Reporting Odds Ratio Analysis of Gemcitabine-Based Chemotherapy Regimens for Biliary and Pancreatic Cancer: Population-Level Toxicity Signals and Hypotheses for High-Altitude Generalizability
- 1Department of Hepatobiliary Surgery, Qinghai Red Cross Hospital, Xining 810000, Qinghai, China
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.
MethodsFour-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.
Results14/17 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%.
ConclusionsThis 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.
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BibTeX
@misc{dang2026reporting,
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}},
author = {Z. Dang and J. Dan and S. Li and L. Yanan and W. Su and G. Ren and Z. Wang and M. Lv and H. Dong and Z. Niu and H. Zhang and Y. Fan and L. Li and Y. Dang and J. Gao},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.24.26363686},
url = {https://www.medrxiv.org/content/10.64898/2026.09.24.26363686v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Reporting Odds Ratio Analysis of Gemcitabine-Based Chemotherapy Regimens for Biliary and Pancreatic Cancer: Population-Level Toxicity Signals and Hypotheses for High-Altitude Generalizability
AU - Z. Dang
AU - J. Dan
AU - S. Li
AU - L. Yanan
AU - W. Su
AU - G. Ren
AU - Z. Wang
AU - M. Lv
AU - H. Dong
AU - Z. Niu
AU - H. Zhang
AU - Y. Fan
AU - L. Li
AU - Y. Dang
AU - J. Gao
PY - 2026
DA - 2026/09/24
PB - medRxiv
DO - 10.64898/2026.09.24.26363686
UR - https://www.medrxiv.org/content/10.64898/2026.09.24.26363686v1
AB - 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. MethodsFour-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. Results14/17 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%. ConclusionsThis 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.
ER -