Thyroid toxicity in lung cancer patients treated with immune-checkpoint inhibitors: a single-center retrospective analysis

Background: Lung cancer is the leading cause of cancer-related mortality worldwide. Immune checkpoint inhibitors (ICIs) have radically changed the treatment of lung cancer gradually entering all treatment settings. Alongside their clinical benefits, ICIs are associated with immune-related adverse events (irAEs), among which endocrine toxicities, particularly thyroid dysfunctions, represent some of the most frequent. Methods: We conducted a retrospective analysis of 420 lung cancer patients referred to the oncology unit of IRCCS Policlinico San Matteo in Pavia, between March 2016 and December 2024. Clinical and treatment-related data were reviewed to identify thyroid irAEs. Comparative analyses between patients with and without thyroid dysfunction were performed using descriptive statistics and survival outcomes. Results: Among 420 lung cancer patients treated with ICIs, 69 (16.4%) developed thyroid irAEs. Most events occurred in the first 6 months, and the majority were grade 1-2 (G1 31.9%, G2 66.7%, G3 1.4%). Thyroid replacement therapy was required in 65.2%, while steroids were used in 13%.Male sex was associated with a lower incidence of thyroid irAEs (p 0.050), non-small cell lung cancer (NSCLC) not otherwise specified (NOS) histology was associated with a higher risk (p 0.021). Disease stage and treatment line were not significantly correlated.Patients experiencing thyroid irAEs were more likely to achieve an objective response (CR/PR) compared with those without (p 0.028). Moreover, patients with PD as best response showed a significantly lower incidence of thyroid irAEs compared to those with SD (p 0.010). Duration of response was significantly longer in patients with thyroid irAEs (median 34 vs 17 months; p 0.047).Time-dependent Cox models did not demonstrate a significant association between thyroid irAEs and progression-free survival - PFS (HR 1.08, p 0.66) or overall survival - OS (HR 1.02, p 0.89). Conclusions: The occurrence of thyroid irAEs correlated with better tumor response rates and prolonged duration of response, while not significantly impacting PFS or OS. These findings support the hypothesis that thyroid irAEs may serve as a favorable immunologic and prognostic biomarker in the context of ICI therapy.