Thyroid Toxicity in Lung Cancer Patients Treated with Immune-Checkpoint Inhibitors: A Retrospect

01 Apr 20264 min read0 viewsJournal Feed

GIST

BackgroundLung 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.MethodsWe 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.ResultsAmong 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%).

Clinical Editorial

Study scope and design

A single-center retrospective analysis assessed 420 lung cancer patients treated with immune checkpoint inhibitors (ICIs) at IRCCS Policlinico San Matteo in Pavia from March 2016 to December 2024.
The primary objective was to identify thyroid immune-related adverse events (irAEs) and to explore associations with clinical characteristics and outcomes.

Population and exposure

The cohort comprised adults with lung cancer receiving ICIs.
Thyroid irAEs were identified and characterized by timing (mostly within the first 6 months) and severity, with grading reflecting established toxicity scales.
Interventions following thyroid irAEs included thyroid replacement therapy in the majority of cases and systemic steroids in a minority.

Key findings on incidence and clinical features

Thyroid irAEs occurred in 69 of 420 patients, representing 16.4% of the cohort.
The majority of events were low-to-moderate grade: G1 in 31.9%, G2 in 66.7%, and G3 in 1.4%.
Male sex showed a trend toward lower risk of thyroid irAEs (p = 0.050).
Histology appeared to influence risk: NSCLC NOS was associated with higher risk (p = 0.021).
Disease stage and line of prior therapy did not show significant correlations with irAE occurrence.

Clinical associations with tumor response

Patients who developed thyroid irAEs were more likely to achieve objective responses (complete or partial) than those without irAEs (p = 0.028).
Among responders, patients achieving progressive disease (PD) as best response had a significantly lower incidence of thyroid irAEs compared with those achieving stable disease (SD) (p = 0.010).
The duration of response was longer in patients with thyroid irAEs (median 34 months) than in those without (median 17 months; p = 0.047).

Survival analyses and limitations

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).
The study is retrospective and single-center, with potential unmeasured confounders.
The analysis did not provide granular details on thyroid irAE subtypes beyond general grading and replacement/steroid use, limiting mechanistic inferences.