Associations between systemic immune-inflammation index and immune-related hypothyroidism in non-small cell lung cancer patients receiving immune checkpoint inhibitors: a retrospective study.
Level 3 - non-randomized controlled study
Retrospective cohort study evaluating prognostic biomarkers
PubMed 42311250 · doi:10.3389/fonc.2026.1844002
What was done
This retrospective cohort study analyzed 160 patients with driver gene-negative locally advanced or metastatic non-small cell lung cancer (NSCLC) who received first-line PD-1 inhibitors combined with chemotherapy at a single hospital between October 2019 and December 2024. Baseline systemic immune-inflammation index (SII), calculated as (platelet count × neutrophil count) / lymphocyte count, was evaluated. Univariate and multivariate logistic regression were used to identify independent predictors of immune-related hypothyroidism (irH), and a nomogram was developed and evaluated using ROC curves, calibration curves, and decision curve analysis.
What was found
Of 160 patients, 65 (40.6%) developed irH and 95 (59.4%) did not. Patients in the irH group had significantly lower baseline log2-SII compared to the non-irH group (8.95 ± 0.65 vs. 9.55 ± 0.80, P < 0.001). Multivariate analysis identified log2-SII as an independent protective factor against irH (OR = 0.13, 95% CI: 0.05–0.27, P < 0.001), alongside independent predictive associations for age, triglycerides, LDL, total bilirubin, fibrinogen, and D-dimer (all P < 0.05). The combined nomogram achieved an AUC of 0.884 (95% CI: 0.832–0.935) with a calibration absolute error of 0.025 and net clinical benefit across threshold probabilities of 5%–90%.
Why it matters
Baseline systemic inflammatory markers, specifically lower SII alongside standard lipid and coagulation parameters, may help identify NSCLC patients at higher risk of thyroid dysfunction during chemoimmunotherapy. If externally validated, this routine laboratory-based nomogram could guide targeted monitoring for endocrine adverse events.
Limits
The study is limited by its single-center retrospective design, modest sample size (n = 160), and lack of external validation for the predictive nomogram. It only included patients with driver gene-negative advanced NSCLC receiving combination chemoimmunotherapy, precluding generalization to other cancer types or immunotherapy monotherapy regimens.
Cited by
- supports The systemic immune-inflammation index is calculated from neutrophil, lymphocyte, and platelet counts on a standard complete blood count, and a score above 2 indicates an inflammatory state.