{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T02:03:29Z","timestamp":1792893809894,"version":"4.5.0"},"reference-count":41,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"15","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,5,20]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Detection of molecular residual disease using circulating tumor DNA (ctDNA) may enable postoperative risk stratification and guide adjuvant therapy. We evaluated the prognostic value of a tissue-free, epigenomic ctDNA assay in patients with stage III colon cancer (CC) enrolled in a phase III adjuvant chemotherapy trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Plasma samples were collected after surgery and before adjuvant infusional fluorouracil, leucovorin, and oxaliplatin alone or combined with cetuximab. ctDNA was analyzed using a tissue-free assay; in ctDNA-positive patients, tumor fraction (TF) was quantified and genotyping was performed with a 739-gene panel. Associations with disease-free survival (DFS), time to recurrence (TTR), and overall survival (OS) were assessed using multivariable Cox models adjusted for covariates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Among 2,260 evaluable patients, 461 (20.4%) were ctDNA-positive with significantly higher detection in advanced T-\/N-stage, high-grade, obstruction\/perforation, and\n                      <jats:italic toggle=\"yes\">BRAF<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic toggle=\"yes\">V600E<\/jats:italic>\n                      <\/jats:sup>\n                      tumors. At a median follow-up of 6.1 years, ctDNA positivity was independently associated with shorter TTR (hazard ratio [HR], 5.96 [95% CI, 5.11 to 6.96]), DFS (HR, 5.03 [95% CI, 4.36 to 5.81]), and OS (HR, 4.45 [95% CI, 3.76 to 5.27]; all\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .0001). The 5-year DFS was 27.7% (95% CI, 23.8 to 32.2)\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      77.1% (95% CI, 75.1 to 79.1) in ctDNA-positive versus ctDNA-negative patients, and adverse prognostic impact was greater in lower T\/N stage, low-risk, and dMMR subsets (interaction\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .0012-.041). Among ctDNA-positive patients, TF was nearly double in those who recurred or died (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .0002) and stratified patients for TTR, DFS, and OS (all adjusted\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .002). Genotyping identified mutations in\n                      <jats:italic toggle=\"yes\">FLT1<\/jats:italic>\n                      (OR, 8.99) and\n                      <jats:italic toggle=\"yes\">PREX2<\/jats:italic>\n                      (OR, 7.73) genes that were most strongly associated with recurrence (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .03).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Evaluation of ctDNA in resected stage III CC using a tissue-free assay provided robust and independent prognostic value. Higher ctDNA burden, dMMR, and specific mutations defined poor prognostic groups among ctDNA-positive patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-02086","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T20:59:07Z","timestamp":1769806747000},"page":"1401-1415","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":15,"title":["Tissue-Free Circulating Tumor DNA Assay and Patient Outcome in a Phase III Trial of FOLFOX-Based Adjuvant Chemotherapy (Alliance N0147)"],"prefix":"10.1200","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2907-1000","authenticated-orcid":true,"given":"Frank A.","family":"Sinicrope","sequence":"first","affiliation":[{"name":"Department of Oncology, Mayo Clinic, Rochester, MN"},{"name":"Gastrointestinal Research Unit, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Segovia","sequence":"additional","affiliation":[{"name":"Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nalin","family":"Sharma","sequence":"additional","affiliation":[{"name":"Gastrointestinal Research Unit, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5835-4122","authenticated-orcid":true,"given":"Steven R.","family":"Alberts","sequence":"additional","affiliation":[{"name":"Department of Oncology, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1231-0658","authenticated-orcid":true,"given":"Aaron","family":"Hardin","sequence":"additional","affiliation":[{"name":"Guardant Health, Palo Alto, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3023-6930","authenticated-orcid":true,"given":"Thereasa","family":"Rich","sequence":"additional","affiliation":[{"name":"Guardant Health, Palo Alto, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4640-8832","authenticated-orcid":true,"given":"Qian","family":"Shi","sequence":"additional","affiliation":[{"name":"Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30527-1"},{"key":"e_1_3_8_3_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.00281"},{"key":"e_1_3_8_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.385"},{"key":"e_1_3_8_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70227-X"},{"key":"e_1_3_8_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2020.07.031"},{"key":"e_1_3_8_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-025-00876-y"},{"key":"e_1_3_8_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-02115-4"},{"key":"e_1_3_8_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2019.3616"},{"key":"e_1_3_8_10_2","article-title":"Impact of circulating tumor DNA-based detection of molecular residual disease on the conduct and design of clinical trials for solid tumors","author":"Kasi PM","unstructured":"Kasi PM, Fehringer G, Taniguchi H, et al: Impact of circulating tumor DNA-based detection of molecular residual disease on the conduct and design of clinical trials for solid tumors. 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