{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:16:21Z","timestamp":1792649781222,"version":"4.5.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Renin-angiotensin system inhibitors (RASi) have been associated with favorable survival outcomes across various cancers, but their association with survival in lung cancer remains uncertain. We conducted a systematic review and meta-analysis to evaluate the association between RASi use and survival outcomes in patients with lung cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PubMed and Embase were searched from inception to 6 July 2026. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup and sensitivity analyses, including large-study restricted analysis and precision-effect test and precision-effect estimate with standard error (PET-PEESE) regression, were performed to explore heterogeneity and assess the potential influence of small-study effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty-six studies involving 403,423 patients were included. RASi use was associated with longer overall survival (OS; HR = 0.76, 95% CI: 0.70\u20130.83;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>2<\/jats:italic>\n                      <\/jats:sup>\n                      = 82.9%) and progression-free survival (PFS; HR = 0.79, 95% CI: 0.70\u20130.89;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>2<\/jats:italic>\n                      <\/jats:sup>\n                      = 40.9%) in conventional random-effects meta-analyses. Subgroup analyses generally showed consistent associations across treatment modalities and geographic regions, although substantial heterogeneity remained in several subgroups. Egger\u2019s test indicated small-study effects for OS. Although the large-study restricted analysis remained significant (HR = 0.82, 95% CI: 0.74\u20130.90), PET-PEESE adjustment attenuated the estimate to the null (HR = 1.00, 95% CI: 0.95\u20131.05). No significant evidence of small-study effects was observed for PFS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Conventional meta-analysis showed an association between RASi use and longer OS and PFS. However, the OS association was attenuated to the null after adjustment for small-study effects, indicating that the magnitude and robustness of the observed OS association remain uncertain. These findings should therefore be interpreted cautiously and require confirmation in well-designed prospective studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero\/display_record.php?ID=CRD420251053671<\/jats:ext-link>\n                      , identifier: CRD420251053671.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1953204","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:35:04Z","timestamp":1789968904000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Renin\u2013angiotensin system inhibitor use and survival outcomes in lung cancer: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Yongqian","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The Second People\u2019s Hospital of Qinzhou","place":["Qinzhou, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhai","family":"Shen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, China Pharmaceutical University","place":["Nanjing, Jiangsu, China"]},{"name":"Center for New Drug Safety Evaluation and Research, China Pharmaceutical University","place":["Nanjing, Jiangsu, China"]},{"name":"School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghe","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Second Affiliated Hospital of Guangxi Medical University","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Guangxi Hospital Division of the First Affiliated Hospital, Sun Yat-sen University","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nengyong","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The Second People\u2019s Hospital of Qinzhou","place":["Qinzhou, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1007\/s40256-023-00605-5","article-title":"The pivotal role of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in hypertension management and cardiovascular and renal protection: a critical appraisal and comparison of international guidelines","volume":"23","author":"Alcocer","year":"2023","journal-title":"Am. 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