{"entity":{"id":"paper-gao-thunder-ann-oncol-2023","kind":"paper","name":"Unintrusive multi-cancer detection by circulating cell-free DNA methylation sequencing (THUNDER): development and independent validation studies","aka":[],"tldr":"The Chinese validation study behind Burning Rock's OverC test: in an independent set of 1,010 people it found about seven in ten of six cancers with about one false positive in a hundred.","summary":"THUNDER (NCT04820868) evaluated enhanced linear-splinter amplification sequencing of cell-free DNA methylation over a panel of 161,984 CpG sites for six cancers (colorectum, oesophagus, liver, lung, ovary and pancreas). Two models were trained on 1,693 retrospective samples and validated in a prospective, independent, age-matched cohort of 1,010 people (505 with cancer). MCDBT-1 had 69.1% sensitivity (64.8 to 73.3), 98.9% specificity (97.6 to 99.7) and 83.2% tissue-origin accuracy; sensitivity for stages I to III was 59.8%. MCDBT-2, at 95.1% specificity, had 75.1% sensitivity. A simulation using Chinese incidence projected reductions in late-stage incidence; that is a model, not an observed outcome.","asOf":"2026-10-29","links":[{"label":"Annals of Oncology 2023: THUNDER","url":"https://doi.org/10.1016/j.annonc.2023.02.010"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36849097/"},{"label":"ClinicalTrials.gov NCT04820868","url":"https://clinicaltrials.gov/study/NCT04820868"}],"tags":[],"related":[],"cancers":[],"sections":["early-detection"],"technologies":["mced","cfdna-methylation-testing"],"targets":[],"drugs":["overc-mcdbt"],"companies":["burning-rock"],"institutions":[],"pathways":[],"terms":[],"trials":["thunder-overc"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2023,"doi":"10.1016/j.annonc.2023.02.010","pmid":"36849097","authors":"Gao Q, Lin YP, Li BS, et al.","paperType":"observational","findings":["MCDBT-1: sensitivity 69.1%, specificity 98.9%, tissue-origin accuracy 83.2% in independent validation.","Stage I to III sensitivity 59.8%; no stage I figure in the abstract."],"whatItMeans":"The strongest published evidence for OverC, still from people already diagnosed with cancer rather than a screening population.","caveats":["Case-control validation, half the set had cancer.","Late-stage reductions are simulated, not observed.","Burning Rock collaborated."],"changedPractice":false,"participants":2703},"route":"/key-papers/paper-gao-thunder-ann-oncol-2023/","neighbours":{"section":[{"id":"early-detection","kind":"section","name":"Early Detection & Screening","route":"/fronts/early-detection/"}],"technology":[{"id":"cfdna-methylation-testing","kind":"technology","name":"Cell-free DNA methylation tests","route":"/technologies/cfdna-methylation-testing/"},{"id":"mced","kind":"technology","name":"Multi-cancer early detection (MCED)","route":"/technologies/mced/"}],"drug":[{"id":"overc-mcdbt","kind":"drug","name":"OverC Multi-Cancer Detection Blood Test","route":"/drugs/overc-mcdbt/"}],"company":[{"id":"burning-rock","kind":"company","name":"Burning Rock Biotech","route":"/companies/burning-rock/"}],"trial":[{"id":"thunder-overc","kind":"trial","name":"THUNDER (blinded validation of Burning Rock's methylation test)","route":"/trials/thunder-overc/"}],"journal":[{"id":"annals-of-oncology","kind":"journal","name":"Annals of Oncology","route":"/journals/annals-of-oncology/"}]}}