{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T06:22:08Z","timestamp":1787638928866,"version":"build-2736575974"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"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>The efficacy and safety of perioperative immune checkpoint inhibitors (ICIs) combined with chemotherapy for resectable gastric\/gastroesophageal junction (GEJ) cancer remain to be definitively established. This meta-analysis aimed to synthesize the latest evidence from randomized controlled trials (RCTs) on this emerging therapeutic strategy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic literature search was conducted in PubMed, Embase, and the Cochrane Library up to June 2026 for RCTs comparing perioperative ICI plus chemotherapy with chemotherapy alone in patients with resectable gastric\/GEJ cancer. Primary outcomes included pathological complete response (pCR), R0 resection rate, and survival endpoints (event-free survival [EFS] and overall survival [OS]). Safety was assessed by the incidence of adverse events. Pooled risk ratios (RRs), hazard ratios (HRs), and 95% confidence intervals (CIs) were calculated using random-effects models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Seven RCTs comprising 3252 patients were included. The addition of ICIs to chemotherapy significantly improved the pCR rate compared to chemotherapy alone (RR: 2.91, 95% CI: 2.16 to 3.93,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001). The ICI-chemotherapy combination also significantly prolonged EFS (HR: 0.74, 95% CI: 0.66 to 0.83,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001) and OS (HR: 0.80, 95% CI: 0.66 to 0.95,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.013). Exploratory subgroup analyses suggested numerically greater pCR benefit in patients with PD-L1 positive expression (CPS \u22651) or microsatellite instability high (MSI-H) tumors. The R0 resection rate was similar between the two groups. Moreover, the incidences of any-grade and severe adverse events showed no statistically significant difference between the two groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This meta-analysis provides updated evidence that the addition of ICIs to perioperative chemotherapy significantly enhances pathological responses and survival outcomes in patients with resectable gastric\/GEJ cancer, with a safety profile that showed no statistically significant difference in adverse events compared to chemotherapy alone. These results further reinforce the use of perioperative ICI-chemotherapy combination as a promising treatment strategy for this patient population, although confirmation in larger trials with longer follow-up is warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1765780","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:34:28Z","timestamp":1787636068000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Perioperative immunochemotherapy for resectable gastric or gastroesophageal junction cancer: a meta-analysis of efficacy and safety from randomized trials"],"prefix":"10.3389","volume":"17","author":[{"given":"Juan","family":"Xu","sequence":"first","affiliation":[{"name":"Beijing Shi Jingshan Cadre Sanatorium of the Beijing Garrison","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-mei","family":"Li","sequence":"additional","affiliation":[{"name":"Laoshan Medical District of No. 971 Hospital of Chinese Navy","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Yang","sequence":"additional","affiliation":[{"name":"Laoshan Medical District of No. 971 Hospital of Chinese Navy","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Rocket Force Characteristic Medical Center","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-lin","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Rocket Force Characteristic Medical Center","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Laoshan Medical District of No. 971 Hospital of Chinese Navy","place":["Qingdao, Shandong, China"]},{"name":"Department of Oncology, Sunshine Union Hospital","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Rocket Force Characteristic Medical Center","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,25]]},"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":"10.1016\/j.annonc.2022.07.004","article-title":"Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"33","author":"Lordick","year":"2022","journal-title":"Ann Oncol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1056\/NEJMoa055531","article-title":"Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer","volume":"355","author":"Cunningham","year":"2006","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(11)61873-4","article-title":"Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial","volume":"379","author":"Bang","year":"2012","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1200\/jco.20.02914","article-title":"PRODIGY: A phase III study of neoadjuvant docetaxel, oxaliplatin, and S-1 plus surgery and adjuvant S-1 versus surgery and adjuvant S-1 for resectable advanced gastric cancer","volume":"39","author":"Kang","year":"2021","journal-title":"J Clin Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(18)32557-1","article-title":"Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2\/3 trial","volume":"393","author":"Al-Batran","year":"2019","journal-title":"Lancet"},{"key":"B7","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/s0140-6736(21)00797-2","article-title":"First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial","volume":"398","author":"Janjigian","year":"2021","journal-title":"Lancet"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(23)00515-6","article-title":"Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial","volume":"24","author":"Rha","year":"2023","journal-title":"Lancet Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1200\/jco.22.00686","article-title":"Neoadjuvant nivolumab plus ipilimumab and adjuvant nivolumab in localized deficient mismatch repair\/microsatellite instability-high gastric or esophagogastric junction adenocarcinoma: the GERCOR NEONIPIGA phase II study","volume":"41","author":"Andr\u00e9","year":"2023","journal-title":"J Clin Oncol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.6263","article-title":"A phase II study of perioperative pembrolizumab plus mFOLFOX in patients with potentially resectable esophagus, gastroesophageal junction (GEJ), and stomach adenocarcinoma","volume":"12","author":"Sun","year":"2023","journal-title":"Cancer Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"Bmj"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane Collaboration's tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins","year":"2011","journal-title":"Bmj"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1186","article-title":"Quantifying heterogeneity in a meta-analysis","volume":"21","author":"Higgins","year":"2002","journal-title":"Stat Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02721-w","article-title":"Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial","volume":"30","author":"Yuan","year":"2024","journal-title":"Nat Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1200\/jco-25-00486","article-title":"Pembrolizumab plus chemotherapy versus chemotherapy as perioperative therapy in locally advanced gastric and gastroesophageal junction cancer: final analysis of the randomized, phase III KEYNOTE-585 study","volume":"43","author":"Shitara","year":"2025","journal-title":"J Clin Oncol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2025.0522","article-title":"Atezolizumab and trastuzumab plus chemotherapy for ERBB2-positive locally advanced resectable gastric cancer: A randomized clinical trial","volume":"11","author":"Peng","year":"2025","journal-title":"JAMA Oncol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1200\/jco.23.00975","article-title":"Perioperative atezolizumab plus fluorouracil, leucovorin, oxaliplatin, and docetaxel for resectable esophagogastric cancer: interim results from the randomized, multicenter, phase II\/III DANTE\/IKF-s633 trial","volume":"42","author":"Lorenzen","year":"2024","journal-title":"J Clin Oncol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2503701","article-title":"Perioperative durvalumab in gastric and gastroesophageal junction cancer","volume":"393","author":"Janjigian","year":"2025","journal-title":"N Engl J Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2025.09.096","article-title":"LBA81 Final overall survival (OS) and the association of pathological outcomes with event-free survival (EFS) in MATTERHORN: A randomised, phase III study of durvalumab (D) plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric \/ gastroesophageal junction (G \/ GEJ) adenocarcinoma","volume":"36","author":"Tabernero","year":"2025","journal-title":"Ann Oncol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1200\/jco-25-02842","article-title":"Perioperative toripalimab plus chemotherapy versus chemotherapy alone in locally advanced gastric or gastroesophageal junction cancer: 3-year follow-up of NEOSUMMIT-01 trial","volume":"44","author":"Nie","year":"2026","journal-title":"J Clin Oncol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(26)00974-8","article-title":"Perioperative serplulimab with neoadjuvant chemotherapy versus perioperative chemotherapy in PD-L1-positive gastric cancer (ASTRUM-006): a randomised, double-blind, multicentre, phase 3 study","volume":"407","author":"Shen","year":"2026","journal-title":"Lancet"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2025.08.2738","article-title":"2118P Perioperative sintilimab plus oxaliplatin and S-1 (SOX) versus SOX alone in resectable locally advanced gastric cancer\/gastroesophageal junction cancer (GC\/GEJC): A multicenter randomized phase II study (PERSIST)","volume":"36","author":"Ding","year":"2025","journal-title":"Ann Oncol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1692336","article-title":"Addition of immunotherapy to perioperative chemotherapy for resectable gastric and gastroesophageal junction cancer: a meta-analysis of phase 2\/3 trials","volume":"16","author":"Lin","year":"2025","journal-title":"Front Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2022.0008","article-title":"Gastric cancer, version 2.2022, NCCN clinical practice guidelines in oncology","volume":"20","author":"Ajani","year":"2022","journal-title":"J Natl Compr Canc Netw"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12516","article-title":"The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023","volume":"44","author":"Wang","year":"2024","journal-title":"Cancer Commun (Lond)"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1339757","article-title":"Evaluation of neoadjuvant immunotherapy in resectable gastric\/gastroesophageal junction tumors: a meta-analysis and systematic review","volume":"15","author":"Wang","year":"2024","journal-title":"Front Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-025-02160-8","article-title":"Perioperative tislelizumab plus chemotherapy for locally advanced gastroesophageal junction adenocarcinoma (NEOSUMMIT-03): a prospective, nonrandomized, open-label, phase 2 trial","volume":"10","author":"Nie","year":"2025","journal-title":"Signal Transduct Target Ther"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1200\/jco.24.00795","article-title":"Pathologic response of phase III study: perioperative camrelizumab plus rivoceranib and chemotherapy versus chemotherapy for locally advanced gastric cancer (DRAGON IV\/CAP 05)","volume":"43","author":"Li","year":"2025","journal-title":"J Clin Oncol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2023.03.010","article-title":"Predictive value of radiological response, pathological response and relapse-free survival for overall survival in neoadjuvant immunotherapy trials: pooled analysis of 29 clinical trials","volume":"186","author":"Nie","year":"2023","journal-title":"Eur J Cancer"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/s2468-1253(24)00156-0","article-title":"Adjuvant nivolumab plus chemotherapy versus placebo plus chemotherapy for stage III gastric or gastro-oesophageal junction cancer after gastrectomy with D2 or more extensive lymph-node dissection (ATTRACTION-5): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial","volume":"9","author":"Kang","year":"2024","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2022.3707","article-title":"Association of PD-L1 expression and other variables with benefit from immune checkpoint inhibition in advanced gastroesophageal cancer: systematic review and meta-analysis of 17 phase 3 randomized clinical trials","volume":"8","author":"Yoon","year":"2022","journal-title":"JAMA Oncol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1765780\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:34:29Z","timestamp":1787636069000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1765780\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,25]]},"references-count":31,"alternative-id":["10.3389\/fimmu.2026.1765780"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1765780","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,25]]},"article-number":"1765780"}}