{"entity":{"id":"lymphoma-ev-ctdna-instead-of-the-interim-scan","kind":"idea","name":"Use circulating tumour DNA instead of the interim scan to decide what happens next","aka":["Molecular response-adapted lymphoma therapy","ctDNA-guided de-escalation in lymphoma"],"tldr":"A blood test detects lymphoma left behind better than a scan does, and no trial has yet used it to change anyone's treatment.","summary":"The practical barriers are assay standardisation and turnaround. Commercial implementations differ in sensitivity and in which mutations they track, and a result that arrives after the next cycle has started cannot direct anything. The scientific barrier is that detecting residual disease is not the same as knowing what to do about it: HD16 showed that a negative interim scan does not mean radiotherapy is unnecessary, and a negative molecular test may turn out to mean the same thing.","asOf":"2026-10-01","links":[],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap","ctdna-tests"],"cancers":["dlbcl","non-hodgkin-lymphoma","hodgkin-lymphoma","early-stage-classical-hodgkin-lymphoma","follicular-lymphoma"],"sections":["diagnostics","early-detection"],"technologies":["liquid-biopsy","ngs","pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","mrd","deauville-score"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-biomarker-validation","b-trial-design"],"keyPapers":["paper-scherer-ctdna-lymphoma-subtypes-genome-evolution-sci-transl-med-2016","paper-kurtz-j-clin-oncol","paper-kurtz-nat-biotechnol","paper-ghsg-hd16-pet-guided-early-favourable-hodgkin-jco-2019"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Treatment adapted to circulating tumour DNA after one or two cycles, rather than to a positron emission tomography scan after two, improves the balance of cure and toxicity in aggressive lymphoma and in Hodgkin lymphoma.","rationale":"Scherer showed that circulating tumour DNA at diagnosis independently predicts outcome, that tracking multiple mutations outperforms imaging for minimal residual disease, and that plasma genotyping reads cell of origin without a biopsy. Kurtz showed it predicts outcome early in treatment. Meanwhile the interim scan has clear limits: it directs intensification well (EORTC H10, hazard ratio 0.42 in scan-positive patients) and de-escalation badly, with HD16 losing 7.3 percentage points of progression-free survival when radiotherapy was omitted on a negative scan. A more sensitive measure of residual disease is the obvious candidate to make de-escalation safe.","test":"A randomised trial in early-stage Hodgkin lymphoma or limited-stage diffuse large B-cell lymphoma comparing treatment adapted to circulating tumour DNA with treatment adapted to the interim scan, powered for non-inferiority on progression-free survival with radiotherapy exposure, cumulative chemotherapy dose and patient-reported outcomes as co-primary. A positive result requires that the molecular test identifies patients who can safely have less, which the scan does not.","maturity":"early-clinical","actor":"research","cost":"large","horizonYears":7},"route":"/ideas/lymphoma-ev-ctdna-instead-of-the-interim-scan/","neighbours":{"roadmap":[{"id":"ctdna-tests","kind":"roadmap","name":"ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment","route":"/roadmaps/ctdna-tests/"},{"id":"lymphoma-roadmap","kind":"roadmap","name":"Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting","route":"/roadmaps/lymphoma-roadmap/"}],"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"early-stage-classical-hodgkin-lymphoma","kind":"cancer","name":"Early-stage classical Hodgkin lymphoma (stage I to II)","route":"/cancers/early-stage-classical-hodgkin-lymphoma/"},{"id":"follicular-lymphoma","kind":"cancer","name":"Follicular lymphoma","route":"/cancers/follicular-lymphoma/"},{"id":"hodgkin-lymphoma","kind":"cancer","name":"Hodgkin lymphoma","route":"/cancers/hodgkin-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"},{"id":"early-detection","kind":"section","name":"Early Detection & Screening","route":"/fronts/early-detection/"}],"technology":[{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"pet-ct","kind":"technology","name":"PET/CT","route":"/technologies/pet-ct/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"deauville-score","kind":"term","name":"Deauville five-point scale","route":"/terms/deauville-score/"},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"},{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"},{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}],"paper":[{"id":"paper-kurtz-j-clin-oncol","kind":"paper","name":"Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-Cell Lymphoma","route":"/key-papers/paper-kurtz-j-clin-oncol/"},{"id":"paper-scherer-ctdna-lymphoma-subtypes-genome-evolution-sci-transl-med-2016","kind":"paper","name":"Distinct biological subtypes and patterns of genome evolution in lymphoma revealed by circulating tumour DNA","route":"/key-papers/paper-scherer-ctdna-lymphoma-subtypes-genome-evolution-sci-transl-med-2016/"},{"id":"paper-kurtz-nat-biotechnol","kind":"paper","name":"Enhanced detection of minimal residual disease by targeted sequencing of phased variants in circulating tumor DNA","route":"/key-papers/paper-kurtz-nat-biotechnol/"},{"id":"paper-ghsg-hd16-pet-guided-early-favourable-hodgkin-jco-2019","kind":"paper","name":"Positron emission tomography-guided treatment in early-stage favorable Hodgkin lymphoma: final results of the international, randomized phase III HD16 trial by the German Hodgkin Study Group","route":"/key-papers/paper-ghsg-hd16-pet-guided-early-favourable-hodgkin-jco-2019/"}]}}