Clinical and genetic features of lung squamous cell cancer in never-smokers

Huang, Yongsheng; Wang, Rui; Pan, Yunjian; Zhang, Yang; Li, Hang; Cheng, Chao; Zheng, Deyou; Zheng, Shanbo; Li, Yuan; Hu, Haichuan; Cai, David; Wang, Shengfei; Zhang, Yawei; Xiang, Jiaqing; Sun, Yihua; Zhang, Jie; Chen, Haiquan

doi:10.18632/oncotarget.8745

Cited by 25 publications

(29 citation statements)

References 29 publications

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“…The overrepresentation of women in this group is also confirmed [7][8][9][10][11][12][14][15][16][17][18][20][21][22]24,26], and supports the notion of the presence of sex-based differences either in vulnerability to non-tobacco associated lung cancer or in exposure to other risk factors, such as environmental tobacco smoke. Due to observed sex imbalances, there has been considerable interest surrounding the possible role of oestrogen [6,9,34,35].…”

Section: Patient Characteristicssupporting

confidence: 72%

“…The observed higher proportion of both younger (<50 years) and older patients (80 years) among never-smoking has, to the best of our knowledge, never been observed before. However, there have also been reports of no differences in age and also the opposite, i.e., a younger age at diagnosis among never-smokers [7][8][9][10]14,15,[17][18][19][20][21][22]26]. None of the studies reporting an older age for never-smokers included an East Asian population.…”

Section: Patient Characteristicsmentioning

confidence: 99%

“…Several studies of different size and design have compared clinical lung cancer characteristics in never-smokers with that of ever-smokers, including assessments of survival . Most of these studies were hospital-based with data from only a small number of hospitals and the majority included less than 2000 lung cancer patients [8,10,12,[15][16][17][18][20][21][22]24,26]. Despite inconsistencies between studies, the collective evidence indicates that the pathogenesis and tumour biology of lung cancer differ by smoking history.…”

Section: Introductionmentioning

confidence: 99%

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Clinical characteristics and survival in non-small cell lung cancer patients by smoking history: a population-based cohort study

et al. 2019

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Introduction: Approximately, 10-15% of lung cancer patients have never smoked. Previous epidemiological studies on non-tobacco associated lung cancer have been hampered by selected data from a small number of hospitals or limited numbers of patients. By use of data from large population-based registers with national coverage, this study aims to compare characteristics and survival of patients with non-small cell lung cancer (NSCLC) with different smoking histories. Methods: Swedish national population-based registers were used to retrieve data on patients diagnosed with primary NSCLC between 2002 and 2016. The Kaplan-Meier method and Cox proportional hazard models were used to estimate overall survival and lung cancer-specific survival by smoking history. Results: In total, 41,262 patients with NSCLC were included. Of those, 4624 (11%) had never smoked. Never-smokers were more often women and older compared to ever smokers (current and former). Adenocarcinoma was proportionally more common in never-smokers (77%) compared to current (52%) and former smokers (57%). Stage IV disease was more common in neversmokers (57%) than in current (48%) and former smokers (48%). Epidermal growth factor receptor mutation was observed more in never-smokers (37%) compared to current (5%) and former smokers (9%). Both lung cancer-specific and overall survival were higher for never-smokers compared to current smokers. Conclusions: The observed differences in characteristics between never-smokers and smokers, and the higher survival in never-smokers compared to smokers from this large population-based study provide further evidence that lung cancer in never-smokers is clinically different to tobacco-associated lung cancer. The findings from this study emphasise the need for an improved understanding of genetics, pathogenesis, mechanisms and progression of non-tobacco associated lung cancer that may help prevent lung cancer or identify individually targeted treatments. ARTICLE HISTORY

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Section: Patient Characteristicssupporting

confidence: 72%

Section: Patient Characteristicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clinical characteristics and survival in non-small cell lung cancer patients by smoking history: a population-based cohort study

et al. 2019

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“…Compared with LUAD, patients with SCC in East Asian are the most suitable population for immunotherapy. Our previous study has shown that SCC in China are characterized by high proportion of never smoker, compared with the reported data of TCGA project from West SCC patients (18)(19)(20). This difference may add to the explanation of relatively low PD-L1 expression in East Asian SCC patients.…”

Section: Discussionmentioning

confidence: 84%

Unique distribution of programmed death ligand 1 (PD-L1) expression in East Asian non-small cell lung cancer

Pan

Zheng

et al. 2017

J. Thorac. Dis.

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Background: To determine the proportion and clinical features of programmed death ligand 1 (PD-L1) expression in East Asian non-small cell lung cancer (NSCLC).Methods: PD-L1 expression was assessed by immunohistochemistry (IHC) and tumor proportion score (TPS) with the use of PD-L1 IHC 22C3 antibody (Dako North America) in 108 surgically resected lung squamous cell carcinomas (SCC) and 221 lung adenocarcinomas (LUADs), and was correlated with clinical variables, histologic subtypes, and common driver mutations.Results: Positive PD-L1 expression was found in 37 lung SCC (37/108, 34.3%), including 15 cases with TPS ≥50% (15/108, 13.9%) and 22 cases with TPS <50% (22/108, 20.4%). In adenocarcinoma cohort, 9 cases were found PD-L1 expression positive (9/221, 4.1%), including 1 case with TPS ≥50% (1/221, 0.5%) and 8 cases with TPS <50% (8/221, 3.9%). Totally, high PD-L1 expression (TPS ≥50%) was significantly associated with male sex (P=0.026), current/ever smoking history (P=0.008) and SCC subtype (P<0.001).Positive PD-L1 expression (including TPS ≥50% and TPS <50% ) in LUAD cohort was significantly associated with male sex (P=0.046), current/ever smoking history (P=0.002), mutation pan-negative status (P=0.038), solid-predominant subtype (P<0.001), large tumor size (P=0.027) and lymph node metastasis (P=0.019). No significant difference was found between PD-L1 high expression group (TPS ≥50%) and low/ negative expression group in SCC cohort.Conclusions: This study revealed the unique distribution of PD-L1 expression in East Asian NSCLCs, which is largely different from Western populations. Since the high response rate of pembrolizumab in the treatment of lung cancer patients with PD-L1 TPS ≥50%, this result indicates that prospective PD-L1 expression testing in specific East Asian patients could facilitate decision making for immunotherapy.

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“…[20][21][22] We did not identify any EGFR mutations in the SCCs or LCNECs included in our study. However, both tumor types showed potential therapeutic targets such as mutations in MET and RET genes.…”

Section: Discussionmentioning

confidence: 99%

Next-Generation Sequencing Approach to Non–Small Cell Lung Carcinoma Yields More Actionable Alterations

Mehrad¹,

Bittar²,

Đačić

2017

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Different testing algorithms and platforms for EGFR mutations and ALK rearrangements in advanced-stage lung adenocarcinoma exist. The multistep approach with single-gene assays has been challenged by more efficient next-generation sequencing (NGS) of a large number of gene alterations. The main criticism of the NGS approach is the detection of genomic alterations of uncertain significance. Objective.— To determine the best testing algorithm for patients with lung cancer in our clinical practice. Design.— Two testing approaches for metastatic lung adenocarcinoma were offered between 2012–2015. One approach was reflex testing for an 8-gene panel composed of DNA Sanger sequencing for EGFR, KRAS, PIK3CA, and BRAF and fluorescence in situ hybridization for ALK, ROS1, MET, and RET. At the oncologist's request, a subset of tumors tested by the 8-gene panel was subjected to a 50-gene Ion AmpliSeq Cancer Panel. Results.— Of 1200 non–small cell lung carcinomas (NSCLCs), 57 including 46 adenocarcinomas and NSCLCs, not otherwise specified; 7 squamous cell carcinomas (SCCs); and 4 large cell neuroendocrine carcinomas (LCNECs) were subjected to Ion AmpliSeq Cancer Panel. Ion AmpliSeq Cancer Panel detected 9 potentially actionable variants in 29 adenocarcinomas that were wild type by the 8-gene panel testing (9 of 29, 31.0%) in the following genes: ERBB2 (3 of 29, 10.3%), STK11 (2 of 29, 6.8%), PTEN (2 of 29, 6.8%), FBXW7 (1 of 29, 3.4%), and BRAF G469A (1 of 29, 3.4%). Four SCCs and 2 LCNECs showed investigational genomic alterations. Conclusions.— The NGS approach would result in the identification of a significant number of actionable gene alterations, increasing the therapeutic options for patients with advanced NSCLCs.

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Clinical and genetic features of lung squamous cell cancer in never-smokers

Cited by 25 publications

References 29 publications

Clinical characteristics and survival in non-small cell lung cancer patients by smoking history: a population-based cohort study

Clinical characteristics and survival in non-small cell lung cancer patients by smoking history: a population-based cohort study

Unique distribution of programmed death ligand 1 (PD-L1) expression in East Asian non-small cell lung cancer

Next-Generation Sequencing Approach to Non–Small Cell Lung Carcinoma Yields More Actionable Alterations

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