Targeted Tissue and Cell-Free Tumor DNA Sequencing of Advanced Lung Squamous-Cell Carcinoma Reveals Clinically Significant Prevalence of Actionable Alterations.


BACKGROUND:Major guidelines do not recommend routine molecular profiling of lung squamous-cell carcinoma (LUSC) because the prevalence of actionable alterations is thought to be low. Increased utilization of next-generation sequencing (NGS), particularly with cell-free circulating tumor DNA, facilitates reevaluation of this premise. PATIENTS AND METHODS: We retrospectively evaluated the prevalence of actionable alterations in 2 distinct LUSC cohorts totaling 492 patients. A total of 410 consecutive patients with stage 3B or 4 LUSC were tested with a targeted cell-free circulating DNA NGS assay, and 82 patients with LUSC of any stage were tested with a tissue NGS cancer panel. RESULTS:In the overall cohort, 467 patients (94.9%) had a diagnosis of LUSC, and 25 patients (5.1%) had mixed histology with a squamous component. A total of 10.5% of the LUSC subgroup had somatic alterations with therapeutic relevance, including in EGFR (2.8%), ALK/ROS1 (1.3%), BRAF (1.5%), and MET amplification or exon 14 skipping (5.1%). Sixteen percent of patients with mixed histology had an actionable alteration. In the LUSC subgroup, 3 evaluable patients were treated with targeted therapy for an actionable alteration; all of them experienced partial response. CONCLUSION:In this large, real-world LUSC cohort, we observed a clinically significant prevalence of actionable alterations. Accurate local histopathologic assessment in advanced-stage LUSC can be challenging. Further evaluation of the genomic landscape in this setting is warranted to potentially identify underappreciated treatment options.


Clin Lung Cancer


Clinical lung cancer


Lam VK,Tran HT,Banks KC,Lanman RB,Rinsurongkawong W,Peled N,Lewis J,Lee JJ,Roth J,Roarty EB,Swisher S,Talasaz A,Futreal PA,Papadimitrakopoulou V,Heymach JV,Zhang J




Has Abstract


2019-01-01 00:00:00














  • Recent Advances and Future Strategies for Immune-Checkpoint Inhibition in Small-Cell Lung Cancer.

    abstract::Small-cell lung cancer (SCLC) is distinguished from non-small-cell lung cancer by its rapid growth and more frequent metastases. Although patients with SCLC are highly responsive to chemotherapy and radiation therapy, long-term prognosis remains poor, with relapse and disease recurrence occurring in almost all cases. ...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章,评审


    authors: Chae YK,Pan A,Davis AA,Mohindra N,Matsangou M,Villaflor V,Giles F

    更新日期:2017-03-01 00:00:00

  • Computed tomography screening for lung cancer: applicability of an international protocol in a single-institution environment.

    abstract:BACKGROUND:The purpose of this study was to assess the applicability of an annual low-dose computed tomography (CT) screening program for lung cancer in a single institution in Israel, which has a relatively lower prevalence of lung cancer compared with other Western countries, and to examine stage distribution of dete...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章


    authors: Shaham D,Breuer R,Copel L,Agid R,Makori A,Kisselgoff D,Goitein O,Izhar U,Berkman N,Heching N,Sosna J,Bar-Ziv J,Libson E

    更新日期:2006-01-01 00:00:00

  • Detection of EGFR-Activating and T790M Mutations Using Liquid Biopsy in Patients With EGFR-Mutated Non-Small-Cell Lung Cancer Whose Disease Has Progressed During Treatment With First- and Second-Generation Tyrosine Kinase Inhibitors: A Multicenter Real-Li

    abstract:BACKGROUND:In advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients whose disease has progressed during treatment with first- and second-generation tyrosine kinase inhibitors (TKIs), liquid biopsy (LB) is routinely used to evaluate the presence of EGFR T790M as an acquired...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章


    authors: Minari R,Mazzaschi G,Bordi P,Gnetti L,Alberti G,Altimari A,Gruppioni E,Sperandi F,Parisi C,Guaitoli G,Bettelli S,Longo L,Bertolini F,Pagano M,Bonelli C,Tagliavini E,Nicoli D,Ubiali A,Zangrandi A,Trubini S,Proietto

    更新日期:2020-09-01 00:00:00

  • Location Matters: Stage I Non-Small-cell Carcinomas of the Lower Lobes Treated With Stereotactic Body Radiation Therapy Are Associated With Poor Outcomes.

    abstract:INTRODUCTION:The lung is a heterogeneous organ with relative overperfusion of the lung bases. We determined whether a lower lobe primary tumor location was associated with poor outcomes in the setting of stage I non-small-cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). PATIENTS AND ME...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章


    authors: Shaverdian N,Veruttipong D,Wang J,Kupelian P,Steinberg M,Lee P

    更新日期:2017-03-01 00:00:00

  • CHAMP: A Phase II Study of Panitumumab With Pemetrexed and Cisplatin Versus Pemetrexed and Cisplatin in the Treatment of Patients With Advanced-Stage Primary Nonsquamous Non-Small-Cell Lung Cancer With Particular Regard to the KRAS Status.

    abstract:INTRODUCTION:The aim of the study was to investigate the efficacy and tolerability of panitumumab, a fully human antiepidermal growth factor receptor monoclonal antibody, in combination with pemetrexed/cisplatin in patients with stage IIIB to IV primary nonsquamous non-small-cell lung cancer and wild type V-Ki-ras2 Kir...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章,随机对照试验


    authors: Schuette W,Behringer D,Stoehlmacher J,Kollmeier J,Schmager S,Fischer von Weikersthal L,Schumann C,Buchmann J

    更新日期:2015-11-01 00:00:00

  • Efficacy and Safety of Lorlatinib in Korean Non-Small-Cell Lung Cancer Patients With ALK or ROS1 Rearrangement Whose Disease Failed to Respond to a Previous Tyrosine Kinase Inhibitor.

    abstract:INTRODUCTION:Non-small-cell lung cancer (NSCLC) patients harboring ALK or ROS1 rearrangements invariably acquire resistance to the first- and second-generation tyrosine kinase inhibitors (TKIs), most notably ALK G1202R and ROS1 G2032R. Lorlatinib, a novel third-generation TKI, produced remarkable results from the first...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章


    authors: Lee J,Sun JM,Lee SH,Ahn JS,Park K,Choi Y,Ahn MJ

    更新日期:2019-05-01 00:00:00

  • Cancer treatments: can we find treasures at the bottom of the sea?

    abstract::Because of the poor results observed after platinum-based first-line chemotherapy, research on new strategies for second-line treatment of advanced non-small-cell lung cancer (NSCLC) is warranted. Current research focuses on the development of new agents and the assessment of a combination of therapies, especially tho...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章,评审


    authors: Provencio M,Sánchez A,Gasent J,Gómez P,Rosell R

    更新日期:2009-07-01 00:00:00

  • Immune modulation as a therapeutic strategy for non-small-cell lung cancer.

    abstract::Active tumor immunotherapy may provide hope for patients with non-small-cell lung cancer (NSCLC) because, in more than 20 years, current therapies have yet to change mortality statistics. Creating an efficacious vaccine involves selection of important tumor antigens and formulation of their immunogenic epitopes into a...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章,评审


    authors: Holt GE,Disis ML

    更新日期:2008-02-01 00:00:00

  • Effect of a Rule-in Biomarker Test on Pulmonary Nodule Management: A Survey of Pulmonologists and Thoracic Surgeons.

    abstract:INTRODUCTION:The field of biomarker development is evolving to assist in determining benign from malignant pulmonary nodules. Although a prospective clinical utility would best to show how a biomarker affects patient treatment and outcomes, we sought to begin to understand how the results might alter management by dete...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章


    authors: Tanner NT,Brasher PB,Jett J,Silvestri GA

    更新日期:2020-03-01 00:00:00

  • The Clinical Use of Genomic Profiling to Distinguish Intrapulmonary Metastases From Synchronous Primaries in Non-Small-Cell Lung Cancer: A Mini-Review.

    abstract::The ability to reliably distinguish synchronous primary non-small-cell lung cancer (NSCLC) from intrapulmonary metastatic spread affects staging and treatment decisions in resected NSCLC. Adjuvant therapy for early-stage NSCLC is complicated and recommendations are primarily based on older data from trials that used n...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章,评审


    authors: Klempner SJ,Ou SH,Costa DB,VanderLaan PA,Sanford EM,Schrock A,Gay L,Ali SM,Miller VA

    更新日期:2015-09-01 00:00:00

  • Survival Outcomes Among Lung Cancer Patients Treated Using a Multidisciplinary Team Approach.

    abstract:BACKGROUND:Evidence favoring a multidisciplinary team (MDT) approach in the treatment of lung cancer is scarce, especially in the United States. The purpose of the present investigation was to evaluate survival outcomes of lung cancer patients treated with an MDT compared with a traditional care model. PATIENTS AND ME...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章


    authors: Bilfinger TV,Albano D,Perwaiz M,Keresztes R,Nemesure B

    更新日期:2018-07-01 00:00:00

  • Developing an effective lung cancer program in a community hospital setting.

    abstract::Lung cancer remains the number one cause of cancer-based mortality in men and women. The importance of proper lung cancer care outside of major academic centers cannot be overemphasized because the vast majority of lung cancer care occurs in community hospital settings. We have had the opportunity to develop a highly ...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章


    authors: Fischel RJ,Dillman RO

    更新日期:2009-07-01 00:00:00

  • Stereotactic Body Radiotherapy for Early-Stage Multiple Primary Lung Cancers.

    abstract:BACKGROUND:Patients with multiple primary lung cancers increasingly receive multiple courses of stereotactic body radiotherapy (SBRT). We aimed to clarify the efficacy and safety of such treatments. PATIENTS AND METHODS:We reviewed a prospective lung SBRT database of patients treated for stage I non-small-cell lung ca...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章


    authors: Nikitas J,DeWees T,Rehman S,Abraham C,Bradley J,Robinson C,Roach M

    更新日期:2019-03-01 00:00:00

  • External Validation of the New International Association for the Study of Lung Cancer Tumor, Node, and Metastasis 8th Edition Staging System and Updated T Descriptors in Determining Prognosis for Patients With Non-Small Cell Lung Cancer Patients With N3 D

    abstract:OBJECTIVE:The objective of this study is to externally validate the 8th Edition of the Tumor, Node, and Metastasis staging system and its updated T descriptors in patients with non-small cell lung cancer with N3 disease. METHODS:Data were extracted from the Surveillance, Epidemiology, and End Results database. Chi-squ...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章


    authors: Shin JY,Yoon JK,Marwaha G

    更新日期:2017-11-01 00:00:00

  • Third-line chemotherapy in small-cell lung cancer: an international analysis.

    abstract:INTRODUCTION:Small-cell lung cancer is an aggressive disease for which the mainstay of treatment is chemotherapy. Despite good initial responses most patients will relapse. Some will receive second-line therapy with clinical benefit, but for third-line chemotherapy there is little evidence to guide treatment decisions ...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章,多中心研究


    authors: Simos D,Sajjady G,Sergi M,Liew MS,Califano R,Ho C,Leighl N,White S,Summers Y,Petrcich W,Wheatley-Price P

    更新日期:2014-03-01 00:00:00

  • Association Between Clinical Tumor Burden and Efficacy of Immune Checkpoint Inhibitor Monotherapy for Advanced Non-Small-Cell Lung Cancer.

    abstract:BACKGROUND:Programmed cell death 1 (PD-1) inhibitors have become a standard treatment, albeit not completely effective, for patients with advanced non-small-cell lung cancer (NSCLC). Previous studies of advanced melanoma have revealed that the tumor burden predicted the response to PD-1 inhibitors, although this relati...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章


    authors: Miyawaki T,Kenmotsu H,Mori K,Miyawaki E,Mamesaya N,Kawamura T,Kobayashi H,Omori S,Wakuda K,Ono A,Naito T,Murakami H,Harada H,Endo M,Ohde Y,Takahashi K,Takahashi T

    更新日期:2020-09-01 00:00:00

  • Current development of adjuvant treatment of non-small-cell lung cancer.

    abstract::Although radical surgery remains the mainstay therapeutic modality for early-stage non-small-cell lung cancer (NSCLC), long-term survival of patients with completely resected NSCLC tumors remains suboptimal. Globally, the 5-year survival rate of patients who undergo complete surgical resection is in the range of 40%-5...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章,评审


    authors: Scagliotti GV,Novello S

    更新日期:2004-12-01 00:00:00

  • Total videothoracoscopic lobectomy versus open thoracotomy for early-stage non small-cell lung cancer.

    abstract::Lobectomy remains the standard procedure for early-stage non small-cell lung cancer (NSCLC). Advances in minimally invasive surgery allow lobectomy to be performed by videothoracoscopy (VATSLOBE). The objective of this study was to compare open thoracotomy (OPENLOBE) to VATSLOBE in the treatment of early-stage NSCLC. ...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章


    authors: Luketich JD,Meehan MA,Landreneau RJ,Christie NA,Close JM,Ferson PF,Keenan RJ,Belani CP

    更新日期:2000-08-01 00:00:00

  • Efficacy of Nivolumab and Pembrolizumab in Patients With Advanced Non-Small-Cell Lung Cancer Needing Treatment Interruption Because of Adverse Events: A Retrospective Multicenter Analysis.

    abstract:INTRODUCTION:The programmed death 1 antibodies (PD-1 Ab) nivolumab and pembrolizumab improve overall survival (OS) in advanced non-small-cell lung cancer (NSCLC). We evaluated the correlation between immune-related adverse events (irAE) and treatment interruption due to irAE on clinical efficacy of PD-1 Ab in advanced ...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章,多中心研究


    authors: Ksienski D,Wai ES,Croteau N,Fiorino L,Brooks E,Poonja Z,Fenton D,Geller G,Glick D,Lesperance M

    更新日期:2019-01-01 00:00:00

  • Thoracic Oncology Multidisciplinary Clinic Reduces Unnecessary Health Care Expenditure Used in the Workup of Patients With Non-small-cell Lung Cancer.

    abstract:BACKGROUND:National costs of lung cancer care exceed $12 billion. We investigate the resource-savings benefit of a single-day thoracic oncology multidisciplinary clinic (MDC) in the diagnostic period prior to non-small-cell lung cancer (NSCLC) treatment. MATERIALS AND METHODS:From July 2007 to January 2015, patients w...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章


    authors: Voong KR,Liang OS,Dugan P,Torto D,Padula WV,Senter JP,Lang M,Hooker CM,Feliciano J,Broderick S,Yarmus L,Khanna K,Narang A,Hales RK

    更新日期:2019-07-01 00:00:00

  • Prognostic Impact of Programmed Death-ligand 1 and Surrounding Immune Status on Stage I Lung Cancer.

    abstract:BACKGROUND:The programmed death 1/programmed death-ligand 1 (PD-L1) pathway reportedly is as an important factor determining effects of immunotherapy; however, its prognostic impact is controversial, and its association with the surrounding immune microenvironment has not yet been elucidated. PATIENTS AND METHODS:We r...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章


    authors: Handa Y,Tsutani Y,Shiroma N,Kai Y,Mimae T,Miyata Y,Takeshima Y,Arihiro K,Okada M

    更新日期:2020-07-01 00:00:00

  • Prognostic Impact and Risk Factors of Immune-Related Pneumonitis in Patients With Non-Small-Cell Lung Cancer Who Received Programmed Death 1 Inhibitors.

    abstract:INTRODUCTION:Pneumonitis is one of the immune-related adverse events of programmed death 1 (PD-1) inhibitors that sometimes cause lethal outcomes. Although some recent reports have described PD-1 inhibitors as more effective in non-small-cell lung cancer (NSCLC) patients with immune-related adverse events than in those...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章,多中心研究


    authors: Fukihara J,Sakamoto K,Koyama J,Ito T,Iwano S,Morise M,Ogawa M,Kondoh Y,Kimura T,Hashimoto N,Hasegawa Y

    更新日期:2019-11-01 00:00:00

  • Programmed Death-Ligand 1 Expression Predicts Tyrosine Kinase Inhibitor Response and Better Prognosis in a Cohort of Patients With Epidermal Growth Factor Receptor Mutation-Positive Lung Adenocarcinoma.

    abstract:BACKGROUND:The immune checkpoint proteins programmed death-1/ligand (PD-1/PD-L1) play a critical role in immune escape of tumor cells. In models of epidermal growth factor receptor (EGFR)-driven non-small-cell lung cancer (NSCLC), EGFR signal upregulates PD-1/PD-L1. However, data on the clinical significance of PD1/PD-...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章


    authors: Lin C,Chen X,Li M,Liu J,Qi X,Yang W,Zhang H,Cai Z,Dai Y,Ouyang X

    更新日期:2015-09-01 00:00:00

  • Moderately Hypofractionated Helical IMRT, FDG-PET/CT-guided, for Progressive Malignant Pleural Mesothelioma in Patients With Intact Lungs.

    abstract:INTRODUCTION:The objective of this study was to present the outcomes of moderately hypofractionated helical intensity-modulated radiation therapy (HT) with/without simultaneous integrated boost (SIB) on fluorodeoxyglucose-positron emission tomography (FDG-PET) positive areas (gross tumor volume [GTV]-PET) for patients ...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章


    authors: Fodor A,Broggi S,Incerti E,Dell'Oca I,Fiorino C,Samanes Gajate AM,Pasetti M,Cattaneo MG,Passoni P,Gianolli L,Calandrino R,Picchio M,Di Muzio N

    更新日期:2019-01-01 00:00:00

  • Results from a single institution phase II trial of concurrent docetaxel/carboplatin/radiotherapy followed by surgical resection and consolidation docetaxel/carboplatin in stage III non-small-cell lung cancer.

    abstract:BACKGROUND:The optimal treatment of locally advanced non-small-cell lung cancer (NSCLC) remains controversial. We hypothesized that using a trimodality approach in selected patients with stage IIIA/IIIB disease would be both feasible and efficacious with reasonable toxicity. PATIENTS/METHODS:We enrolled 13 patients wi...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章


    authors: Das M,Donington JS,Murphy J,Kozak M,Eclov N,Whyte RI,Hoang CD,Zhou L,Le QT,Loo BW,Wakelee H

    更新日期:2011-09-01 00:00:00

  • Disparities in the Management of Patients With Stage I Small Cell Lung Carcinoma (SCLC): A Surveillance, Epidemiology and End Results (SEER) Analysis.

    abstract:INTRODUCTION:Patients with stage I small cell lung carcinoma (SCLC) are candidates for surgery; however, not much is known regarding the utilization of surgical resection in the management of stage I SCLC and the factors that determine the patient's ability to receive surgery. METHODS:The Surveillance, Epidemiology an...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章


    authors: Ahmed Z,Kujtan L,Kennedy KF,Davis JR,Subramanian J

    更新日期:2017-09-01 00:00:00

  • EGFR Testing in Advanced Non-Small-Cell Lung Cancer, A Mini-Review.

    abstract::Expert consensus guidelines have defined minimum requirements for routine testing and identification of classical epidermal growth factor (EGFR) mutations (ie, exon 19 deletions and exon 21 L858R substitution) and anaplastic lymphoma kinase (ALK) rearrangements in advanced non-small-cell lung cancers of adenocarcinoma...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章,评审


    authors: Sheikine Y,Rangachari D,McDonald DC,Huberman MS,Folch ES,VanderLaan PA,Costa DB

    更新日期:2016-11-01 00:00:00

  • Analysis of single nucleotide polymorphisms and radiation sensitivity of the lung assessed with an objective radiologic endpoin.

    abstract:BACKGROUND:The primary objective of this study was to evaluate the association between radiation sensitivity of the lungs and candidate single nucleotide polymorphisms (SNP) in genes implicated in radiation-induced toxicity. METHODS:Patients with lung cancer who received radiation therapy (RT) had pre-RT and serial po...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章


    authors: Kelsey CR,Jackson IL,Langdon S,Owzar K,Hubbs J,Vujaskovic Z,Das S,Marks LB

    更新日期:2013-05-01 00:00:00

  • Presence of Even a Small Ground-Glass Component in Lung Adenocarcinoma Predicts Better Survival.

    abstract:BACKGROUND:While lepidic-predominant lung adenocarcinomas are known to have better outcomes than similarly sized solid tumors, the impact of smaller noninvasive foci within predominantly solid tumors is less clearly characterized. We tested the hypothesis that lung adenocarcinomas with even a small ground-glass opacity...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章


    authors: Berry MF,Gao R,Kunder CA,Backhus L,Khuong A,Kadoch M,Leung A,Shrager J

    更新日期:2018-01-01 00:00:00

  • EGFR Tyrosine Kinase Inhibitor (TKI) Combined With Concurrent or Sequential Chemotherapy for Patients With Advanced Lung Cancer and Gradual Progression After First-Line EGFR-TKI Therapy: A Randomized Controlled Study.

    abstract:INTRODUCTION:Continuing tyrosine kinase inhibitor (TKI) therapy may be beneficial when patients with non-small-cell lung cancer and EGFR mutations experience gradual disease progression after initial EGFR-TKI treatment. We aimed to compare the efficacy of simultaneous EGFR-TKI and chemotherapy with that of sequential t...

    journal_title:Clinical lung cancer

    pub_type: 杂志文章


    authors: Chang Q,Xu J,Qiang H,Teng J,Qian J,Lv M,Zhang Y,Lou Y,Zhao Y,Zhong R,Han B,Chu T

    更新日期:2020-07-06 00:00:00