{
  "abstract": "BackgroundGemcitabine-based chemotherapy is first-line for advanced biliary tract cancer (BTC) and pancreatic ductal adenocarcinoma (PDAC), but toxicity patterns are poorly defined at high altitude (>2,000 m). Clinical observations of heightened treatment toxicity at our high-altitude institution (Xining, [~]2,261 m) prompted this population-level baseline study of gemcitabine toxicity signals. The present analysis uses only publicly available, de-identified FAERS data; institutional clinical experience motivates but does not validate the signals reported here.\n\nMethodsFour-metric disproportionality analysis (ROR primary, PRR, IC BCPNN, EBGM MGPS) of FAERS 2014-2026 (18.37M reports) across five non-exclusive gemcitabine groups (monotherapy, +ICI, +TKI, triple, BTC/PDAC disease-specific). Liver toxicity stratified into three MedDRA PT groups; fatal toxicity analyzed with dual definitions. BTC/PDAC queried via correct patient.drug.drugindication field. BH-FDR post hoc. EBGM used two implementations: a non-standard single-pair {gamma}(1,1) closed-form approximation (positivity-screening column in S1) and the standard openEBGM two-component MGPS. Complete-MGPS EB05 > 2 is the primary Bayesian criterion (10/17 pass); closed-form count (12/17) is labeled non-standard.\n\nResults14/17 exposure-AE combinations passed the three frequentist criteria (ROR/PRR/IC lower bounds); 10/17 additionally passed complete-MGPS EB05 > 2 (standard openEBGM caers fit). The non-standard closed-form count (12/17) is a labeled approximation only. Myelosuppression is the most consistent signal across all regimens (ROR 3.35-7.74); under complete MGPS the sparse all-role triple-combination cell had EB05=1.59. Triple combo liver toxicity (ROR=10.32, a=28, n=181 all-role) is driven by the Severe failure-hepatitis PT group (ROR=23.51); this cell is unstable under primary-suspect restriction (ROR=1.62, a=0, n=31; Supplementary S9) and is hypothesis-generating. Restricted[->]expanded fatal bridge: triple ROR 1.62[->]4.64 (zero overlap verified). BTC/PDAC thrombocytopenia (ROR=19.36) was independently reproduced at 19.70 after deduplication/PS filtering; PPV=94%.\n\nConclusionsThis study establishes baseline gemcitabine toxicity signals from a largely sea-level FAERS population. The fatal-liver-failure bridge and PT-stratified liver toxicity are hypothesis-generating signals. High-altitude hypotheses are mechanistic and not FAERS-testable; they require prospective validation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Hepatobiliary Surgery, Qinghai Red Cross Hospital, Xining 810000, Qinghai, China"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Z. Dang"
    },
    {
      "name": "J. Dan"
    },
    {
      "name": "S. Li"
    },
    {
      "name": "L. Yanan"
    },
    {
      "name": "W. Su"
    },
    {
      "name": "G. Ren"
    },
    {
      "name": "Z. Wang"
    },
    {
      "name": "M. Lv"
    },
    {
      "name": "H. Dong"
    },
    {
      "name": "Z. Niu"
    },
    {
      "name": "H. Zhang"
    },
    {
      "name": "Y. Fan"
    },
    {
      "name": "L. Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Y. Dang"
    },
    {
      "name": "J. Gao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8k72bvm1gedc4.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.24.26363686",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.24.26363686v1.full",
  "id": "8k72bvm1gedc4",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.24.26363686v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "pharmacology and therapeutics"
    ],
    [
      "openalex",
      "3005|Pharmacovigilance and Adverse Drug Reactions"
    ]
  ],
  "openalex": "W7214532277",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.24.26363686v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/8k72bvm1gedc4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:30Z",
      "native_id": "10.64898/2026.09.24.26363686",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.24.26363686v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:pharmacology and therapeutics",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Reporting Odds Ratio Analysis of Gemcitabine-Based Chemotherapy Regimens for Biliary and Pancreatic Cancer: Population-Level Toxicity Signals and Hypotheses for High-Altitude Generalizability",
  "title_text": "Reporting Odds Ratio Analysis of Gemcitabine-Based Chemotherapy Regimens for Biliary and Pancreatic Cancer: Population-Level Toxicity Signals and Hypotheses for High-Altitude Generalizability",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:30Z",
  "url": "https://research.draconitic.com/paper/8k72bvm1gedc4",
  "venue": "medRxiv",
  "versions": []
}