{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T21:53:08Z","timestamp":1794001988733,"version":"4.8.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Approximately 40-60% of patients with locally advanced esophageal squamous cell carcinoma (ESCC) exhibit suboptimal responses to neoadjuvant chemoimmunotherapy (NCIT), highlighting the need for predictive biomarkers of pathological response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We prospectively enrolled 29 stage II-III ESCC patients receiving NCIT (albumin-paclitaxel\/carboplatin + anti-PD-1). Baseline tumor tissues were firstly analyzed via 437-gene targeted sequencing. Serial preoperative plasma samples collected before NCIT, during NCIT and post-NCIT\/pre-surgery, along with baseline tissue, were profiled using a 2365-gene panel for tumor-informed molecular residual disease (MRD) monitoring. Associations between clinicopathological features, genomic alterations, MRD status, and major pathological response (MPR) were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      No clinicopathological feature significantly correlated with MPR. MPR was significantly associated with baseline\n                      <jats:italic>NOTCH1<\/jats:italic>\n                      mutations (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.014) and higher chromosomal instability score (CIS,\n                      <jats:italic>p<\/jats:italic>\n                      =\u00a00.032). Absence of MRD and lower ctDNA levels after NCIT completion, but not before and during, strongly correlated with MPR. Distinct change patterns of ctDNA level from on- to post-NCIT were observed in MPR versus non-MPR patients. A model integrating baseline\n                      <jats:italic>NOTCH1<\/jats:italic>\n                      mutation and post-NCIT MRD status achieved superior MPR prediction (AUC\u00a0=\u00a00.954), outperforming either factor alone (\n                      <jats:italic>NOTCH1<\/jats:italic>\n                      , AUC\u00a0=\u00a00.769; post-NCIT MRD, AUC\u00a0=\u00a00.882).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Dynamic MRD monitoring, particularly post-treatment, provides strong predictive value for pathological response to NCIT in locally advanced ESCC. Integrating baseline\n                      <jats:italic>NOTCH1<\/jats:italic>\n                      mutation status with post-NCIT MRD assessment significantly improves MPR prediction, indicating the potential to inform clinical decision-making for these patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1681959","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T05:39:44Z","timestamp":1777527584000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Genomic alterations and dynamic molecular residual disease monitoring predict pathological response to neoadjuvant chemoimmunotherapy in esophageal squamous cell carcinoma"],"prefix":"10.3389","volume":"17","author":[{"given":"Dijian","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Thoracic Oncology Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxiao","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junrong","family":"Yan","sequence":"additional","affiliation":[{"name":"Medical Department, Nanjing Geneseeq Technology Inc.","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weishan","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyi","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyun","family":"Wang","sequence":"additional","affiliation":[{"name":"Medical Department, Nanjing Geneseeq Technology Inc.","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology Surgery, Zhejiang Cancer 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