{"entity":{"id":"paper-kotani-galaxy-molecular-residual-disease-nat-med-2023","kind":"paper","name":"Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer (GALAXY, CIRCULATE-Japan)","aka":[],"tldr":"In 1,039 Japanese patients, tumour DNA in blood four weeks after surgery was the strongest predictor of recurrence ever measured in this disease, and picked out exactly the patients whose chemotherapy did some good.","summary":"Kotani, Oki, Nakamura and colleagues report results from GALAXY, the observational arm of the ongoing CIRCULATE-Japan study, which analysed presurgical and postsurgical circulating tumour DNA in 1,039 patients with stage II to IV resectable colorectal cancer, with a median follow-up of 16.74 months.\n\nThe study is the largest prospective analysis of circulating tumour DNA in resectable colorectal cancer and supports using the test both to identify patients at increased risk of recurrence and to identify those likely to benefit from adjuvant chemotherapy.","asOf":"2026-09-24","links":[{"label":"Nat Med 2023","url":"https://doi.org/10.1038/s41591-022-02115-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36646802/"},{"label":"Europe PMC full text (PMC9873552)","url":"https://europepmc.org/article/MED/36646802"}],"tags":["colorectal-evidence"],"related":["paper-tie-dynamic-ctdna-guided-adjuvant-stage-ii-colon-nejm-2022","idea-ctdna-guided-adjuvant-crc"],"cancers":["colorectal","colon-cancer"],"sections":["diagnostics"],"technologies":["mrd-testing","liquid-biopsy","signatera"],"targets":[],"drugs":[],"companies":["natera"],"institutions":["ncc-japan"],"pathways":[],"terms":["ctdna","mrd"],"trials":["circulate-japan"],"people":["yoshino-takayuki"],"bottlenecks":["b-dormancy-mrd"],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2023,"doi":"10.1038/s41591-022-02115-4","pmid":"36646802","authors":"Kotani D, Oki E, Nakamura Y, et al.","paperType":"observational","findings":["Postsurgical circulating tumour DNA positivity at four weeks was associated with higher recurrence risk (hazard ratio 10.0, p<0.0001).","In stage II or III disease it was the most significant prognostic factor for recurrence (hazard ratio 10.82, p<0.001).","Postsurgical positivity identified the stage II or III patients who derived benefit from adjuvant chemotherapy (hazard ratio 6.59, p<0.0001)."],"whatItMeans":"The predictive half of the ctDNA case: chemotherapy after surgery helps the patients whose blood test is positive and appears to do little for those whose test is negative, which is the rationale for the randomised CIRCULATE trials now running in Japan, the United States and Europe.","caveats":["Observational: the chemotherapy comparison is not randomised and is confounded by why patients were or were not treated.","Median follow-up 16.74 months, short for recurrence in stage II disease.","The interventional arms (VEGA, ALTAIR) are what turn this into evidence for a strategy, and ALTAIR's escalation approach was negative."],"changedPractice":true,"participants":1039},"route":"/key-papers/paper-kotani-galaxy-molecular-residual-disease-nat-med-2023/","neighbours":{"paper":[{"id":"paper-tie-dynamic-ctdna-guided-adjuvant-stage-ii-colon-nejm-2022","kind":"paper","name":"Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer (DYNAMIC)","route":"/key-papers/paper-tie-dynamic-ctdna-guided-adjuvant-stage-ii-colon-nejm-2022/"}],"idea":[{"id":"idea-ctdna-guided-adjuvant-crc","kind":"idea","name":"ctDNA-guided adjuvant therapy as the default in stage II-III colon cancer","route":"/ideas/idea-ctdna-guided-adjuvant-crc/"},{"id":"idea-crc-ctdna-de-escalation-beyond-stage-ii","kind":"idea","name":"Take ctDNA-guided de-escalation beyond stage II, and stop escalating on a positive result until a trial says it helps","route":"/ideas/idea-crc-ctdna-de-escalation-beyond-stage-ii/"}],"cancer":[{"id":"colon-cancer","kind":"cancer","name":"Colon cancer (adenocarcinoma of the colon)","route":"/cancers/colon-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"}],"technology":[{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"}],"drug":[{"id":"signatera","kind":"drug","name":"Signatera","route":"/drugs/signatera/"}],"company":[{"id":"natera","kind":"company","name":"Natera","route":"/companies/natera/"}],"institution":[{"id":"ncc-japan","kind":"institution","name":"National Cancer Center Hospital","route":"/institutions/ncc-japan/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"}],"trial":[{"id":"circulate-japan","kind":"trial","name":"CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)","route":"/trials/circulate-japan/"}],"person":[{"id":"yoshino-takayuki","kind":"person","name":"Takayuki Yoshino","route":"/people/yoshino-takayuki/"}],"bottleneck":[{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"}],"journal":[{"id":"nature-medicine","kind":"journal","name":"Nature Medicine","route":"/journals/nature-medicine/"}],"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/"}]}}