Clinical features of never smoker patients with lung squamous cell carcinoma: a retrospective multicenter study

Abstract

Background: Squamous cell carcinoma of the lung (LSCC) is the second most common histological subtype of non-small cell lung cancer (NSCLC) having smoking habit as the major risk factor. LSCC in non-smokers is an exceptional finding possibly related to professional exposure and subsequent carcinogenesis even though clinical and biological landscape is largely unexplored. Methods: This is a retrospective multicenter study investigating clinical features of never-smoker LSCC patients (pts) referred to three Italian Centers between 2010 and 2016. Relapse (RFS) or progression free (PFS) and overall (OS) survival curves were calculated by Kaplan-Meier method. Cox regression proportional hazards model was used to estimate the impact of covariates on OS. Results: Among 810 LSCC pts, 39(4,8%) occurred in never-smokers; our case series included 21 males and 18 females with a median age of 63 years. ECOG PS was 0-1 in 31(79%) pts. Median Charlson Comorbidity Index (CCI) was 7. Two(5%) pts referred second-hand smoking history and 13(33%) occupational exposure. Additional tumor history was reported by 18(46%) patients: head and neck (N=5), basocellular skin (N=5), breast (N=2), lung (N=2), prostate (N=1) cancer and leukemia (N=1). Molecular characterization was performed in 13(33%)pts: in two different pts were found a KRAS mutation and an ALK rearrangement, respectively; an EGFR mutation has been identified in 2 pts. Median time from symptoms appearance and diagnosis was 7 weeks. Thirteen (33%) pts showed a limited stage, while the other 26(67%) showed advanced/metastatic disease at the diagnosis. Nineteen(49%) pts received a first-line palliative chemotherapy (pct), mostly platinum-based doublets plus gemcitabine (N=11) or taxane (N=3), achieving a response rate and disease control rate of 37% and 58% respectively. Three patients harbouring a druggable molecular alteration were treated with gefitinib (N=2) and crizotinib (N=1), achieving partial response. Median RFS in resected patients (N=9) was 21 months. Median PFS and OS after firstline pct were 5months and 8.5 months respectively, without covariates impact. Conclusions: Never-smoker LSCC pts represent a rare subgroup characterized by more females, younger age and a not negligible CCI and second-tumor history compared with the known features of smoker LSCC. Molecular assessment should be considered. Treatment outcome after pct for advanced disease is still dismal as for most LSCC pts.