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Record W4224675640 · doi:10.1371/journal.pone.0266623

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

2022· article· en· W4224675640 on OpenAlexafffund
Andi Flory, Kristina M. Kruglyak, John A. Tynan, Lisa M. McLennan, Jill M. Rafalko, Patrick C. Fiaux, Gilberto E. Hernandez, Francesco Marass, Prachi Nakashe, Carlos A. Ruiz-Pérez, Donna M. Fath, Thuy Jennings, Rita Motalli-Pepio, Kate Wotrang, Angela L. McCleary‐Wheeler, Susan E. Lana, Brenda Phillips, Brian K. Flesner, Nicole F. Leibman, Tracy A. LaDue, Chelsea Tripp, Brenda L. Coomber, J. Paul Woods, Mairin Miller, Sean W. Aiken, Amber Wolf‐Ringwall, Antonella Borgatti, Kathleen Kraska, Chris Thomson, Alane Kosanovich Cahalane, Rebecca L. Murray, William C. Kisseberth, M. 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. Díaz, Daniel S. Grosu, Arthur Polk, Kalle Marsal, Susan Cho Hicks, Katherine M. Lytle, Lauren E. Holtvoigt, Jason Chibuk, Ilya Chorny, Dana W.Y. Tsui

Bibliographic record

VenuePLoS ONE · 2022
Typearticle
Languageen
FieldMedicine
TopicVeterinary Oncology Research
Canadian institutionsUniversity of Guelph
FundersNational Cancer InstituteUniversity of GuelphUniversity of MissouriUniversity of MinnesotaColorado State UniversityOhio State University
KeywordsCancerMedicineLiquid biopsySarcomaBiopsyPathologyHemangiosarcomaLymphomaOsteosarcomaCancer screeningInternal medicineSoft tissue sarcomaOncologyAngiosarcoma

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.008
metaresearch head score (Gemma)0.009
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.008
Threshold uncertainty score0.043

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0080.009
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.000
Science and technology studies0.0000.001
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.393
GPT teacher head0.419
Teacher spread0.026 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations56
Published2022
Admission routes2
Has abstractyes

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