History of Radiation to the Neck Increases the Risk of Denovo Thyroid Dysfunction after Receiving Immune Checkpoint Inhibitors

Koosha Paydary,Ankit Mangla,Muhammad Zain Farooq

doi:10.3390/endocrines1020008

Abstract

Thyroid dysfunction is a common endocrine side effect of immune checkpoint inhibitors (ICI). We designed a retrospective study, including patients who received ICI for any cancer at our institution. Thyroid-stimulating hormone (TSH), free T4 levels, and time to development of thyroid dysfunction were measured, and medication used to treat thyroid dysfunction were identified. We reviewed the charts of 104 patients with complete records obtained from our tumor registry. A total of 91 patients were included in the analysis, after excluding 13 patients with a pre-existing thyroid disorder. Twenty-eight (30.77%) patients developed thyroid dysfunction after starting ICI. Race (p-0.048), age (p-0.014), history of radiation therapy (RT) to the neck (p-0.004), history of RT to the chest (p-0.012), and history of venous thrombosis (p-0.004) were significantly associated with thyroid dysfunction on univariate analysis. For multivariate analysis, the history of RT to the neck, adjusted for age, race, and sex, was significantly associated with thyroid dysfunction (adjusted OR-9.64, 95%CI: 1.88, 49.36, p-0.007). In patients receiving ICI for any type of cancer, the previous history of RT to the neck was significantly associated with the development of thyroid dysfunction after starting ICI.

Highlights

Immune checkpoint inhibitors (ICI) have introduced a new paradigm in cancer treatment, especially when we consider the durable responses it can achieve in patients with metastatic disease.ICI principally blocks cytotoxic T-lymphocyte protein 4 (CTLA-4), programmed cell death-1 (PD-1), or programmed cell death receptor ligand-1 (PDL-1) [1]
The concept of cancer immunotherapy is based on the notion that cancer cells develop mechanisms to evade immune systems, and CTLA-4 and/or PD-1/PDL-1 play a critical part in the process [1]
Thirteen patients had a history of thyroid dysfunction before starting treatment with ICI and were excluded from the final analysis

Summary

Introduction

ICI principally blocks cytotoxic T-lymphocyte protein 4 (CTLA-4), programmed cell death-1 (PD-1), or programmed cell death receptor ligand-1 (PDL-1) [1]. The concept of cancer immunotherapy is based on the notion that cancer cells develop mechanisms to evade immune systems, and CTLA-4 and/or PD-1/PDL-1 play a critical part in the process [1]. Blocking these receptors with ICI therapy can result in a clinical response that has been demonstrated in multiple tumor types. The use of ICI therapy can block these receptors on any ‘’normal” body organ, and lead to a unique set of adverse events known as immune-related adverse events (irAE) [1]

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Discussion

Conclusion