Browsing by Subject "non-small cell lung cancer"

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    Machine Learning to Build and Validate a Model for Radiation Pneumonitis Prediction in Patients with Non–Small Cell Lung Cancer
    (AACR, 2019-07) Yu, Hao; Wu, Huanmei; Wang, Weili; Jolly, Shruti; Jin, Jianyue; Hu, Chen; Kong, Feng-Ming (Spring); BioHealth Informatics, School of Informatics and Computing
    Purpose: Radiation pneumonitis is an important adverse event in patients with non–small cell lung cancer (NSCLC) receiving thoracic radiotherapy. However, the risk of radiation pneumonitis grade ≥ 2 (RP2) has not been well predicted. This study hypothesized that inflammatory cytokines or the dynamic changes during radiotherapy can improve predictive accuracy for RP2. Experimental Design: Levels of 30 inflammatory cytokines and clinical information in patients with stages I–III NSCLC treated with radiotherapy were from our prospective studies. Statistical analysis was used to select predictive cytokine candidates and clinical covariates for adjustment. Machine learning algorithm was used to develop the generalized linear model for predicting risk RP2. Results: A total of 131 patients were eligible and 17 (13.0%) developed RP2. IL8 and CCL2 had significantly (Bonferroni) lower expression levels in patients with RP2 than without RP2. But none of the changes in cytokine levels during radiotherapy was significantly associated with RP2. The final predictive GLM model for RP2 was established, including IL8 and CCL2 at baseline level and two clinical variables. Nomogram was constructed based on the GLM model. The model's predicting ability was validated in the completely independent test set (AUC = 0.863, accuracy = 80.0%, sensitivity = 100%, specificity = 76.5%). Conclusions: By machine learning, this study has developed and validated a comprehensive model integrating inflammatory cytokines with clinical variables to predict RP2 before radiotherapy that provides an opportunity to guide clinicians.
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    Prognostic variables associated with improved outcomes in patients with stage III NSCLC treated with chemoradiation followed by consolidation Pembrolizumab: a subset analysis of a phase II study from the Hoosier Cancer Research Network LUN 14-179
    (Elsevier, 2019) Anouti, Bilal; Althouse, Sandra; Durm, Greg; Hanna, Nasser; Medicine, School of Medicine
    Introduction HCRN LUN 14-179 is a phase II trial of consolidation pembrolizumab following concurrent chemoradiation for the treatment of patients with stage III NSCLC. Time to metastatic disease, progression free survival and overall survival appear superior to historical controls of chemoradiation alone. Unfortunately, not all patients benefit from consolidation immunotherapy. We performed a univariate analysis evaluating variables associated with PFS, metastatic disease, and OS. Methods We conducted a retrospective analysis from patients enrolled on HCRN LUN14-179. Data collected included age, sex, stage, smoking status, PD-L1 status, >G2 vs G3 pneumonitis, duration of pembrolizumab (<4 vs. >4 cycles), chemotherapy regimen, PS 0 vs 1, time to start pembrolizumab (4-6 vs. 6-8 weeks from radiation), V20 (<20% vs. >20%). Univariable Cox regression was performed to determine the variables associated with 3 endpoints: TMDD; PFS; and OS. Results From April 2015 to December 2016, 93 patients were enrolled and 92 were included in the efficacy analysis (1 patient was ineligible). For TMDD, improved outcomes may be associated (p<0.1) with stage IIIA, non-squamous cell, >4 cycles of pembrolizumab, and V20< 20%. For PFS, improved outcomes (p<0.1) may be seen for >4 cycles of pembrolizumab, and V20< 20%. For OS, improved outcomes (p<0.1) may be seen for non-squamous histology, >4 cycles of pembrolizumab. Conclusion Non-squamous NSCLC, longer duration of pembrolizumab, and V20< 20% may be associated with prolonged time to metastatic disease or death, PFS, and OS for patients with stage III NSCLC treated with chemoradiation followed by pembrolizumab.
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    Second Line Chemotherapy and Beyond for Non-Small Cell Lung Cancer (NSCLC)
    (Elsevier, 2017-02) Durm, Greg; Hanna, Nasser; Department of Medicine, School of Medicine
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    Single-cell transcriptome and antigen-immunoglobin analysis reveals the diversity of B cells in non-small cell lung cancer
    (BMC, 2020-06-24) Chen, Jian; Tan, Yun; Sun, Fenghuan; Hou, Likun; Zhang, Chi; Ge, Tao; Yu, Huansha; Wu, Chunxiao; Zhu, Yuming; Duan, Liang; Wu, Liang; Song, Nan; Zhang, Liping; Zhang, Wei; Wang, Di; Chen, Chang; Wu, Chunyan; Jiang, Gening; Zhang, Peng; Medical and Molecular Genetics, School of Medicine
    Background Malignant transformation and progression of cancer are driven by the co-evolution of cancer cells and their dysregulated tumor microenvironment (TME). Recent studies on immunotherapy demonstrate the efficacy in reverting the anti-tumoral function of T cells, highlighting the therapeutic potential in targeting certain cell types in TME. However, the functions of other immune cell types remain largely unexplored. Results We conduct a single-cell RNA-seq analysis of cells isolated from tumor tissue samples of non-small cell lung cancer (NSCLC) patients, and identify subtypes of tumor-infiltrated B cells and their diverse functions in the progression of NSCLC. Flow cytometry and immunohistochemistry experiments on two independent cohorts confirm the co-existence of the two major subtypes of B cells, namely the naïve-like and plasma-like B cells. The naïve-like B cells are decreased in advanced NSCLC, and their lower level is associated with poor prognosis. Co-culture of isolated naïve-like B cells from NSCLC patients with two lung cancer cell lines demonstrate that the naïve-like B cells suppress the growth of lung cancer cells by secreting four factors negatively regulating the cell growth. We also demonstrate that the plasma-like B cells inhibit cancer cell growth in the early stage of NSCLC, but promote cell growth in the advanced stage of NSCLC. The roles of the plasma-like B cell produced immunoglobulins, and their interacting proteins in the progression of NSCLC are further validated by proteomics data. Conclusion Our analysis reveals versatile functions of tumor-infiltrating B cells and their potential clinical implications in NSCLC.
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    XPC Protects against Carcinogen-Induced Histologic Progression to Lung Squamous Cell Carcinoma by Reduced Basal Epithelial Cell Proliferation
    (MDPI, 2024-04-13) Sears, Catherine R.; Zhou, Huaxin; Hulsey, Emily; Aidoo, Bea A.; Sandusky, George E.; Al Nasrallah, Nawar; Medicine, School of Medicine
    Lung squamous cell carcinoma (LUSC) is the second leading cause of lung cancer. Although characterized by high DNA mutational burdens and genomic complexity, the role of DNA repair in LUSC development is poorly understood. We sought to better understand the role of the DNA repair protein Xeroderma Pigmentosum Group C (XPC) in LUSC development. XPC knock-out (KO), heterozygous, and wild-type (WT) mice were exposed topically to N-nitroso-tris-chloroethylurea (NTCU), and lungs were evaluated for histology and pre-malignant progression in a blinded fashion at various time-points from 8-24 weeks. High-grade dysplasia and LUSC were increased in XPC KO compared with XPC WT NTCU mice (56% vs. 34%), associated with a higher mean LUSC lung involvement (p < 0.05). N-acetylcysteine pre-treatment decreased bronchoalveolar inflammation but did not prevent LUSC development. Proliferation, measured as %Ki67+ cells, increased with NTCU treatment, in high-grade dysplasia and LUSC, and in XPC deficiency (p < 0.01, ANOVA). Finally, pre-LUSC dysplasia developed earlier and progressed to higher histologic classification sooner in XPC KO compared with WT mice. Overall, this supports the protective role of XPC in squamous dysplasia progression to LUSC. Mouse models of early LUSC development are limited; this may provide a valuable model to study mechanisms of LUSC development and progression.