Molecular profile analysis of non-small cell lung cancer (NSCLC) in straw and string cigarette users

Keywords

NSCLC - KRAS - straw cigarette - genomic profiling

Introduction: Tobacco-related lung cancer harbors elevated PD-L1 expression, with KRAS as the main driver mutation, present in about 30% of smokers and around 13% having the KRAS G12C mutation. Tobacco can be consumed in straw cigarettes, a type of roll-your-own cigarette made from cornhusk. In clinical practice, the overall perception is that straw cigarette users are more debilitated with worse performance status than paper cigarette users. This observation prompted the question of whether their molecular impact on lung cancer differs or is more pronounced compared to paper cigarette users. We hypothesized that straw or string cigarette users have a significantly higher incidence of KRAS, STK11 and KEAP1 mutations, as well as higher PD-L1 expression, compared to the literature on paper cigarette smokers.

Methods: We conducted a retrospective multicenter study of current or former straw or string cigarette smokers with molecularly evaluated NSCLC. This is the first analysis of this cohort, focused on describing the molecular alterations in this population. Data was extracted from electronic medical records and entered RedCAP. We hypothesized that the incidence of KRAS mutations would be 40% among 172 patients, assuming a statistically significant p-value of 0.05, using 30% as the expected KRAS mutation range of paper-cigarette smokers.

Results: 132 NSCLC patients were included. Median age to start smoking was 16 years, with an average of 48 years of tobacco use and a median of 5 straw cigarettes per day. Most patients were diagnosed as stage 4 (60.6%). Most common metastatic sites were the lung (33%), bones (28%) and central nervous system (23.5%). Sequencing platforms for the molecular analysis: Basic Platform, Foundation One, Oncofoco and others (41.7%, 38.5%, 8%, and 11%, respectively). KRAS mutations were identified in 53.3% of the cohort, with KRAS G12C being the most common alteration (46.9%). STK11 was mutated in 26.7%, KEAP1 in 24.4% and TP53 was mutated in 33%. PD-L1 was negative in 41% of the cases, whereas 27.6% had PD-L1 ≥ 50%. Lastly, 44% of patients had known driver mutations: EGFR 17,4%, BRAF 6,1%, HER2 5,3%, ALK rearrangements 3%, ROS1 1,5%, MET, NTRK and RET 0,8%.

Conclusion: Our data analysis revealed that the prevalence of KRAS mutations in NSCLC among straw cigarette smokers is significantly higher than the initially hypothesized 40%. STK11 and KEAP1 mutations were also more frequent.

Corresponding author: Beatriz de Menezes Dobbert (e-mail: [e-mail]).