{"entity":{"id":"paper-klein-ccga3-mced-validation-ann-oncol-2021","kind":"paper","name":"Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set","aka":[],"tldr":"The methylation blood test now sold as Galleri detected half of all cancers and one in six stage I cancers in 4,077 people, while wrongly flagging one healthy person in 200, and named the organ correctly in 89% of positives.","summary":"The third and final substudy of the Circulating Cell-free Genome Atlas validated a multi-cancer early detection test using cell-free DNA methylation sequencing with machine learning in 4,077 participants (2,823 cancer, 1,254 non-cancer confirmed at one year). Specificity for cancer signal detection was 99.5%; overall sensitivity was 51.5%, rising by stage (I 16.8%, II 40.4%, III 77.0%, IV 90.1%). Stage I to III sensitivity was 67.6% in 12 pre-specified cancers accounting for about two-thirds of US cancer deaths and 40.7% across all cancers. Cancer signals were detected across more than 50 cancer types and accuracy of cancer signal origin prediction was 88.7%.","asOf":"2026-09-24","links":[{"label":"Klein et al., Ann Oncol 2021: CCGA3 validation of the Galleri methylation test in 4,077 participants","url":"https://doi.org/10.1016/j.annonc.2021.05.806"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34176681/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["mced","cfdna-methylation-testing","methylation-profiling","liquid-biopsy"],"targets":[],"drugs":["galleri"],"companies":["grail"],"institutions":[],"pathways":[],"terms":["cfdna","ctdna"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2021,"doi":"10.1016/j.annonc.2021.05.806","pmid":"34176681","authors":"Klein EA, Richards D, Cohn A, et al.","paperType":"observational","findings":["Specificity 99.5%; overall sensitivity 51.5%.","Stage I sensitivity 16.8%; stage IV 90.1%.","Cancer signal origin correct in 88.7% of true positives."],"whatItMeans":"Methylation-based screening is real but weakest exactly where pancreatic cancer needs it, at stage I, which is why high-risk surveillance rather than population screening carries the field here.","caveats":["Case-control validation, not a screening population.","Pancreas-specific stage I sensitivity is not given in the abstract."],"changedPractice":false,"participants":4077},"route":"/key-papers/paper-klein-ccga3-mced-validation-ann-oncol-2021/","neighbours":{"cancer":[{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"cfdna-methylation-testing","kind":"technology","name":"Cell-free DNA methylation tests","route":"/technologies/cfdna-methylation-testing/"},{"id":"methylation-profiling","kind":"technology","name":"DNA methylation profiling","route":"/technologies/methylation-profiling/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"mced","kind":"technology","name":"Multi-cancer early detection (MCED)","route":"/technologies/mced/"}],"drug":[{"id":"galleri","kind":"drug","name":"Galleri","route":"/drugs/galleri/"}],"company":[{"id":"grail","kind":"company","name":"GRAIL","route":"/companies/grail/"}],"term":[{"id":"ccga-study","kind":"term","name":"CCGA: the Circulating Cell-free Genome Atlas behind the Galleri methylation test","route":"/terms/ccga-study/"},{"id":"cfdna","kind":"term","name":"Cell-free DNA (cfDNA)","route":"/terms/cfdna/"},{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"}],"journal":[{"id":"annals-of-oncology","kind":"journal","name":"Annals of Oncology","route":"/journals/annals-of-oncology/"}]}}