Vidit Munshi

Comparative analysis of 5 lung cancer natural history and screening models that reproduce outcomes of the NLST and PLCO trials.

The National Lung Screening Trial (NLST) demonstrated that low‐dose computed tomography screening is an effective way of reducing lung cancer (LC) mortality. However, optimal screening strategies have not been determined to date and it is uncertain whether lighter smokers than those examined in the NLST may also benefit from screening. To address these questions, it is necessary to first develop LC natural history models that can reproduce NLST outcomes and simulate screening programs at the population level.

Comparing Benefits from Many Possible Computed Tomography Lung Cancer Screening Programs: Extrapolating from the National Lung Screening Trial Using Comparative Modeling

Background The National Lung Screening Trial (NLST) demonstrated that in current and former smokers aged 55 to 74 years, with at least 30 pack-years of cigarette smoking history and who had quit smoking no more than 15 years ago, 3 annual computed tomography (CT) screens reduced lung cancer-specific mortality by 20% relative to 3 annual chest X-ray screens. We compared the benefits achievable with 576 lung cancer screening programs that varied CT screen number and frequency, ages of screening, and eligibility based on smoking. Methods and Findings We used five independent microsimulation models with lung cancer natural history parameters previously calibrated to the NLST to simulate life histories of the US cohort born in 1950 under all 576 programs. ‘Efficient’ (within model) programs prevented the greatest number of lung cancer deaths, compared to no screening, for a given number of CT screens. Among 120 ‘consensus efficient’ (identified as efficient across models) programs, the average starting age was 55 years, the stopping age was 80 or 85 years, the average minimum pack-years was 27, and the maximum years since quitting was 20. Among consensus efficient programs, 11% to 40% of the cohort was screened, and 153 to 846 lung cancer deaths were averted per 100,000 people. In all models, annual screening based on age and smoking eligibility in NLST was not efficient; continuing screening to age 80 or 85 years was more efficient. Conclusions Consensus results from five models identified a set of efficient screening programs that include annual CT lung cancer screening using criteria like NLST eligibility but extended to older ages. Guidelines for screening should also consider harms of screening and individual patient characteristics.

Personalizing annual lung cancer screening for patients with chronic obstructive pulmonary disease: A decision analysis

Lung cancer screening with annual chest computed tomography (CT) is recommended for current and former smokers with a ≥30‐pack‐year smoking history. Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of developing lung cancer and may benefit from screening at lower pack‐year thresholds.

The impact of overdiagnosis on the selection of efficient lung cancer screening strategies

The U.S. Preventive Services Task Force (USPSTF) recently updated their national lung screening guidelines and recommended low‐dose computed tomography (LDCT) for lung cancer (LC) screening through age 80. However, the risk of overdiagnosis among older populations is a concern. Using four comparative models from the Cancer Intervention and Surveillance Modeling Network, we evaluate the overdiagnosis of the screening program recommended by USPSTF in the U.S. 1950 birth cohort. We estimate the number of LC deaths averted by screening (D) per overdiagnosed case (O), yielding the ratio D/O, to quantify the trade‐off between the harms and benefits of LDCT. We analyze 576 hypothetical screening strategies that vary by age, smoking, and screening frequency and evaluate efficient screening strategies that maximize the D/O ratio and other metrics including D and life‐years gained (LYG) per overdiagnosed case. The estimated D/O ratio for the USPSTF screening program is 2.85 (model range: 1.5–4.5) in the 1950 birth cohort, implying LDCT can prevent ∼3 LC deaths per overdiagnosed case. This D/O ratio increases by 22% when the program stops screening at an earlier age 75 instead of 80. Efficiency frontier analysis shows that while the most efficient screening strategies that maximize the mortality reduction (D) irrespective of overdiagnosis screen through age 80, screening strategies that stop at age 75 versus 80 produce greater efficiency in increasing life‐years gained per overdiagnosed case. Given the risk of overdiagnosis with LC screening, the stopping age of screening merits further consideration when balancing benefits and harms.

Importance of Smoking Cessation in a Lung Cancer Screening Program

Abstract Early detection of lung cancer and smoking cessation interventions can decrease lung cancer mortality, but information on the effectiveness and interaction between smoking cessation and lung cancer screening is sparse and inconsistent. This review aims to synthesize recent studies in two major areas of interest. First, we explore the interactions and potential for synergies between lung cancer screening programs and smoking cessation by summarizing reported changes in smoking behavior observed in major screening trials in the US and Europe, as well as attempts to use smoking cessation interventions to augment the benefits from lung cancer screening programs. Second, we review the interaction between smoking habits and pre-/post-operative pulmonary resection outcomes, including changes in smoking behavior post-diagnosis and post-treatment. Information from these areas should allow us to maximize benefits from smoking cessation interventions through the entire lung cancer screening process, from the screen itself through potential curative resection after diagnosis.

Cost-Effectiveness of Follow-Up of Pulmonary Nodules Incidentally Detected on Cardiac Computed Tomographic Angiography in Patients With Suspected Coronary Artery DiseaseCLINICAL PERSPECTIVE

Background— Pulmonary nodules (PNs) are often detected incidentally during coronary computed tomographic (CT) angiography, which is increasingly being used to evaluate patients with chest pain symptoms. However, the efficiency of following up on incidentally detected PN is unknown. Methods and Results— We determined demographic and clinical characteristics of stable symptomatic patients referred for coronary CT angiography in whom incidentally detected PNs warranted follow-up. A validated lung cancer simulation model was populated with data from these patients, and clinical and economic consequences of follow-up per Fleischner guidelines versus no follow-up were simulated. Of the 3665 patients referred for coronary CT angiography, 591 (16%) had PNs requiring follow-up. The mean age of patients with PNs was 59±10 years; 66% were male; 67% had ever smoked; and 21% had obstructive coronary artery disease. The projected overall lung cancer incidence was 5.8% in these patients, but the majority died of coronary artery disease (38%) and other causes (57%). Follow-up of PNs was associated with a 4.6% relative reduction in cumulative lung cancer mortality (absolute mortality: follow-up, 4.33% versus non–follow-up, 4.54%), more downstream testing (follow-up, 2.34 CTs per patient versus non–follow-up, 1.01 CTs per patient), and an average increase in quality-adjusted life of 7 days. Costs per quality-adjusted life-year gained were

Cost-Effectiveness of Follow-Up of Pulmonary Nodules Incidentally Detected on Cardiac CT Angiography in Patients with Suspected Coronary Artery Disease

154 700 to follow up the entire cohort and

Benefits and Harms of Computed Tomography Lung Cancer Screening Strategies: A Comparative Modeling Study for the U.S. Preventive Services Task Force

129 800 per quality-adjusted life-year when only smokers were included. Conclusions— Follow-up of PNs incidentally detected in patients undergoing coronary CT angiography for chest pain evaluation is associated with a small reduction in lung cancer mortality. However, significant downstream testing contributes to limited efficiency, as demonstrated by a high cost per quality-adjusted life-year, especially in nonsmokers.

Specific killing of multiple myeloma cells by (-)-epigallocatechin-3-gallate extracted from green tea: biologic activity and therapeutic implications

Background— Pulmonary nodules (PNs) are often detected incidentally during coronary computed tomographic (CT) angiography, which is increasingly being used to evaluate patients with chest pain symptoms. However, the efficiency of following up on incidentally detected PN is unknown. Methods and Results— We determined demographic and clinical characteristics of stable symptomatic patients referred for coronary CT angiography in whom incidentally detected PNs warranted follow-up. A validated lung cancer simulation model was populated with data from these patients, and clinical and economic consequences of follow-up per Fleischner guidelines versus no follow-up were simulated. Of the 3665 patients referred for coronary CT angiography, 591 (16%) had PNs requiring follow-up. The mean age of patients with PNs was 59±10 years; 66% were male; 67% had ever smoked; and 21% had obstructive coronary artery disease. The projected overall lung cancer incidence was 5.8% in these patients, but the majority died of coronary artery disease (38%) and other causes (57%). Follow-up of PNs was associated with a 4.6% relative reduction in cumulative lung cancer mortality (absolute mortality: follow-up, 4.33% versus non–follow-up, 4.54%), more downstream testing (follow-up, 2.34 CTs per patient versus non–follow-up, 1.01 CTs per patient), and an average increase in quality-adjusted life of 7 days. Costs per quality-adjusted life-year gained were

A clinically relevant SCID-hu in vivo model of human multiple myeloma

154 700 to follow up the entire cohort and