Lung Cancer

The CISNET Lung Working Group (LWG) consists of six modeling groups and a coordinating center. Lung cancer remains the leading cause of cancer related mortality in the US and globally accounting for 1.8 million deaths annually. The CISNET LWG has contributed to the development of US national strategies for reducing the lung cancer burden by quantifying the impact of tobacco control on smoking, lung cancer, and overall mortality, and by evaluating the population benefits and harms of lung cancer screening in the US. In the current funding round, the LWG will extend existing models to assess the impacts of future tobacco control interventions in the ever-changing tobacco market landscape, improvements in lung cancer screening and other emerging early detection strategies, innovations in lung cancer treatment, and their synergistic interactions, on lung cancer rates and overall mortality in the US and globally.

Highlights

The CISNET Lung Working group was commissioned by the U.S. Preventive Services Task Force (USPSTF) in 2011-2013 and 2019-2021 to conduct decision analyses to inform their lung cancer screening recommendations.

CISNET investigators launched an online tool that simulates the potential effects of tobacco control policies on population health.

ten Haaf K, Jeon J, Tammemägi MC, et al. Risk prediction models for selection of lung cancer screening participants: a retrospective validation study. PLoS Medicine 2017; 14(4): e1002277

Investigators

Comparative Modeling of Lung Cancer Prevention and Control Policies


Principal Investigator:

BC Cancer Research Institute
Co-Principal Investigators:

Massachusetts General Hospital

Erasmus MC

Yale University

Icahn School of Medicine at Mount Sinai

Georgetown University

Stanford University

Grant Number: U01CA253858

Abstract & Aims

Abstract: Lung cancer remains the leading cause of cancer related mortality in the US and globally— responsible for ~1.8 million deaths annually. As collaborative investigators of the CISNET Lung Working Group (LWG), we have contributed to the development of US national strategies for reducing the lung cancer burden by quantifying the impact of tobacco control on smoking, lung cancer, and overall mortality, and by evaluating the population benefits and harms of lung cancer screening in the US. Due to ongoing reductions in smoking in the US, lung cancer mortality is projected to continue declining. However, lung cancer is still expected to result in over 4 million deaths over the next 50 years. Thus, in addition to tobacco control efforts, a focus on early detection and treatment interventions will be critical for further reduce the lung cancer burden in the US.  Moreover, as new tobacco products, such as e-cigarettes (e-cigs) become more popular, there are concerns that the gains achieved in the fight against smoking could reverse.

The specific aims are:

  1. Evaluate the impact of current and future tobacco control policies and the adoption of e-cigarettes on smoking rates and lung cancer incidence/mortality, accounting for differences by sociodemographic factors and geographic location.
  2. Estimate the individual and population impacts of personalized approaches to lung cancer screening and early detection, with consideration for implementation challenges in real-world settings.
  3. Project the impact of targeted therapies and immunotherapies on US lung cancer mortality.
  4. Assess the impact of tobacco control strategies on the lung cancer burden in low- and middle-income countries (LMICs).

Major Analyses & Contributions

Comparative Analyses

Quantifying the impact of tobacco control policies on lung cancer mortality in the United States

Using five CISNET lung cancer models and detailed information on cigarette smoking, the CISNET lung group is quantifying the impact of tobacco control policies and increased awareness of the health effects of smoking following the seminal Surgeon General's report on past and future lung cancer mortality in the United States. The CISNET group is quantifying the levels of smoking and associated lung cancer deaths that would have occurred if the tobacco control efforts starting mid-century had never been initiated, as well as quantifying the number of lung cancer deaths that would have been avoided had tobacco control been perfect (i.e., if, following the Surgeon General's report, all current smokers quit and there was no new initiation).

Initial projections of the impact of tobacco control on lung cancer mortality from 1975-2000 highlighted the number of lung cancer deaths that were avoided due to the tobacco control efforts that did occur, and an upper bound on how many more deaths could have been avoided if the efforts had been perfect. The results of this comparative modeling project were published in the Journal of the National Cancer Institute (Moolgavkar, Holford et al. 2012), and also as a special monograph in the journal Risk Analysis (2012). In addition to the population-based models, this project resulted in the development of other sophisticated tools for the investigation of the association between smoking habits and human health. These included life tables for mortality associated with specific levels of smoking and a smoking history generator (SHG) (Jeon, Meza et al. 2012) that allows the stochastic simulation of individual smoking histories for the US birth cohorts from 1864-2012, while adjusting for smoking-related mortality.

We are extending this work to project the impact of tobacco control and lung cancer screening policies on current and future lung cancer rates in the US for the overall population, and also for different socio-demographic groups. We will also be extending our analyses to assess the effectiveness of tobacco control policies in middle-income countries (specifically Mexico, Thailand, and China).

Hypothesized Impact of Tobacco Control Policies on U.S. Smoking Prevalence

Hypothesized impact of tobacco control policies on US smoking prevalence

Hypothesized impact of tobacco control policies on U.S. smoking prevalence. Percentage of smokers among the white U.S. male population in a given year (19002000) by given year at birth (different colors). Solid lines represent the percentage of smokers estimated based on National Health Interview Survey data. Dashed lines represent the percentages (hypothesized) that would have been observed if tobacco control efforts had never been initiated.(Adapted with permission from Moolgavkar, Holford et al. 2012)

Other Achievements

Lung Cancer Other Achievements: Highlights

What is the effect of tobacco control programs on reducing smoking prevalence and tobacco-related mortality?

The CISNET lung model (SimSmoke) developed by the Georgetown University group can be used to retrospectively estimate the impact of various tobacco control policies on observed declines in smoking rates and on tobacco-related mortality, as well as to project the potential impact of tobacco control policies on reducing these rates. The model has been applied to estimate effects at the state and national levels:

Results consistently showed that cigarette price increases and educational media campaigns had the largest impact on smoking rates, with substantially smaller effects attributable to telephone quit lines, youth access policies, and clean air laws. Models of this type can assist policy makers at the state and national levels by demonstrating tobacco control progress in specific states, explaining the policies that have contributed to declines in smoking prevalence, and determining the potential impact of enhanced tobacco control efforts in other regions of the country.

The CISNET smoking population model was used to estimate the impact of tobacco control on overall mortality in the US since the publication of the 1964 Surgeon General’s report (SGR) (Holford, Meza et al. 2014). Counterfactual scenarios were first developed projecting smoking prevalence in the absence of tobacco control from 1964 forward. The model estimated that approximately 8 million premature deaths were prevented by tobacco control in the US since 1964, resulting in an estimated 157 million years of life saved, with about 20 years of additional life per each life saved (Holford, Meza et al. 2014). These analyses were prominently featured as part of activities commemorating the 50th anniversary of the first SGR on Smoking and Health. Moreover, the estimated smoking prevalence, initiation, cessation, and intensity rates in the US by birth-cohort from 1965-2009 (Holford, Levy et al. 2014) were incorporated into the SGR 50th anniversary issue: Chapter 13. Patterns of Tobacco Use Among U.S. Youth, Young Adults, and Adults.

What are the potential public health impacts of raising the minimum age for purchasing tobacco products?

CISNET investigators participated in an Institute of Medicine (IOM) Committee to assess the health consequences of raising the minimum age for purchasing tobacco products in the US. The CISNET smoking population model and the SimSmoke model were used by the IOM Committee to simulate the impact of raising the minimum age on future US smoking prevalence and several health outcomes including smoking-related mortality, lung cancer mortality, and maternal and child health outcomes. The IOM report concluded that raising the minimum age would lead to considerable positive health effects. In particular, if the minimum age were raised to age 21 nationwide, for the cohort of people born between 2000 and 2019, the models project that there would be approximately 249,000 fewer premature deaths, 45,000 fewer deaths from lung cancer, and 4.2 million fewer years of life lost. In addition, raising the minimum age would lead to improvements in maternal, fetal, and infant health outcomes by reducing the likelihood of maternal and paternal smoking. Specifically, if the minimum age were raised to 21 nationwide, the SimSmoke model projects that by 2100 there would be approximately 286,000 fewer pre-term births, 438,000 fewer cases of low birth weight, and roughly 4,000 fewer sudden infant death cases among mothers ages 15-49 (IOM report 2015External Web Site Policy).

How do smoking habits influence the initiation and promotion of lung carcinogenesis?

A two-stage clonal expansion (TSCE) model was used to analyze data from five large cohorts. The TSCE model, which is based on the biological paradigm of initiation, promotion, and progression in carcinogenesis, recognizes that carcinogenesis is a process of mutation accumulation and clonal expansion of partially altered cells on the pathway to malignancy. The model may be used to generate biological hypotheses regarding the mechanism of tobacco-induced lung cancer and to explore the extent to which projected risks depend on such biological mechanisms. The first study, using data from the British Doctors' cohort and two American Cancer Society Cohorts (Cancer Prevention Studies I and II), indicated that clonal expansion (promotion) of partially altered (initiated) cells by cigarette smoke is the dominant model mechanism (Hazelton, Clements, Moolgavkar 2005). A second study, based on analyses of data from the Nurses' Health and Health Professionals Follow-up Studies, confirmed these findings (Meza, Hazelton et al. 2008). The second study also showed that lung cancer incidence among non-smokers, continuing smokers, and ex-smokers was similar in these two cohorts, suggesting that there is little difference in lung cancer risk between men and women, whether related to smoking or not. These two studies show that the importance of smoking duration on lung cancer risk is a direct consequence of smoking-related promotion. These studies were also extended to analyze lung cancer mortality data from the Nurses' Health and Health Professionals Follow-up Studies (Hazelton, Jeon et al. 2012). These models served as central dose-response modules for several of the CISNET lung cancer models (Moolgavkar, Holford et al. 2012, Meza, ten Haaf et al. 2014).

What are the potential benefits associated with the use of low-nitrosamine smokeless tobacco products?

CISNET investigators from the Georgetown University convened expert panels to predict the mortality risks (Levy, Mumford et al. 2004) and impact on tobacco use (Levy, Mumford et al. 2006) in the United States of a "harm reduction" policy requiring that smokeless tobacco products meet low nitrosamine standards but could be marketed with a warning label consistent with the evidence of relative health risks. The panel concluded that low-nitrosamine smokeless tobacco products may have a substantially lower risk than smoking, and that the new policy could produce a modest acceleration in the decline in smoking prevalence over 5 years. Efforts to quantify the impact of policies of this type provide starting values for tobacco control modeling efforts, and provide a basis for furthering the public policy debate.

Model Profiles & Registry

Model profiles are standardized descriptions that facilitate the comparison of models and their results. The Joint Profile provided includes profiles for all lung cancer models. Individual profiles for each model are also provided and may be more current than the joint profile document.

For additional high-level information about the lung models visit the lung overview page on the CISNET Model Registry.