Clinical Features of Never Smoker Patients with Lung Squamous Cell Carcinoma: a Retrospective Multicenter Study

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 791 LSCC pts, 37(4,6%) occurred in never-smokers; our case series included 19 males and 18 females with a median age of 63 years. ECOG PS was 0-1 in 30(81%) pts. Median Charlson Comorbidity Index (CCI) was 6. Two (5%) pts referred second-hand smoking history and 13(35%) occupational exposure. Additional tumor history was reported by 15(41%) patients: head and neck (N=4), basocellular skin (N=5), breast (N=2), lung (N=2), prostate (N=1) cancer and leukemia (N=1). Molecular characterization was performed in 12(32%)pts: EGFR and KRAS mutations were found in 2 and 1 pts respectively. Median time from symptoms appearance and diagnosis was 7 weeks. Twelve (32%) pts showed a limited stage, while the other 25(68%) showed advanced/metastatic disease at the diagnosis. Nineteen (52%) 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. Median RFS in resected patients (N=9) was 21 months. Median PFS and OS after first-line pct were 5 months and 8.5 months respectively. No covariate significantly impacted on OS. 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. Treatment outcome of advanced disease is still dismal as for most LSCC pts. Legal entity responsible for the study: Istituto Oncologico Veneto IRCCS Funding: None Disclosure: All authors have declared no conflicts of interest.