Obesity-Specific Association of Statin Use and Reduced Risk of Recurrence of Early Stage NSCLC.

INTRODUCTION: Statins, used for their lipid-lowering activity, have anti-inflammatory and anticancer properties as well. We evaluated this potential benefit of statin use in patients with NSCLC. METHODS: All 613 patients with pathologic stage 1 or 2 NSCLC who had lobectomy without neoadjuvant therapy at our institution during 2008 to 2015 were included. Association between presurgery statin use and overall survival and recurrence-free survival (RFS) was analyzed using Cox proportional hazards regression. Association of statin use with tumor transcriptome was evaluated in another 350 lung cancer cases. RESULTS: Univariable analyses did not reveal a statistically significant association of statin use with either overall survival or RFS, with hazard ratio equals to 1.19 and 0.70 (Wald p = 0.28 and 0.09), respectively. In subgroup analyses, significantly improved RFS was found in statin users, but only in overweight/obese patients (body mass index [BMI] > 25; n = 422), with univariable and multivariable hazard ratio of 0.49 and 0.46 (p = 0.005 and 0.002), respectively, but not in patients with BMI less than or equal to 25 (n = 191; univariable p = 0.21). Transcriptomes of tumor statin users had high expression of tumoricidal genes such as granzyme A and interferon-γ compared with those of nonusers among high- but not low-BMI patients with lung cancer. CONCLUSIONS: Our study suggests that statins may improve the outcome of early stage NSCLC but only in overweight or obese patients. This benefit may stem from a favorable reprogramming of the antitumor immune response that statins perpetrate specifically in the obese.

Visceral Obesity Promotes Lung Cancer Progression-Toward Resolution of the Obesity Paradox in Lung Cancer.

INTRODUCTION: Although obesity is associated with adverse cancer outcomes in general, most retrospective clinical studies suggest a beneficial effect of obesity in NSCLC. METHODS: Hypothesizing that this "obesity paradox" arises partly from the limitations of using body mass index (BMI) to measure obesity, we quantified adiposity using preoperative computed tomography images. This allowed the specific determination of central obesity as abdominal visceral fat area normalized to total fat area (visceral fat index [VFI]). In addition, owing to the previously reported salutary effect of metformin on high-BMI patients with lung cancer, metformin users were excluded. We then explored associations between visceral obesity and outcomes after surgical resection of stage I and II NSCLC. We also explored potential immunologic underpinnings of such association using complimentary analyses of tumor gene expression data from NSCLC tumors and the tumor transcriptome and immune microenvironment in an immunocompetent model of lung cancer with diet-induced obesity. RESULTS: We found that in 513 patients with stage I and II NSCLC undergoing lobectomy, a high VFI is associated with decreased recurrence-free and overall survival. VFI was also inversely related to an inflammatory transcriptomic signature in NSCLC tumors, consistent with observations made in immunocompetent murine models wherein diet-induced obesity promoted cancer progression while exacerbating elements of immune suppression in the tumor niche. CONCLUSIONS: In all, this study uses multiple lines of evidence to reveal the adverse effects of visceral obesity in patients with NSCLC, which align with those found in animal models. Thus, the obesity paradox may, at least in part, be secondary to the use of BMI as a measure of obesity and the confounding effects of metformin use.

Tobacco Dependence Treatment in Oncology: Initial Patient Clinical Characteristics and Outcomes from Roswell Park Comprehensive Cancer Center.

Despite the importance of smoking cessation to cancer care treatment, historically, few cancer centers have provided treatment for tobacco dependence. To address this gap, the National Cancer Institute (NCI) launched the Cancer Center Cessation Initiative (C3i). As part of this effort, this study examined implementation outcomes in a cohort of cancer survivors (CSs) who smoked cigarettes in the first year of an ongoing process to develop and implement a robust Tobacco Treatment Service at Roswell Park Comprehensive Cancer Center. We provide a comprehensive description of the new tobacco use assessment and referral process, and of the characteristics of cancer survivors who agreed to treatment including traditional tobacco-related psychosocial and cancer treatment-related characteristics and novel characteristics such as delay discounting rates. We also examine characteristic differences among those who agreed to treatment between those who attended and those who did not attend treatment. As the new tobacco assessment was implemented, the number of referrals increased dramatically. The mean number of treatment sessions attended was 4.45 (SD = 2.98) and the six-month point prevalence intention to treat abstinence rate among those who attended was 22.7%. However, only 6.4% agreed to treatment and 4% attended at least one treatment session. A large proportion of cancer survivors who agreed to treatment were women, of older age, of lower socioeconomic status (SES), and who had high levels of depressive symptomology. The findings demonstrate that the implementation of system changes can significantly improve the identification of cancer survivors who use tobacco and are referred to tobacco use treatment. Among those who attend, treatment is effective. However, the findings also suggest that a systematic assessment of barriers to engagement is needed and that cancer survivors may benefit from additional treatment tailoring. We present plans to address these implementation challenges. Systematic electronic medical record (EMR)-sourced referral to tobacco treatment is a powerful tool for reaching cancer survivors who smoke, but more research is needed to determine how to enhance engagement and tailor treatment processes.

Body Mass Index Influences the Salutary Effects of Metformin on Survival After Lobectomy for Stage I NSCLC.

INTRODUCTION: Metformin, a common medication used in the treatment of diabetes mellitus is known to have anticancer effects. We hypothesized that the salutary effect of metformin on the survival of patients with stage I NSCLC is influenced by body mass index (BMI). METHODS: Patients undergoing lobectomy for stage I NSCLC without neoadjuvant therapy were included. Univariate and multivariate survival analyses to examine the association between metformin use and overall survival (OS), disease-specific survival (DSS), and recurrence-free survival were performed, stratified by BMI (>25 kg/m2 and ≤25 kg/m2). Expression of immune checkpoints in patients on metformin and not was performed in a separate cohort of 205 patients with advanced disease. RESULTS: Four hundred thirty-four stage I patients (including 74 metformin users) were deemed eligible for analysis. Univariate and multivariate analysis revealed an association between metformin use and OS (hazard ratio [HR] = 0.52; p = 0.04) as well as DSS (HR = 0.21; p = 0.04) but not recurrence-free survival (HR = 0.67; p = 0.33) in high-BMI patients only. In a separate cohort of 205 patients with tumors of all stages (including 35 metformin users), downregulation of immune checkpoint gene expression (programmed cell death 1, cytotoxic T-lymphocyte associated protein 4, B and T lymphocyte associated, CD27 molecule, lymphocyte activating 3, and inducible T cell costimulator) in metformin users was seen only in high-BMI patients, with upregulation of these genes seen in low-BMI patients with metformin use. CONCLUSIONS: Metformin use may be associated with better OS and DSS only in high-BMI patients. This hypothesis is supported by gene expression data of immune checkpoint genes in metformin users using a separate cohort of advanced-stage tumors. Further studies examining the interaction of BMI with metformin in NSCLC are worthwhile.