Baseline TSH Level is Associated with Risk of Anti–PD-1–Induced Thyroid Dysfunction

Pollack, Rena; Kagan, M. Z.; Lotem, Michal; Dresner–Pollak, Rivka

doi:10.4158/ep-2018-0472

Cited by 38 publications

(23 citation statements)

References 23 publications

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“…In our study, any type of thyroid dysfunction was observed in 32.4% of cancer patients, while an overt dysfunction in 16.2% of the cohort. Our results agree with most published studies [ 15 , 17 , 18 , 25 , 26 ]. Specifically, in a retrospective monocentric study including a large number of patients, the rate of all thyroid dysfunctions was of 30% with the lowest rate found in patients treated with ipilimumab in monotherapy (23%), an intermediate rate in those treated with anti-PD-1 in monotherapy (39%) and the highest in those treated with a combination therapy (ipilimumab + nivolumab) (50%) [ 27 ].…”

Section: Discussionsupporting

confidence: 94%

“…The role of thyroid antibodies in the pathogenesis and/or in predicting an increased risk of ICIs-induced thyroid abnormalities remains to be defined. Some studies did not observe any association [14][15][16][17][18][19], while recent studies have reported an increased risk of thyroid dysfunction in patients with positive TPO antibodies [20][21][22] or TgAbs [23]. In our cohort of patients, we found a significantly higher rate of positive TPOAbs, at the baseline, in patients with thyroid dysfunction (30%) compared to patients without thyroid dysfunction (1.9%).…”

Section: Discussioncontrasting

confidence: 64%

“…We demonstrated that patients with TSH < 1.7 mU/l (sensitivity and NPV of 100%), at the baseline, did not develop overt thyroid dysfunction suggesting that in case of TSH below this cut-off, additional tests during ICIs therapy may be not routinely performed at each cycle. Recently, Pollack et al reported that a TSH > 2.19 mU/l, at the baseline, was significantly associated with the development of thyroid dysfunction [ 17 ]. However, applying this cut-off for predicting the occurrence of thyroid dysfunction may affect its utility in the clinical practice because of the high rate of false positives (about 30%) and negatives (about 50%) results.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, 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].…”

Section: Introductionmentioning

confidence: 99%

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

Brilli

Danielli²,

Campanile

et al. 2020

J Endocrinol Invest

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Purpose Immunotherapy 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. Methods This 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. Results Eleven 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). Conclusions Pre-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.

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Section: Discussionsupporting

confidence: 94%

Section: Discussioncontrasting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Brilli

Danielli²,

Campanile

et al. 2020

J Endocrinol Invest

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“…Two studies have reported that baseline thyroid stimulating hormone (TSH) was associated with thyroid dysfunction due to anti-PD-1 or combined therapy, although cut-off values used were different ( 30 , 43 ). Among 168 anti-PD-1 treated patients, Kimbara et al.…”

Section: Biomarkersmentioning

confidence: 99%

Biomarkers of Checkpoint Inhibitor Induced Immune-Related Adverse Events—A Comprehensive Review

et al. 2021

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Immune checkpoint inhibitors (ICIs) have substantially improved the prognosis of patients with different types of cancer. Through blockade of cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1), negative feedback mechanisms of the immune system are inhibited, potentially resulting in very durable anti-tumor responses. Despite their promise, ICIs can also elicit auto-immune toxicities. These immune-related adverse events (irAEs) can be severe and sometimes even fatal. Therefore, being able to predict severe irAEs in patients would be of added value in clinical decision making. A search was performed using “adverse events”, “immune checkpoint inhibitor”, “biomarker”, and synonyms in PubMed, yielding 3580 search results. After screening title and abstract on the relevance to the review question, statistical significance of reported potential biomarkers, and evaluation of the remaining full papers, 35 articles were included. Five additional reports were obtained by means of citations and by using the similar article function on PubMed. The current knowledge is presented in comprehensive tables summarizing blood-based, immunogenetic and microbial biomarkers predicting irAEs prior to and during ICI therapy. Until now, no single biomarker has proven to be sufficiently predictive for irAE development. Recommendations for further research on this topic are presented.

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Immune Checkpoint Inhibition

Isaacs,

Shariff,

Crawford

2023

Side Effects of Cancer Therapy

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Baseline TSH Level is Associated with Risk of Anti–PD-1–Induced Thyroid Dysfunction

Cited by 38 publications

References 23 publications

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

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

Biomarkers of Checkpoint Inhibitor Induced Immune-Related Adverse Events—A Comprehensive Review

Immune Checkpoint Inhibition

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