Anti-PD-1 Immunotherapy Changed the Spectrum of Thyroid Dysfunction during Radiotherapy in Patients with Nasopharyngeal Carcinoma

Abstract

<h3>Purpose/Objective(s)</h3> Programmed cell death protein-1 (PD-1) blockade therapies have demonstrated their efficacy in a variety of malignancies, including nasopharyngeal carcinoma (NPC). Thyroid dysfunction is among the most common immune-related adverse event. However, presently we have a paucity of data on thyroid dysfunction associated with PD-1 blockade in non-metastatic NPC. This study aimed to study the incidence and pattern of immune-related thyroid dysfunction in non-metastatic NPC during radiotherapy <h3>Materials/Methods</h3> From January 1, 2019 to December 31, 2021, 165 pairs of non-metastatic NPC patients matching by propensity score matching (PSM) method to balance prognostic factors were included in this study: 165 cases in control group received conventional treatment (introduction chemotherapy and concurrent chemoradiotherapy), 165 cases in immunotherapy group received conventional treatment and anti-PD-1 immunotherapy before completion of radiotherapy. Thyroid function test and antithyroid antibodies were assessed prospectively before each immunotherapy cycle, beginning before the first treatment. Incidence and clinical pattern of thyroid dysfunction, and association with anti-thyroid antibodies was evaluated. <h3>Results</h3> In control group, 51 patients (30.91%) had thyroid dysfunctions. Among them, 12 patients had hypothyroidism (23.53%), 39 had thyrotoxicosis (76.47%) and none had biphasic hypothyroidism. In immunotherapy group, 47 patients (28.49%) had thyroid dysfunctions. Among them, 24 patients had hypothyroidism (51.06%), 18 had thyrotoxicosis (38.31%) and 5 had biphasic hypothyroidism (10.63%), a distinct pattern only observed in patients received immunotherapy. The positive rates of antithyroid peroxidase antibody (A-TPO) were similar between two groups, 12.12% in control group and 12.73% in immunotherapy group (<i>P</i> = 1). A-TPO was positive in 12 of 47 patients who developed thyroid dysfunction, compared with 11 of 118 who did not (25.53% vs 9.32%, <i>P</i> = 0.014). Especially, all patients with biphasic hypothyroidism had positive A-TPO, and the onset of A-TPO was earlier than that of transient hyperthyroidism. In patients with positive A-TPO and hypothyroidism or thyrotoxicosis, the A-TPO onset coincided with onset of thyroid dysfunction. <h3>Conclusion</h3> In non-metastatic NPC patients, thyroid dysfunction is common during treatment. Hypothyroidism and thyrotoxicosis are the most frequent presentations. Compared with conventional treatment, anti-PD-1 immunotherapy changed the spectrum of thyroid dysfunction but not the incidence. Patients who received anti-PD-1 immunotherapy developed a distinct pattern of thyroid dysfunction, biphasic hypothyroidism. The early elevation of A-TPO without aberrant TSH and FT4 may be a predictive marker for biphasic hypothyroidism. Our result suggested that thyroid functions should be under regular and intensive surveillance in clinical practice of anti-PD-1 immunotherapy in non-metastatic NPC patients.