{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T20:48:04Z","timestamp":1792529284883,"version":"4.5.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"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>Neoadjuvant chemoradiotherapy (NCRT) is standard for locally advanced esophageal squamous cell carcinoma (ESCC), while neoadjuvant immune-chemotherapy (NICT) is a promising alternative. This study compared pathological response and long-term survival between NICT and NCRT followed by surgery using a target trial emulation framework.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We emulated a target trial in 288 consecutive patients with locally advanced thoracic ESCC who underwent neoadjuvant therapy and esophagectomy between March 2018 and December 2022. Eligible patients were aged 18\u201380 years and had clinical stage cT1N+M0 or cT2\u20134aN0\u20133M0 disease. The primary endpoints were overall survival (OS) and disease-free survival (DFS), with cancer-specific survival (CSS) and recurrence-free survival (RFS) as additional endpoints. Baseline characteristics were balanced after inverse probability of treatment weighting (IPTW). Bootstrap-weighted Cox models were applied to small subgroups for exploratory analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Median follow-up was 49.3 months. Both pre- and post-IPTW, the NCRT group experienced a significantly higher incidence of severe (grade\u00a03-4) myelosuppression compared with NICT (P\u00a0&amp;lt;\u00a00.001), whereas no significant differences were observed between the two cohorts in surgery-related outcomes. In the unadjusted cohort, patients receiving NCRT achieved superior pathological responses, with higher rates of pathological complete response (pCR) and tumor regression grade (TRG). After IPTW, all pathologic endpoints were well balanced except for TRG 0, which remained marginally different (P\u00a0=\u00a00.051, SMD\u00a0=\u00a00.376). Before IPTW, there were no significant differences between NCRT and NICT in OS or DFS (OS: HR\u00a0=\u00a01.08, 95% CI 0.72-1.63, P\u00a0=\u00a00.701; DFS: HR\u00a0=\u00a01.02, 95% CI 0.70-1.48, P\u00a0=\u00a00.915). Although the KM curves for CSS and RFS showed a separation trend, the differences were not significant (CSS: HR\u00a0=\u00a00.74, 95% CI 0.44-1.23, P\u00a0=\u00a00.245; RFS: HR\u00a0=\u00a00.72, 95% CI 0.46-1.14, P\u00a0=\u00a00.163). After IPTW weighting, OS and DFS remained comparable between the two groups, whereas NICT demonstrated advantages in RFS (HR\u00a0=\u00a00.47, 95% CI 0.27-0.82, P\u00a0=\u00a00.008) and CSS (HR\u00a0=\u00a00.49, 95% CI 0.26-0.89, P\u00a0=\u00a00.020). Multivariable analysis identified higher ypN stage as independent predictors of worse OS and DFS. Lower ypN stage and receipt of NICT were associated with better CSS and RFS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Among patients with locally advanced ESCC receiving neoadjuvant therapy, NCRT was associated with superior pathological response but also a higher risk of severe myelosuppression. After IPTW adjustment, NICT and NCRT showed comparable OS and DFS, while NICT was associated with significantly better RFS and CSS. These findings suggest that NICT may be a feasible alternative to NCRT in this population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1916623","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:43:15Z","timestamp":1788417795000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparative outcomes of neoadjuvant immunochemotherapy versus neoadjuvant chemoradiotherapy in locally advanced thoracic esophageal squamous cell carcinoma: a target trial emulation"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhiyu","family":"Li","sequence":"first","affiliation":[{"name":"School of Pharmacy, Faculty of Medicine, Macau University of Science and Technology","place":["Macao SAR, China"]},{"name":"Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuxi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of General Internal Medicine, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongtao","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefeng","family":"Leng","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Leshan People\u2019s Hospital","place":["Leshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwu","family":"He","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/cm9.0000000000002108","article-title":"Cancer statistics in China and United States 2022: profiles, trends, and determinants","volume":"135","author":"Xia","year":"2022","journal-title":"Chin Med J (Engl)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"393","DOI":"10.6004\/jnccn.2023.0019","article-title":"Esophageal and esophagogastric junction cancers, version 2.2023, NCCN clinical practice guidelines in oncology","volume":"21","author":"Ajani","year":"2023","journal-title":"J Natl Compr Canc Netw"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1097\/sla.0000000000004329","article-title":"Neoadjuvant chemoradiotherapy using cisplatin and 5-fluorouracil (PF) versus carboplatin and paclitaxel (CROSS regimen) for esophageal squamous cell carcinoma (ESCC): a propensity score-matched study","volume":"272","author":"Wong","year":"2020","journal-title":"Ann Surg"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2020.08.002","article-title":"Recurrence patterns after neoadjuvant chemoradiotherapy compared with surgery alone in oesophageal squamous cell carcinoma: results from the multicenter phase III trial NEOCRTEC5010","volume":"138","author":"Liu","year":"2020","journal-title":"Eur J Cancer"},{"key":"B6","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1245\/s10434-011-2049-9","article-title":"A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907)","volume":"19","author":"Ando","year":"2012","journal-title":"Ann Surg Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2020.100422","article-title":"Clinical evidence for association of neoadjuvant chemotherapy or chemoradiotherapy with efficacy and safety in patients with resectable esophageal carcinoma (NewEC study)","volume":"24","author":"Zhou","year":"2020","journal-title":"EClinicalMedicine"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2021-0021","article-title":"Survival and complications after neoadjuvant chemotherapy or chemoradiotherapy for esophageal cancer: a meta-analysis","volume":"17","author":"Han","year":"2021","journal-title":"Future Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1001\/jamasurg.2021.0133","article-title":"Morbidity and mortality of patients who underwent minimally invasive esophagectomy after neoadjuvant chemoradiotherapy vs neoadjuvant chemotherapy for locally advanced esophageal squamous cell carcinoma: a randomized clinical trial","volume":"156","author":"Wang","year":"2021","journal-title":"JAMA Surg"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-021-03659-7","article-title":"Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for the treatment of esophageal squamous cell carcinoma: a propensity score-matched study from the National Cancer Center in China","volume":"148","author":"Zhang","year":"2022","journal-title":"J Cancer Res Clin Oncol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(21)01234-4","article-title":"Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study","volume":"398","author":"Sun","year":"2021","journal-title":"Lancet"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2032125","article-title":"Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer","volume":"384","author":"Kelly","year":"2021","journal-title":"N Engl J Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1001\/jamasurg.2025.0220","article-title":"Neoadjuvant chemoradiotherapy vs chemoimmunotherapy for esophageal squamous cell carcinoma","volume":"160","author":"Guo","year":"2025","journal-title":"JAMA Surg"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1016\/j.ijrobp.2023.06.2423","article-title":"Comparison of pathologic response and survival outcomes between neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant immunochemotherapy (nICT) in patients with locally advanced esophageal squamous cell carcinoma: a propensity score-matched analysis","volume":"24","author":"Wang","year":"2024","journal-title":"BMC Cancer"},{"key":"B15","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.jtcvs.2024.06.020","article-title":"Perioperative outcomes and survival after neoadjuvant immunochemotherapy for locally advanced esophageal squamous cell carcinoma","volume":"169","author":"Yang","year":"2025","journal-title":"J Thorac Cardiovasc Surg"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1093\/dote\/doac031","article-title":"Safety and efficacy of neoadjuvant treatment with immune checkpoint inhibitors in esophageal cancer: real-world multicenter retrospective study in China","volume":"35","author":"Yang","year":"2022","journal-title":"Dis Esophagus"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-004291","article-title":"Multicenter, single-arm, phase II trial of camrelizumab and chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma","volume":"10","author":"Liu","year":"2022","journal-title":"J Immunother Cancer"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003497","article-title":"Neoadjuvant programmed cell death 1 blockade combined with chemotherapy for resectable esophageal squamous cell carcinoma","volume":"10","author":"Yang","year":"2022","journal-title":"J Immunother Cancer"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2023.12.030","article-title":"Neoadjuvant chemotherapy combined with immunotherapy versus neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma","volume":"168","author":"Yu","year":"2024","journal-title":"J Thorac Cardiovasc Surg"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2021.39.15_suppl.4028","article-title":"Neoadjuvant camrelizumab plus chemotherapy for resectable, locally advanced esophageal squamous cell carcinoma (NIC-ESCC2019): a multicenter, phase 2 study","volume":"151","author":"Liu","year":"2022","journal-title":"Int J Cancer"},{"key":"B21","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/s0140-6736(24)00745-1","article-title":"Doublet chemotherapy, triplet chemotherapy, or doublet chemotherapy combined with radiotherapy as neoadjuvant treatment for locally advanced oesophageal cancer (JCOG1109 NExT): a randomised, controlled, open-label, phase 3 trial","volume":"404","author":"Kato","year":"2024","journal-title":"Lancet"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2007.12.9593","article-title":"Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781","volume":"26","author":"Tepper","year":"2008","journal-title":"J Clin Oncol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.10.508","article-title":"Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma: a prospective multicenter randomized clinical trial","volume":"34","author":"Tang","year":"2023","journal-title":"Ann Oncol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2026.1882240","article-title":"Neoadjuvant chemoimmunotherapy versus chemoradiotherapy for esophageal squamous cell carcinoma: a multicenter cohort study","volume":"17","author":"Zhu","year":"2026","journal-title":"Front Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1126\/science.aaa8172","article-title":"The future of immune checkpoint therapy","volume":"348","author":"Sharma","year":"2015","journal-title":"Science"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(15)00007-8","article-title":"Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy","volume":"16","author":"Sharabi","year":"2015","journal-title":"Lancet Oncol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.887525","article-title":"Efficacy and safety of radiotherapy\/chemoradiotherapy combined with immune checkpoint inhibitors for locally advanced stages of esophageal cancer: a systematic review and meta-analysis","volume":"12","author":"Wu","year":"2022","journal-title":"Front Oncol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.5306\/wjco.v16.i7.104959","article-title":"Expanding horizons in esophageal squamous cell carcinoma: the promise of induction chemoimmunotherapy with radiotherapy","volume":"16","author":"Ma","year":"2025","journal-title":"World J Clin Oncol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s10388-024-01097-1","article-title":"Optimizing neoadjuvant radiotherapy for locally advanced esophageal squamous cell carcinoma: a comprehensive review on the role of concomitant or sequential immune checkpoint inhibitors","volume":"22","author":"Ghalehtaki","year":"2025","journal-title":"Esophagus"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1916623\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:43:17Z","timestamp":1788417797000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1916623\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":29,"alternative-id":["10.3389\/fimmu.2026.1916623"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1916623","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]},"article-number":"1916623"}}