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Specimen Handling & Ancillary Testing

+Rapid On-Site Evaluation of Endobronchial Ultrasound-Guided Transbronchial Needle Aspirations for the Diagnosis of Lung Cancer: A Perspective From Members of the PulmonaryPathology Society
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Tumor spread through air spaces (STAS) is a recognized pattern of invasion in lung adenocarcinoma.


Rapid On-Site Evaluation of Endobronchial Ultrasound-Guided Transbronchial Needle Aspirations for the Diagnosis of Lung Cancer: A Perspective From Members of the PulmonaryPathology Society

Jain D, Allen TC, Aisner DL, et al.

In this article, the benefits of rapid on-site evaluation (ROSE) of transbronchial needle aspirations is reviewed.
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General Handling Considerations

+Pathologists' Staging of Multiple Foci of Lung Cancer
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The article highlights the difficulties with staging multiple synchronous lung tumors.


Pathologists' Staging of Multiple Foci of Lung Cancer

Robert J. Homer, MD, PhD

The article highlights the difficulties with staging multiple synchronous lung tumors. This paper should be added also: Frank Schneider, Veronica Derrick, Jon M Davison, Diane Strollo, Pimpin Incharoen and Sanja Dacic. Morphological and molecular approach to synchronous non-small cell lung carcinomas: impact on staging. Modern Pathology (2016) 29, 735–742; doi:10.1038.
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+Do More With Less: Tips and Techniques for Maximizing Small Biopsy and Cytology Specimens for Molecular and Ancillary Testing
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The authors describe their techniques and experience in handling small biopsy specimens to increase yields for ancillary testing.


Do More With Less: Tips and Techniques for Maximizing Small Biopsy and Cytology Specimens for Molecular and Ancillary Testing

Aisner DL, Rumery MD, Merrick DT, et al.

The authors describe their techniques and experience in handling small biopsy specimens to increase yields for ancillary testing. This is a very helpful reference for laboratories looking to decrease QNS rates.
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+Tumor Spread Through Air Spaces Is an Independent Predictor of Recurrence-free Survival in Patients With Resected Lung Squamous Cell Carcinoma
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Tumor spread through air spaces (STAS) is a recognized pattern of invasion in lung adenocarcinoma. The authors investigate this pattern in squamous cell carcinomas and show that STAS is associated with aggressive tumor behavior.


Tumor Spread Through Air Spaces Is an Independent Predictor of Recurrence-free Survival in Patients With Resected Lung Squamous Cell Carcinoma

Kadota, Kyuichi; Kushida, Yoshio; Katsuki, Naomi, et al.  

Tumor spread through air spaces (STAS) is a recognized pattern of invasion in lung adenocarcinoma. The authors investigate this pattern in squamous cell carcinomas and show that STAS is associated with aggressive tumor behavior. 
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+Measurement Bias of Gross Pathologic Compared With Radiologic Tumor Size of Resected LungAdenocarcinomas: Implications for the T-Stage Revisions in the Eighth Edition of the American Joint Committee on Cancer Staging Manual
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This article emphasized the importance of accurate gross tumor size measurement by the pathologists.


Measurement Bias of Gross Pathologic Compared With Radiologic Tumor Size of Resected LungAdenocarcinomas: Implications for the T-Stage Revisions in the Eighth Edition of the American Joint Committee on Cancer Staging Manual

Anderson, Heidinger, Chen, et al.

This article emphasized the importance of accurate gross tumor size measurement by the pathologists.
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+Measurement Bias of Gross Pathologic Compared With Radiologic Tumor Size of Resected Lung Adenocarcinomas: Implications for the T-Stage Revisions in the Eighth Edition of the American Joint Committee on Cancer Staging Manual
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This article emphasized the importance of accurate gross tumor size measurement by the pathologists.


Measurement Bias of Gross Pathologic Compared With Radiologic Tumor Size of Resected Lung Adenocarcinomas: Implications for the T-Stage Revisions in the Eighth Edition of the American Joint Committee on Cancer Staging Manual

Anderson, Heidinger, Chen, et al.

This article emphasized the importance of accurate gross tumor size measurement by the pathologists.
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Immunohistochemistry (IHC) and special stains

+Utility and pitfalls of immunohistochemistry in the differential diagnosis between epithelioid mesothelioma and poorly differentiated lung squamous cell carcinoma
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A study evaluating the best panel of IHC markers for distinguishing solid adenocarcinoma from solid epithelioid mesothelioma


Utility and pitfalls of immunohistochemistry in the differential diagnosis between epithelioid mesothelioma and poorly differentiated lung squamous cell carcinoma

Kushitani K, et al.

A study evaluating the best panel of IHC markers for distinguishing solid adenocarcinoma from solid epithelioid mesothelioma
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+The Use of Immunohistochemistry Improves the Diagnosis of Small Cell Lung Cancer and Its Differential Diagnosis. An International Reproducibility Study in a Demanding Set of Cases
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A study of diagnostic reproducibility of small cell carcinoma, evaluating the use of IHC to more accurately diagnose small cell carcinoma.


The Use of Immunohistochemistry Improves the Diagnosis of Small Cell Lung Cancer and Its Differential Diagnosis. An International Reproducibility Study in a Demanding Set of Cases

Thunnissen E, et al.

A study of diagnostic reproducibility of small cell carcinoma, evaluating the use of IHC to more accurately diagnose small cell carcinoma.
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+Programmed Death Ligand-1 Immunohistochemistry--A New Challenge for Pathologists: A Perspective From Members of the Pulmonary Pathology Society
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A nice review of the current state of PD-L1 testing and challenges associated with implementation of this testing in laboratories


Programmed Death Ligand-1 Immunohistochemistry--A New Challenge for Pathologists: A Perspective From Members of the Pulmonary Pathology Society

Sholl LM, et al.

A nice review of the current state of PD-L1 testing and challenges associated with implementation of this testing in laboratories
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+Immunohistochemistry of Pulmonary Biomarkers: A Perspective From Members of the Pulmonary Pathology Society
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This article discusses the application and utility of immunohistochemistry stains including predictive biomarkers in non-small cell lung cancer


Immunohistochemistry of Pulmonary Biomarkers: A Perspective From Members of the Pulmonary Pathology Society

Erik Thunnissen, Timothy Craig Allen, Julien Adam, et al.

This article discusses the application and utility of immunohistochemistry stains including predictive biomarkers in non-small cell lung cancer
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+Biomarker Testing in Lung Carcinoma Cytology Specimens: A Perspective From Members of the Pulmonary Pathology Society
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This article focuses on the opportunities and challenges of using cytologic specimens for molecular diagnosis of lung cancer and the role of cytopathology in the molecular era.


Biomarker Testing in Lung Carcinoma Cytology Specimens: A Perspective From Members of the Pulmonary Pathology Society

Roy-Chowdhuri S, Aisner DL, Allen TC, Beasley MB, et al.

This article focuses on the opportunities and challenges of using cytologic specimens for molecular diagnosis of lung cancer and the role of cytopathology in the molecular era.
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+Reevaluation and Reclassification of Resected Lung Carcinomas Originally Diagnosed as Squamous Cell Carcinoma Using Immunohistochemical Analysis
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This article discusses the importance of using immunohistochemistry in accurate classification of lung carcinomas, even on resection specimens.


Reevaluation and Reclassification of Resected Lung Carcinomas Originally Diagnosed as Squamous Cell Carcinoma Using Immunohistochemical Analysis

Kadota, Kyuichi MD, PhD; Nitadori, Jun-ichi MD, PhD; Rekhtman, Natasha MD, et al.

This article discusses the importance of using immunohistochemistry in accurate classification of lung carcinomas, even on resection specimens.
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+MUC4, a novel immunohistochemical marker identified by gene expression profiling, differentiates pleural sarcomatoid mesothelioma from lung sarcomatoid carcinoma
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A study evaluating the utility of MUC4 as an IHC marker of mesothelial differentiation for evaluation of malignant sarcomatoid pleural proliferations.


MUC4, a novel immunohistochemical marker identified by gene expression profiling, differentiates pleural sarcomatoid mesothelioma from lung sarcomatoid carcinoma

Amatya VJ, et al.

A study evaluating the utility of MUC4 as an IHC marker of mesothelial differentiation for evaluation of malignant sarcomatoid pleural proliferations
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+The differential diagnosis between pleural sarcomatoid mesothelioma and spindlecell/pleomorphic (sarcomatoid) carcinomas of the lung: Evidence-Based guidelines from the International Mesothelioma Panel and the MESOPATH National Reference Center
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The authors suggest guidelines to distinguish sarcomatoid malignant mesotheliomas from spindle cell and pleomorphic carcinomas of the lung.


The differential diagnosis between pleural sarcomatoid mesothelioma and spindlecell/pleomorphic (sarcomatoid) carcinomas of the lung: Evidence-Based guidelines from the International Mesothelioma Panel and the MESOPATH National Reference Center

Marchevsky, LeStang, Hiroshim, et al.

The authors suggest guidelines to distinguish sarcomatoid malignant mesotheliomas from spindle cell and pleomorphic carcinomas of the lung.
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+A Sensitive ALK Immunohistochemistry Companion Diagnostic Test Identifies Patients Eligible For Treatment with Crizotinib
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Authors present data on the recently approved Ventana ALK (D5F3) CDx Assay (Ventana Medical Systems, Tucson, AZ), the only immunohistochemistry (IHC)-based assay linked to treatment outcome.


A Sensitive ALK Immunohistochemistry Companion Diagnostic Test Identifies Patients Eligible For Treatment with Crizotinib

Thorne-Nuzzo, Williams, Catallini, et al.

Authors present data on the recently approved Ventana ALK (D5F3) CDx Assay (Ventana Medical Systems, Tucson, AZ), the only immunohistochemistry (IHC)-based assay linked to treatment outcome. The results show that ALK (D5F3) IHC is an effective option to accurately and rapidly identify patients with ALK-positive NSCLC.
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FISH and molecular testing

+Identification of Factors Affecting the Success of Next-Generation Sequencing Testing in Solid Tumors
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In this study they identified the most common factors that affect NGS efficacy.


Identification of Factors Affecting the Success of Next-Generation Sequencing Testing in Solid Tumors

Rashmi S. Goswami, MD, PhD, Rajyalakshmi Luthra, PhD, Rajesh R. Singh, PhD, et al.

In this study they identified the most common factors that affect NGS efficacy.
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+BRAF Alternations as Therapeutic Targets in Non-Small-Cell Lung Cancer
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BRAF mutation as a targetable driver mutation is discussed in this article.


BRAF Alternations as Therapeutic Targets in Non-Small-Cell Lung Cancer

Tu Nguyen-Ngoc, MD, PhD; Hasna Bouchaab, MD; Alex A Adjei, MD, PhD, et al.

BRAF mutation as a targetable driver mutation is discussed in this article.
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+Using Multiplexed Assays of Oncogenic Drivers in Lung Cancers to Select Targeted Drugs
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Actionable drivers were studied in a large cohort of over 1000 patients. Actionable mutations were detected in 64% of lung adenocarcinomas.


Using Multiplexed Assays of Oncogenic Drivers in Lung Cancers to Select Targeted Drugs

Mark G. Kris, MD; Bruce E. Johnson, MD; Lynne D. Berry, PhD, et al.

Actionable drivers were studied in a large cohort of over 1000 patients. Actionable mutations were detected in 64% of lung adenocarcinomas.
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+Molecular Testing for Targeted Therapy in Advanced Non-Small Cell Lung Cancer
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The utility of EGFR/KRAS/ALK testing was studied in EBUS samples and showed that EBUS can be effectively used not just for diagnosis but also for complete mutational testing


Molecular Testing for Targeted Therapy in Advanced Non-Small Cell Lung Cancer

Chiara Casadio, MD; Juliana Guarize, MD; Stefano Donghi, MD, et al.

The utility of EGFR/KRAS/ALK testing was studied in EBUS samples and showed that EBUS can be effectively used not just for diagnosis but also for complete mutational testing
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+Non-p.V600E BRAF Mutations Are Common Using a More Sensitive and Broad Detection Tool
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The authors showed that there are different variants of BRAF mutations in various tumors, including lung adenocarcinomas.


Non-p.V600E BRAF Mutations Are Common Using a More Sensitive and Broad Detection Tool

Jamal Carter, MD; Li-Hui Tseng, MD, PhD, Gang Zheng, MD, PhD, et al.

The authors showed that there are different variants of BRAF mutations in various tumors, including lung adenocarcinomas; lung adenocarcinomas also showed more unique BRAF mutations and a higher prevalence of exon 11 mutations and non–codon 600.
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+Comparison of Next-Generation Sequencing and Mutation-Specific Platforms in Clinical Practice
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Single gene assay is compared to next generation sequencing for EGFR and KRAS, and authors found comparable results for these two genes.

Comparison of Next-Generation Sequencing and Mutation-Specific Platforms in Clinical Practice

John W. J. Hinrichs, PhD; W.T. Marja van Blokland; Michiel J. Moons, et al.

Single gene assay is compared to next generation sequencing for EGFR and KRAS, and authors found comparable results for these two genes.
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+Testing for ROS1 in non-small cell lung cancer: a review with recommendations
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A nice review of ROS1 testing methods and handling issues.


Testing for ROS1 in non-small cell lung cancer: a review with recommendations

Bubendorf L, et al.

A nice review of ROS1 testing methods and handling issues.
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+Biomarkers in Lung Adenocarcinoma: A Decade of Progress
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This is an overview of the molecular biomarkers that are used prognostically and therapeutically in advanced lung adeocarcioma.


Biomarkers in Lung Adenocarcinoma: A Decade of Progress

Lynette M. Sholl, MD

This is an overview of the molecular biomarkers that are used prognostically and therapeutically in advanced lung adenocarcinomas
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+KRAS Mutation Is a Significant Prognostic Factor in Early-stage Lung Adenocarcinoma
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The prognostic significance of KRAS and EGFR driver mutations is investigated in a large cohort of early-stage lung adenocarcinomas.


KRAS Mutation Is a Significant Prognostic Factor in Early-stage Lung Adenocarcinoma

Kadota, Kyuichi MD, PhD; Sima, Camelia S. MD, MS; Arcila, Maria E. MD, et al.

The prognostic significance of KRAS and EGFR driver mutations is investigated in a large cohort of early-stage lung adenocarcinomas.
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+Associations Between Mutations and Histologic Patterns of Mucin in Lung Adenocarcinoma: Invasive Mucinous Pattern and Extracellular Mucin Are Associated With KRAS Mutation
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This study investigates the association between mucinous histologic features of lung adenocarcinoma and driver mutations.


Associations Between Mutations and Histologic Patterns of Mucin in Lung Adenocarcinoma: Invasive Mucinous Pattern and Extracellular Mucin Are Associated With KRAS Mutation

Kadota, Kyuichi MD, PhD; Yeh, Yi-Chen MD D'Angelo, Sandra P. MD, et al.

This study investigates the association between mucinous histologic features of lung adenocarcinoma and driver mutations. They find mucinous lung adenocarcinomas are associated with KRAS mutation.
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+Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs
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This article reviews the findings from the Lung Cancer Mutation Consortium project.


Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs

Kris MG, Johnson BE, Berry LD, et al.

This article reviews the findings from the Lung Cancer Mutation Consortium project. The project looked at frequency of 10 driver mutations in tumors from 1007 patients.
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+Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology
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Reviews guidelines for testing EGFR and ALK alterations.


Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology

Lindeman NI, Cagle PT, Beasley MB, et al.

Reviews guidelines for testing EGFR and ALK alterations.
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+UMolecular Testing Turnaround Time for Non-Small Cell Lung Cancer in Routine Clinical Practice Confirms Feasibility of CAP/IASLC/AMP Guideline Recommendations: A Single-center Analysis
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Study analyzes one center's TAT for molecular testing, finding an average of 9 working days from the time the material is received in the laboratory.


Molecular Testing Turnaround Time for Non-Small Cell Lung Cancer in Routine Clinical Practice Confirms Feasibility of CAP/IASLC/AMP Guideline Recommendations: A Single-center Analysis

DiStasio M, Chen Y, Rangachari D, Costa DB, Heher YK, VanderLaan PA.

Study analyzes one center's TAT for molecular testing, finding an average of 9 working days from the time the material is received in the laboratory.
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+Improving Selection Criteria for ALK Inhibitor Therapy in Non–Small Cell Lung Cancer: A Pooled-Data Analysis on Diagnostic Operating Characteristics of Immunohistochemistry
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This study evaluates the diagnostic role of ALK immunohistochemistry (IHC) in identification of ALK rearrangement compared to FISH.


Improving Selection Criteria for ALK Inhibitor Therapy in Non–Small Cell Lung Cancer: A Pooled-Data Analysis on Diagnostic Operating Characteristics of Immunohistochemistry

Jiang, Long MD, PhD; Yang, Haihong MD, PhD; He, Ping MD, PhD, et al.

This study evaluates the diagnostic role of ALK immunohistochemistry (IHC) in identification of ALK rearrangement compared to FISH. Authors conclude that IHC scores of 0 and 3+ were nearly 100% concordant with FISH-negative and FISH-positive status, respectively. However, IHC scores 1+ and 2+ might require further confirmatory testing by FISH assay. IHC assay using D5F3 and 5A4 antibodies reliably detected NSCLC with ALK rearrangement and may be useful as a screening method to identify these tumors.
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+Pulmonary Sarcomatoid Carcinomas Commonly Harbor Either Potentially Targetable Genomic Alterations or High Tumor Mutational Burden as Observed by Comprehensive Genomic Profiling
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Mutation analysis for potential targeted therapy is recommended in these highly aggressive lung tumors


Pulmonary Sarcomatoid Carcinomas Commonly Harbor Either Potentially Targetable Genomic Alterations or High Tumor Mutational Burden as Observed by Comprehensive Genomic Profiling

Schrock, Framptom, et al.

Mutation analysis for potential targeted therapy is recommended in these highly aggressive lung tumors
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+Driven by Mutations: The Predictive Value of Mutation Subtype in EGFR-Mutated Non–Small Cell Lung Cancer
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Different types and their respective optional therapies for EGFR-mutated NSCLCs are discussed.


Driven by Mutations: The Predictive Value of Mutation Subtype in EGFR-Mutated Non–Small Cell Lung Cancer

Castellanos, Feld, Horn, et al.

Different types and their respective optional therapies for EGFR-mutated NSCLCs are discussed.
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+Plasma ctDNA Analysis for Detection of the EGFR T790M Mutation in Patients with Advanced Non–Small Cell Lung Cancer
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The feasibility of plasma testing for detecting EGFR mutations in advanced NSCLC is discussed.


Plasma ctDNA Analysis for Detection of the EGFR T790M Mutation in Patients with Advanced Non–Small Cell Lung Cancer

Jenkins, Yang, Ramalingam, et al.

The feasibility of plasma testing for detecting EGFR mutations in advanced NSCLC is discussed.
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+Whole Cancer Genome Sequencing by Next-Generation Methods
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Review of older NGS platforms. It is from 2011 but worth including for historical background.


Whole Cancer Genome Sequencing by Next-Generation Methods

Jeffrey S. Ross, MD and Maureen Cronin, PhD

Review of older NGS platforms. It is from 2011 but worth including for historical background.
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