Changes in thyroid hormone levels indicate immunotherapy efficacy in gastric cancer

Immune-related thyroid dysfunction (irTD) has been associated with clinical outcomes in non-endocrine tumors. However, the association between irTD and therapeutic efficacy or prognosis in gastric cancer remains unclear. The present study retrospectively investigated the occurrence of irTD during immunotherapy for gastric cancer and analyzed its association with clinical efficacy and patient prognosis. A total of 106 patients with advanced gastric cancer, treated with either first-line or second-line programmed cell death protein 1 (PD-1) monoclonal antibody (MAB) in combination with chemotherapy between January 2019 and December 2022 at the Department of Oncology of Changzhou Tumor Hospital (Changzhou, China), were included. Thyroid hormone levels, including thyroid-stimulating hormone, free thyroxine, free triiodothyronine and thyroid peroxidase (TPO), were determined before and after treatment using the electroluminescence method. The changes in the levels of thyroid hormones based on various clinical characteristics were evaluated in relation to the treatment outcomes, including progression-free survival (PFS) and overall survival (OS), in response to PD-1 MAB therapy. No significant associations were detected between the thyroid hormone levels and different clinical characteristics. Among the patients receiving first-line treatment, 40.6% developed irTD and 49.3% experienced TPO abnormalities. Patients with irTD demonstrated a significantly longer median PFS time than those without irTD (312.0±47.6 vs. 222.0±14.7 days; P=0.040), although no significant difference was noted in the median OS time. Similarly, patients with TPO abnormalities exhibited a longer median PFS time when compared to those without abnormalities (312.0±52.5 vs. 222.0±13.6 days; P=0.006), yet no significant difference was noted in the median OS time. In the second-line treatment, the incidence of irTD was 45.9, and 59.5% of the patients showed TPO abnormalities. Although there were no statistically significant differences in the median PFS or OS times between patients without or with irTD or TPO abnormalities, a trend toward longer PFS and OS was recorded in patients with TPO abnormalities. In conclusion, the occurrence of irTD and TPO abnormalities is associated with better efficacy and prolonged survival in patients with gastric cancer undergoing immunotherapy. These thyroid-related changes may serve as valuable biomarkers for predicting the response to PD-1 MAB therapy in this patient population.