Predictive Biomarkers of Thyroid Dysfunctions Associated with the Treatment of Non-Small Cell Lung Cancer and Cervical Cancer with Immune Checkpoint Inhibitors

Abstract

BACKGROUND: Treatment with immune checkpoint inhibitors (ICIs) for advanced malignancies has been associated with developing immune- related adverse events (irAEs) severe enough to require the cessation of life-saving tumor immunotherapy. OBJECTIVES: The present study aimed to identify predictive inflammatory markers of the development of immune-related thyroid dysfunctions in patients with cervical cancer (CC) and non–small cell lung cancer (NSCLC) treated by ICIs. METHODS: A retrospective study was conducted on twenty-seven patients with CC and NSCLC treated by ICIs. The data were collected before and 12 weeks after treatment. Complete blood count-derived inflammatory markers: dNLR (derived neutrophil to lymphocyte ratio), NLR (neutrophil to lymphocyte ratio), SSI (systemic inflammation index), PLR (platelet to lymphocyte ratio), WHR (white blood cells to hemoglobin ratio) were calculated. In addition, thyroid functional tests were collected. Data statistical analysis was performed by STATISTICA (Stat soft, Inc, USA). RESULTS: Five patients out of twenty-seven with CC treated by PD-1 and CTLA-4 inhibitors who developed hypothyroidism showed significantly high baseline PLR and low WHR compared to patients without clinical symptoms of hypothyroidism and reference levels TSH and FT4. Association between NLR, dNLR, SSI, and thyroid dysfunction was not observed. CONCLUSIONS: Our findings show a strong correlation between hypothyroidism and WHR and PLR biomarkers. As a result, using these biomarkers for early identification of hypothyroidism helps treat thyroid dysfunction and improves cancer immunotherapy outcomes.