Thyroid dysfunction in lung cancer patients treated with immune checkpoint inhibitors (ICI): Role of race, gender, and concurrent chemotherapy in a multiethnic urban cohort.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21622-e21622
Author(s):  
Angelica D'Aiello ◽  
Rasim A. Gucalp ◽  
Vafa Tabatabaie ◽  
Haiying Cheng ◽  
Noah A. Bloomgarden ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Thyroid Function ◽  
Thyroid Dysfunction ◽  
Checkpoint Inhibitors ◽  
Retrospective Chart Review ◽  
Thyroid Stimulating Hormone ◽  
Concurrent Chemotherapy ◽  
Event Analysis ◽  
Lung Cancer Patients

e21622 Background: Immune-related adverse events (irAE) associated with ICI have been reported, but remain poorly understood. We sought to characterize patterns of thyroid dysfunction—one of the most common irAE—in a large cohort of ethnically-diverse lung cancer patients treated with ICI. Methods: A retrospective chart review of lung cancer patients receiving an anti-PD1 or PD-L1 agent from January 2016 to July 2019 was performed. Subjects included had normal baseline thyroid function. Thyrotoxicosis and hypothyroidism was defined as thyroid-stimulating hormone level less than 0.4 and greater than 4.6, respectively. Time to event analysis with inverted Kaplan Meier curves and log-rank tests were used to compare thyroid dysfunction among race, gender, and treatment subgroups. Results: We identified 256 subjects: 206 had normal baseline thyroid function and 76 went on to develop thyroid dysfunction. Rates of thyroid dysfunction by one year occurred at similar frequencies among all races. Thyrotoxicosis occurred at significantly higher rates in Black (25, 31.7%) than in White (8, 12.9%) and Hispanic (7, 16.7%) subjects. In contrast, hypothyroidism occurred more often in White (13, 21.0%) and Hispanic (18, 42.9%) than in Black (12, 15.2%) subjects. Gender and concurrent chemotherapy showed no significant association with thyroid dysfunction. Of subjects with thyrotoxicosis (N = 42), hypothyroidism followed in 33.3% (N = 14) with 1 subject receiving methimazole and 13 levothyroxine. In those subjects, median time to thyrotoxicosis and hypothyroidism was 4.0 and 7.2 weeks, respectively. Conclusions: Despite the higher prevalence of non-ICI-related thyroid disease among females and the anticipated immunosuppressive effect of chemotherapy, neither gender nor chemotherapy correlated with thyroid dysfunction; however, race did. Black subjects exhibited significantly higher rates of thyrotoxicosis. Our findings are consistent with prior research showing that thyrotoxicosis, including Graves’ disease, occurs more often in Blacks. While the pathogenesis of ICI-related thyroid dysfunction is unclear, the early onset of thyrotoxicosis demonstrated by our study calls for careful monitoring, especially for particular races. [Table: see text]

scholarly journals Thyroid Dysfunction in Lung Cancer Patients Treated with Immune Checkpoint Inhibitors (ICIs): Outcomes in a Multiethnic Urban Cohort

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1464
Author(s):  
Angelica D’Aiello ◽  
Juan Lin ◽  
Rasim Gucalp ◽  
Vafa Tabatabaie ◽  
Haiying Cheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Thyroid Dysfunction ◽  
Cox Regression ◽  
Clinical Symptoms ◽  
Checkpoint Inhibitors ◽  
Rank Test ◽  
Lung Cancer Patients ◽  
Log Rank Test ◽  
Treatment Type

We sought to characterize thyroid dysfunction and its association with baseline clinical and demographic characteristics, as well as progression-free survival (PFS), in a multiethnic cohort of lung cancer patients treated with ICIs. A retrospective chart review of lung cancer patients receiving an anti-PD1 or PD-L1 agent was performed. Multivariate Cox proportional hazards were fitted to compare time to thyroid dysfunction among race subgroups controlling for age, gender, treatment type, and duration. Thyroid dysfunction was based on laboratory testing; clinical symptoms were not required. PFS at a 24-week landmark analysis point among patients with and without thyroid dysfunction was compared using a log-rank test. We identified 205 subjects that received ICIs, including 76 (37.1%) who developed thyroid dysfunction. Rates of thyroid dysfunction by one year occurred at similar frequencies among all races (p = 0.92). Gender and concurrent chemotherapy showed no significant association with thyroid dysfunction (p = 0.81 and p = 0.67, respectively). Thyrotoxicosis occurred at higher rates in Black (25, 31.6%) subjects than in White (7, 16.7%) and Hispanic (8, 12.7%) subjects when employing the log-rank test (p = 0.016) and multivariate Cox regression (HR 0.48, p = 0.09 for White and HR 0.36, p = 0.01 for Hispanic compared to Black subjects). PFS was similar among subjects with and without thyroid dysfunction when applying the log-rank test (p = 0.353). Gender, concurrent treatment with chemotherapy, and PFS were not associated with thyroid dysfunction in patients receiving ICIs; however, Black race was a risk factor for thyrotoxicosis. The mechanisms underlying the role of race in the development of irAEs warrant further study.

scholarly journals Circulating regulatory T cells predict efficacy and atypical responses in lung cancer patients treated with PD-1/PD-L1 inhibitors

2021 ◽  
Author(s):  
Da Hyun Kang ◽  
Chaeuk Chung ◽  
Pureum Sun ◽  
Da Hye Lee ◽  
Song-I Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Advanced Nsclc ◽  
Checkpoint Inhibitors ◽  
Standard Of Care ◽  
Treg Cells ◽  
University Hospital ◽  
X Rays ◽  
Lung Cancer Patients ◽  
National University

Abstract Background Immune checkpoint inhibitors (ICIs) have become the standard of care for a variety of cancers, including non-small cell lung cancer (NSCLC). In this study, we investigated the frequency of pseudoprogression and hyperprogression in lung cancer patients treated with ICIs in the real world and aimed to discover a novel candidate marker to distinguish pseudoprogression from hyperprogression soon after ICI treatment. Methods This study included 74 patients with advanced NSCLC who were treated with PD-1/PD-L1 inhibitors at Chungnam National University Hospital (CNUH) between January 2018 and August 2020. Chest X-rays were examined on day 7 after the first ICI dose to identify changes in the primary mass, and the response was assessed by computed tomography (CT). We evaluated circulating regulatory T (Treg) cells using flow cytometry and correlated the findings with clinical outcomes. Results The incidence of pseudoprogression was 13.5%, and that of hyperprogression was 8.1%. On day 7 after initiation of treatment, the frequency of CD4+CD25+CD127loFoxP3+ Treg cells was significantly decreased compared with baseline (P = 0.038) in patients who experienced pseudoprogression and significantly increased compared with baseline (P = 0.024) in patients who experienced hyperprogression. In the responder group, the frequencies of CD4+CD25+CD127loFoxP3+ Treg cells and PD-1+CD4+CD25+CD127loFoxP3+ Treg cells were significantly decreased 7 days after commencement of treatment compared with baseline (P = 0.034 and P < 0.001, respectively). Conclusion Circulating Treg cells represent a promising potential dynamic biomarker to predict efficacy and differentiate atypical responses, including pseudoprogression and hyperprogression, after immunotherapy in patients with NSCLC.

scholarly journals Higher CD4/CD8 ratio of pleural effusion predicts better survival for lung cancer patients receiving immune checkpoint inhibitors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Po-Hsin Lee ◽  
Tsung-Ying Yang ◽  
Kun-Chieh Chen ◽  
Yen-Hsiang Huang ◽  
Jeng-Sen Tseng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Pleural Effusion ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Lung Cancer Patients ◽  
Predicting Factor ◽  
Type 3

AbstractPleural effusion is a rare immune-related adverse event for lung cancer patients receiving immune checkpoint inhibitors (ICIs). We enrolled 281 lung cancer patients treated with ICIs and 17 were analyzed. We categorized the formation of pleural effusion into 3 patterns: type 1, rapid and massive; type 2, slow and indolent; and type 3, with disease progression. CD4/CD8 ratio of 1.93 was selected as the cutoff threshold to predict survival. Most patients of types 1 and 2 effusions possessed pleural effusion with CD4/CD8 ratios ≥ 1.93. The median OS time in type 1, 2, and 3 patients were not reached, 24.8, and 2.6 months, respectively. The median PFS time in type 1, 2, and 3 patients were 35.5, 30.2, and 1.4 months, respectively. The median OS for the group with pleural effusion CD4/CD8 ≥ 1.93 and < 1.93 were not reached and 2.6 months. The median PFS of those with pleural effusion CD4/CD8 ≥ 1.93 and < 1.93 were 18.4 and 1.2 months. In conclusion, patients with type 1 and 2 effusion patterns had better survival than those with type 3. Type 1 might be interpreted as pseudoprogression of malignant pleural effusion. CD4/CD8 ratio ≥ 1.93 in pleural effusion is a good predicting factor for PFS.

scholarly journals Association of Brain Metastases With Immune Checkpoint Inhibitors Efficacy in Advanced Lung Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Yanning Wang ◽  
Qianning Zhang ◽  
Chuansheng Chen ◽  
Yuxuan Hu ◽  
Liyun Miao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Brain Metastases ◽  
Cancer Patients ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Advanced Lung Cancer ◽  
Lung Cancer Patients ◽  
Hazard Ratios

BackgroundIn pivotal immunotherapy trials, the efficacy of immune checkpoint inhibitors as treatments for lung cancer patients with brain metastases remains controversial. The aim of this study was to assess the relative efficacy of immunotherapy versus standard systemic therapy in advanced lung cancer patients with and without brain metastases.MethodsSystematic searches of PubMed, Embase, Cochrane database, and conference proceedings up to Aug 6, 2020 without year and language restrictions. The main outcomes were the overall survival in patients with and without brain metastases measured by hazard ratios, and the difference in efficacy between patients with and without brain metastases was measured by ratio of hazard ratios.ResultsNine eligible randomized controlled trials involving 6241 patients (682 [11%] with brain metastases and 5559 [89%] without brain metastases) were included in the analysis. A survival benefit of immunotherapy was observed for both patients with brain metastases (HR, 0.75; 95%CI, 0.53-0.97; P = .026) and patients without brain metastases (HR, 0.75; 95%CI, 0.67-0.83; P &lt;.001). However, patients without brain metastases benefit more from immunotherapy than patients with brain metastases (HR, 1.37; 95%CI, 1.15-1.63; P = .001). Additionally, subgroup analyses indicated that tumor type affect the efficacy of immunotherapy in patients with brain metastases (HR, 1.04 vs 1.54; interaction, P = .041).ConclusionsImmunotherapy can significantly improve overall survival for advanced lung cancer patients with asymptomatic brain metastases, especially in patients with non-small-cell lung cancer, but the magnitude of benefit is brain metastases dependent.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020206597.

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