{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:51:16Z","timestamp":1791355876436,"version":"4.3.1"},"reference-count":30,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Although combining programmed cell death protein 1 (PD\u20101)\/programmed death\u2010ligand 1 (PD\u2010L1) and cytotoxic T\u2010lymphocyte\u2010associated protein 4 (CTLA\u20104) inhibitors in neoadjuvant therapy is effective for deficient mismatch repair (dMMR) or microsatellite instability\u2010high (MSI\u2010H) gastric or esophagogastric junction (EGJ) adenocarcinoma, few T4 stage patients have been studied. The effectiveness and safety of this dual immunotherapy for T4 locally advanced dMMR\/MSI\u2010H gastric\/EGJ adenocarcinoma is largely unknown. Patients with T4 locally advanced dMMR\/MSI\u2010H gastric\/EGJ adenocarcinoma treated with dual immune checkpoint inhibitors as neoadjuvant therapy were identified from a prospectively maintained gastric\/EGJ adenocarcinoma database. The primary endpoint was the pathological complete response (pCR) rate. Twenty\u2010three patients were included in this study. Of these, 22 (95.7%) completed dual immunotherapy before surgery, while one missed a dose due to immune\u2010related hypophysitis. Sixteen patients (69.6%) underwent surgery, achieving a 100% R0 resection rate. The pCR rate was 81.3% (95% confidence interval (CI): 57.0%\u201393.4%) and the major pathological response (MPR) rate was 93.8%. Seven patients did not have surgery; five of them, with complete clinical response, opted for a \u201cwatch\u2010and\u2010wait\u201d strategy. The event\u2010free survival rate was 95.5% at a median follow\u2010up of 22.1\u2009months, with manageable adverse events. Dual immunotherapy shows promise for T4 locally advanced dMMR\/MSI\u2010H gastric\/EGJ adenocarcinoma, and the \u201cwatch\u2010and\u2010wait\u201d strategy deserves further study in dMMR\/MSI\u2010H cases. Larger studies are needed to confirm these results and optimize treatment.<\/jats:p>","DOI":"10.1002\/ijc.70763","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:07:47Z","timestamp":1791353267000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neoadjuvant Dual Immunotherapy in\n                    <scp>T4<\/scp>\n                    Locally Advanced Deficient Mismatch Repair Gastric or Esophagogastric Junction (\n                    <scp>EGJ<\/scp>\n                    ) Adenocarcinoma"],"prefix":"10.1002","author":[{"given":"Qiancheng","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Cancer Center, West China Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Gastric Cancer Center West China Hospital, Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Cancer Center, West China Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Gastric Cancer Center West China Hospital, Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Cancer Center, West China Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Gastric Cancer Center West China Hospital, Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9654-7374","authenticated-orcid":false,"given":"Yuan","family":"Yin","sequence":"additional","affiliation":[{"name":"Gastric Cancer Center West China Hospital, Sichuan University  Chengdu Sichuan China"},{"name":"Department of General Surgery, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolong","family":"Chen","sequence":"additional","affiliation":[{"name":"Gastric Cancer Center West China Hospital, Sichuan University  Chengdu Sichuan China"},{"name":"Department of General Surgery, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mojin","family":"Wang","sequence":"additional","affiliation":[{"name":"Gastric Cancer Center West China Hospital, Sichuan University  Chengdu Sichuan China"},{"name":"Department of General Surgery, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Gastric Cancer Center West China Hospital, Sichuan University  Chengdu Sichuan China"},{"name":"Department of General Surgery, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Gastric Cancer Center West China Hospital, Sichuan University  Chengdu Sichuan China"},{"name":"Department of General Surgery, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8426-3611","authenticated-orcid":false,"given":"Chaoyong","family":"Shen","sequence":"additional","affiliation":[{"name":"Gastric Cancer Center West China Hospital, Sichuan University  Chengdu Sichuan China"},{"name":"Department of General Surgery, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Cancer Center, West China Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Gastric Cancer Center West China Hospital, Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuming","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Clinical Research Management, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Yang","sequence":"additional","affiliation":[{"name":"Gastric Cancer Center West China Hospital, Sichuan University  Chengdu Sichuan China"},{"name":"Department of General Surgery, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiankun","family":"Hu","sequence":"additional","affiliation":[{"name":"Gastric Cancer Center West China Hospital, Sichuan University  Chengdu Sichuan China"},{"name":"Department of General Surgery, West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2071-6773","authenticated-orcid":false,"given":"Hongfeng","family":"Gou","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Cancer Center, West China Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Gastric Cancer Center West China Hospital, Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"issue":"9","key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1136\/gutjnl-2020-321600","article-title":"Global Burden of Oesophageal and Gastric Cancer by Histology and Subsite in 2018","volume":"69","author":"Arnold M.","year":"2020","journal-title":"Gut"},{"issue":"3","key":"e_1_2_12_3_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung H.","year":"2021","journal-title":"CA: a Cancer Journal for Clinicians"},{"issue":"4","key":"e_1_2_12_4_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.clinre.2021.101691","article-title":"Prevalence and Prognosis of Microsatellite Instability in Oesogastric Adenocarcinoma, NORDICAP 16\u201001","volume":"45","author":"Tran\u2010Minh M. L.","year":"2021","journal-title":"Clinics and Research in Hepatology and Gastroenterology"},{"issue":"35","key":"e_1_2_12_5_1","doi-asserted-by":"crossref","first-page":"3392","DOI":"10.1200\/JCO.19.01124","article-title":"Individual Patient Data Meta\u2010Analysis of the Value of Microsatellite Instability as a Biomarker in Gastric Cancer","volume":"37","author":"Pietrantonio F.","year":"2019","journal-title":"Journal of Clinical Oncology"},{"issue":"2","key":"e_1_2_12_6_1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1097\/SLA.0000000000002803","article-title":"Microsatellite Instability and Programmed Cell Death\u2010Ligand 1 Expression in Stage II\/III Gastric Cancer: Post Hoc Analysis of the CLASSIC Randomized Controlled Study","volume":"270","author":"Choi Y. Y.","year":"2019","journal-title":"Annals of Surgery"},{"issue":"9","key":"e_1_2_12_7_1","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1001\/jamaoncol.2016.6762","article-title":"Mismatch Repair Deficiency, Microsatellite Instability, and Survival: An Exploratory Analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) Trial","volume":"3","author":"Smyth E. C.","year":"2017","journal-title":"JAMA Oncology"},{"issue":"7","key":"e_1_2_12_8_1","doi-asserted-by":"crossref","DOI":"10.1002\/cncr.35831","article-title":"Perioperative Chemotherapy for Gastric Cancer Patients With Microsatellite Instability or Deficient Mismatch Repair: A Systematic Review and Meta\u2010Analysis","volume":"131","author":"Liu B.","year":"2025","journal-title":"Cancer"},{"issue":"4","key":"e_1_2_12_9_1","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1245\/s10434-021-11050-6","article-title":"Adjuvant Chemotherapy for Gastric Cancer Patients With Mismatch Repair Deficiency or Microsatellite Instability: Systematic Review and Meta\u2010Analysis","volume":"29","author":"Nie R. C.","year":"2022","journal-title":"Annals of Surgical Oncology"},{"issue":"2","key":"e_1_2_12_10_1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/jso.23618","article-title":"Is Microsatellite Instability a Prognostic Marker in Gastric Cancer? A Systematic Review With Meta\u2010Analysis","volume":"110","author":"Choi Y. Y.","year":"2014","journal-title":"Journal of Surgical Oncology"},{"issue":"19","key":"e_1_2_12_11_1","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1200\/JCO-24-02463","article-title":"Phase II Study (NO LIMIT, WJOG13320G) of First\u2010Line Nivolumab Plus Low\u2010Dose Ipilimumab for Microsatellite Instability\u2010High Advanced Gastric or Esophagogastric Junction Cancer","volume":"43","author":"Kawakami H.","year":"2025","journal-title":"Journal of Clinical Oncology"},{"issue":"6","key":"e_1_2_12_12_1","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1001\/jamaoncol.2021.0275","article-title":"Assessment of Pembrolizumab Therapy for the Treatment of Microsatellite Instability\u2010High Gastric or Gastroesophageal Junction Cancer Among Patients in the KEYNOTE\u2010059, KEYNOTE\u2010061, and KEYNOTE\u2010062 Clinical Trials","volume":"7","author":"Chao J.","year":"2021","journal-title":"JAMA Oncology"},{"issue":"7","key":"e_1_2_12_13_1","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1200\/JCO.22.02331","article-title":"Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer: ASCO Guideline","volume":"41","author":"Shah M. A.","year":"2023","journal-title":"Journal of Clinical Oncology"},{"issue":"6","key":"e_1_2_12_14_1","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2023-007104","article-title":"Outcomes and a Prognostic Classifier in Patients With Microsatellite Instability\u2010High Metastatic Gastric Cancer Receiving PD\u20101 Blockade","volume":"11","author":"Randon G.","year":"2023","journal-title":"Journal for Immunotherapy of Cancer"},{"key":"e_1_2_12_15_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.eclinm.2025.103421","article-title":"Efficacy and Safety of Neoadjuvant Toripalimab Plus Chemotherapy in Localized Deficient Mismatch Repair\/Microsatellite Instability\u2010High Gastric or Esophagogastric Junction Adenocarcinoma (NICE): A Multicentre, Single\u2010Arm, Exploratory Phase 2 Study","volume":"87","author":"Zhao L.","year":"2025","journal-title":"EClinicalMedicine"},{"issue":"32","key":"e_1_2_12_16_1","doi-asserted-by":"crossref","first-page":"3457","DOI":"10.1200\/JCO-25-00447","article-title":"Neoadjuvant CTLA\u20104\/PD\u2010(L)1 Blockade Versus Surgery +\/\u2212 Chemotherapy in Deficient Mismatch Repair\/Microsatellite Instability\u2010High Resectable Gastroesophageal Adenocarcinoma: Individual Patient Data Pooled Analysis","volume":"43","author":"Raimondi A.","year":"2025","journal-title":"Journal of Clinical Oncology"},{"issue":"4","key":"e_1_2_12_17_1","doi-asserted-by":"crossref","first-page":"410","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\u2010s633 Trial","volume":"42","author":"Lorenzen S.","year":"2024","journal-title":"Journal of Clinical Oncology"},{"issue":"2","key":"e_1_2_12_18_1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1200\/JCO.22.00686","article-title":"Neoadjuvant Nivolumab Plus Ipilimumab and Adjuvant Nivolumab in Localized Deficient Mismatch Repair\/Microsatellite Instability\u2010High Gastric or Esophagogastric Junction Adenocarcinoma: The GERCOR NEONIPIGA Phase II Study","volume":"41","author":"Andr\u00e9 T.","year":"2023","journal-title":"Journal of Clinical Oncology"},{"issue":"3","key":"e_1_2_12_19_1","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.annonc.2024.11.016","article-title":"Tremelimumab and Durvalumab as Neoadjuvant or Non\u2010Operative Management Strategy of Patients With Microsatellite Instability\u2010High Resectable Gastric or Gastroesophageal Junction Adenocarcinoma: The INFINITY Study by GONO","volume":"36","author":"Raimondi A.","year":"2025","journal-title":"Annals of Oncology"},{"issue":"11","key":"e_1_2_12_20_1","doi-asserted-by":"crossref","DOI":"10.3390\/cancers13112839","article-title":"TremelImumab and Durvalumab Combination for the Non\u2010OperatIve Management (NOM) of Microsatellite InstabiliTY (MSI)\u2010High Resectable Gastric or Gastroesophageal Junction Cancer: The Multicentre, Single\u2010Arm, Multi\u2010Cohort, Phase II INFINITY Study","volume":"13","author":"Raimondi A.","year":"2021","journal-title":"Cancers (Basel)"},{"issue":"8","key":"e_1_2_12_21_1","doi-asserted-by":"crossref","first-page":"3669","DOI":"10.1007\/s00520-016-3297-9","article-title":"The Association Between Clinician\u2010Based Common Terminology Criteria for Adverse Events (CTCAE) and Patient\u2010Reported Outcomes (PRO): A Systematic Review","volume":"24","author":"Atkinson T. M.","year":"2016","journal-title":"Supportive Care in Cancer"},{"issue":"2","key":"e_1_2_12_22_1","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1097\/01.sla.0000133083.54934.ae","article-title":"Classification of Surgical Complications: A New Proposal With Evaluation in a Cohort of 6336 Patients and Results of a Survey","volume":"240","author":"Dindo D.","year":"2004","journal-title":"Annals of Surgery"},{"issue":"1","key":"e_1_2_12_23_1","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s41392-024-02031-8","article-title":"Spatial Interactions of Immune Cells as Potential Predictors to Efficacy of Toripalimab Plus Chemotherapy in Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma: A Phase Ib\/II Trial","volume":"9","author":"Cheng K.","year":"2024","journal-title":"Signal Transduction and Targeted Therapy"},{"issue":"10294","key":"e_1_2_12_24_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0140-6736(21)00797-2","article-title":"First\u2010Line Nivolumab Plus Chemotherapy Versus Chemotherapy Alone for Advanced Gastric, Gastro\u2010Oesophageal Junction, and Oesophageal Adenocarcinoma (CheckMate 649): A Randomised, Open\u2010Label, Phase 3 Trial","volume":"398","author":"Janjigian Y. Y.","year":"2021","journal-title":"Lancet"},{"issue":"4","key":"e_1_2_12_25_1","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1002\/ijc.34296","article-title":"First\u2010Line Nivolumab Plus Chemotherapy vs Chemotherapy in Patients With Advanced Gastric, Gastroesophageal Junction and Esophageal Adenocarcinoma: CheckMate 649 Chinese Subgroup Analysis","volume":"152","author":"Liu T.","year":"2023","journal-title":"International Journal of Cancer"},{"issue":"21","key":"e_1_2_12_26_1","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1001\/jama.2023.19918","article-title":"Sintilimab Plus Chemotherapy for Unresectable Gastric or Gastroesophageal Junction Cancer: The ORIENT\u201016 Randomized Clinical Trial","volume":"330","author":"Xu J.","year":"2023","journal-title":"JAMA"},{"issue":"3","key":"e_1_2_12_27_1","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1002\/bjs.10663","article-title":"Meta\u2010Analysis of Microsatellite Instability in Relation to Clinicopathological Characteristics and Overall Survival in Gastric Cancer","volume":"105","author":"Polom K.","year":"2018","journal-title":"British Journal of Surgery"},{"issue":"5","key":"e_1_2_12_28_1","first-page":"2579","article-title":"Clinicopathological Features and Prognostic Value of Mismatch Repair Protein Deficiency in Gastric Cancer","volume":"11","author":"Zhang Q.","year":"2018","journal-title":"International Journal of Clinical and Experimental Pathology"},{"issue":"25","key":"e_1_2_12_29_1","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1056\/NEJMoa2201445","article-title":"PD\u20101 Blockade in Mismatch Repair\u2010Deficient, Locally Advanced Rectal Cancer","volume":"386","author":"Cercek A.","year":"2022","journal-title":"New England Journal of Medicine"},{"issue":"1","key":"e_1_2_12_30_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/S2468-1253(21)00348-4","article-title":"Neoadjuvant PD\u20101 Blockade With Toripalimab, With or Without Celecoxib, in Mismatch Repair\u2010Deficient or Microsatellite Instability\u2010High, Locally Advanced, Colorectal Cancer (PICC): A Single\u2010Centre, Parallel\u2010Group, Non\u2010Comparative, Randomised, Phase 2 Trial","volume":"7","author":"Hu H.","year":"2022","journal-title":"Lancet Gastroenterology & Hepatology"},{"issue":"4","key":"e_1_2_12_31_1","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/s41591-020-0805-8","article-title":"Neoadjuvant Immunotherapy Leads to Pathological Responses in MMR\u2010Proficient and MMR\u2010Deficient Early\u2010Stage Colon Cancers","volume":"26","author":"Chalabi M.","year":"2020","journal-title":"Nature Medicine"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.70763","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.70763","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.70763","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:07:52Z","timestamp":1791353272000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.70763"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,6]]},"references-count":30,"alternative-id":["10.1002\/ijc.70763"],"URL":"https:\/\/doi.org\/10.1002\/ijc.70763","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,6]]},"assertion":[{"value":"2025-12-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"ijc.70763"}}