Baseline serum TSH levels predict the absence of thyroid dysfunction in cancer patients treated with immunotherapy

A Cartocci,M G Castagna,L Brilli,C Secchi,L Calabrò,A M Di Giacomo,T Pilli,F Pacini,R Danielli,M Campanile,C Ciuoli

doi:10.1007/s40618-020-01480-6

Abstract

PurposeImmunotherapy against immune checkpoints has significantly improved survival both in metastatic and adjuvant setting in several types of cancers. Thyroid dysfunction is the most common endocrine adverse event reported. Patients who are at risk of developing thyroid dysfunction remain to be defined. We aimed to identify predictive factors for the development of thyroid dysfunction during immunotherapy.MethodsThis is a retrospective study including a total of 68 patients who were treated with immune checkpoint inhibitors (ICIs) for metastatic or unresectable advanced cancers. The majority of patients were treated with anti-PD1 drugs in monotherapy or in combination with anti-CTLA4 inhibitors. Thyroid function and anti-thyroid antibodies, before starting immunotherapy and during treatment, were evaluated. Thyroid ultrasound was also performed in a subgroup of patients at the time of enrolment in the study.ResultsEleven out of 68 patients (16.1%) developed immune-related overt thyroid dysfunction. By ROC curve analysis, we found that a serum TSH cut-off of 1.72 mUI/l, at baseline, had a good diagnostic accuracy in identifying patients without overt thyroid dysfunction (NPV = 100%, p = 0.0029). At multivariate analysis, both TSH and positive anti-thyroid antibodies (ATAbs) levels, before ICIs treatment, were independently associated with the development of overt thyroid dysfunction during immunotherapy (p = 0.0001 and p = 0.009, respectively).ConclusionsPre-treatment serum TSH and ATAbs levels may help to identify patients at high risk for primary thyroid dysfunction. Our study suggests guidance for an appropriate timely screening and for a tailored management of thyroid dysfunctions in patients treated with ICIs.

Highlights

Immune checkpoint inhibitors (ICIs), targeting the programmed cell death signaling pathway (PD-1/ PD-L1), have significantly improved the outcome of several advanced cancers
In patients who developed overt thyroid dysfunction, baseline serum thyroid-stimulating hormone levels (TSH) levels were significantly higher [median 2.6 mU/l] than those seen in patients without overt thyroid dysfunction [median 1.6 mU/l] (p = 0.003) (Table 1)
By receiver operating characteristic (ROC) curve analysis, we found that a serum TSH cut-off of 1.72 mUI/l had a good diagnostic accuracy in identifying patients without overt thyroid dysfunction during follow-up [area under the ROC curve (AUC) 0.785, p = 0.0029] (Fig. 2)

Summary

Introduction

Immune checkpoint inhibitors (ICIs), targeting the programmed cell death signaling pathway (PD-1/ PD-L1), have significantly improved the outcome of several advanced cancers. Since immune checkpoints are involved in the immunological tolerance towards the self-antigens, it is not surprising that their inhibition may lead to the activation of the T cells and the development of the immunerelated adverse events (irAEs) that can virtually affect every apparatus [1,2,3]. Randomized clinical trials reported a prevalence of endocrine irAEs during treatment with PD-1 inhibitors in monotherapy ranged from 3.8 to 20.8%, rising to 14.4–34% in case of combined treatment (anti-PD1+ antiCTLA4) [4]. It is not possible to predict which patient, who is started on ICIs, is at risk to develop thyroid dysfunction. The potential relationship between the anti-thyroid antibodies levels (ATAbs), at baseline and/or during follow-up, and the development of thyroid dysfunction has been investigated in some studies and no association was found [14,15,16,17,18,19]

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