{"doi":"10.1200/po.24.00288","title":"Circulating Tumor DNA as a Prognostic Biomarker for Recurrence in Patients With Locoregional Esophagogastric Cancers With a Pathologic Complete Response","abstract":"<jats:sec>\n            <jats:title>PURPOSE</jats:title>\n            <jats:p>After neoadjuvant therapy (NAT) and surgery, up to one third and one half of patients with esophagogastric adenocarcinoma with a pathologic complete response (pCR; tumor regression grade 0 [TRG-0]) and near-pCR (TRG-1) will recur, respectively. Our study aims to evaluate postoperative circulating tumor DNA (ctDNA) as a predictor of recurrence in patients with pCR or near-pCR after curative-intent neoadjuvant chemotherapy or neoadjuvant chemoradiation and surgery.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>METHODS</jats:title>\n            <jats:p>We retrospectively identified patients from 11 institutions with stages I-IV esophagogastric cancers (EGCs) who completed NAT and had TRG-0/1 scores at the time of curative-intent surgery. Postoperative plasma samples were collected for ctDNA analysis within a 16-week molecular residual disease (MRD) window after definitive surgery, and during surveillance from January 7, 2020, to November 9, 2023, at the provider's discretion. ctDNA was assessed using a clinically validated, personalized, tumor-informed ctDNA assay (Signatera, Natera, Inc). The primary outcome was recurrence-free survival (RFS).</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS</jats:title>\n            <jats:p>\n              We obtained 309 blood samples from 42 patients with esophagogastric adenocarcinoma with a pCR after neoadjuvant treatment over a median follow-up time of 28.5 months (range, 0.2-81.7). Detectable ctDNA in the 16-week MRD window (N = 23) correlated with higher rates of recurrence (67%; 2/3) compared with undetectable ctDNA (15%; 3/20). Detectable ctDNA within the MRD window was associated with a significantly shorter RFS (hazard ratio [HR], 6.2;\n              <jats:italic>P</jats:italic>\n              = .049). Among 32 patients who had ctDNA analyzed in the surveillance setting, the recurrence rate was 100% (5/5) in the ctDNA-positive cohort compared with 7.4% (2/27) in ctDNA-negative patients and was associated with shorter RFS (HR, 37.6;\n              <jats:italic>P</jats:italic>\n              &lt; .001).\n            </jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION</jats:title>\n            <jats:p>Within the subgroup of patients with EGC and favorable pathologic responses (TRG 0-1) after NAT, the presence of postoperative ctDNA identified patients with elevated recurrence risk.</jats:p>\n          </jats:sec>","journal":"JCO Precision Oncology","year":2024,"id":636307,"datarank":0.38474240361923057,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.0,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":493867,"name":"Vasily N. Aushev","orcid":"0000-0001-8003-358X","position":1,"is_corresponding":false},{"id":317719,"name":"Brandon M. Huffman","orcid":"0000-0002-0768-3145","position":2,"is_corresponding":false},{"id":1651383,"name":"Diana Hanna","orcid":null,"position":3,"is_corresponding":false},{"id":1086942,"name":"Punashi Dutta","orcid":"0000-0002-5963-7212","position":4,"is_corresponding":false},{"id":1187338,"name":"Jenifer Ferguson","orcid":null,"position":5,"is_corresponding":false},{"id":286447,"name":"Shruti Sharma","orcid":"0000-0001-8200-108X","position":6,"is_corresponding":false},{"id":1165966,"name":"Adham Jurdi","orcid":"0000-0002-2985-3053","position":7,"is_corresponding":false},{"id":242419,"name":"Minetta C. Liu","orcid":"0000-0002-8206-5232","position":8,"is_corresponding":false},{"id":332456,"name":"Cathy Eng","orcid":"0000-0003-2335-0612","position":9,"is_corresponding":false},{"id":314970,"name":"Samuel J. Klempner","orcid":"0000-0002-4062-0808","position":10,"is_corresponding":false},{"id":530527,"name":"Michael K. Gibson","orcid":"0000-0002-1500-9281","position":11,"is_corresponding":false},{"id":1101404,"name":"Eric Lander","orcid":"0000-0002-2843-7744","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Circulating Tumor DNA as a Prognostic Biomarker for Recurrence in Patients With Locoregional Esophagogastric Cancers With a Pathologic Complete Response","abstract":"<jats:sec>\n            <jats:title>PURPOSE</jats:title>\n            <jats:p>After neoadjuvant therapy (NAT) and surgery, up to one third and one half of patients with esophagogastric adenocarcinoma with a pathologic complete response (pCR; tumor regression grade 0 [TRG-0]) and near-pCR (TRG-1) will recur, respectively. Our study aims to evaluate postoperative circulating tumor DNA (ctDNA) as a predictor of recurrence in patients with pCR or near-pCR after curative-intent neoadjuvant chemotherapy or neoadjuvant chemoradiation and surgery.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>METHODS</jats:title>\n            <jats:p>We retrospectively identified patients from 11 institutions with stages I-IV esophagogastric cancers (EGCs) who completed NAT and had TRG-0/1 scores at the time of curative-intent surgery. Postoperative plasma samples were collected for ctDNA analysis within a 16-week molecular residual disease (MRD) window after definitive surgery, and during surveillance from January 7, 2020, to November 9, 2023, at the provider's discretion. ctDNA was assessed using a clinically validated, personalized, tumor-informed ctDNA assay (Signatera, Natera, Inc). The primary outcome was recurrence-free survival (RFS).</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS</jats:title>\n            <jats:p>\n              We obtained 309 blood samples from 42 patients with esophagogastric adenocarcinoma with a pCR after neoadjuvant treatment over a median follow-up time of 28.5 months (range, 0.2-81.7). Detectable ctDNA in the 16-week MRD window (N = 23) correlated with higher rates of recurrence (67%; 2/3) compared with undetectable ctDNA (15%; 3/20). Detectable ctDNA within the MRD window was associated with a significantly shorter RFS (hazard ratio [HR], 6.2;\n              <jats:italic>P</jats:italic>\n              = .049). Among 32 patients who had ctDNA analyzed in the surveillance setting, the recurrence rate was 100% (5/5) in the ctDNA-positive cohort compared with 7.4% (2/27) in ctDNA-negative patients and was associated with shorter RFS (HR, 37.6;\n              <jats:italic>P</jats:italic>\n              &lt; .001).\n            </jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION</jats:title>\n            <jats:p>Within the subgroup of patients with EGC and favorable pathologic responses (TRG 0-1) after NAT, the presence of postoperative ctDNA identified patients with elevated recurrence risk.</jats:p>\n          </jats:sec>","is_dataset_classified":null,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39642325","pmcid":"PMC11634147","openalex_id":"https://openalex.org/W4405100180","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"T32 CA217834","title":null},{"funder_name":"National Institutes of Health","grant_id":"2T32CA217834-06","title":"VOLT (Vanderbilt Oncology Training Program)"}],"total_grants":2,"fwci":2.1781,"citation_percentile":0.89362039,"influential_citations":0,"citation_trend":[{"year":2025,"count":4},{"year":2026,"count":8}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1200/po.24.00288","host_type":"journal"},{"url":"https://doi.org/10.1200/po.24.00288","host_type":"publisher"},{"url":"https://ascopubs.org/doi/pdfdirect/10.1200/PO.24.00288","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39642325","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11634147","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11634147/pdf/po-8-e2400288.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11634147","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11634147?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1200/PO.24.00288","host_type":""}],"fields_of_study":["Cancer Genomics and Diagnostics","Esophageal Cancer Research and Treatment","Cancer Cells and Metastasis","03 medical and health sciences","0302 clinical medicine","Humans","Esophageal Neoplasms","Circulating Tumor DNA","Male","Female","Middle Aged","Aged","Neoplasm Recurrence, Local","Retrospective Studies","Stomach Neoplasms","Biomarkers, Tumor","Prognosis","Neoadjuvant Therapy","Adenocarcinoma","Adult","Aged, 80 and over","Esophagogastric Junction","Pathologic Complete Response"],"mesh_terms":["Circulating Tumor DNA","Pathologic Complete Response","Adenocarcinoma","Adult","Aged","Aged, 80 and over","Esophageal Neoplasms","Esophagogastric Junction","Female","Humans","Male","Middle Aged","Neoplasm Recurrence, Local","Prognosis","Retrospective Studies","Stomach Neoplasms","Biomarkers, Tumor","Neoadjuvant Therapy"],"keywords":["Medicine","Internal medicine","Hazard ratio","Neoadjuvant therapy","Oncology","Adenocarcinoma","Circulating tumor DNA","Gastroenterology","Radiation therapy","Cancer","Confidence interval","Breast cancer","Male","Adult","Aged, 80 and over","Esophageal Neoplasms","Middle Aged","Prognosis","Stomach Neoplasms","Original Reports","Biomarkers, Tumor","Pathologic Complete Response","Humans","Female","Esophagogastric Junction","Neoplasm Recurrence, Local","Aged","Retrospective Studies"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T16:47:37.380440Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}