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Introduction: The relationship between Body-Mass-Index (BMI) and lung cancer prognosis is heterogeneous. We evaluated the impact of sex, smoking and race on the relationship between BMI and overall survival (OS) in non-small-cell-lung-cancer (NSCLC)., Methods: Data from 16 individual ILCCO studies were pooled to assess interactions between BMI and the following factors on OS: self-reported race, smoking status and sex, using Cox models (adjusted hazard ratios; aHR) with interaction terms and adjusted penalized smoothing spline plots in stratified analyses., Results: Among 20,937 NSCLC patients with BMI values, females = 47 %; never-smokers = 14 %; White-patients = 76 %. BMI showed differential survival according to race whereby compared to normal-BMI patients, being underweight was associated with poor survival among white patients (OS, aHR = 1.66) but not among black patients (aHR = 1.06; p interaction  = 0.02). Comparing overweight/obese to normal weight patients, Black NSCLC patients who were overweight/obese also had relatively better OS (p interaction  = 0.06) when compared to White-patients. BMI was least associated with survival in Asian-patients and never-smokers. The outcomes of female ever-smokers at the extremes of BMI were associated with worse outcomes in both the underweight (p interaction <0.001) and obese categories (p interaction  = 0.004) relative to the normal-BMI category, when compared to male ever-smokers., Conclusion: Underweight and obese female ever-smokers were associated with worse outcomes in White-patients. These BMI associations were not observed in Asian-patients and never-smokers. Black-patients had more favorable outcomes in the extremes of BMI when compared to White-patients. Body composition in Black-patients, and NSCLC subtypes more commonly seen in Asian-patients and never-smokers, may account for differences in these BMI-OS relationships., (Copyright © 2020. Published by Elsevier B.V.)

Objectives: Immune-checkpoint blockades have exhibited durable responses and improved long-term survival in a subset of advanced non-small cell lung cancer (NSCLC) patients. However, highly predictive markers of positive and negative responses to immunotherapy are a significant unmet clinical need. The objective of this study was to identify clinical and computational image-based predictors of rapid disease progression phenotypes in NSCLC patients treated with immune-checkpoint blockades., Materials and Methods: Using time-to-progression (TTP) and/or tumor growth rates, rapid disease progression phenotypes were developed including hyperprogressive disease. The pre-treatment baseline predictors that were used to identify these phenotypes included patient demographics, clinical data, driver mutations, hematology data, and computational image-based features (radiomics) that were extracted from pre-treatment computed tomography scans. Synthetic Minority Oversampling Technique (SMOTE) was used to subsample minority groups to eliminate classification bias. Patient-level probabilities were calculated from the final clinical-radiomic models to subgroup patients by progression-free survival (PFS)., Results: Among 228 NSCLC patients treated with single agent or double agent immunotherapy, we identified parsimonious clinical-radiomic models with modest to high ability to predict rapid disease progression phenotypes with area under the receiver-operator characteristics ranging from 0.804 to 0.865. Patients who had TTP < 2 months or hyperprogressive disease were classified with 73.41% and 82.28% accuracy after SMOTE subsampling, respectively. When the patient subgroups based on patient-level probabilities were analyzed for survival outcomes, patients with higher probability scores had significantly worse PFS., Conclusions: The models found in this study have potential important translational implications to identify highly vulnerable NSCLC patients treated with immunotherapy that experience rapid disease progression and poor survival outcomes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Until recently, there has not been a valid and reliable screening test for lung cancer. As compared to chest X-ray, low-dose computed tomography (LDCT) lung cancer screening has demonstrated greater sensitivity resulting in lung cancer diagnosis at an earlier stage, thereby reducing lung cancer mortality among high-risk individuals by 20%. In the current study, we sought to examine knowledge and attitudes about LDCT screening for lung cancer among an ethnically and racially diverse sample of high risk (HR) community members and primary care providers (PCP)., Methods: Eligible individuals participated in a focus group using semi-structured interview guides. Focus groups were conducted with PCPs (by telephone) and HRs (in-person). Sessions were audio-taped and transcribed verbatim. The constant comparison method and content analysis were used to analyze results., Results: The majority of PCPs had limited knowledge of lung cancer CT screening. PCPs cited barriers to recommendation including, cost/insurance barriers and the potential for false positives. PCPs perceived the main benefit to be early detection of lung cancer. The majority of HRs had never heard of lung LDCT screening and had never had a healthcare provider recommend it to them. Perceived barriers included fear of results (bad news) and financial costs. The main perceived benefit was early detection., Conclusion: Lack of knowledge about LDCT was a key a barrier across both the PCP and HR., Respondents: Understanding the barriers to lung screening across diverse community populations is necessary to improve screening rates and shared decision-making., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: An assessment of temporal trends in patient survival is important to determine the progress toward patient outcomes and to reveal where advancements must be made. This study assessed temporal changes spanning 22years in demographics, clinical characteristics, and overall survival of small cell lung cancer (SCLC) patients., Materials and Methods: This analysis included 1032 SCLC patients spanning two time-periods from the H. Lee Moffitt Cancer Center and Research Institute: 1986-1999 (N=410) and 2000-2008 (N=622). Kaplan-Meier survival curves and log-rank statistics were used to assess survival rates across the two time-periods and multivariable Cox proportional hazards models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: The overall 5-year survival rate significantly increased from 8.3% for the 1986-1999 time-period to 11.0% (P<0.001) for the 2000-2008 time-period, and the median survival time increased from 11.3months (95% CI 10.5-12.7) to 15.2months (95% CI 13.6-16.6). We also observed significant increases in stage-specific median survival times and survival rates across the two time-periods. A multivariable Cox proportional hazards model for the entire cohort revealed significant increased risk of death for patients diagnosed in 1986-1999 (HR=1.29; 95% CI 1.11-1.49), patients diagnosed between 60 and 69years of age (HR=1.33; 95% CI 1.04-1.49) and over 70years of age (HR=1.63; 95% CI 1.26-2.11), men (HR=1.33; 95% CI 1.16-1.53), patients with no first course treatment (HR=2.17; 95% CI 1.57-3.00) and extensive stage SCLC (HR=2.79; 95% CI 2.35-3.30)., Conclusion: This analysis demonstrated significant improvements in overall and stage-specific median survival times and survival rates of SCLC patients treated at the Moffitt Cancer Center from 1986 to 2008., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Glutathione transferases (GSTs), a multiple gene family of phase II enzymes, catalyze detoxifying endogenous reactions with glutathione and protect cellular macromolecules from damage caused by cytotoxic and carcinogenic agents. Glutathione S-transferase p1 (GSTP1), the most abundant GST isoform in the lung, metabolizes numerous carcinogenic compounds including benzo[a]pyrene, a tobacco carcinogen. Previous studies suggest that genetic polymorphisms of GSTP1 exon 5 (Ile105Val) and exon 6 (Ala114Val) have functional effects on the GST gene product resulting in reduced enzyme activity. Individuals with reduced GST enzymatic activity may be at a greater risk for cancer due to decreased detoxification of carcinogenic and mutagenic compounds. Utilizing a hospital-based case-control study, we investigated the association between GSTP1 polymorphisms at exons 5 and 6 with lung cancer risk. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was used to successfully genotype the GSTP1 exons 5 and 6 polymorphism in 582 Caucasian lung cancer cases and 600 frequency matched Caucasian controls. There was no association between the exon 5 variant genotypes (A/G+G/G) and overall lung cancer risk (OR=1.09; 95% CI 0.82-1.45) nor when stratified by age, gender, and smoking status. However, the exon 6 variant genotypes (C/T+T/T) were associated with a statistically significant elevated lung cancer risk (OR=1.40; 95% CI 1.06-1.92). Additionally, there was an increase in lung cancer risk for the exon 6 variant genotypes in younger individuals (<62 years) (OR=1.63; 95% C.I. 1.07-2.49) but no effect in older individuals (OR=1.14; 95% CI 0.72-1.81). A statistically significant increased risk of lung cancer was also observed for the exon 6 variant genotypes among men (OR=2.17; 95% CI 1.41-3.33), but not among women (OR=0.80; 95% CI 0.51-1.28). Among ever smokers, the exon 6 variant genotypes were associated with an elevated lung cancer risk (OR=1.58; 95% CI 1.14-2.19), which was not evident for never smokers (OR=0.53; 95% CI 0.21-1.33). These data demonstrate that the GSTP1 exon 6 polymorphism, but not the exon 5 polymorphism, is associated with lung cancer risk that is especially evident in men, younger individuals, and ever smokers.

Myeloperoxidase (MPO) is a metabolic/oxidative enzyme found in neutrophils and monocytes that contributes to pulmonary carcinogenesis through activation of specific procarcinogens including benzo[a]pyrene intermediates, 4-aminobiphenyl and the arylamines. There is a G-->A polymorphism located in the 5' untranslated region of the MPO gene that may be responsible for reduced transcriptional activity due to the decreased binding affinity for the SP1 transcription factor. Individuals with one or two copies of the A-allele may be afforded protection due to decreased transcriptional activity of MPO and subsequent decreased metabolic activation of procarcinogens. Previous studies have reported a range of protective effects in different ethnic populations. We employed a restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) assay to identify the MPO genotypes in 375 lung cancer cases and 378 healthy controls, all of whom were Caucasian. Our results demonstrate a reduced risk of lung cancer when the A-allele genotypes (G/A+A/A) were combined (odds ratio (OR)=0.66; 95% confidence interval (CI) 0.49-0.90). We also noted a protective effect (OR=0.63; 95% CI 0.45-0.87) in ever smokers with the A-allele genotypes which was not evident in never smokers (OR=1.14; 95% CI 0.42-3.11). We observed an incremental decrease in the protective effects as cigarette pack-years increased. Thus, lightest smokers were provided the greatest protection. When the data were stratified by gender, there was a statistically significant reduced risk of lung cancer among men (OR=0.55; 95% CI 0.36-0.84), but not among women (OR=0.81; 95% CI 0.55-1.26) for the A-allele genotypes. Lastly, an age effect was evident only in men but not women. The protective effects of the A-allele genotypes decreased with increasing age. This report provides further support for the hypothesis that a single nucleotide polymorphism in the MPO gene is a protective factor in lung cancer carcinogenesis.