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

Brilli, Lucia; Danielli, Riccardo; Campanile, M; Secchi, Chiara; Ciuoli, Cristina; Calabrò, Luana; Pilli, Tania; Cartocci, Alessandra; Pacini, Furio; Giacomo, Anna Maria Di; Castagna, Maria Grazia

doi:10.1007/s40618-020-01480-6

Cited by 32 publications

(21 citation statements)

References 32 publications

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“…At the same time, however, it should be noted that palliative radiotherapy was not associated with detectable increase in risk ( Table 1 ), which echoes the findings of other investigators and is an important consideration for everyday practice ( 35 , 36 ). Other examples of organ-related factors that modulate the risk of specific irAE are preexisting interstitial lung disease, which is a strict ICI contraindication due to the very high risk of pneumonitis ( 37 , 38 ), as well as an increased baseline TSH, which is associated with subsequent development of thyroiditis ( 39 , 40 ). However, no reliable predictive scheme has been devised yet.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic and Prognostic Implications of Immune-Related Adverse Events in Advanced Non-Small-Cell Lung Cancer

et al. 2021

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IntroductionPD-(L)1 inhibitors have improved prognosis of non-small-cell lung cancer (NSCLC), but can also cause immune-related adverse events (irAEs) that complicate management.MethodsWe analyzed NSCLC patients receiving PD-(L)1 inhibitors from 2012 to 2020 in a German academic center.ResultsIrAE showed comparable frequencies in stage IV (198/894 or 22%) vs. III (14/45 or 31%, p = 0.15), after anti-PD-(L)1 monotherapy vs. chemoimmunotherapy (139/483 vs. 58/213, p = 0.75), and across treatment lines. In stage IV, irAE occurred after 3.1 months in median, affected multiple organs (median 2) in 27/894 patients and were associated with PD-L1 positivity (25 vs. 14%, p = 0.003), lower neutrophil-to-lymphocyte ratios (29 vs. 17%, p < 0.001 for NLR dichotomized at 5), better ECOG status (26 vs. 18% for 0 vs. 1, p = 0.004), but not related to age, sex, smoking and palliative radiotherapy. Two hundred thirty two irAEs occurred mostly in endocrine glands (4.9%), lungs (4.4%), the musculoskeletal system (4.2%), colon (4.1%), liver (3.7%), and skin (2.6%), while pneumonitis was most frequent with durvalumab following definitive chemoradiation (16% or 7/45, p < 0.01). IrAE severity was grade 1 in 11%, 2 in 41%, 3 in 36%, and 4 in 11% events, while two were lethal (<1%, myocarditis and pneumonitis). Therapy was suspended in 72%, while steroids were initiated in 66% and complemented by other immunosuppressants in 6%, with longest treatment duration for rheumatic events (mean >3 months), and average cumulative prednisone doses >700 mg for all organs, except for skin. Patients developing irAE had longer progression-free (PFS) and overall survival (OS) in multivariable 12/14-week landmark analyses including ECOG status, treatment line, treatment type, PD-L1 TPS, and NLR (median PFS 17 vs. 10 months, HR = 0.68, p = 0.009; median OS 37 vs. 15 months, HR = 0.40, p < 0.001), regardless of grade. OS was longest with skin (95% at 2 years) and shortest with pneumonitis, hepatitis, neurologic, and cardiologic irAE (38, 37, 28, and 0% at 2 years, p < 0.001).ConclusionsApproximately one-fourth of immunotherapy-treated NSCLC patients develop irAEs, most of which necessitate treatment suspension and steroids. Despite more frequent occurrence with PD-L1 positive tumors, lower NLR, and better ECOG PS, irAEs are independently associated with longer survival, especially when affecting the skin. Lethality is below 1%.

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Section: Discussionmentioning

confidence: 99%

Therapeutic and Prognostic Implications of Immune-Related Adverse Events in Advanced Non-Small-Cell Lung Cancer

et al. 2021

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“…The median time interval for development was three months after starting therapy. Detection of anti-thyroid peroxidase antibody at baseline and anti-thyroglobulin antibody during the therapy was significantly linked to the development of overt hypothyroidism in these patients ( 108 – 110 ).…”

Section: Biomarkers For Iraesmentioning

confidence: 98%

“…Autoantibody detection - anti-GNAL, anti-ITM2B, and anti-CD74, rheumatoid factor, anti-nuclear and anti-thyroid antibody, anti-thyroid peroxidase antibody, anti-thyroglobulin antibody ( 106 – 110 )…”

Section: Biomarkers For Iraesmentioning

confidence: 99%

“…In melanoma treated with Ipilimumab, lower baseline soluble major histocompatibility complex class I chain-related protein A (MICA), lower soluble CD25, and a significant rise in soluble CD163 correlates with higher irAEs ( 93 , 101 , 111 ). Thyroid irAE was frequent in patients with higher baseline thyroid-stimulating hormone levels (and long duration of therapy) ( 108 – 110 ). The median time interval for development was three months after starting therapy.…”

Section: Biomarkers For Iraesmentioning

confidence: 99%

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Risk Factors and Biomarkers for Immune-Related Adverse Events: A Practical Guide to Identifying High-Risk Patients and Rechallenging Immune Checkpoint Inhibitors

et al. 2022

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Immune-related adverse events (irAEs) are a range of complications associated with the use of immune-checkpoint inhibitors (ICIs). Two major classes of ICIs widely used are Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed Cell death-1 (PD-1)/Programmed death-ligand 1 (PD-L1) inhibitors. High-grade irAEs are life-threatening and often cause a severe decline in performance status in such that patients do not qualify for any further anticancer treatments. It is difficult to generalize the evidence in the current literature on risk factors or biomarkers for the entire class of ICIs as the studies so far are either disease-specific (e.g., lung cancer or melanoma) or ICI agent-specific (e.g., pembrolizumab, ipilimumab) or irAE-specific (e.g., pneumonitis or gastritis). In this review, risk factors and biomarkers to consider before initiating or monitoring ICI are listed with a practical purpose in day-to-day practice. Risk factors are grouped into demographics and social history, medical history, and medication history, tumor-specific and agent-specific risk factors. A higher risk of irAE is associated with age <60 years, high body mass index, women on CTLA4 and men on PD-1/PD-L1 agents, and chronic smokers. Patients with significant kidney (Stage IV-V), cardiac (heart failure, coronary artery disease, myocardial infarction, hypertension), and lung (asthma, pulmonary fibrosis, and chronic obstructive pulmonary disease) are at a higher risk of respective organ-specific irAEs. Pre-existing autoimmune disease and chronic use of certain drugs (proton pump inhibitors, diuretics, anti-inflammatory drugs) also increase the irAE-risk. Biomarkers are categorized into circulating blood counts, cytokines, autoantibodies, HLA genotypes, microRNA, gene expression profiling, and serum proteins. The blood counts and certain protein markers (albumin and thyroid-stimulating hormone) are readily accessible in current practice. High neutrophil-lymphocyte ratio, eosinophil/monocyte/lymphocyte counts; TSH and troponins at diagnosis and drop in the white count and lymphocyte count can predict irAE. Other biomarkers with limited evidence are cytokines, autoantibodies, HLA genotypes, microRNA, and gene expression profiling. With fast-expanding approvals for ICIs in various cancer types, knowledge on risk factors and biomarkers can help providers assess the irAE-risk of their patients. Prospective disease and agent-specific studies are needed to provide further insight on this essential aspect of ICI therapy.

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“…Another possible mechanism is that pre-existing chronic thyroiditis was unleashed by ICI treatment [ 28 ]. Patients with high baseline TSH concentration and positive anti-thyroid antibody (ATAb) before ICIs treatment were prone to have TD [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Thyroid Dysfunction as a Predictive Indicator in Camrelizumab of Advanced Esophageal Squamous Cell Carcinoma

Chen

Zhuang

Zhang

et al. 2022

Journal of Immunology Research

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Thyroid dysfunction (TD) induced by programmed death-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) has been widely reported. However, the effects of ICI-induced TD on the survival of patients with esophageal squamous cell carcinoma (ESCC) have not been described. Herein, a retrospective study was conducted, which 82 patients with advanced metastatic or recurrent ESCC treated with camrelizumab were enrolled. Twenty patients (24.4%) experienced TD during camrelizumab treatment with or without chemotherapy. The median onset time of TD was 1.7 months. The incidence of TD was 35.6% in patients who previously received thoracic radiotherapy versus 10.8% in patients who did not (P =0.009). Patients with TD had significantly longer median progression-free survival (5.5 months vs 3.5 months, P =0.035) and overall survival (26.7 months vs 11.5 months, P <0.001). TD is frequently observed in ESCC patients treated with camrelizumab and especially in patients who received radiotherapy previously. ESCC patients with TD during ICIs treatment often have better prognosis.

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

Cited by 32 publications

References 32 publications

Therapeutic and Prognostic Implications of Immune-Related Adverse Events in Advanced Non-Small-Cell Lung Cancer

Therapeutic and Prognostic Implications of Immune-Related Adverse Events in Advanced Non-Small-Cell Lung Cancer

Risk Factors and Biomarkers for Immune-Related Adverse Events: A Practical Guide to Identifying High-Risk Patients and Rechallenging Immune Checkpoint Inhibitors

Thyroid Dysfunction as a Predictive Indicator in Camrelizumab of Advanced Esophageal Squamous Cell Carcinoma

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