Researchers develop lung cancer risk prediction model for never smokers

Researchers have developed a new personalized assessment tool that could more accurately predict lung cancer risk in never, light, and heavy smokers using a large Taiwanese prospective cohort study, according to data published online in Nature’s Scientific Reports.

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This study is the first to develop a tool for personalized risk assessment in never smokers in a large prospective cohort design.

This study is the first to develop a tool for personalized risk assessment in never smokers in a large prospective cohort design.

This study, from The University of Texas MD Anderson Cancer Center, is the first to develop a tool for personalized risk assessment in never smokers in a large prospective cohort design. By incorporating risk factors in addition to smoking history, this tool is better able to classify those in greatest need of lung cancer screening and reduce false positives.

The American Cancer Society estimates that 224,390 people will be diagnosed with lung cancer this year in the United States and 158,080 will die from the disease. While the majority of these cases will be diagnosed in smokers, as many as 20% of lung cancers in the US occur in those who do not smoke.

“Currently, there are no criteria to select high-risk individuals for lung cancer in never smokers,” explains lead author Xifeng Wu, MD, PhD, professor of Epidemiology. “Lung cancer screening criteria is based only on age and smoking information, but from this study we can differentiate risk in those who have never smoked in addition to light and heavy smokers.”

Based on the results of the National Lung Screening Trial (NLST), low-dose computed tomography (LDCT) lung cancer screening is recommended for individuals between the ages of 55 and 74 with a smoking history of 30 pack-years, which is defined as smoking one pack per day for 30 years. Thus, light and never smokers would not normally be candidates for lung cancer screening.

However, according to Dr. Wu, roughly only one-quarter of lung cancers diagnosed in the US meet the strict screening criteria from the NLST, indicating a need for better risk stratification across all smoking types.

In this study, researchers analyzed a prospective cohort of 395,875 participants in Taiwan, recruited by MJ Health Group to participate in a health-screening program across Taiwan. Mean age of the participants was 40.4 and 52% of the cohort was female. Heavy smokers were classified as those with a smoking history of 30 pack-years or greater, and light smokers had less than a 30 pack-year history.

These analyses were conducted after a median 7.3 years of follow-up. Among the participants, 1,117 cases of lung cancer were diagnosed at a mean age of 60.2. Forty-seven percent of the lung cancers were diagnosed in never-smokers, which constituted 71% of the participants, and 38% of the lung cancers occurred in females.

In addition to age, gender, and smoking history, the researchers incorporated personal and family cancer history, body mass index, a lung function test, and four blood biomarkers to determine five- and 10-year risk probabilities for never, light, and heavy smokers.

In the current study, the 5-year estimated risk of lung cancer ranged from 0.01% to 15.82% in never smokers, from 0% to 7.39% in light smokers, and from 0.02% to 7.48% in heavy smokers.

The 10-year estimated risks ranged from 0.02% to 32.97% in never smokers, from 0.01% to 16.31% in light smokers, and 0.06% to 18.13% in heavy smokers.

“Our model was able to stratify light and never smokers into groups with dramatically different probabilities of developing lung cancer over time. According to our results, a small number of never smokers have lung cancer risks as high as some heavy smokers,” Dr. Wu points out.

These findings highlight varying degrees of risk across each type of smoker, underscoring the need to consider alternative factors when recommending LDCT screening for lung cancer, explains Dr. Wu. Through more accurate classification of lung cancer risk, the researchers hope to reduce unnecessary screening and false positives in lower-risk smokers and improve screening for high-risk non-smokers.

Despite the large number of participants included in this study, the findings are limited by studying a distinct Taiwanese population. Additional validations in independent cohorts will be necessary to determine the true predictive ability of this model across non-Asian populations, notes Dr. Wu, who is actively working to identify appropriate cohorts for future studies.

Other MD Anderson authors on the study include: Yuanqing Ye, PhD, Xia Pu, PhD, Wong-Ho Chow, PhD, Chad Huff, PhD, Sonia Cunningham, PhD, Maosheng Huang, MD, and Jian Gu, PhD, all of Epidemiology; Jack A. Roth, MD, Thoracic and Cardiovascular Surgery. Additional authors include: Chi Pang Wen, MD, DrPH, MinKwang Tsai, and Shuanbei Wu, all of National Health Research Institutes, Zhunan, Taiwan and China Medical University Hospital, Taichung, Taiwan; Christopher Wen, MD, University of California at Irvine; Chwen Keng Tsao, MJ Health Management Institution, Taipei, Taiwan; and Scott M. Lippman, MD, UC San Diego Moores Cancer Center.

The work was supported by The University of Texas MD Anderson Cancer Center Research Trust, The Center for Translational and Public Health Genomics, Duncan Family Institute for Cancer Prevention and Risk Assessment, The University of Texas MD Anderson Cancer Center, and Taiwan Department of Health Clinical Trial and Research Center of Excellence (DOH101-TD-B-111-004).