Tumor mutational burden by smoking status in small cell lung cancer: Insights from a limited cohort.

Abstract

e20122 Background: Tumor mutational burden (TMB) is a potential biomarker in small cell lung cancer (SCLC) and is often influenced by tobacco exposure. We evaluated the relationship between TMB and smoking history in publicly available SCLC datasets, acknowledging the limited sample size. Methods: We analyzed 120 patients with SCLC (median age 65 years; 76 male, 44 female). Smoking status was categorized as current (n=56), former (n=47), or never (n=3); 14 patients with missing smoking data were excluded from analyses. TMB was obtained from whole-genome sequencing, with a median of 7.5 mutations per megabase (range 0–24.43). TMB was compared between ever-smokers (current or former) and never-smokers using the Mann–Whitney U test. Correlation between TMB and reported pack-years was assessed using Spearman’s rank correlation. Results: Median TMB in ever-smokers was 7.5 (mean 8.19, range 0–24.43) versus 7.63 (mean 8.36, range 0–17.43) in never-smokers (Mann–Whitney U p=0.980). There was a weak, non-significant correlation between TMB and pack-years (Spearman rho=0.12, p=0.294). Exploratory survival analyses were not performed due to the limited sample size and incomplete treatment annotation. Conclusions: In this limited public SCLC cohort, no clear association between smoking history and TMB was observed. These findings should be interpreted cautiously given the small number of never-smokers and highlight the need for larger studies to evaluate the impact of tobacco exposure on TMB and its potential clinical relevance.