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.

A retrospective review of nutritional status and immunotherapy in lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14112-e14112
Author(s):  
Chung-Shien Lee ◽  
Rebecca Sin ◽  
Joanna Stein Fishbein ◽  
Craig E. Devoe ◽  
Xinhua Zhu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Nutritional Status ◽  
Cancer Patients ◽  
Retrospective Review ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Normal Weight ◽  
Rank Test ◽  
Cancer Center ◽  
Lung Cancer Patients

e14112 Background: Immunotherapy has transformed cancer treatment, including lung cancer. Approximately 20-25% of patients respond, therefore making it pivotal in understanding what factors may effect outcomes. There have been previous reports of obesity associated with an increased efficacy of PD-1/PD-L1 blockade and cachectic patients not responding as well. In this study, we aim to assess the association of body mass index (BMI) with outcomes of lung cancer patients being treated with immunotherapy. Methods: An IRB approved retrospective review of lung cancer patients receiving immunotherapy between 2014 and 2017 at the Monter Cancer Center, Northwell Health was conducted. Patients were categorized in underweight (BMI < 18.5), normal weight (BMI of 18.5 to < 25), overweight (BMI 25 to 30) or obese (BMI > 30) arms. The groups were compared using the log-rank test. Kaplan-Meier was used for overall survival (OS) and progression free survival (PFS) and Cox regression models were used to adjust for potential confounders. Results: A total of 116 were included in the analysis, with a median age of 70 (95% CI, 62.5 to 75.5). Ten (8.6%) were underweight, 44 (37.9%) were normal weight, 32 (27.6%) were overweight, and 30 (25.9%) were obese. BMI classification were not found to be a significant predictor of survival, after adjusting for therapy duration (p = 0.44). PFS was 6.6, 6.0, and 6.9 months for patients in the underweight, normal weight, and overweight/obese groups, respectively. Of 116 subjects, 46 (40%) died within the follow up period: 3 (30%), 17 (39%), 11 (34%), and 15 (50%) respectively. Additional post hoc analysis showed that patients with low nutritional status as defined by either a BMI < 18.5 and/or baseline albumin < 3.5 mg/dL had a median PFS of 2.2 months compared to those who did not of 5.2 months (p < 0.00032). Conclusions: In this single institution retrospective review, BMI or albumin as solitary factors did not have a significant effect on outcomes receiving immunotherapy in lung cancer patients. However, a more comprehensive nutritional assessment using a composite endpoint of BMI and serum albumin predicted response to checkpoint inhibitors. Additional studies are needed to validate these findings.

A nomogram to predict outcomes of lung cancer patients after pneumonectomy based on 47 indicators.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20014-e20014
Author(s):  
Bo Cheng ◽  
Cong Wang ◽  
Xue Meng
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Cox Regression ◽  
Clinical Care ◽  
External Validation ◽  
Categorical Variables ◽  
Rank Test ◽  
Survival Prediction ◽  
Cox Regression Analysis ◽  
Lung Cancer Patients

e20014 Background: Nomograms are commonly used tools to estimate prognosis in oncology and medicine.We aimed to establish a nomogram with patients’ characteristics and all available hematological biomarkers for lung cancer patients. Methods: All indexes were cataloged according to clinical significance. Principle component analysis (PCA) was used to reduce the dimensions. Each component was transformed into categorical variables based on recognized cut-off values from receiver operating characteristic (ROC) curve. Kaplan-Meier analysis with log-rank test was used to evaluate the prognostic value of each component. Multivariate analysis was used to determine the promising prognostic biomarkers. Five components were entered into a predictive nomogram. The model was subjected to bootstrap internal validation and to external validation with a separate cohort from Shandong Cancer Hospital. The predictive accuracy and discriminative ability were measured by concordance index (C index) and risk group stratification. Results: Two hundred thirty-six patients were retrospectively analyzed in this study, with 134 in the Discovery Group and 102 in the Validation Group. Forty-seven indexes were sorted into 8 subgroups, and 20 principle components were extracted for further survival analysis. Via cox regression analysis, five components were significant and entered into predictive nomograms. The calibration curves for probability of 3-, and 5-year overall survival (OS) showed optimal agreement between nomogram prediction and actual observation. The new scoring system according to nomogram allowed significant distinction between survival curves within respective tumor-node-metastasis (TNM) subgroups. Conclusions: A nomogram based on the clinical indexes was established for survival prediction of lung cancer patients, which can be used for treatment therapy selection and clinical care option. PCA makes big data analysis feasible.

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 Survival and Factors Affecting it in Lung Cancer Patients Referred to Imam Khomeini Clinic in Hamadan Province

2019 ◽  
Vol 8 (2) ◽  
pp. 85-89
Author(s):  
Fatemeh Gohari-Ensaf ◽  
Zeinab Berangi ◽  
Mohammad Abbasi ◽  
Ghodratollah Roshanaei
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Screening Program ◽  
Rank Test ◽  
P Value ◽  
Survival Times ◽  
Related Factors ◽  
Factors Affecting ◽  
Lung Cancer Patients ◽  
Log Rank Test

Background: Lung cancer is one of the most common cancers and the leading cause of death due to cancer in the world. It has the highest mortality rate compared to breast, prostate, and other cancers. Different factors can be effective in the survival of lung cancer patients. The present study has evaluated survival and its related factors. Materials and Methods: The present study was performed on 157 lung cancer patients referred to Imam Khomeini Specialized Clinic in Hamadan during 2003-2017. Patient follow-up was performed through periodic referrals and telephone calls with patients’ relatives. The survival rate was evaluated using Kaplan-Meier method and the log-rank test was used to compare the survival of different levels of variables. Data analysis was then carried out using SPSS version 23.0 and STATA version14.0. P value < 0.05 was considered statistically significant in all tests. Results: Of 157 patients with lung cancer, 86% were male. The mean and median survival times of patients were 15 and 11 months, respectively. The results of log-rank test indicated that metastasis and site of metastasis were effective in patient survival (P < 0.05). Conclusion: The results of the present study showed that the presence of metastasis is a strong factor for the survival of patients; therefore, it seems necessary to diagnose the disease as early as possible using a screening program.

Alterations in STK11 to limit response to immune checkpoint inhibitors in lung cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21503-e21503
Author(s):  
Jeremy Fricke ◽  
Isa Mambetsariev ◽  
Rebecca Pharaon ◽  
Angel Ray Baroz ◽  
Dan Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Stage Iv ◽  
Rank Test ◽  
Alk Rearrangement ◽  
Lung Cancer Patients ◽  
Significant Difference

e21503 Background: The use of immune checkpoint inhibitors (ICIs) drastically transformed the treatment of lung cancer. However, a variety of response rates have been observed in patients due to intrinsic or acquired resistances. STK11 mutated patients represent a subgroup of lung cancer patients with diminished outcomes when given ICIs, with some of these patients developing hyperprogressive disease (HPD). Methods: In this study, a retrospective cohort of 384 lung cancer patients previously treated with ICIs was identified from the City of Hope Thoracic Registry (THOR) with a cutoff date of November 11, 2018. Next-generational sequencing (NGS) was performed on 246 patients. 24 of these patients were harboring an alteration in STK11. Data was collected on these patients until December 31, 2019. HPD was exclusively defined by time-to-treatment failure (TTF) < 2 months (TTF is defined as the time from the start of treatment with ICI to ICI discontinuation for any reason, including progression, patient preference, toxicity, or death). Overall survival (OS) and progression free survival (PFS) was started from the initiation of ICI therapy. OS and PFS was calculated between 2 groups (HPD vs non-HPD) using the Mantel-Cox Log-rank test. Results: Almost half (11/13; 45.8%) of the patients with STK11 developed HPD. There was a significant difference between HPD and non-HPD patients in median OS (2 vs 23 months; p = 0.0013) and median PFS (1 v 9 months; p < 0.0001). The median age was 66 (range, 41-90) years old with the majority of patients female (14/24; 58.3%). Most of the patients are deceased (16/24; 66.7%). 91.7% of STK11 patients histologically were adenocarcinoma and 91.7% were smokers with a median pack year history of 40 (range, 4-90). All of the patients had metastatic disease presenting with stage IV disease (21/24; 87.5%). ICI therapies used were pembrolizumab (11/24; 45.8%), Atezolizumab (8/24; 33.3%), nivolumab (4/24; 16.7%), and durvalumab (1/24; 4.2%). PD-L1 expression varied: negative (8/24; 33.3%), 1%- < 50% (7/24; 29.2%), ≥50% (4/24; 16.7%), and not reported (5/24; 20.8%). The most commonly occurring co-mutations were found in TP53 (14/24; 58.3%), KRAS (12/24; 50.0%), SMARCA4 (9/24; 37.5%), PRKDC (8/24; 33.3%) and LRP1B (8/24; 33.3%). Three patients had a pathological co-mutation that is targetable (1 ALK rearrangement, 1 EGFR exon 19 deletion, and 1 RET fusion). Conclusions: STK11 patients who developed HPD had worse OS and PFS compared to STK11 patients without HPD. These results are preliminary and additional analysis is needed to compare differences between various cohorts.

scholarly journals Survival analysis in lung cancer patients with interstitial lung disease

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0255375
Author(s):  
Hassan Alomaish ◽  
Yee Ung ◽  
Stella Wang ◽  
Pascal N. Tyrrell ◽  
Saly Abo Zahra ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Cancer Patients ◽  
Clinical Staging ◽  
Rank Test ◽  
Control Group ◽  
Lung Cancer Patients ◽  
Log Rank Test ◽  
Significant Difference

Objective Lung cancer patients with interstitial lung disease (ILD) are prone for higher morbidity and mortality and their treatment is challenging. The purpose of this study is to investigate whether the survival of lung cancer patients is affected by the presence of ILD documented on CT. Materials and methods 146 patients with ILD at initial chest CT were retrospectively included in the study. 146 lung cancer controls without ILD were selected. Chest CTs were evaluated for the presence of pulmonary fibrosis which was classified in 4 categories. Presence and type of emphysema, extent of ILD and emphysema, location and histologic type of cancer, clinical staging and treatment were evaluated. Kaplan-Meier estimates and Cox regression models were used to assess survival probability and hazard of death of different groups. P value < 0.05 was considered significant. Results 5-year survival for the study group was 41% versus 48% for the control group (log-rank test p = 0.0092). No significant difference in survival rate was found between the four different categories of ILD (log-rank test, p = 0.195) and the different histologic types (log-rank test, p = 0.4005). A cox proportional hazard model was used including presence of ILD, clinical stage and age. The hazard of death among patients with ILD was 1.522 times that among patients without ILD (95%CI, p = 0.029). Conclusion Patients with lung cancer and CT evidence of ILD have a significantly shorter survival compared to patients with lung cancer only. Documenting the type and grading the severity of ILD in lung cancer patients will significantly contribute to their challenging management.

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.

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