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Towards Personalised Screening for Lung Cancer: A Sex-Stratified Approach in a Danish Cohort Integrating Pre-Diagnostic Systemic Inflammatory Indexes with Smoking Status and Age
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DOI：10.1159/000551648.png)
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Abstract
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Introduction: Sex disparities in lung cancer risk assessment may lead to inequities in screening eligibility. Criteria based on smoking history and age can underrepresent women. Systemic inflammatory indexes derived from routine blood tests are potential biomarkers in cancer risk assessment. We investigated the association between systemic inflammatory indexes and lung cancer risk, stratified by sex, in a Danish cohort. Methods: We conducted a population-based cohort study using data from the Lolland-Falster Health Study (LOFUS) linked to the Danish Pathology Data Bank (Patobank). Participants aged 40-74 years without a history of lung cancer were included. We calculated four systemic inflammatory indexes and assessed their association with lung cancer using logistic regression models adjusted for age, sex, and smoking status. Optimal cut-off points were determined using the Youden index. Bootstrapping was applied for internal validation. Results: Among 10,887 participants with complete data, 58 (0.53%) were diagnosed with lung cancer during a maximum follow-up period of 6.6 years. High levels of all four inflammatory indexes were associated with increased lung cancer risk. Sex-stratified analyses revealed stronger associations between Neutrophil-to-Lymphocyte Ratio (NLR) and Systemic Immune Inflammatory Index (SII) and lung cancer in men, and between C-reactive protein to albumin ratio (CAR) and lung cancer in women. Model discrimination improved after adding inflammatory indexes. Conclusion: Our findings support sex-specific lung cancer risk assessment and personalised screening strategies. Pre-diagnostic inflammatory indexes may serve as biomarkers to complement existing screening criteria. Further research is needed to validate their potential in improving lung cancer prediction models. Lung cancer is the most common cause of cancer death worldwide. A way to find people at risk of developing lung cancer early is through special health checks. However, not everyone is invited to these checks. Today, the decision is mostly based on age and how much a person has smoked. These rules often leave women out, even though women can also get lung cancer with less smoking. One possible way to improve this process is to utilise information from simple blood tests that many people already undergo. These tests can measure changes in the blood linked to inflammation called inflammatory indexes. In our study, we followed more than 10,000 people in Denmark. We looked at their inflammatory indexes and checked who later developed lung cancer. We found that people with higher inflammation indexes were more likely to develop lung cancer. When we looked at women and men separately, some indexes worked better for men and others for women. This means that these indexes could help make early detection of lung cancer more accurate and more fair. They may help determine who should be invited for early checks, allowing both women and men at risk to be diagnosed and treated in time.
Keywords:
Lung cancer screening
Sex differences
Systemic inflammatory indexes
Lolland-Falster Health Study
Biomarkers
Personalised medicine
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