This pan-omic liquid biopsy analyses the full complement of tumour and immune-derived markers present within blood derivatives and could facilitate the earlier detection of multiple cancer types. There is a low barrier to integrating this blood test into existing diagnostic pathways since the technology is rapid, simple to use, only minute sample volumes are required, and sample preparation is minimal. In addition, the spectroscopic liquid biopsy described in this study has the potential to be combined with other orthogonal tests, such as cell-free DNA, which could provide an efficient route to diagnosis. Cancer treatment can be more effective when given earlier, and this low-cost strategy has the potential to improve patient prognosis.

Dataset Information

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.

Publications

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.

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