scholarly journals Survival Impact of Aggressive Treatment and PD-L1 Expression in Oligometastatic NSCLC

2021 ◽  
Vol 28 (1) ◽  
pp. 593-605
Author(s):  
Camille Gauvin ◽  
Vimal Krishnan ◽  
Imane Kaci ◽  
Danh Tran-Thanh ◽  
Karine Bédard ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Treatment Group ◽  
Programmed Cell Death ◽  
Prognostic Impact ◽  
Aggressive Treatment ◽  
Palliative Approach ◽  
Oligometastatic Disease ◽  
Group A ◽  
Group B

Background: Studies have shown that aggressive treatment of non-small cell lung cancer (NSCLC) with oligometastatic disease improves the overall survival (OS) compared to a palliative approach and some immunotherapy checkpoint inhibitors, such as anti-programmed cell death ligand 1 (PD-L1), anti-programmed cell death protein 1 (PD-1), and T-Lymphocyte-associated antigen 4 (CTLA-4) inhibitors are now part of the standard of care for advanced NSCLC. However, the prognostic impact of PD-L1 expression in the oligometastatic setting remains unknown. Methods: Patients with oligometastatic NSCLC were identified from the patient database of the Centre hospitalier de l’Université de Montréal (CHUM). “Oligometastatic disease” definition chosen is one synchronous metastasis based on the M1b staging of the eight IASLC (The International Association for the Study of Lung Cancer) Classification (within sixth months of diagnosis) or up to three cerebral metastasis based on the methodology of the previous major phase II randomized study of Gomez et al. We compared the OS between patients receiving aggressive treatment at both metastatic and primary sites (Group A) and patients receiving non-aggressive treatment (Group B). Subgroup analysis was performed using tumor PD-L1 expression. Results: Among 643 metastatic NSCLC patients, we identified 67 patients with oligometastasis (10%). Median follow-up was 13.3 months. Twenty-nine patients (43%) received radical treatment at metastatic and primary sites (Group A), and 38 patients (57%) received non-aggressive treatment (Group B). The median OS (mOS) of Group A was significantly longer than for Group B (26 months vs. 5 months, p = 0.0001). Median progression-free survival (mPFS) of Group A was superior than Group B (17.5 months vs. 3.4 months, p = 0.0001). This difference was still significant when controlled for primary tumor staging: stage I (p = 0.316), stage II (p = 0.024), and stage III (p = 0.001). In the cohort of patients who were not treated with PD-L1 inhibitors, PD-L1 expression negatively correlated with mOS. Conclusions: Aggressive treatments of oligometastatic NSCLC significantly improve mOS and mPFS compared to a more palliative approach. PD-L1 expression is a negative prognostic factor which suggests a possible role for immunotherapy in this setting.

scholarly journals Current landscape of immunotherapy for the treatment of metastatic non-small-cell lung cancer

2018 ◽  
Vol 25 ◽  
pp. 94 ◽  
Author(s):  
A. Pabani ◽  
C.A. Butts
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Significant Toxicity ◽  
Line Setting

For patients with advanced non-small-cell lung cancer (nsclc) lacking a targetable molecular driver, the mainstay of treatment has been cytotoxic chemotherapy. The survival benefit of chemotherapy in this setting is modest and comes with the potential for significant toxicity. The introduction of immunotherapeutic agents targeting the programmed cell death 1 protein (PD-1) and the programmed cell death ligand 1 (PD-L1) has drastically changed the treatment paradigms for these patients. Three agents—atezolizumab, nivolumab, and pembrolizumab—have been shown to be superior to chemotherapy in the second-line setting. For patients with tumours strongly expressing PD-L1, pembrolizumab has been associated with improved outcomes in the first-line setting.Demonstration of the significant benefits of immunotherapy in nsclc has focused attention on new questions. Combination checkpoint regimens, with acceptable toxicity and potentially enhanced efficacy, have been developed, as have combinations of immunotherapy with chemotherapy. In this review, we focus on the published trials that have changed the treatment landscape in advanced nsclc and on the ongoing clinical trials that offer hope to further improve outcomes for patients with advanced nsclc.

scholarly journals miR-103 Functions as a Tumor Suppressor by Directly Targeting Programmed Cell Death 10 in NSCLC

2018 ◽  
Vol 26 (4) ◽  
pp. 519-528 ◽  
Author(s):  
Dong Yang ◽  
Jian-Jun Wang ◽  
Jin-Song Li ◽  
Qian-Yu Xu
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Tumor Size ◽  
Apoptotic Cell ◽  
A549 Cells ◽  
Invasion And Migration ◽  
Metastatic Capacity ◽  
And Migration

Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases. Absence of miR-103 has recently been identified to be associated with metastatic capacity of primary lung tumors. However, the exact role of miR-103 in NSCLC and the molecular mechanism are unclear. In the present study, we showed that miR-103 expression was reduced in NSCLC tissues and cells. miR-103 expression was negatively correlated with tumor size and stage. The overall survival was longer in patients with higher miR-103 level than in those with lower miR-103 expression. miR-103 inhibited cell proliferation in A549 cells, decreased tumor weight and volume, and prolonged survival of tumor-implanted nude mice. miR-103 increased apoptotic cell death in A549 cells. Furthermore, miR-103 decreased the invasion and migration abilities in A549 cells, as evidenced by Transwell and wound healing results. Downregulation of miR-103 significantly reduced the level of programmed cell death 10 (PDCD10). We found a significant decrease in the relative luciferase activity of the reporter gene in A549 cells cotransfected with the miR-103 mimic and pGL3-PDCD10 WT 3′-UTR, but not pGL3-PDCD10 mut 3′-UTR. We showed that overexpression of PDCD10 significantly inhibited miR-103-induced inhibition of cell proliferation, increased apoptosis, and decreased invasion and migration in A549 cells. Moreover, we found that PDCD10 expression was increased in NSCLC tissues and cells. PDCD10 expression was positively correlated with tumor size and stage. Overexpression of PDCD10 increased cell proliferation and inhibited apoptosis in A549 cells. The data demonstrated that dysregulation of the miR-103/PDCD10 signal may be a novel therapeutic target for the treatment of NSCLC.

Augmenting Real-World Data Through Modeling Key Clinical Trial Eligibility Criteria: An Example of Patients With Non–small-Cell Lung Cancer Treated With Pembrolizumab

2021 ◽  
pp. 849-858
Author(s):  
Thomas Jemielita ◽  
Xiaoyun (Nicole) Li ◽  
Thomas Burke ◽  
Kai-Li Liaw ◽  
Wei Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Small Cell Lung Cancer ◽  
Real World ◽  
Small Cell ◽  
Small Cell Lung ◽  
Real World Data ◽  
Eligibility Criteria ◽  
Baseline Characteristics

PURPOSE To compare and characterize baseline characteristics and overall survival (OS) differences by key oncology eligibility criteria for real-world patients from the Flatiron Health database with advanced non–small-cell lung cancer (NSCLC) who received pembrolizumab monotherapy. METHODS Real world data (RWD) were from the Flatiron Health advanced NSCLC database and include patients who initiated pembrolizumab monotherapy (first, second, or third line of therapy) by November 30, 2019. At the data cutoff (May 31, 2020), the median survival follow-up time was 8.4 months. Eligible patients satisfy the criteria of Eastern Cooperative Oncology Group performance status of 0/1 and laboratory values indicative of adequate organ function. RWD were analyzed for all patients and patients with a programmed cell death ligand-1 tumor proportion score ≥ 1%. Patients were divided into three categories: ineligible, eligible, and unknown (who satisfy all observed criteria, with at least one missing). An augmented population was also formed, which combines the latter two groups through a propensity-based adjustment. RESULTS At the data cutoff, N = 3,877 patients with NSCLC received pembrolizumab monotherapy (1L = 2,682, 2L = 946, and 3L = 249). OS was consistently lower for the ineligible with similar survival for the eligible and augmented. Among all patients, the median OS in months (95% CI) was 8.2 (7.5 to 9.6), 16.3 (14.5 to 18.4), 16.4 (15.1 to 19.3), and 16.8 (15.6 to 18.5) for the ineligible (47%, n = 1,827), unknown (27%, n = 1,045), eligible (26%, n = 1,005), and augmented, respectively. The results were similar for patients with a programmed cell death ligand-1 tumor proportion score ≥ 1%. CONCLUSION Real-world patients who received pembrolizumab monotherapy and meet key clinical eligibility criteria exhibited similar baseline characteristics and OS profiles as the unknown and augmented patient groups. Population augmentation is a feasible approach for improving the power of RWD analysis.

STUDY OF GHRELIN LEVELS IN HYPOTHYROID PATIENTS BEFORE AND AFTER TREATMENT

2021 ◽  
pp. 52-54
Author(s):  
Peeyush Yadav ◽  
G. G. Kaushik
Keyword(s):  
Treatment Group ◽  
Thyroid Hormones ◽  
Hdl Cholesterol ◽  
Metabolic Disturbances ◽  
Free T4 ◽  
Before And After ◽  
Group A ◽  
Group B ◽  
Serum Ghrelin ◽  
Hypothyroid Patients

Objective: Aim of the present study was to evaluate the levels of ghrelin in hypothyroid patients before and after treatment with L-thyroxine and to nd a possible relationship between ghrelin and thyroid hormones. Material & Methods: The present study was conducted on 100 hypothyroid patients (44 Males & 56 Females) before treatment (Group A) and after treatment (Group B) attending the outpatient clinics or admitted in wards of J.L.N. Hospitals, Ajmer. 100 healthy control subjects (Group C) of same age group of either gender were selected for the study. Blood samples were drawn from patients and controls, after overnight fast of at least 8 hours. Estimation of Serum Ghrelin, free T3, free T4, and TSH was done by using Enzyme- Linked Immunosorbant Assay (ELISA) technique. Total Cholesterol, Triglyceride, HDL – Cholesterol were measured by automated analyser (Beckman & Coulter's AU680). VLDL – Cholesterol, LDL – Cholesterol were calculated by Friedwald's formula. Differences in the parameters among the groups were analyzed by ANOVA test followed by its Tukey HSD post hoc analysis. Correlations between variables were tested using the Pearson rho (r: Correlation coefcient) correlation test. Results: Findings of the present study shows that the levels of serum fT3 (1.79 ± 0.29 pg/mL) and serum fT4 (0.34 ± 0.11 ng/dL) were signicantly lower in Group A compared to Group B (fT3 = 3.00 ± 0.32 pg/mL & fT4 = 0.81 ± 0.15 ng/dL) and Group C (fT3 = 3.12 ± 0.31 pg/mL & fT4 = 0.85 ± 0.11ng/dL) whereas serum TSH levels were signicantly higher in Group A (40.59 ± 13.55 μIU/mL) compared to Group B (5.34 ± 1.47 μIU/mL) and Group C (3.23 ± 1.04 μIU/mL). Levels of serum Ghrelin were signicantly higher in Group A (918.19 ± 48.47 pg/mL) compared to Group B (700.34 ± 46.35 pg/mL) and Group C (681.49 ± 35.80 pg/mL). A non signicant correlation of Ghrelin with S.fT4 and TSH was found in both Group A and Group B whereas S.fT3 and BMI shows a non signicant correlation in Group A in comparison to a signicant correlation in Group B. Conclusion: There is a reversible increase in the levels of serum ghrelin which became normalized after L-thyroxine substitution in hypothyroid patients. Alteration in the levels of serum ghrelin in thyroid disorders indicates a compensatory role of ghrelin in metabolic disturbances and also suggests a possible association between thyroid hormones and serum ghrelin levels.

scholarly journals Expression of programmed cell death ligand 1 in non–small cell lung cancer: Comparison between cytologic smears, core biopsies, and whole sections using the SP263 assay

2018 ◽  
Vol 127 (1) ◽  
pp. 52-61 ◽  
Author(s):  
Enrico Munari ◽  
Giuseppe Zamboni ◽  
Giorgia Sighele ◽  
Marcella Marconi ◽  
Marco Sommaggio ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung
Sign in / Sign up

Export Citation Format

Share Document