Low-Dose CT Screening in East Asian Women Who Have Never Smoked: Association Between Family History of Lung Cancer and Ground-Glass Nodule Prevalence and Growth

Academic Background

Lung cancer is the leading cause of cancer-related mortality worldwide, and smoking is a well-established risk factor for lung cancer. Low-dose CT (LDCT) is an effective tool for early screening of lung cancer in smokers. However, global statistics estimate that approximately 25% of lung cancer cases occur in individuals who have never smoked, with over one-third of non-small cell lung cancer (NSCLC) cases in Asian patients occurring in non-smokers. Additionally, individuals who have never smoked account for one-third of lung cancer deaths. This highlights a significant gap in lung cancer screening for non-smokers compared to the established LDCT screening programs for smokers.

In Asia, the tobacco-attributable fraction of lung cancer is lower among women (58%) than among men (81%), and over 50% of lung cancers in Asian women occur in individuals who have never smoked. A recent meta-analysis showed that the relative risk of lung cancer detected via LDCT screening was substantially higher in Asian women who had never smoked than in men with or without a history of smoking. The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) prospectively demonstrated a high rate of cancer detection among female participants, particularly those with a family history of lung cancer (FHLC). These findings emphasize the need for Asian-specific lung cancer risk models and screening programs tailored to the unique epidemiologic characteristics of this population.

Source of the Paper

This paper was co-authored by Ji Young Lee, Seung Ho Choi, Hyungjin Kim, Jin Mo Goo, and Soon Ho Yoon from the Department of Radiology at Seoul National University Hospital and was published in Radiology, Volume 313, Issue 3, 2024. The study was supported by a research program funded by Seoul National University Hospital (Grant No. 05-2023-0010).

Research Objective

This study aimed to investigate the differences in the progression of ground-glass nodules (GGNs) to lung cancer in East Asian women who have never smoked, with and without FHLC, and to examine the associations between FHLC and GGN prevalence and growth.

Research Methods

Study Population

This single-center retrospective study included East Asian women who underwent baseline LDCT for health checkups at Seoul National University Hospital between January 2011 and December 2015. Exclusion criteria were a personal history of lung cancer or a current or past history of smoking. A total of 10,151 patients were included, of whom 694 (6.8%) reported FHLC and 9,457 (93.2%) did not.

Identification and Assessment of GGNs

Throughout the study period, board-certified radiologists interpreted chest CT scans and wrote formal reports. GGNs included part-solid GGNs (with both ground-glass and solid components) and pure GGNs (without any completely solid components). The study coordinator searched CT reports using keywords to identify the presence of GGNs. Lesion persistence was confirmed through multiple CT scans of the same patient. According to the Fleischner Society guidelines, follow-up CT was recommended 3 months to 1 year after the initial detection of a GGN. If the lesion persisted at the first follow-up, annual follow-up CT was recommended.

Data Analysis

Patients were categorized based on the presence or absence of FHLC. The χ2 test or Fisher exact test and the two-sample t test or Mann-Whitney U test were used to compare categorical and continuous data, respectively. The χ2 test was used to compare the persistence, multiplicity, and growth of GGNs and the incidence of lung cancer. Univariable and multivariable logistic regression analyses were performed to explore potential associations between baseline characteristics and the prevalence of persistent and multiple GGNs. For GGN growth, Kaplan-Meier plots were constructed, and the log-rank test was used to compare the cumulative incidence of GGN growth between patients with and without FHLC. Univariable and multivariable Cox regression analyses were performed to evaluate the prognostic utility of FHLC for GGN growth.

Research Results

Baseline Characteristics and GGN and Lung Cancer Outcomes

Among the 10,151 patients, 515 (5.1%) had persistent GGNs, 199 (2.0%) had multiple GGNs, 49 (0.5%) experienced GGN growth, and 31 (0.3%) were diagnosed with lung cancer. Patients with FHLC had a significantly higher prevalence of persistent GGNs (8.2% vs. 4.8%), multiple GGNs (3.7% vs. 1.8%), GGN growth (1.3% vs. 0.4%), and lung cancer incidence (0.9% vs. 0.3%) compared to those without FHLC.

Association Between GGN Growth and Lung Cancer

In multivariable analysis, FHLC was associated with an increased prevalence of persistent GGNs (OR, 1.69; p < .001) and multiple GGNs (OR, 2.02; p = .001) and was an independent risk factor for GGN growth over a 10-year period (HR, 2.14; p = .04).

Conclusion

In East Asian women who have never smoked, FHLC was associated with an increased prevalence of persistent and multiple GGNs and was an independent risk factor for GGN growth over a 10-year period. This suggests that tailored CT screening and management strategies are needed for this high-risk population to improve early detection and treatment of lung cancer, ultimately prolonging survival.

Research Highlights

1. Key Findings: FHLC significantly increased the prevalence of persistent and multiple GGNs in East Asian women who have never smoked and was an independent risk factor for GGN growth.
2. Methodological Innovation: This study is the first to systematically investigate the impact of FHLC on GGN growth and lung cancer development, filling a gap in the field.
3. Application Value: The findings provide important evidence for developing lung cancer screening strategies tailored to East Asian women who have never smoked, helping to improve early diagnosis and treatment outcomes.

Other Valuable Information

The study also found that personal or family history of other cancers was associated with the persistence of GGNs but not with GGN growth. This suggests that future research should further explore the potential role of these factors in lung cancer screening. Additionally, the study highlights the importance of avoiding overdiagnosis in lung cancer screening, particularly in the management of GGNs.