{"entity":{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","aka":[],"tldr":"A blood test that reads fragments of DNA shed by the tumour, so you can genotype or monitor cancer without a needle in the tumour.","summary":"Circulating tumour DNA assays (Guardant360 CDx, FoundationOne Liquid CDx) are approved companion diagnostics for EGFR, PIK3CA, ESR1, and others. Used when tissue is insufficient, to track resistance mutations (EGFR T790M, ESR1), and to follow clonal dynamics. Fragmentomics and methylation extend it to tumour-agnostic detection.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Liquid_biopsy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Liquid_biopsy"},{"label":"NICE NG122: lung cancer, diagnosis and staging","url":"https://www.nice.org.uk/guidance/ng122/chapter/Diagnosis-and-staging"},{"label":"NHS: genetic and genomic testing","url":"https://www.nhs.uk/tests-and-treatments/genetic-and-genomic-testing/"},{"label":"Kurtz et al., Nat Biotechnol 2021: PhasED-seq, phased variants for residual disease detection in B-cell lymphoma (213 participants)","url":"https://doi.org/10.1038/s41587-021-00981-w"},{"label":"Scherer et al., Sci Transl Med 2016: ctDNA genotyping classifies cell of origin and tracks genome evolution in lymphoma (92 patients)","url":"https://doi.org/10.1126/scitranslmed.aai8545"}],"tags":[],"related":["ctdna-tests","cellsearch-ctc-count","parsortix-ctc-harvest","serum-tumour-markers","cea-surveillance-colorectal","multitarget-stool-rna-test"],"cancers":["pancreatic","colorectal","lung-cancer","nsclc","dlbcl","non-hodgkin-lymphoma"],"sections":["diagnostics"],"technologies":["mrd-testing","mced"],"targets":[],"drugs":[],"companies":["guardant-health","foundation-medicine","natera","adela","aoa-dx","billiontoone","biodesix","c2i-genomics","cambridge-cancer-genomics","clearnote-health","delee","elypta","exai-bio","haystack-oncology","helio-genomics","inivata","insight-molecular-diagnostics","lucence","naveris","nonagen-bioscience","nucleix","numen","universal-dx","volitionrx","x-zell","belay-diagnostics","cnside-diagnostics","rgcc-international"],"institutions":[],"pathways":[],"terms":["ctdna","vaf"],"trials":["nct07510828"],"people":[],"bottlenecks":[],"keyPapers":["paper-sausen-ctdna-pancreatic-resection-nat-commun-2015","paper-groot-kras-ctdna-clinical-test-resected-pancreatic-ccr-2019","paper-pietrasz-ctdna-prognostic-pancreatic-ccr-2017","paper-cohen-ctdna-protein-liquid-biopsy-pancreatic-pnas-2017","paper-diaz-molecular-evolution-egfr-resistance-colorectal-nature-2012","paper-misale-kras-acquired-resistance-anti-egfr-colorectal-nature-2012","paper-nakamura-triumph-ctdna-pertuzumab-trastuzumab-her2-colorectal-nat-med-2021","paper-leighl-nile-cfdna-tissue-genotyping-ccr-2019","paper-aggarwal-plasma-genotyping-personalised-therapy-jama-oncol-2019","paper-oxnard-osimertinib-resistance-mechanisms-jama-oncol-2018","paper-lindeman-lung-molecular-testing-guideline-jto-2018"],"journals":[],"dependsOn":["cgp","ngs-bioinformatics-software","preanalytics-sample-stabilisation"],"notes":["Pancreatic cancer: plasma KRAS is detectable in 30 to 43% of resectable and about half of advanced disease, with 100% concordance with the tumour mutation when found; detection and allele fraction are prognostic and post-resection detection predicts recurrence months before imaging, but sensitivity in early disease is the limiting factor (Cohen 2017, Sausen 2015, Groot 2019, Pietrasz 2017).","Colorectal cancer: plasma sequencing does three jobs here. It genotypes RAS and BRAF when tissue is exhausted; it watches resistance emerge, with KRAS-mutant clones appearing in 9 of 24 initially wild-type patients on panitumumab and detectable up to 10 months before imaging (Diaz 2012, Misale 2012); and it can select patients for treatment, with plasma HER2 copy number matching tissue for enrolment accuracy in TRIUMPH (Nakamura 2021).","Lung cancer: a blood test for tumour DNA can sometimes return a targetable result sooner than a repeat tissue sample, or where the sample was too small. NICE NG122 (1.2.11) asks for samples adequate to permit assessment of molecular markers without unacceptable risk to the person, and (1.2.13) to choose investigations that give the most information with the least risk, which is the trade-off a blood test is weighed against. A blood test cannot show a change in how the cancer looks under the microscope, so where that is the question a tissue sample is still needed.","Lung cancer: plasma sequencing does three jobs. At diagnosis it matches tissue and is faster, finding a guideline biomarker in 27.3% of 282 patients against 21.3% by tissue, with 100% positive predictive value for the alterations that have approved drugs and a median turnaround of 9 days against 15; using both raised detection by 48% (Leighl 2019), and in routine practice plasma-only testing found a targetable alteration in a third of patients and spared them a biopsy (Aggarwal 2019). At progression it reads resistance, including the early kinetics that separate patients whose resistant clone was already present (Oxnard 2018). What it cannot do is exclude: clinical sensitivity against tissue was 80%, the misses concentrate in low-shedding and brain-confined disease, and the guideline allows plasma to rule a mutation in but not out (Lindeman 2018).","Lymphoma: plasma is an unusually good sample here, because the mutation density produced by somatic hypermutation gives many variants to track and allows several to be phased onto one fragment, which is what PhasED-seq exploits (Kurtz 2021). Genotyping including cell of origin can be done from blood (Scherer 2016). What is still missing is a trial that changes treatment on the answer."],"principle":"Cell-free DNA extracted from plasma; deep NGS with error suppression detects variants at <0.1% allele fraction.","strengths":["Minimally invasive, repeatable","Whole-body clonal picture"],"limitations":["Low shedding in some tumours (brain, early-stage)","Clonal haematopoiesis false positives"]},"route":"/technologies/liquid-biopsy/","neighbours":{"roadmap":[{"id":"colorectal-roadmap","kind":"roadmap","name":"Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation","route":"/roadmaps/colorectal-roadmap/"},{"id":"ctdna-tests","kind":"roadmap","name":"ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide 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