ArticleFrontiers in endocrinology2026
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.
Article in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: 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. Methods: This multicenter retrospective cohort enrolled 420 patients with cT2-4bN_anyM0 LAGC/GEJC from five Hebei centers (2019-2024). 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 0.55-2.50 mIU/L, FT3 ≥4.30 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. Results: 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<0.001) and MPR (61.4% vs. 35.6%; OR 3.42, P<0.001). TeTD independently predicted higher pCR (38.1% vs. 18.4%; OR 3.26, P<0.001) and MPR. Non-thyroid irAEs and discontinuation were similar (P = 0.082). 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<0.001) and 3-year OS 99.0% vs. 78.4% (HR0.11, P<0.001). A thyroid-inclusive pCR nomogram achieved AUC 0.82 (95% CI 0.77-0.86) versus 0.73 for a staging-only model (P<0.001), with adequate calibration (Hosmer-Lemeshow P = 0.84). Effects were robust across all subgroups and sensitivity analyses. Conclusions: 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.
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