{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T21:49:27Z","timestamp":1792532967924,"version":"4.5.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"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. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Thyroid dysfunction is among the most frequent endocrine immune-related adverse events (irAEs) during PD-1\/PD-L1 blockade, but whether baseline thyroid function and treatment-emergent thyroid dysfunction (TeTD) predict pathological response and survival after neoadjuvant immunochemotherapy in locally advanced gastric or gastroesophageal junction adenocarcinoma (LAGC\/GEJC) remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicenter retrospective cohort enrolled 420 patients with cT2\u20134bN_anyM0 LAGC\/GEJC from five Hebei centers (2019\u20132024). All received four cycles of neoadjuvant PD-1 inhibitor plus SOX or XELOX, followed by D2 gastrectomy. Baseline TSH, FT3, FT4, TPOAb, and TgAb were measured. A favorable baseline thyroid profile was prespecified as TSH 0.55\u20132.50 mIU\/L, FT3 \u22654.30 pmol\/L, normal FT4, and negative autoantibodies. TeTD was defined as new-onset hypothyroidism, thyrotoxicosis, or biphasic thyroiditis during therapy. Logistic and Cox regression, subgroup and sensitivity analyses, and a pCR nomogram were applied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 420 patients (median age 60, 66.9% male), 114 (27.1%) had a favorable thyroid profile and 105 (25.0%) developed TeTD; tumor-intrinsic factors were balanced. Overall pCR was 23.3% and MPR 42.6%. Favorable profile predicted higher pCR (43.0% vs. 16.0%; adjusted OR 6.08, P&amp;lt;0.001) and MPR (61.4% vs. 35.6%; OR 3.42, P&amp;lt;0.001). TeTD independently predicted higher pCR (38.1% vs. 18.4%; OR 3.26, P&amp;lt;0.001) and MPR. Non-thyroid irAEs and discontinuation were similar (P\u00a0=\u00a00.082). At 39.2 months median follow-up, 3-year DFS was 77.7% vs. 49.8% (TeTD vs. non-TeTD; adjusted HR 0.35, P&amp;lt;0.001) and 3-year OS 99.0% vs. 78.4% (HR0.11, P&amp;lt;0.001). A thyroid-inclusive pCR nomogram achieved AUC 0.82 (95% CI 0.77\u20130.86) versus 0.73 for a staging-only model (P&amp;lt;0.001), with adequate calibration (Hosmer\u2013Lemeshow P\u00a0=\u00a00.84). Effects were robust across all subgroups and sensitivity analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Pretreatment thyroid function and on-treatment thyroid dysfunction are independent and complementary host-factor predictors of pathological response and long-term survival after neoadjuvant PD-1 inhibitor plus platinum-based chemotherapy in LAGC\/GEJC. Incorporating these inexpensive thyroid-axis variables into pretreatment risk stratification provides additional prognostic information beyond conventional staging and tissue biomarkers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1872057","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T04:24:54Z","timestamp":1785126294000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Baseline thyroid function and treatment-emergent thyroid dysfunction predict pathological response and survival after neoadjuvant PD-1 inhibitor plus platinum-based chemotherapy in locally advanced gastric and gastroesophageal junction adenocarcinoma: a multicenter cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhiqiang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery, Shijiazhuang People\u2019s 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