{
  "abstract": "BackgroundImmune checkpoint inhibitors (ICIs) have entered the perioperative treatment of resectable gastric and gastroesophageal junction (G/GEJ) adenocarcinoma, and perioperative durvalumab plus FLOT is now the standard of care. Numerous meta-analyses on this question have appeared. This umbrella review appraises their methodological quality, quantifies their overlap, grades the credibility of each pooled outcome and re-analyses the randomized evidence at the trial level.MethodsPubMed/MEDLINE, Embase, Web of Science, Scopus and the Cochrane Library were searched from January 1, 2020 to July 31, 2026 for systematic reviews with meta-analysis of perioperative (neoadjuvant and/or adjuvant) ICI therapy in resectable G/GEJ adenocarcinoma.ResultsNineteen meta-analyses met the eligibility criteria (six comparative RCT-only, seven comparative mixed-design, six single-arm syntheses). The comparative reviews re-analyze nine randomized trials comprising 2,974 unique randomized participants (2,718 in the six pivotal datasets); overlap was very high (CCA 44.4% across all randomized comparisons, 100% for EFS and OS). pCR was consistently increased (Rodrigues et al. RR 2.93, 95% CI 2.39–3.59; umbrella re-analysis of six randomized datasets, n=2,718: 17.7% vs 6.2%, Ioannidis Class II). Event-free survival improved (HR 0.76, 95% CI 0.66–0.86; Class III). OS improved in the RCT-only synthesis that incorporates the final MATTERHORN analysis (HR 0.82, 95% CI 0.71–0.94, P = .005; Class IV by the strict P-value threshold) and in MATTERHORN itself (HR 0.78, 95% CI 0.63–0.96, P = .021). Grade ≥3 treatment-related adverse events were not increased (RR 1.07, 95% CI 0.97–1.17), immune-related adverse events were (RR 3.18, 95% CI 2.48–4.08; Class II), and surgical morbidity, R0 resection and 30-day mortality were unchanged. MSI-H/dMMR status predicted the largest pCR gain (RR 5.18, 95% CI 2.43– 11.05); PD-L1 was an assay-dependent modifier and MATTERHORN’s benefit was independent of PD-L1.ConclusionsPerioperative chemo-immunotherapy is a new standard of care for resectable G/GEJ adenocarcinoma with demonstrated pCR, EFS and OS benefit. The many meta-analyses are not independent corroboration but repeated re-analyses of a small shared set of trials, and their credibility is bounded by the primary trials, not by their number. Immune-related toxicity, not surgical morbidity, is the principal cost; MSI/MMR and assay-specified PD-L1 testing should inform, but not gate, patient selection.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420261474260, identifier CRD420261474260.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Systematic Review",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "Michele Ghidini"
    },
    {
      "name": "Gloria Arena"
    },
    {
      "name": "Lorenzo Dottorini"
    },
    {
      "name": "Valentina Rampulla"
    },
    {
      "name": "Annamaria De Giorgi"
    },
    {
      "name": "Gianluca Tomasello"
    },
    {
      "name": "Fausto Petrelli"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d9s0ksvqzp62k.bib",
  "cited_by": 0,
  "doi": "10.3389/fonc.2026.1911150",
  "fulltext_url": null,
  "id": "d9s0ksvqzp62k",
  "issns": [
    "2234-943X"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1911150",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "feed-journal",
      "medicine/oncology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-05",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/d9s0ksvqzp62k.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T06:20:20Z",
      "native_id": "10.3389/fonc.2026.1911150",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1911150"
    },
    {
      "first_seen": "2026-11-05T12:21:27Z",
      "native_id": "10.3389/fonc.2026.1911150",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1911150/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "feed-journal:medicine/oncology",
      "subfield": "oncology"
    }
  ],
  "title": "Umbrella review of meta-analyses: perioperative immune checkpoint inhibitor therapy in resectable gastric and gastroesophageal junction adenocarcinoma",
  "title_text": "Umbrella review of meta-analyses: perioperative immune checkpoint inhibitor therapy in resectable gastric and gastroesophageal junction adenocarcinoma",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T00:21:24Z",
  "url": "https://research.draconitic.com/paper/d9s0ksvqzp62k",
  "venue": "Frontiers in Oncology",
  "versions": []
}