{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:49:44Z","timestamp":1792648184119,"version":"4.5.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T00:00:00Z","timestamp":1728604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["por-journal.com"],"crossmark-restriction":true},"short-container-title":["Pathol. Oncol. Res."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>To clarify the prognostic value of lymph node regression (LNR) status including the lymph node regression grade (LNRG) and N downstaging in patients with esophageal cancer receiving neoadjuvant therapy based on available evidence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Several databases were searched up to 25 March 2024. The main outcomes included overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were combined. Subgroup analyses based on the neoadjuvant therapy and pathological type were also conducted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 14 retrospective studies with 3,212 participants were included. Nine and five studies explored the relationship between LNRG and N downstaging and survival, respectively. Pooled results indicated that complete LNR predicted significantly improved OS (HR = 0.47, 95% CI: 0.41\u20130.55, P &amp;lt; 0.001) and DFS (HR = 0.42, 95% CI: 0.32\u20130.55, P &amp;lt; 0.001) and subgroup analysis based on neoadjuvant therapy and pathological type manifested similar results. Besides, N downstaging was also significantly related to improved OS (HR = 0.40, 95% CI: 0.21\u20130.77, P = 0.006) and CSS (HR = 0.27, 95% CI: 0.12\u20130.60, P &amp;lt; 0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>LNR could serve as a novel and reliable prognostic factor in patients with esophageal cancer receiving neoadjuvant therapy and complete LNR and N downstaging predict better survival.<\/jats:p><\/jats:sec>","DOI":"10.3389\/pore.2024.1611844","type":"journal-article","created":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T04:11:29Z","timestamp":1728619889000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Prognostic role of lymph node regression in patients with esophageal cancer undergoing neoadjuvant therapy"],"prefix":"10.3389","volume":"30","author":[{"given":"Pingrun","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maojia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijie","family":"Bu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guowei","family":"Che","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1007\/s11427-022-2218-x","article-title":"Cancer statistics in Chinese older people, 2022: current burden, time trends, and comparisons with the US, Japan, and the Republic of Korea","volume":"66","author":"Ju","year":"2023","journal-title":"Sci China Life Sci"},{"key":"B2","doi-asserted-by":"publisher","first-page":"584","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":"252","DOI":"10.1007\/s12032-023-02097-4","article-title":"Current neoadjuvant therapy for operable locally advanced esophageal cancer","volume":"40","author":"Yang","year":"2023","journal-title":"Med Oncol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e36785","DOI":"10.1097\/MD.0000000000036785","article-title":"Efficacy and safety of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy in locally advanced esophageal cancer: an updated meta-analysis","volume":"103","author":"Liang","year":"2024","journal-title":"Medicine (Baltimore)"},{"key":"B5","doi-asserted-by":"publisher","first-page":"163","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":"B6","doi-asserted-by":"publisher","first-page":"1995","DOI":"10.1200\/JCO.20.03614","article-title":"Ten-year outcome of neoadjuvant chemoradiotherapy plus surgery for esophageal cancer: the randomized controlled CROSS trial","volume":"39","author":"Eyck","year":"2021","journal-title":"J Clin Oncol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1051841","DOI":"10.3389\/fimmu.2022.1051841","article-title":"Neoadjuvant immunotherapy for resectable esophageal cancer: a review","volume":"13","author":"Li","year":"2022","journal-title":"Front Immunol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1097\/COC.0000000000000258","article-title":"Correlation between standardized uptake value in preneoadjuvant and postneoadjuvant chemoradiotherapy and tumor regression grade in patients with locally advanced esophageal cancer","volume":"41","author":"Baksh","year":"2018","journal-title":"Am J Clin Oncol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"3623","DOI":"10.1002\/cam4.4748","article-title":"Tumor regression grade combined with lymph node status in esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy","volume":"11","author":"Yun","year":"2022","journal-title":"Cancer Med"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1818","DOI":"10.1080\/08941939.2022.2127036","article-title":"Is tumor regression grade sufficient to predict survival in esophageal cancer with trimodal therapy?","volume":"35","author":"Gu","year":"2022","journal-title":"J Invest Surg"},{"key":"B11","doi-asserted-by":"publisher","first-page":"2599","DOI":"10.1245\/s10434-014-4299-9","article-title":"Prognostic significance of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET)-Positive lymph nodes following neoadjuvant chemotherapy and surgery for resectable thoracic esophageal squamous cell carcinoma","volume":"22","author":"Yasuda","year":"2015","journal-title":"Ann Surg Oncol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1142\/S0192415X20500639","article-title":"PRISMA (preferred reporting Items for systematic reviews and meta-analyses) extension for Chinese herbal medicines 2020 (PRISMA-CHM 2020)","volume":"48","author":"Zhang","year":"2020","journal-title":"Am J Chin Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1893","DOI":"10.1016\/j.jtho.2021.07.001","article-title":"Risk and influencing factors for subsequent primary lung cancer after treatment of breast cancer: a systematic review and two meta-analyses based on four million cases","volume":"16","author":"Wang","year":"2021","journal-title":"J Thorac Oncol : official Publ Int Assoc Study Lung Cancer"},{"key":"B14","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1093\/icvts\/ivy163","article-title":"Statistical Primer: heterogeneity, random- or fixed-effects model analyses?","volume":"27","author":"Barili","year":"2018","journal-title":"Interact Cardiovasc Thorac Surg"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.2307\/2533446","article-title":"Operating characteristics of a rank correlation test for publication bias","volume":"50","author":"Begg","year":"1994","journal-title":"Biometrics"},{"key":"B16","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1136\/bmj.315.7109.629","article-title":"Bias in meta-analysis detected by a simple, graphical test","volume":"315","author":"Egger","year":"1997","journal-title":"BMJ (Clinical research ed)"},{"key":"B17","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1067\/mtc.2001.112470","article-title":"N1 esophageal carcinoma: the importance of staging and downstaging","volume":"121","author":"Rice","year":"2001","journal-title":"J Thorac Cardiovasc Surg"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.1016\/j.athoracsur.2011.06.091","article-title":"Prognostic significance of a new grading system of lymph node morphology after neoadjuvant radiochemotherapy for esophageal","volume":"92","author":"Bollschweiler","year":"2011","journal-title":"Ann Thorac Surg"},{"key":"B19","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1097\/SLA.0b013e3182a66588","article-title":"Classification of pathologic response to neoadjuvant therapy in esophageal and junctional cancer: assessment of existing measures and proposal of a novel 3-point standard","volume":"258","author":"Donohoe","year":"2013","journal-title":"Ann Surg"},{"key":"B20","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.athoracsur.2014.07.037","article-title":"Neoadjuvant treatment response in negative nodes is an important prognosticator after esophagectomy","volume":"99","author":"Nieman","year":"2015","journal-title":"Ann Thorac Surg"},{"key":"B21","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1053\/j.semtcvs.2016.04.003","article-title":"Prognostic relevance of lymph node regression after neoadjuvant chemoradiation for esophageal cancer","volume":"28","author":"Philippron","year":"2016","journal-title":"Semin Thorac Cardiovasc Surg"},{"key":"B22","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1245\/s10434-016-5440-8","article-title":"ypN0: does it matter how you get there? Nodal downstaging in esophageal cancer","volume":"23","author":"Zanoni","year":"2016","journal-title":"Ann Surg Oncol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1816","DOI":"10.1002\/bjs.10627","article-title":"Multicentre cohort study to define and validate pathological assessment of response to neoadjuvant therapy in oesophagogastric adenocarcinoma","volume":"104","author":"Noble","year":"2017","journal-title":"Br J Surg"},{"key":"B24","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1097\/SLA.0000000000001630","article-title":"Prognostic value of pretreatment pathological tumor extent in patients treated with neoadjuvant chemoradiotherapy plus surgery for esophageal or junctional cancer","volume":"265","author":"Shapiro","year":"2017","journal-title":"Ann Surg"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.1002\/bjs.10900","article-title":"Lymph node regression and survival following neoadjuvant chemotherapy in oesophageal adenocarcinoma","volume":"105","author":"Davies","year":"2018","journal-title":"Br J Surg"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2048","DOI":"10.1245\/s10434-020-09363-z","article-title":"Clinicopathological significance of pathologic complete lymph node regression after neoadjuvant chemoradiotherapy in esophageal squamous cell carcinoma","volume":"28","author":"Hsu","year":"2021","journal-title":"Ann Surg Oncol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1007\/s10388-020-00777-y","article-title":"Lymph node response to chemoradiotherapy in oesophageal cancer patients: relationship with radiotherapy fields","volume":"18","author":"Koemans","year":"2021","journal-title":"Esophagus"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1016\/j.ejso.2021.12.021","article-title":"Impact of neoadjuvant chemotherapy on nodal regression and survival in oesophageal adenocarcinoma","volume":"48","author":"Evans","year":"2022","journal-title":"Eur J Surg Oncol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"4522","DOI":"10.1200\/JCO.23.00139","article-title":"Pathologic lymph node regression after neoadjuvant chemotherapy predicts recurrence and survival in esophageal adenocarcinoma: a multicenter study in the United Kingdom","volume":"41","author":"Moore","year":"2023","journal-title":"J Clin Oncol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1002\/jso.27555","article-title":"Prognostic significance of positive lymph node regression grade to neoadjuvant chemoradiation for esophageal squamous cell carcinoma","volume":"129","author":"Yehan","year":"2024","journal-title":"J Surg Oncol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"doab021","DOI":"10.1093\/dote\/doab021","article-title":"Prognostic relevance of lymph node regression on survival in esophageal cancer: a systematic review and meta-analysis","volume":"35","author":"Hagens","year":"2022","journal-title":"Dis Esophagus"},{"key":"B32","doi-asserted-by":"publisher","first-page":"3811","DOI":"10.1038\/s41598-018-22115-0","article-title":"Genetic heterogeneity of primary lesion and metastasis in small intestine neuroendocrine tumors","volume":"8","author":"Walter","year":"2018","journal-title":"Sci Rep"},{"key":"B33","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1302\/2046-3758.105.BJR-2020-0262.R3","article-title":"GNAQ knockdown promotes bone metastasis through epithelial-mesenchymal transition in lung cancer cells","volume":"10","author":"Choi","year":"2021","journal-title":"Bone Joint Res"},{"key":"B34","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1007\/s00292-005-0749-2","article-title":"Regression and therapy-resistance of primary liver tumors and liver metastases after regional chemotherapy and local tumor ablation","volume":"26","author":"Fischer","year":"2005","journal-title":"Pathologe"},{"key":"B35","doi-asserted-by":"publisher","first-page":"2277","DOI":"10.21037\/tlcr-20-175","article-title":"Primary tumor and metastasis-sectioning the different steps of the metastatic cascade","volume":"9","author":"Popper","year":"2020","journal-title":"Transl Lung Cancer Res"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12967-019-02189-8","article-title":"Tumor microenvironment differences between primary tumor and brain metastases","volume":"18","author":"Cacho-D\u00edaz","year":"2020","journal-title":"J Transl Med"},{"key":"B37","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/j.ctrv.2013.10.001","article-title":"The role of the tumor-microenvironment in lung cancer-metastasis and its relationship to potential therapeutic targets","volume":"40","author":"Wood","year":"2014","journal-title":"Cancer Treat Rev"},{"key":"B38","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1111\/1759-7714.12455","article-title":"Comparison of the c-MET gene amplification between primary tumor and metastatic lymph nodes in non-small cell lung cancer","volume":"8","author":"Xu","year":"2017","journal-title":"Thorac Cancer"}],"container-title":["Pathology and Oncology Research"],"original-title":[],"link":[{"URL":"https:\/\/www.por-journal.com\/articles\/10.3389\/pore.2024.1611844\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T04:11:31Z","timestamp":1728619891000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.por-journal.com\/articles\/10.3389\/pore.2024.1611844\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,11]]},"references-count":38,"alternative-id":["10.3389\/pore.2024.1611844"],"URL":"https:\/\/doi.org\/10.3389\/pore.2024.1611844","relation":{},"ISSN":["1532-2807"],"issn-type":[{"value":"1532-2807","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,11]]},"article-number":"1611844"}}