Baseline markers and exploratory analysis of post-treatment thyroid autoantibody seroconversion for immune-related thyroid dysfunction in patients with advanced non-small-cell lung cancer treated with ICIs: a prospective single-center cohort study
- 1Department of Nuclear Medicine, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University
- 2Office of Medical Research, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University
- 3Department of Oncology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University
Abstract
Objective: To evaluate the predictive value of baseline thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb), and post-treatment seroconversion for thyroid immune-related adverse events (irAEs) in patients with advanced non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs).
Methods: Treatment-naive patients with advanced NSCLC who received ICIs between January 2021 and June 2026 were prospectively enrolled. Patients with pre-existing thyroid disorders, other autoimmune diseases, or baseline use of immunosuppressive-dose glucocorticoids/immunosuppressants were excluded. Thyroid function, TPOAb, and TgAb were measured prior to ICI initiation. Competing risk analysis was applied to assess the cumulative incidence of thyroid irAEs, with death treated as the competing event. Cox regression assessed baseline antibody status, baseline TSH, and seroconversion (as a time-dependent covariate) in relation to irAE risk. The proportional hazards assumption was assessed, and a stratified Cox model with a time-dependent covariate was used when violated.
Results: A total of 312 patients with complete follow-up data were included in the final analysis. The median follow-up duration was 6.4 months. Baseline TPOAb and TgAb positive rates were 18.9% and 14.1%. The overall incidence of thyroid-related irAEs was 27.9% (87/312). Positive baseline TPOAb and TgAb were associated with higher irAE incidence (57.6% vs. 20.9% and 61.4% vs. 22.4%, both P < 0.001). In the competing-risk setting accounting for death as a competing event, patients with positive baseline thyroid antibodies had a significantly greater cumulative incidence of thyroid irAEs during follow-up (sHR = 3.353, P < 0.001). In the final time-dependent model, baseline antibody positivity was significantly associated with irAEs at baseline (HR = 17.529, P < 0.001), with a significant time interaction ( P < 0.001). Baseline TSH remained an independent predictor (HR = 2.471, 95% CI: 1.845-3.309, P < 0.001). In the crude analysis, seroconversion was associated with a higher incidence of thyroid irAEs. However, in the time-dependent Cox model restricted to baseline double-negative patients, seroconversion was not an independent predictor of thyroid irAEs (HR = 0.236, 95% CI: 0.05-1.041, P = 0.056). The area under the receiver operating characteristic (ROC) curve for baseline TSH was 0.818, with an exploratory cut-off value of 2.985 mIU/L.
Conclusion: In this single-center exploratory cohort, baseline TPOAb/TgAb positivity and elevated TSH were associated with thyroid irAEs after ICIs. These findings are hypothesis-generating and require external validation. The TSH cut-off (2.985 mIU/L) is exploratory and not clinically actionable. Post-treatment antibody seroconversion was not an independent predictor and remains exploratory. Serial monitoring may aid risk stratification but needs validation.
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BibTeX
@article{ming2026baseline,
title = {{Baseline markers and exploratory analysis of post-treatment thyroid autoantibody seroconversion for immune-related thyroid dysfunction in patients with advanced non-small-cell lung cancer treated with ICIs: a prospective single-center cohort study}},
author = {Hui Ming and Qun Liang and Wenbing Hu and Yuanhao Chen and Hui Yu},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1975574},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1975574/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Baseline markers and exploratory analysis of post-treatment thyroid autoantibody seroconversion for immune-related thyroid dysfunction in patients with advanced non-small-cell lung cancer treated with ICIs: a prospective single-center cohort study
AU - Hui Ming
AU - Qun Liang
AU - Wenbing Hu
AU - Yuanhao Chen
AU - Hui Yu
PY - 2026
DA - 2026/10/20
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1975574
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1975574/full
AB - Objective: To evaluate the predictive value of baseline thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb), and post-treatment seroconversion for thyroid immune-related adverse events (irAEs) in patients with advanced non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs). Methods: Treatment-naive patients with advanced NSCLC who received ICIs between January 2021 and June 2026 were prospectively enrolled. Patients with pre-existing thyroid disorders, other autoimmune diseases, or baseline use of immunosuppressive-dose glucocorticoids/immunosuppressants were excluded. Thyroid function, TPOAb, and TgAb were measured prior to ICI initiation. Competing risk analysis was applied to assess the cumulative incidence of thyroid irAEs, with death treated as the competing event. Cox regression assessed baseline antibody status, baseline TSH, and seroconversion (as a time-dependent covariate) in relation to irAE risk. The proportional hazards assumption was assessed, and a stratified Cox model with a time-dependent covariate was used when violated. Results: A total of 312 patients with complete follow-up data were included in the final analysis. The median follow-up duration was 6.4 months. Baseline TPOAb and TgAb positive rates were 18.9% and 14.1%. The overall incidence of thyroid-related irAEs was 27.9% (87/312). Positive baseline TPOAb and TgAb were associated with higher irAE incidence (57.6% vs. 20.9% and 61.4% vs. 22.4%, both P < 0.001). In the competing-risk setting accounting for death as a competing event, patients with positive baseline thyroid antibodies had a significantly greater cumulative incidence of thyroid irAEs during follow-up (sHR = 3.353, P < 0.001). In the final time-dependent model, baseline antibody positivity was significantly associated with irAEs at baseline (HR = 17.529, P < 0.001), with a significant time interaction ( P < 0.001). Baseline TSH remained an independent predictor (HR = 2.471, 95% CI: 1.845-3.309, P < 0.001). In the crude analysis, seroconversion was associated with a higher incidence of thyroid irAEs. However, in the time-dependent Cox model restricted to baseline double-negative patients, seroconversion was not an independent predictor of thyroid irAEs (HR = 0.236, 95% CI: 0.05-1.041, P = 0.056). The area under the receiver operating characteristic (ROC) curve for baseline TSH was 0.818, with an exploratory cut-off value of 2.985 mIU/L. Conclusion: In this single-center exploratory cohort, baseline TPOAb/TgAb positivity and elevated TSH were associated with thyroid irAEs after ICIs. These findings are hypothesis-generating and require external validation. The TSH cut-off (2.985 mIU/L) is exploratory and not clinically actionable. Post-treatment antibody seroconversion was not an independent predictor and remains exploratory. Serial monitoring may aid risk stratification but needs validation.
SN - 2234-943X
ER -