Small-cell Lung Cancer In Never-smokers Research Articles

Small-cell lung cancer in never-smokers

BackgroundLung cancer is a public health problem worldwide. Small-cell lung cancer (SCLC) is the most aggressive histologic type, with a 5-year survival <10%. SCLC is closely associated with tobacco consumption and infrequent in never-smokers. We aim to describe SCLC characteristics in never-smokers recruited in a radon-prone area.Patients and methodsWe designed a multicentric case series where SCLC cases were recruited consecutively following histologic confirmation. Detailed information was obtained for indoor radon exposure, occupation and environmental tobacco smoke. We also collected different clinical characteristics such as extended or limited disease at diagnosis.ResultsWe recruited 32 never-smoking SCLC cases. Median age was 75 years and 87.5% were women; 47% had extended disease. Median radon concentration was 182 Bq/m3. There were no statistically significant differences in residential radon concentration neither regarding age at diagnosis nor regarding sex. The most frequent symptoms were constitutional syndrome (23.1%) and coughing (23.1%). As much as 63% of cases had an Eastern Cooperative Oncology Group Study (ECOG) status of 0-2. The 1- and 2-year survival rates were 34.4% and 21.9%, respectively. The 2-year survival rate with a localized tumor was 26.7%, compared with 18.8% for extended disease.ConclusionsThese results show, for the first time, that indoor radon might not be associated with SCLC characteristics at diagnosis in never-smokers, and also confirms the low survival of this aggressive type of lung cancer also for never-smokers.

Clinical and Genomic Characteristics of Small Cell Lung Cancer in Never Smokers: Results From a Retrospective Multicenter Cohort Study

Small cell lung cancer (SCLC) has the strongest association with smoking among lung cancers. The characteristics of never smokers with SCLC is not known. Are the clinical characteristics, prognostic factors, survival, genomic alterations, and tumor mutational burdens of SCLC in patients who have never smoked different from those who have smoked? A retrospective multicenter cohort study of patients with clinician-confirmed SCLC was performed with the use of a longitudinal and nationally representative electronic medical records database. Smoking history was assessed through technology-enabled abstraction and confirmed for never smokers via chart review. Genomic characteristics of never smoker patients with SCLC were examined with the use of a next-generation sequencing-based gene panel and whole exome sequencing. One hundred of 5,632 patients (1.8%) with SCLC were never smokers. Relative to smokers, never smokers were more likely to be female (66.0%vs52.4%; P= .009) and present with extensive stage (70.0%vs62.2%; P= .028). Never smokers had a higher proportion of patients in age groups 35 to 49 years (7.0%vs3.0%; P= .006) and≥80 years (17.0%vs8.2%; P= .006). Known risk factors for lung cancer were found in<20%of never smokers. There were no overall survival differences between never smokers and smokers. Among patients with available genomic data (n= 9), never smoker SCLC were characterized by lower tumor mutational burden, a lower frequency of TP53 mutations, and an absence of mutational signatures related to tobacco exposure. The sex- and age-specific distribution of SCLC among never smokers, along with differences that were identified by genomic analyses, suggests a distinct biology of SCLC in never smokers compared with smokers.

Multigene Mutation Profiling and Clinical Characteristics of Small-Cell Lung Cancer in Never-Smokers vs. Heavy Smokers (Geno1.3-CLICaP)

Objectives: Lung cancer is a heterogeneous disease. Presentation and prognosis are known to vary according to several factors, such as genetic and demographic characteristics. Small-cell lung cancer incidence is increasing in never-smokers. However, the disease phenotype in this population is different compared with patients who have a smoking history.Material and Methods: To further investigate the clinical and genetic characteristics of this patient subgroup, a cohort of small cell lung cancer patients was divided into smokers (n = 10) and never/ever-smokers (n = 10). A somatic mutation profile was obtained using a comprehensive NGS assay. Clinical outcomes were compared using the Kaplan-Meier method and Cox proportional models.Results: Median age was 63 years (46–81), 40% were men, and 90% had extended disease. Smoker patients had significantly more cerebral metastases (p = 0.04) and were older (p = 0.03) compared to their non-smoker counterparts. For never/ever smokers, the main genetic mutations were TP53 (80%), RB1 (40%), CYLD (30%), and EGFR (30%). Smoker patients had more RB1 (80%, p = 0.04), CDKN2A (30%, p = 0.05), and CEBPA (30%, p = 0.05) mutations. Response rates to first-line therapy with etoposide plus cisplatin/carboplatin were 50% in smokers and 90% in never/ever smokers (p = 0.141). Median overall survival was significantly longer in never smokers compared with smokers (29.1 months [23.5–34.6] vs. 17.3 months [4.8–29.7]; p = 0.0054). Never/ever smoking history (HR 0.543, 95% CI 0.41–0.80), limited-stage disease (HR 0.56, 95% CI 0.40–0.91) and response to first-line platinum-based chemotherapy (HR 0.63, 95% CI 0.60–0.92) were independently associated with good prognosis.Conclusion: Our data supports that never/ever smoker patients with small-cell lung cancer have better prognosis compared to their smoker counterparts. Further, patients with never/ever smoking history who present with small-cell lung cancer have a different mutation profile compared with smokers, including a high frequency of EGFR, MET, and SMAD4 mutations. Further studies are required to assess whether the differential mutation profile is a consequence of a diverse pathological mechanism for disease onset.

Lung cancer in never smokers-the East Asian experience.

Approximately one third of all lung cancer patients in East Asia are never-smokers. Furthermore, the proportion of lung cancer in never smokers (LCINS) has been increasing over time. Never-smokers are more often diagnosed with adenocarcinoma in East Asia, a subtype largely defined by oncogenic drivers. In this subgroup of patients, as high as 90% of patients have been found to harbor well-known oncogenic mutations and can be successfully managed with targeted therapies inhibiting specific oncogenic mutant kinases. EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment has been the most important targeted therapy in lung adenocarcinoma from East Asian never-smokers as approximately 70% of these patients have the opportunity to receive EGFR-TKI treatment. Lung squamous cell carcinoma (SQCC) and small cell lung cancer (SCLC) are two common histologic types of smoking-related non-small cell lung cancer (NSCLC). The proportion of never-smokers with SQCC and SCLC in East Asian patients seems to be higher than that in Caucasian patients. Recent studies also suggest that lung SQCC and SCLC in never-smokers may be distinct subtypes. Therefore, better understanding of the biologic characteristics of these subtypes of patients may provide new insights for the treatment. In this review, we will provide an overview of East Asian experience in the treatment of advanced, never-smoking lung cancer, focusing on etiologic factors in the development of LCINS, targeted therapy for never-smokers with adenocarcinoma, distinct characteristics of never-smokers with lung SQCC and SCLC, and the role of immunotherapy in never-smokers with NSCLC.

Small-cell lung cancer detection in never-smokers: clinical characteristics and multigene mutation profiling using targeted next-generation sequencing

BackgroundOnce regarded as a smoker's disease, small-cell lung cancer (SCLC) has been occasionally detected in never-smokers as smoking rates decrease worldwide. We investigated the clinical and genetic characteristics of SCLC in never-smokers. Patients and methodsPatients diagnosed with SCLC were grouped into smokers and never-smokers. The clinical outcomes of the two groups were compared. For SCLC in never-smokers, somatic mutation profiling was carried out using the AmpliSeq™ Cancer Hotspot Panel v2 and semiconductor sequencing technology. Epidermal growth factor receptor (EGFR) mutation was confirmed by PNAClamp™. ResultsIn total, 391 SCLC patients treated over a 5-year period were analyzed. Fifty patients (13%) were never-smokers. The median overall survival was 18.2 months in never-smokers and 13.1 months in smokers (P = 0.054). Never-smoking history was independently a good prognostic factor [hazard ratio = 0.645, 95% confidence interval (CI) 0.456–0.914], as were limited disease (HR = 0.372, 95% CI 0.294–0.471), and lower age (HR = 0.709, 95% CI 0.566–0.888). The objective response rates to first-line etoposide/cisplatin therapy were similar between never-smokers and smokers (75% versus 81%). Of 28 genetically evaluable never-smokers, EGFR mutations were detected in four cases (two L858R, one deletion in exon 19, and one G719A). Other mutations were in TP53 (n = 26), RB1 (n = 7), PTEN (n = 5), MET (n = 4), and SMAD4 (n = 3). ConclusionsNever-smokers with SCLC are increasingly prevalent and have a better prognosis than smokers with SCLC in Korea. Our study warrants further investigation in this group.

Small-Cell Lung Cancer in Never-Smokers: A Case Series With Information on Family History of Cancer and Environmental Tobacco Smoke

Introduction The proportion of small-cell lung cancer (SCLC) has steadily decreased in the United States and Japan as the smoking rate has declined, currently representing approximately 13% to 20% of all ung cancers. Although the cause of the disease is closely associated with smoking, there are a small number of SCLC patients reported who never smoked. Non–small-cell lung cancer (NSCLC) in nevr-smokers has been studied intensively to date, and almost 80% of ncogenic mutations have been demonstrated in the molecular bioarkers which include epidermal growth factor receptor (EGFR),

Small-Cell Carcinoma With an Epidermal Growth Factor Receptor Mutation in a Never-Smoker With Gefitinib-Responsive Adenocarcinoma of the Lung

Activating mutations in the epidermal growth factor receptor (EGFR) gene are extremely rare in small-cell lung cancer (SCLC). Here, we present a case of an EGFR-mutant gefitinib-responsive non–small-cell lung cancer (NSCLC) of adenocarcinoma histology occurring in a never-smoker followed by subsequent diagnosis of metastatic SCLC carrying an EGFR mutation. Although gefitinib therapy of the primary NSCLC resulted in disease control for over 3 years, the patient subsequently developed metastatic SCLC to the liver. Epidermal growth factor receptor mutation analysis revealed that the exon 21 L858R activating mutation was present in both the original lung adenocarcinoma and the metastatic SCLC. We hypothesize that SCLC either evolved from the previously diagnosed NSCLC or that both arose from a common precursor. Further comparative molecular analysis of these histologically distinct tumors would be of value to better understand the potential role of EGFR in the pathogenesis of SCLC in never-smokers, and the role of selection for an EGFR-mutant SCLC subclone as an unusual mechanism of acquired resistance to EGFR inhibitors in NSCLC.

The combination of Young's syndrome and small cell lung cancer—A spiky connection?

Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma typically associated with smoking. The incidence of the disease has reduced in recent years in Western Europe as smoking habits have changed [1]. SCLC in never smokers is rare and aetiology unclear. Young's syndrome is another rare condition, characterized by chronic sinopulmonary infection and obstructive azoospermia. The pathobiology of this is also poorly understood. Here we describe a case of both Young syndrome and SCLC in a never smoker, and raise the possibility of a common aetiology underpinned by aberrant hedgehog signalling.