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Introduction: Non-small-cell lung cancer (NSCLC) is a leading cause of death for people living with HIV (PWH). Nevertheless, there are no clinical trial data regarding the management of early-stage lung cancer in PWH. Using data from large HIV and cancer cohorts we parameterized a simulation model to compare treatments for stage I NSCLC according to patient characteristics., Materials and Methods: To parameterize the model we analyzed PWH and NSCLC patient outcomes and quality of life data from several large cohort studies. Comparative effectiveness of 4 stage I NSCLC treatments (lobectomy, segmentectomy, wedge resection, and stereotactic body radiotherapy) was estimated using evidence synthesis methods. We then simulated trials comparing treatments according to quality adjusted life year (QALY) gains by age, tumor size and histology, HIV disease characteristics and major comorbidities., Results: Lobectomy and segmentectomy yielded the greatest QALY gains among all simulated age, tumor size and comorbidity groups. Optimal treatment strategies differed by patient sex, age, and HIV disease status; wedge resection was among the optimal strategies for women aged 80 to 84 years with tumors 0 to 2 cm in size. Stereotactic body radiotherapy was included in some optimal strategies for patients aged 80 to 84 years with multimorbidity and in sensitivity analyses was a non-inferior option for many older patients or those with poor HIV disease control., Conclusion: In simulated comparative trials of treatments for stage I NSCLC in PWH, extensive surgical resection was often associated with the greatest projected QALY gains although less aggressive strategies were predicted to be non-inferior in some older, comorbid patient groups., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Randomized controlled trials (RCTs) have demonstrated a survival benefit for adjuvant platinum-based chemotherapy after resection of locoregional non-small cell lung cancer (NSCLC). The relative benefits and harms and optimal approach to treatment for NSCLC patients who have major comorbidities (chronic obstructive pulmonary disease [COPD], coronary artery disease [CAD], and congestive heart failure [CHF]) are unclear, however., Methods: We used a simulation model to run in-silico comparative trials of adjuvant chemotherapy versus observation in locoregional NSCLC in patients with comorbidities. The model estimated quality-adjusted life years (QALYs) gained by each treatment strategy stratified by age, comorbidity, and stage. The model was parameterized using outcomes and quality-of-life data from RCTs and primary analyses from large cancer databases., Results: Adjuvant chemotherapy was associated with clinically significant QALY gains for all patient age/stage combinations with COPD except for patients >80 years old with Stage IB and IIA cancers. For patients with CHF and Stage IB and IIA disease, adjuvant chemotherapy was not advantageous; in contrast, it was associated with QALY gains for more advanced stages for younger patients with CHF. For stages IIB and IIIA NSCLC, most patient groups benefited from adjuvant chemotherapy. However, In general, patients with multiple comorbidities benefited less from adjuvant chemotherapy than those with single comorbidities and women with comorbidities in older age categories benefited more from adjuvant chemotherapy than their male counterparts., Conclusions: Older, multimorbid patients may derive QALY gains from adjuvant chemotherapy after NSCLC surgery. These results help extend existing clinical trial data to specific unstudied, high-risk populations and may reduce the uncertainty regarding adjuvant chemotherapy use in these patients., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: MKG has received royalties from UpToDate and research support through his institution from Medial EarlySign. RRV has served on advisory boards for Bristol-Myers Squibb, Astrazeneca, Merck, Novocure, BerGenBio, and Regeneron; on unbranded speaker’s bureau of Astrazeneca, received consulting honorarium from Beigene and Novartis, and research grants from BMS, Astrazeneca, Onconova Therapeutics and Boehringer Ingelheim. CBS reports honoraria from Astra Zeneca JPW reports consulting honoraria from Atea, Sanofi, and Banook, and PPD and research grants from Sanofi, Regeneron and Arnold Consultants. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare., (Copyright: © 2022 Leiter et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Veterans with locoregional non-small cell lung cancer (NSCLC) may benefit from adjuvant chemotherapy. However, comorbidities and other factors may impact the harms and benefits of this treatment. Here, we identified the optimal indications for adjuvant chemotherapy in Veterans with NSCLC, chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), and/or coronary artery disease (CAD). We used data from randomized controlled trials (RCTs) and Veterans Administration (VA) databases to enhance a simulation model. Then, we conducted in-silico RCTs comparing adjuvant chemotherapy vs observation among Veterans with stage II-IIIA NSCLC. Among Veterans without COPD or CKD, adjuvant chemotherapy was the optimal strategy regardless of the presence or absence of CAD except for patients >70 years with squamous cell carcinoma. Conversely, most veterans without COPD but with CKD were optimally managed with observation. Veterans with COPD but without CKD, benefited from adjuvant chemotherapy if they were ≤70 years with stage II-IIIA adenocarcinoma or <60 years with stage II-IIIA squamous cell carcinoma. Adjuvant chemotherapy was only beneficial for Veterans with both COPD and CKD among stage II-IIIA adenocarcinoma <60 years of age. Veterans with stages II-IIIA squamous cell carcinoma, COPD, and CKD were optimally managed with observation. Many Veterans with comorbidities are optimally managed with observation post-surgical resection. However, we also identified several groups of Veterans whom the benefits of adjuvant chemotherapy outweighed the risks of early toxicity. Our findings could inform patient-provider discussions and potentially reduce physicians' uncertainty about the role of adjuvant chemotherapy in this population., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Many World Trade Center disaster (WTC) rescue and recovery workers (WTC RRWV) were exposed to toxic inhalable particles. The impact of WTC exposures on lung cancer risk is unclear., Methods: Data from the WTC Health Program General Responders Cohort (WTCGRC) were linked to health information from a large New York City health system to identify incident lung cancer cases. Incidence rates for lung cancer were then calculated. As a comparison group, we created a microsimulation model that generated expected lung cancer incidence rates for a WTC- and occupationally-unexposed cohort with similar characteristics. We also fitted a Poisson regression model to determine specific lung cancer risk factors for WTC RRWV., Results: The incidence of lung cancer for WTC RRWV was 39.5 (95% confidence interval [CI]: 30.7-49.9) per 100,000 person-years. When compared to the simulated unexposed cohort, no significant elevation in incidence was found among WTC RRWV (incidence rate ratio [IRR] 1.34; 95% CI: 0.92-1.96). Predictors of lung cancer incidence included age, smoking intensity, and years since quitting for former smokers. In adjusted models evaluating airway obstruction and individual pre-WTC occupational exposures, only mineral dust work was associated with lung cancer risk (IRR: 2.03; 95% CI: 1.07-3.86)., Discussion: In a sample from a large, prospective cohort of WTC RRWV we found a lung cancer incidence rate that was similar to that expected of a WTC- and occupationally-unexposed cohort with similar individual risk profiles. Guideline-concordant lung cancer surveillance and periodic evaluations of population-level lung cancer risk should continue in this group., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Non-small cell lung cancer (NSCLC) patients frequently have major comorbidities but there is scarce data regarding the impact of these conditions on management strategies. We used simulation modeling to compare different treatments for stage I NSCLC for patients with common major comorbidities., Methods: We used data on NSCLC patinet outcomes and quality of life from: (1) the Surveillance Epidemiology and End Results (SEER) database linked to Medicare claims; (2) Kaiser Permanente Southern California electronic health records; and (3) SEER-Medical Health Outcomes Survey to parameterize a novel simulation model of management and outcomes for stage I NSCLC. Relative efficacy of treatment modalities (lobectomy, segmentectomy, wedge resection and stereotactic body radiotherapy [SBRT]) was collected from existing literature and combined using evidence synthesis methods. We then simulated multiple randomized trials comparing these treatments in a variety of scenarios, estimating quality adjusted life expectancy (QALE) according to age, tumor size, histologic subtype, and comorbidity status., Results: Lobectomy and segmentectomy yielded the greatest QALE gains among all simulated age, tumor size and comorbidity groups. Optimal treatment strategies differed by patient sex and age; wedge resection was among the optimal strategies for women aged 80-84 with tumors 0-2 cm in size. SBRT was included in some optimal strategies for patients aged 80-84 with multimorbidity., Conclusions: In simulated comparative trials of four common treatments for stage I NSCLC, aggressive surgical management was typically associated with the greatest projected QALE gains despite the presence of comorbidities, although less aggressive strategies were predicted to be non-inferior in some older comorbid patient groups., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: We used data from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial to examine the impact of self-reported chronic obstructive pulmonary disease, coronary artery disease, stroke, and diabetes mellitus on diagnostic complications in lung cancer screening evaluation., Methods: In our analysis, we included individuals from the usual care and intervention (annual chest x-ray) of the lung cancer screening trial with equal or greater than 55 years of age with a 20 pack-year smoking history who had undergone an invasive procedure. We performed multivariate logistic regression analysis to estimate the association of comorbidity on procedure complication. Our primary outcome was the incidence of major or moderate complications., Results: Features associated with high-risk complication included older age (OR = 1.03 per year, P = .001), history of coronary artery disease (OR = 1.40, P = .03), history of diabetes mellitus (OR = 0.41, P < .001, current smoking status (OR = 1.46, P ≤ .001), surgical biopsy (OR = 7.39, P < .001), needle biopsy (OR = 1.94, P < .001), and other invasive procedure (OR = 1.58, P < .001). We did not find an associated with complication and history of stroke (OR = 0.84, P = .53) or chronic obstructive pulmonary disease (OR = 1.27, P = .06)., Conclusion: Patient and procedure-level factors may alter the benefits of lung cancer screening. Data concerning individual risk factors and high-risk complications should therefore be incorporated into diagnostic algorithms to optimize clinical benefit and minimize harm. Further study and validation of the risk factors identified herein are warranted., (Copyright © 2022. Published by Elsevier Inc.)

Background: Independent of CD4 cell count, a low CD4/CD8 ratio in people with HIV (PWH) is associated with deleterious immune senescence, activation, and inflammation, which may contribute to carcinogenesis and excess cancer risk. We examined whether low CD4/CD8 ratios predicted cancer among PWH in the United States and Canada., Methods: We examined all cancer-free PWH with 1 or more CD4/CD8 values from North American AIDS Cohort Collaboration on Research and Design observational cohorts with validated cancer diagnoses between 1998 and 2016. We evaluated the association between time-lagged CD4/CD8 ratio and risk of specific cancers in multivariable, time-updated Cox proportional hazard models using restricted cubic spines. Models were adjusted for age, sex, race and ethnicity, hepatitis C virus, and time-updated CD4 cell count, HIV RNA, and history of AIDS-defining illness., Results: Among 83 893 PWH, there were 5628 incident cancers, including lung cancer (n = 755), Kaposi sarcoma (n = 501), non-Hodgkin lymphoma (n = 497), and anal cancer (n = 439). The median age at cohort entry was 43 years. The overall median 6-month lagged CD4/CD8 ratio was 0.52 (interquartile range = 0.30-0.82). Compared with a 6-month lagged CD4/CD8 of 0.80, a CD4/CD8 of 0.30 was associated with increased risk of any incident cancer (adjusted hazard ratio = 1.24 [95% confidence interval = 1.14 to 1.35]). The CD4/CD8 ratio was also inversely associated with non-Hodgkin lymphoma, Kaposi sarcoma, lung cancer, anal cancer, and colorectal cancer in adjusted analyses (all 2-sided P < .05). Results were similar using 12-, 18-, and 24-month lagged CD4/CD8 values., Conclusions: A low CD4/CD8 ratio up to 24 months before cancer diagnosis was independently associated with increased cancer risk in PWH and may serve as a clinical biomarker., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The long-term risk of cardiovascular outcomes from either stereotactic body radiation therapy (SBRT) or three-dimensional conformal radiation therapy (3DCRT) plus intensity-modulated radiation therapy (IMRT) to treat early stage non-small cell lung cancer (NSCLC) is largely unknown. As continued adoption of SBRT accelerates, it is important to delineate unforeseen cardiovascular risks associated with treatment., Research Question: Does the long-term risk of cardiovascular outcomes for patients with early stage NSCLC treated with either SBRT or 3DCRT plus IMRT differ by tumor laterality?, Study Design and Methods: Data from the Surveillance, Epidemiology, and End Results registry linked to Medicare was analyzed to identify a sample of 3,256 patients (1,506 treated with SBRT and 1,750 treated with 3DCRT plus IMRT) with node-negative stage I or IIA NSCLC. Cardiovascular events were identified using diagnosis codes, and outcomes were compared between left- and right-sided tumors. We assumed that tumor laterality was random and that the radiation field for left-sided tumors likely would result in greater dose to cardiac tissues. Cox regression models were fit to quantify the association of laterality on outcomes., Results: Patients were followed up for a median of 2 years. Those treated with SBRT showed no difference in hazard of any cardiovascular outcomes by tumor laterality, including the cardiovascular composite (hazard ratio [HR] comparing left- vs right-sided tumors, 0.98; 95% CI, 0.84-1.15). In contrast, patients treated with 3DCRT plus IMRT showed a greater risk of congestive heart failure (HR, 1.23; 95% CI, 1.01-1.48) and percutaneous coronary artery intervention (HR, 2.24; 95% CI, 1.12-4.47)., Interpretation: Patients with left- vs right-sided early stage NSCLC showed similar rates of cardiovascular events when treated with SBRT. However, these patients also showed higher rates of select cardiac events when they were treated with 3DCRT plus IMRT. This study provides evidence that SBRT may provide a safer option over 3DCRT plus IMRT for patients with left-sided early stage NSCLC and underscores the need for long-term follow-up for patients treated with radiation therapy., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

The National Lung Screening Trial (NLST) found that low-dose computed tomography (LDCT) screening provided lung cancer (LC) mortality benefit compared to chest radiography (CXR). Considerable research concerns identifying the differential treatment effects that may exist in certain subpopulations. We shed light on several important issues in existing research and highlight the need for further investigation of the heterogeneous comparative effect of LDCT versus CXR, using more flexible and rigorous statistical approaches. We used a high-performance Bayesian machine learning approach designed for censored survival data, accelerated failure time Bayesian additive regression trees model (AFT-BART), to flexibly capture the relationships between the failure time and predictors. We then used the counterfactual framework to draw Markov chain Monte Carlo samples of the individual treatment effect for each participant. Using these posterior samples, we explored the possible treatment effect heterogeneity via a stepwise binary tree approach. When re-analyzed with AFT-BART, LDCT did not have a statistically significant LC or overall mortality benefit compared to CXR. The Asian and Black (particularly those with pack-year ≥ 37 years and without emphysema) NLST population were shown to have enhanced overall mortality benefit from LDCT than the population average. Although inconclusive for LC mortality benefit, Asians, Blacks and Whites with history of chronic obstructive pulmonary disease showed a small trend towards benefit from LDCT. Causal inference with flexible machine learning modeling can provide valuable knowledge for informing treatment decision and planning targeted clinical trials emphasizing personalized medicine approaches., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Veterans are at increased risk of lung cancer and many have comorbidities such as chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD). We used simulation modeling to assess projected outcomes associated with different management strategies of Veterans with stage I non-small cell lung cancer (NSCLC) with COPD and/or CAD., Patients and Methods: Using data from a cohort of 14,029 Veterans (years 2000-2015) with NSCLC we extended a well-validated mathematical model of lung cancer to represent the management and outcomes of Veterans with stage I NSCLC with COPD, with or without comorbid CAD. We simulated multiple randomized trials to compare treatment with lobectomy, limited resection, or stereotactic body radiation therapy (SBRT). Model output estimated expected quality adjusted life years (QALY) of Veterans with stage I NSCLC according to age, tumor size, histologic subtype, COPD severity and CAD diagnosis., Results: For Veterans <70 years old lobectomy was associated with greater projected quality-adjusted life expectancy regardless of comorbidity status. For most combinations of tumors and comorbidity profiles there was no dominant treatment for Veterans ≥80 years of age, but less invasive treatments were often superior to lobectomy. Dominant treatment choices differed by CAD status for older patients in a third of scenarios, but not for patients <70 years old., Conclusions: The harm/benefit ratio of treatments for stage I NSCLC among Veterans may vary according to COPD severity and the presence of CAD. This information can be used to direct future research study design for Veterans with stage I lung cancer and COPD and/or CAD., Competing Interests: Dr. Wisnivesky has received consulting honorarium from Sanofi, Glaxosmithkline and Banook and research grants from Sanofi and Quorum. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Robotic-assisted surgery (RAS) is a novel surgical approach increasingly used for patients with non-small cell lung cancer (NSCLC). However, data comparing the effectiveness and costs of RAS vs open thoracotomy and video-assisted thoracoscopic surgery (VATS) for NSCLC are limited., Methods: Patients > 65 years old with stage I to IIIA NSCLC treated with RAS, VATS, or open thoracotomy were identified from the Surveillance, Epidemiology, and End Results-Medicare database and matched according to age, sex, stage, and extent of resection. Propensity score methods were used to compare adjusted rates of postoperative complications, adequate lymph node staging, survival, and treatment-related costs., Results: In this matched study cohort of 2,766 patients with resected NSCLC, RAS was associated with lower complication rates (OR, 0.57; 95% CI, 0.42-0.79) compared with open thoracotomy, and similar complication rates (OR, 1.02; 95% CI, 0.76-1.37) compared with VATS. Patients undergoing RAS were as likely to have adequate lymph node sampling as those undergoing open thoracotomy (OR, 1.28; 95% CI, 0.94-1.74) or VATS (OR, 0.88; 95% CI, 0.66-1.18). There was no significant difference in overall survival after RAS vs open thoracotomy (hazard ratio, 0.81; 95% CI, 0.63-1.04) or VATS (hazard ratio, 0.91; 95% CI, 0.70-1.18). Costs were similar for RAS ($54,702) vs open thoracotomy ($57,104; P = .08), and higher compared with VATS ($48,729; P = .02)., Conclusions: RAS led to improved operative outcomes compared with open thoracotomy but may not offer an advantage over VATS. The comparative effectiveness of RAS should be further evaluated prior to widespread adoption., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: While previous cost-effectiveness studies on pembrolizumab in stage IV non-small cell lung cancer (NSCLC) have found these regimens to be cost-effective, their reliance on randomized controlled trial (RCT) data with strict inclusion criteria limits generalizability to patients with comorbidities. We estimated the cost-effectiveness of first-line pembrolizumab for patients with various comorbidities., Materials and Methods: In our base case analysis, we studied pembrolizumab plus chemotherapy (pembrolizumab combination therapy) versus chemotherapy alone. In a secondary analysis, we considered only patients with PD-L1 expression of at least 50% (PD-L1-high) and evaluated pembrolizumab monotherapy, pembrolizumab combination therapy, and chemotherapy alone. Microsimulation models were developed for the base case and the PD-L1-high analyses. To estimate outcomes of patients with differing comorbidities, we combined survival data from patients with few or no comorbidities from the RCTs with estimates from the general population obtained from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Comorbidity burden level was divided into three groups based on the Charlson score (equal to 0, 1, or 2+); patients with various other specific comorbidities were also analyzed. Incremental cost-effectiveness ratios (ICER) were compared to a willingness-to-pay (WTP) threshold of $100,000/quality-adjusted life-year (QALY)., Results: In the Charlson 0, Charlson 1, and Charlson 2+ patient populations, estimated ICERs for pembrolizumab combination therapy in the base case model were $173,919/QALY, $175,165/QALY, and $181,777/QALY, respectively, compared to chemotherapy. In the PD-L1-high model, the Charlson 0, Charlson 1, and Charlson 2+ patients had ICERs of $147,406/QALY, $149,026/QALY, and $154,521/QALY with pembrolizumab combination therapy versus chemotherapy. Pembrolizumab monotherapy was weakly dominated for each comorbidity group in the PD-L1-high model., Conclusion: For patients with stage IV NSCLC and varying comorbidity burden, first-line treatment with pembrolizumab does not represent a cost-effective strategy compared to chemotherapy. Resources should be focused on collecting immunotherapy survival data for more representative NSCLC patient populations., Competing Interests: Dr. Wisnivesky is a member of the research board of EHE International and has received consulting honorarium from Quintiles, Merck, and AstraZeneca and research grants from Sanofi and Quorum. All other authors declare no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Some interstitial lung diseases are associated with lung cancer. However, it is unclear whether asymptomatic interstitial lung abnormalities convey an independent risk., Objectives: The goal of this study was to assess whether interstitial lung abnormalities are associated with an increased risk of lung cancer., Methods: Data from all participants in the National Lung Cancer Trial were analyzed, except for subjects with preexisting interstitial lung disease or prevalent lung cancers. The primary analysis included those who underwent low-dose CT imaging; those undergoing chest radiography were included in a confirmatory analysis. Participants with evidence of reticular/reticulonodular opacities, honeycombing, fibrosis, or scarring were classified as having interstitial lung abnormalities. Lung cancer incidence and mortality in participants with and without interstitial lung abnormalities were compared by using Poisson and Cox regression, respectively., Results: Of the 25,041 participants undergoing low-dose CT imaging included in the primary analysis, 20.2% had interstitial lung abnormalities. Participants with interstitial lung abnormalities had a higher incidence of lung cancer (incidence rate ratio, 1.61; 95% CI, 1.30-1.99). Interstitial lung abnormalities were associated with higher lung cancer incidence on adjusted analyses (incidence rate ratio, 1.33; 95% CI, 1.07-1.65). Lung cancer-specific mortality was also greater in participants with interstitial lung abnormalities. Similar findings were obtained in the analysis of participants undergoing chest radiography., Conclusions: Asymptomatic interstitial lung abnormalities are an independent risk factor for lung cancer that can be incorporated into risk score models., (Copyright © 2019. Published by Elsevier Inc.)

Purpose: Lung cancer risk models optimise screening by identifying subjects at highest risk, but none of them consider emphysema, a risk factor identifiable on baseline screen. Subjects with a negative baseline low-dose CT (LDCT) screen are at lower risk for subsequent diagnosis and may benefit from risk stratification prior to additional screening, thus we investigated the role of radiographic emphysema as an additional predictor of lung cancer diagnosis in participants with negative baseline LDCT screens of the National Lung Screening Trial., Methods: Our cohorts consist of participants with a negative baseline (T0) LDCT screen (n=16 624) and participants who subsequently had a negative 1-year follow-up (T1) screen (n=14 530). Lung cancer risk scores were calculated using the Bach, PLCOm2012 and Liverpool Lung Project models. Risk of incident lung cancer diagnosis at the end of the study and number screened per incident lung cancer were compared between participants with and without radiographic emphysema., Results: Radiographic emphysema was independently associated with nearly double the hazard of lung cancer diagnosis at both the second (T1) and third (T2) annual LDCT in all three risk models (HR range 1.9-2.0, p<0.001 for all comparisons). The number screened per incident lung cancer was considerably lower in participants with radiographic emphysema (62 vs 28 at T1 and 91 vs 40 at T2)., Conclusion: Radiographic emphysema is an independent predictor of lung cancer diagnosis and may help guide decisions surrounding further screening for eligible patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Lung cancer is the leading cause of non-AIDS-defining cancer deaths among HIV-infected individuals. Although lung cancer screening with low-dose computed tomography (LDCT) is endorsed by multiple national organizations, whether HIV-infected individuals would have similar benefit as uninfected individuals from lung cancer screening is unknown. Our objective was to determine the benefits and harms of lung cancer screening among HIV-infected individuals., Design: We modified an existing simulation model, the Lung Cancer Policy Model, for HIV-infected patients., Data Sources: Veterans Aging Cohort Study, Kaiser Permanente Northern California HIV Cohort, and medical literature., Target Population: HIV-infected current and former smokers., Time Horizon: Lifetime., Perspective: Population., Intervention: Annual LDCT screening from ages 45, 50, or 55 until ages 72 or 77 years., Main Outcome Measures: Benefits assessed included lung cancer mortality reduction and life-years gained; harms assessed included numbers of LDCT examinations, false-positive results, and overdiagnosed cases., Results of Base-Case Analysis: For HIV-infected patients with CD4 cell count at least 500 cells/μl and 100% antiretroviral therapy adherence, screening using the Centers for Medicare & Medicaid Services criteria (age 55-77, 30 pack-years of smoking, current smoker or quit within 15 years of screening) would reduce lung cancer mortality by 18.9%, similar to the mortality reduction of uninfected individuals. Alternative screening strategies utilizing lower screening age and/or pack-years criteria increase mortality reduction, but require more LDCT examinations., Limitations: Strategies assumed 100% screening adherence., Conclusion: Lung cancer screening reduces mortality in HIV-infected patients with CD4 cell count at least 500 cells/μl, with a number of efficient strategies for eligibility, including the current Centers for Medicare & Medicaid Services criteria.

Background: Overdiagnosis among clinically detected lung cancers likely consists of cases that are non-aggressive and slowly progressive and will never disseminate, cause symptoms or be a threat to a subject's survival, even if untreated. In this study, we estimate the prevalence of non-aggressive lung cancers from a large, population-based cancer registry., Methods: We identified individuals ≥65 years with histologically confirmed, untreated stage I non-small cell lung cancers (NSCLCs) from the Surveillance, Epidemiology, and End Results-Medicare registry. We estimated the rate of non-aggressive lung cancers by determining the point at which the cumulative lung cancer-specific survival curve no longer changed (ie, the slope approaches zero). At this point, there are no additional deaths due to progressive lung cancer observed among untreated patients after adjusting for deaths from competing risks (these long-term survivors can be considered 'non-aggressive cases)., Results: The overall rate of non-aggressive cancers among 2197 clinically detected cases of untreated stage I NSCLC was 2.4%, 95% CI: 1.0% to 3.8%. The rate of non-aggressive cancer was 1.9% (95% CI: 0.0% to 4.9%) for women and 2.4% (95% CI: 0.7% to 4.1%) for men (p=0.84). When stratifying by tumour size, non-aggressive cancer rates were 10.2% (95% CI: 0.0% to 29.3%), 2.1% (95% CI: 0.0% to 9.2%), 4.9% (95% CI: 0.0% to 10.3%), 1.8% (95% CI: 0.0% to 5.2%) and 0.0% (95% CI: 0.0% to 1.0%) for tumour sizes <15 mm, 15-24 mm, 25-34 mm, 35-44 mm and ≥45 mm, respectively. In comparison with the smallest tumour sizes (<15 mm), the rates of non-aggressive cancers were not statistically significantly different for tumour sizes 15-24 mm (p=0.36), 25-34 mm (p=0.57), 35-44 mm (p=0.38) and tumour sizes >45 mm (p=0.30)., Discussion: We found relatively low rates of non-aggressive cancers among clinically detected, stage I NSCLC regardless of sex or size. Our findings suggest that most clinically diagnosed early stage cancers should be treated with curative intent., Competing Interests: Competing interests: JPW is a member of the research board of EHE International, has received consulting honorarium from Quintiles, AstraZeneca and Merck and a research grant from Aventis Pharmaceutical and Quorum. KS has received honorarium from Gilead., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Rationale: Video-assisted thoracoscopic surgery (VATS) and open lobectomy are both standard of care for the treatment of early-stage non-small cell lung cancer (NSCLC) because of equivalent long-term survival., Objectives: To evaluate whether the improved perioperative outcomes associated with VATS lobectomy are explained by surgeon characteristics, including case volume and specialty training., Methods: We analyzed the Surveillance, Epidemiology, and End Results-Medicare-linked registry to identify stage I-II NSCLC in patients above 65 years of age. We used a propensity score model to adjust for differences in patient characteristics undergoing VATS versus open lobectomy. Perioperative complications, extended length of stay, and perioperative mortality among patients were compared after adjustment for surgeon's volume and specialty using linear mixed models. We compared survival using a Cox model with robust standard errors., Results: We identified 9,508 patients in the registry who underwent lobectomy for early-stage NSCLC. VATS lobectomies were more commonly performed by high-volume surgeons (P < 0.001) and thoracic surgeons (P = 0.01). VATS lobectomy was associated with decreased adjusted odds of cardiovascular complications (odds ratio [OR] = 0.65; 95% confidence interval [CI] = 0.47-0.90), thromboembolic complications (OR = 0.47; 95% CI = 0.38-0.58), extrapulmonary infections (OR = 0.75; 95% CI = 0.61-0.94), extended length of stay (OR = 0.47; 95% CI = 0.40-0.56), and perioperative mortality (OR = 0.33; 95% CI = 0.23-0.48) even after controlling for differences in surgeon volume and specialty. Long-term survival was equivalent for VATS and open lobectomy (hazard ratio = 0.95; 95% CI = 0.85-1.08) after controlling for patient and tumor characteristics, surgeon volume, and specialization., Conclusions: VATS lobectomy for NSCLC is associated with better postoperative outcomes, but similar long-term survival, compared with open lobectomy among older adults, even after controlling for surgeon experience.

Background: Lung cancer is a major cause of death in HIV-infected (HIV+) persons. In this study, we compared the prevalence of tumour EGFR and KRAS mutations in a cohort of lung adenocarcinoma patients by HIV status., Methods: We collected data from 55 HIV+ patients with lung adenocarcinoma matched to 136 uninfected comparators. We compared the prevalence of EGFR and KRAS mutations by HIV status. We then compared survival by HIV status and by cancer mutation status among HIV+ subjects., Results: Presence of KRAS and EGFR genetic alterations did not vary by HIV status (all P>0.1). There was no difference in overall survival by HIV status or by mutation status among HIV+ subjects., Conclusions: We found no major differences in the prevalence of EGFR or KRAS lung adenocarcinoma mutations by HIV status, suggesting that mutational testing should be conducted similarly regardless of the HIV status.

Objectives: Toxicity is a main concern limiting the use of chemotherapy and radiotherapy (RT) for elderly patients with non-small cell lung cancer (NSCLC). The objective of this study was to assess the rates of treatment-related toxicity among elderly stage IIIB and IV NSCLC patients., Materials and Methods: We used the Surveillance, Epidemiology, and End Results registry linked to Medicare records to identify 2596 stage IIIB and 14,803 stage IV NSCLC patients aged 70 years and above, diagnosed in 2000 or later. We compared rates of toxicity requiring hospitalization according to treatment (chemotherapy, RT, or chemoradiation [CRT]) in unadjusted and adjusted models controlling for selection bias using propensity scores., Results: Among stage IIIB patients, rates of any severe toxicity were 10.1%, 23.8%, 30.4%, and 39.2% for patients who received no treatment, RT, chemotherapy alone, and CRT, respectively. In stage IV patients, rates of any severe toxicity were 31.5% versus 13.5% among those treated with and without chemotherapy, respectively. In stage IIIB patients treated with CRT, the most common toxicities was esophagitis (odds ratio, 48.5; 95% confidence interval, 6.7-350.5). Among stage IV patients treated with chemotherapy, the risk of toxicity was highest for neutropenia (odds ratio, 8.4; 95% confidence interval, 6.1-11.5)., Conclusions: Toxicity was relatively common among stage IIIB patients with up to a 6-fold increase in elderly individuals treated with CRT and a 4-fold increase in toxicities among stage IV patients. This information should be helpful to guide discussions about the risk-benefit ratio of chemotherapy and RT in elderly patients with advanced NSCLC.

Background: HIV infection is independently associated with risk of lung cancer, but few data exist for the relation between longitudinal measurements of immune function and lung-cancer risk in people living with HIV., Methods: We followed up participants with HIV from the Veterans Aging Cohort Study for a minimum of 3 years between Jan 1, 1998, and Dec 31, 2012, and used cancer registry data to identify incident cases of lung cancer. The index date for each patient was the later of the date HIV care began or Jan 1, 1998. We excluded patients with less than 3 years' follow-up, prevalent diagnoses of lung cancer, or incomplete laboratory data. We used Cox regression models to investigate the relation between different time-updated lagged and cumulative exposures (CD4 cell count, CD8 cell count, CD4/CD8 ratio, HIV RNA, and bacterial pneumonia) and risk of lung cancer. Models were adjusted for age, race or ethnicity, smoking, hepatitis C virus infection, alcohol use disorders, drug use disorders, and history of chronic obstructive pulmonary disease and occupational lung disease., Findings: We identified 277 cases of incident lung cancer in 21 666 participants with HIV. In separate models for each time-updated 12 month lagged, 24 month simple moving average cumulative exposure, increased risk of lung cancer was associated with low CD4 cell count (p trend=0·001), low CD4/CD8 ratio (p trend=0·0001), high HIV RNA concentration (p=0·004), and more cumulative bacterial pneumonia episodes (12 month lag only; p trend=0·0004). In a mutually adjusted model including these factors, CD4/CD8 ratio and cumulative bacterial pneumonia episodes remained significant (p trends 0·003 and 0·004, respectively)., Interpretation: In our large HIV cohort in the antiretroviral therapy era, we found evidence that dysfunctional immune activation and chronic inflammation contribute to the development of lung cancer in the setting of HIV infection. These findings could be used to target lung-cancer prevention measures to high-risk groups., Funding: US National Institutes of Health., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose of Review: Lung cancer is emerging as a leading cause of death in HIV-infected persons. This review will discuss the latest scientific evidence regarding the mechanisms driving lung cancer risk in HIV infection, the clinical presentation of lung cancer in HIV-infected persons and recent data regarding the outcomes, treatment and prevention of lung cancer in this group., Recent Findings: Increased risk of lung cancer in HIV-infected persons is primarily due to higher smoking rates, but emerging evidence also implicates immunosuppression and inflammatory processes. Lung cancer outcomes may be worse in HIV-infected persons in the antiretroviral era, but this may stem, in part, from treatment disparities. Early detection of lung cancer using chest computed tomography (CT) is being increasingly adopted for smokers in the general population, and recent studies suggest that it may be safe and efficacious in HIV-infected smokers., Summary: Lung cancer is an important complication associated with chronic HIV infection. It is associated with unique HIV-related causal mechanisms, and may be associated with worse outcomes in some HIV-infected persons. Smoking cessation and early cancer detection with chest CT are likely to benefit HIV-infected smokers., Competing Interests: The authors report no potential conflicts of interest related to this work.

Rationale: In the treatment of stage III non-small cell lung cancer (NSCLC), three-dimensional conformal radiotherapy (3D-RT) is the standard method for radiation delivery; however, intensity-modulated radiotherapy (IMRT) has been rapidly adopted. These two modalities may lead to similar survival, warranting a closer scrutiny of the costs involved., Objectives: The purpose of this study is to compare radiotherapy-related and total costs of older patients with NSCLC treated with 3D-RT versus IMRT., Methods: We conducted a population-based study of all Medicare beneficiaries aged 65 years or older in a Surveillance, Epidemiology and End Results region. Patients were diagnosed with stage III NSCLC diagnosed between 2002 and 2009. Patients received IMRT or 3D-RT in combination with chemotherapy within 4 months of diagnosis. Radiotherapy-related and total adjusted cost and survival of patients receiving 3D-RT versus IMRT were compared using propensity scores methods., Measurements and Main Results: Of the 2,418 patients in study, 314 (13%) received IMRT. Adjusted analyses showed no difference in overall survival (hazard ratio, 0.97; 95% confidence interval [CI], 0.85-1.12) in patients treated with 3D-RT versus IMRT. After adjusting for propensity scores, RT-related costs (estimated difference, $6,850; 95% CI, $5,532-$8,168) and total costs (estimated difference, $8,713; 95% CI, $4,376-$13,051) were significantly higher among patients undergoing IMRT., Conclusions: The rapid adoption of IMRT for the treatment of stage III NSCLC has occurred in the absence of evidence from prospective randomized trials. Our results show that IMRT is associated with similar survival but increased costs, underscoring the need for continued research in IMRT and other new technologies.

Objectives: Prior studies have shown an anticancer effect of statins in patients with certain malignancies. However, it is unclear whether statins have a mortality benefit in lung cancer. We compared survival of patients with stage IV non-small cell lung cancer (NSCLC) receiving vs. not receiving statins prior to diagnosis., Methods: Using data from the Surveillance, Epidemiology and End Results registry linked to Medicare claims, we identified 5118 patients  >65 years of age diagnosed with stage IV NSCLC between 2007 and 2009. We used propensity score methods to assess the association of statin use with overall and lung cancer-specific survival while controlling for measured confounders., Results: Overall, 27% of patients were on statins at time of lung cancer diagnosis. Median survival in the statin group was 7 months, compared to 4 months in patients not treated with statins (p<0.001). Propensity score analyses found that statin use was associated with improvement in overall (hazard ratio [HR]: 0.76, 95% confidence interval [CI]: 0.73-0.79) and lung cancer-specific survival (HR: 0.77, 95% CI: 0.73-0.81), after controlling for baseline patient characteristics, cancer characteristics, staging work-up and chemotherapy use., Conclusions: Statin use is associated with improved survival among patients with stage IV NSCLC suggesting a potential anticancer effect. Further research should evaluate plausible biological mechanisms as well as test the effect of statins in prospective clinical trials., Competing Interests: All other authors are without any conflicts of interest., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Pulmonary malignancies are a major source of morbidity and mortality in HIV-infected persons. Non-AIDS-defining lung cancers (mostly non-small cell lung cancers) are now a leading cause of cancer death among HIV-infected persons. HIV-associated factors appear to affect the risk of lung cancer and may adversely impact cancer treatment and outcomes. HIV infection also may modify the potential harms and benefits of lung cancer screening with computed tomography. AIDS-defining lung malignancies include pulmonary Kaposi sarcoma and pulmonary lymphoma, both of which are less prevalent with widespread adoption of antiretroviral therapy., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Treatment-related immunosuppression in organ transplant recipients has been linked to increased incidence and risk of progression for several malignancies. Using a population-based cancer cohort, we evaluated whether organ transplantation was associated with worse prognosis in elderly patients with non-small cell lung cancer (NSCLC)., Methods: Using the Surveillance, Epidemiology, and End Results Registry linked to Medicare claims, we identified 597 patients aged 65 years or older with NSCLC who had received organ transplants (kidney, liver, heart, or lung) before cancer diagnosis. These cases were compared to 114,410 untransplanted NSCLC patients. We compared overall survival (OS) by transplant status using Kaplan-Meier methods and Cox regression. To account for an increased risk of non-lung cancer death (competing risks) in transplant recipients, we used conditional probability function (CPF) analyses. Multiple CPF regression was used to evaluate lung cancer prognosis in organ transplant recipients while adjusting for confounders., Results: Transplant recipients presented with earlier stage lung cancer (P = 0.002) and were more likely to have squamous cell carcinoma (P = 0.02). Cox regression analyses showed that having received a non-lung organ transplant was associated with poorer OS (P < 0.05), whereas lung transplantation was associated with no difference in prognosis. After accounting for competing risks of death using CPF regression, no differences in cancer-specific survival were noted between non-lung transplant recipients and nontransplant patients., Conclusions: Non-lung solid organ transplant recipients who developed NSCLC had worse OS than nontransplant recipients due to competing risks of death. Lung cancer-specific survival analyses suggest that NSCLC tumor behavior may be similar in these 2 groups.

Rationale: Prior studies have shown an anticancer effect of metformin in patients with breast and colorectal cancer. It is unclear, however, whether metformin has a mortality benefit in lung cancer., Objectives: To compare overall survival of patients with diabetes with stage IV non-small cell lung cancer (NSCLC) taking metformin versus those not on metformin., Methods: Using data from the Surveillance, Epidemiology, and End Results registry linked to Medicare claims, we identified 750 patients with diabetes 65-80 years of age diagnosed with stage IV NSCLC between 2007 and 2009. We used propensity score methods to assess the association of metformin use with overall survival while controlling for potential confounders., Measurements and Main Results: Overall, 61% of patients were on metformin at the time of lung cancer diagnosis. Median survival in the metformin group was 5 months, compared with 3 months in patients not treated with metformin (P < 0.001). Propensity score analyses showed that metformin use was associated with a statistically significant improvement in survival (hazard ratio, 0.80; 95% confidence interval, 0.71-0.89), after controlling for sociodemographics, diabetes severity, other diabetes medications, cancer characteristics, and treatment., Conclusions: Metformin is associated with improved survival among patients with diabetes with stage IV NSCLC, suggesting a potential anticancer effect. Further research should evaluate plausible biologic mechanisms and test the effect of metformin in prospective clinical trials.

Background: HIV-infected persons have a two-fold to five-fold increased unadjusted risk of lung cancer. In the National Lung Screening Trial (NLST), computed tomography (CT) screening was associated with a reduction in lung cancer mortality among high-risk smokers. These results may not generalize to HIV-infected persons, particularly if they are more likely to have false-positive chest CT findings., Methods: We utilized data including standardized chest CT scans from 160 HIV infected and 139 uninfected Veterans enrolled between 2009 and 2012 in the multicenter Examinations of HIV Associated Lung Emphysema (EXHALE) Study. Abnormal CT findings were abstracted from clinical interpretations of the scans and classified as positive by NLST criteria vs. other findings. Clinical evaluations and diagnoses that ensued were abstracted from the medical record., Results: There was no significant difference by HIV in the proportion of CT scans classified as positive by NLST criteria (29% of HIV infected and 24% of HIV uninfected, P=0.3). However, HIV-infected participants with CD4 cell counts less than 200 cells/μl had significantly higher odds of positive scans, a finding that persisted in multivariable analysis. Evaluations triggered by abnormal CT scans were also similar in HIV-infected and uninfected participants (all P>0.05)., Conclusion: HIV status was not associated with an increased risk of abnormal findings on CT or increased rates of follow-up testing in clinically stable outpatients with CD4 cell count more than 200. These data reflect favorably on the balance of benefits and harms associated with lung cancer screening for HIV-infected smokers with less severe immunodeficiency.

Objective: Cancer mortality is higher in individuals with schizophrenia, a finding that may be due, in part, to inequalities in care. We evaluated gaps in lung cancer diagnosis, treatment, and survival among elderly individuals with schizophrenia., Methods: The Surveillance, Epidemiology, and End Results database linked to Medicare records was used to identify patients 66 years or older with primary non-small cell lung cancer. Lung cancer stage, diagnostic evaluation, and rates of stage-appropriate treatment were compared among patients with and without schizophrenia using unadjusted and multiple regression analyses. Survival was compared among groups using Kaplan-Meier methods., Results: Of the 96,702 patients with non-small cell lung cancer in the Surveillance, Epidemiology, and End Results database, 1303 (1.3%) had schizophrenia. In comparison with the general population, patients with schizophrenia were less likely to present with late-stage disease after controlling for age, sex, marital status, race/ethnicity, income, histology, and comorbidities (odds ratio = 0.82, 95% confidence interval = 0.73-0.93) and were less likely to undergo appropriate evaluation (p < .050 for all comparisons). Adjusting for similar factors, patients with schizophrenia were also less likely to receive stage-appropriate treatment (odds ratio = 0.50, 95% confidence interval = 0.43-0.58). Survival was decreased among patients with schizophrenia (mean survival = 22.3 versus 26.3 months, p = .002); however, no differences were observed after controlling for treatment received (p = .40)., Conclusions: Elderly patients with schizophrenia present with earlier stages of lung cancer but are less likely to undergo diagnostic evaluation or to receive stage-appropriate treatment, resulting in poorer outcomes. Efforts to increase treatment rates for elderly patients with schizophrenia may lead to improved survival in this group.

Purpose: Chemoradiotherapy is the standard of care for unresectable stage III non-small cell lung cancer (NSCLC). Elderly patients, who are often considered unfit for combined chemoradiotherapy, frequently receive radiation therapy (RT) alone. Using population-based data, we evaluated the effectiveness and tolerability of lone RT in unresected elderly stage III NSCLC patients., Methods and Materials: Using the Surveillance, Epidemiology and End Results (SEER) registry linked to Medicare records we identified 10,376 cases of unresected stage III NSCLC that were not treated with chemotherapy, diagnosed between 1992 and 2007. We used logistic regression to determine propensity scores for RT treatment using patients' pre-treatment characteristics. We then compared survival of patients who underwent lone RT vs. no treatment using a Cox regression model adjusting for propensity scores. The adjusted odds for toxicity among patients treated with and without RT were also estimated., Results: Overall, 6468 (62%) patients received lone RT. Adjusted analyses showed that RT was associated with improved overall survival in unresected stage III NCSLC (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.74-0.79) after controlling for propensity scores. RT treated patients had an increased adjusted risk of hospitalization for pneumonitis (odds ratio [OR]: 89, 95% CI: 12-636), and esophagitis (OR: 8, 95% CI: 3-21)., Conclusions: These data suggest that use of RT alone may improve the outcomes of elderly patients with unresected stage III NSCLC. Severe toxicity, however, was considerably higher in the RT treated group. The potential risks and benefits of RT should be carefully discussed with eligible elderly NSCLC patients., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: We conducted a population-based study to evaluate whether non-small cell lung cancer (NSCLC) prognosis was worse in HIV-infected compared with HIV-uninfected patients., Methods: Using the Surveillance, Epidemiology and End Results (SEER) registry linked to Medicare claims, we identified 267 HIV-infected patients and 1428 similar controls with no evidence of HIV diagnosed with NSCLC between 1996 and 2007. We used conditional probability function (CPF) analyses to compare survival by HIV status accounting for an increased risk of non-lung cancer death (competing risks) in HIV-infected patients. We used multivariable CPF regression to evaluate lung cancer prognosis by HIV status adjusted for confounders., Results: Stage at presentation and use of stage-appropriate lung cancer treatment did not differ by HIV status. Median survival was 6 months (95% confidence interval (CI): 5-8 months) among HIV-infected NSCLC patients compared with 20 months (95% CI: 17-23 months) in patients without evidence of HIV. Multivariable CPF regression showed that HIV was associated with a greater risk of lung cancer-specific death after controlling for confounders and competing risks., Conclusion: NSCLC patients with HIV have a poorer prognosis than patients without evidence of HIV. NSCLC may exhibit more aggressive behaviour in the setting of HIV.

Background: The postoperative management of elderly patients with T4, N0-1, M0 non-small cell lung cancer (NSCLC) remains controversial. The objective of this study was to evaluate the association of adjuvant chemotherapy with survival and toxicity among these patients., Methods: Using surveillance, epidemiology and end results registry data linked to Medicare claims, we identified 389 elderly patients with resected T4, N0-1, M0 NSCLC diagnosed between 1992 and 2007. We compared survival of patients treated with and without platinum-based chemotherapy using a Cox regression adjusting for propensity scores for chemotherapy use and use of radiotherapy. We used logistic regression to assess the risk of adverse events in patients receiving chemotherapy., Results: No benefit was noted in overall survival with adjuvant chemotherapy after PS adjustment for both N0 (hazard ratio 0.78, 95% confidence interval 0.50-1.23) and N1 (hazard ratio 1.01, 95% confidence interval 0.67-1.53) cancers. Patients receiving adjuvant chemotherapy experienced severe adverse events more frequently than patients who did not receive chemotherapy., Conclusions: Use of adjuvant chemotherapy in elderly patients with T4, N0-1, M0 NSCLC was not associated with a survival advantage and was associated with higher rates of severe toxicity.

Background: It is unclear whether the elevated rate of lung cancer among HIV-infected persons is due to biological effects of HIV, surveillance bias, or excess smoking. We compared the incidence of lung cancer between HIV-infected and demographically similar HIV-uninfected patients, accounting for smoking and stage of lung cancer at diagnosis., Design: Data from the Veterans Aging Cohort Study Virtual Cohort were linked to data from the Veterans Affairs Central Cancer Registry, resulting in an analytic cohort of 37,294 HIV-infected patients and 75,750 uninfected patients., Methods: We calculated incidence rates of pathologically confirmed lung cancer by dividing numbers of cases by numbers of person-years at risk. We used Poisson regression to determine incidence rate ratios (IRRs), adjusting for age, sex, race/ethnicity, smoking prevalence, previous bacterial pneumonia, and chronic obstructive pulmonary disease., Results: The incidence rate of lung cancer in HIV-infected patients was 204 cases per 100,000 person-years [95% confidence interval (CI) 167-249] and among uninfected patients was 119 cases per 100,000 person-years (95% CI 110-129). The IRR of lung cancer associated with HIV infection remained significant after multivariable adjustment (IRR 1.7; 95% CI 1.5-1.9). Lung cancer stage at presentation did not differ between HIV-infected and uninfected patients., Conclusion: In our cohort of demographically similar HIV-infected and uninfected patients, HIV infection was an independent risk factor for lung cancer after controlling for potential confounders including smoking. The similar stage distribution between the two groups indicated that surveillance bias was an unlikely explanation for this finding.

Background: Elderly patients with early-stage lung cancer are less likely to undergo tumor resection because of concerns about their ability to tolerate surgery or perceived limited life expectancy. The objective of this study was to evaluate the impact of age and competing risks on outcomes of elderly patients with stage I non-small-cell lung cancer (NSCLC)., Methods: We identified 27,859 cases of histologically confirmed, stage I NSCLC from the Surveillance, Epidemiology, and End Results registry. Patients were grouped by age (<60, 61-69, 70-79, >or=80 years) and surgical resection status. Relative survival rates were compared amongst treatment groups by age strata to determine the potential impact of surgery and the contribution of competing risks to overall mortality., Results: Patients aged <60, 61-69, 70-79, and >or=80 years represented 20%, 32%, 37%, and 11% of cases. The rate of surgical resections declined from 95% of patients <60 years, to 79% of patients aged >or=80 years. While 5-year relative survival rates were somewhat lower among males >or=80 years compared with those <60 years (63.5% versus 69.2%), there were no significant differences in relative survival among resected women or unresected patients, regardless of sex. Most deaths in unresected patients were attributed to lung cancer across all age groups., Conclusions: Elderly patients who undergo resection achieve relative survival rates that are comparable to their younger counterparts. In unresected patients, lung cancer is the major source of mortality, even in the oldest age groups, suggesting that elderly patients with stage I lung cancer should receive aggressive surgical management when possible.