scholarly journals Biomarkers for Selection of Therapy for Adenocarcinoma of the Lung

2017 ◽  
Vol 13 (4) ◽  
pp. 221-227 ◽  
Author(s):  
Eric H. Bernicker ◽  
Ross A. Miller ◽  
Phillip T. Cagle
Keyword(s):  
Kinase Inhibitors ◽  
Cytotoxic Chemotherapy ◽  
Driver Mutations ◽  
Molecular Testing ◽  
Small Cell Lung ◽  
Clinical Predictors ◽  
Adenocarcinoma Of The Lung ◽  
The Many ◽  
Work Up ◽  
Selection Of

To suggest that the discovery of targetable driver mutations in many patients with advanced adenocarcinoma of the lung has completely transformed the work-up and therapeutic options for this disease would not be hyperbole. Although not curative, small-molecule tyrosine kinase inhibitors directed at oncogene-addicted tumors have led to significantly improved response rates compared with cytotoxic chemotherapy, with often manageable toxicities and better tolerance. However, the absence of reliable clinical predictors has made molecular testing essential to ensure that patients receive the proper medical management. We outline the many recent advances with regard to diagnosis and treatment of oncogene-addicted advanced nonsquamous non–small-cell lung cancer.

The targetable mutation landscape of Chinese patients with non-small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13018-e13018
Author(s):  
Jun Li ◽  
Cuiyun Zhang ◽  
Jiuzhou Zhao ◽  
Zhizhong Wang ◽  
Bing Wei ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Small Cell ◽  
Chinese Patients ◽  
Molecular Testing ◽  
Small Cell Lung ◽  
Essential Information ◽  
Nsclc Patients

e13018 Background: In recent years, the prognosis of non-small cell lung cancer (NSCLC) patients has been substantially improved by targeted therapies against specific molecular aberrations, i.e. tyrosine kinase inhibitors (TKIs) for Epidermal Growth Factor Receptor ( EGFR) etc. Several genes have been suggested by NCCN guideline (v7.2017) to test for NSCLC patients, including EGFR, ALK, ROS1, BRAF, MET, RET, HER2 and KRAS. The aim of this study is to profile the landscape of actionable mutations in Chinese NSCLC patients. Methods: From 2015 to 2017 621 treatment naïve NSCLC patients enrolled in the affiliated cancer hospital of Zhengzhou University were included in this analysis. DNA was extracted from the FFPE biopsies of these patients and processed for target capture sequencing covering the exons and flanking splicing regions of the 8 genes suggested by NCCN guideline, as well as introns of ROS, ALK and RET. Results: In total, 593 out of the 621 NSCLC patients harbor one or more mutations in these 8 genes, accounting for 95.5% of all the cases. EGFR, ALK and HER2 are the top 3 mutants, with a frequency of 52%, 32% and 26% respectively. Genetic aberrations in BRAF, MET, ROS1, KRAS and RET occur in 22%, 18%, 16% and 14% of the patients. The most common variation is missense; T > G, C > T and C > A changes are more often observed than T > C, T > A and C > G; the median number of variants per sample is 2, ranging from 1 to 13. There are 418 mutations detected on EGFR, of which 206 (49.28%) are clinically relevant. EGFR L858R, Exon19 deletion, Exon20 insertion, G719, A750P were observed in 123 (29.43%), 43 (10.29%), 8 (1.91%), 6 (1.44%) and 6 (1.44%) cases respectively. Gene fusions were identified in 78 cases, and the EML4- ALK is the most common one occurred in 54 patients, other fusion genes include KIF5B- ALK (11) ， CCDC6- RET (4), CD74- ROS1 (4), EZR- ROS1 (2), ERC1- RET (1), , SDC4- ROS1 (1) and TCOF1- ROS1 (1). Conclusions: Target sequencing of the 8 genes suggested by NCCN guideline for NSCLC patients reveals essential information for designing personalized therapeutic regimen. Chinese patients, maybe other Asian countries also, may benefit more from this molecular testing, because of the high occurrence of actionable mutations.

Clinical Predictors of Response to EGFR Tyrosine Kinase Inhibitors in Patients with EGFR-Mutant Non-Small Cell Lung Cancer

Oncology ◽  
2014 ◽  
Vol 86 (2) ◽  
pp. 86-93 ◽  
Author(s):  
Jun Fukihara ◽  
Naohiro Watanabe ◽  
Hiroyuki Taniguchi ◽  
Yasuhiro Kondoh ◽  
Tomoki Kimura ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Clinical Predictors ◽  
Predictors Of Response ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Egfr Mutant

scholarly journals Cytology Smears in the Era of Molecular Biomarkers in Non–Small Cell Lung Cancer: Doing More With Less

2018 ◽  
Vol 142 (3) ◽  
pp. 291-298 ◽  
Author(s):  
Maria D. Lozano ◽  
José I. Echeveste ◽  
Marta Abengozar ◽  
Luis D. Mejías ◽  
Miguel A. Idoate ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Data Sources ◽  
Molecular Testing ◽  
Signal Loss ◽  
Small Cell Lung ◽  
The Many ◽  
Quality Material

Context.— The rapid advances in targeted therapies in non–small cell lung cancer (NSCLC) make the optimization and implementation of cytology specimens for molecular testing a priority. Up to 70% of patients with NSCLC are diagnosed at advanced stages and tissue biopsies often cannot be taken. Although cytology samples provide high-quality material for molecular testing, molecular cytopathology is not yet well known or widely used. Objective.— To report the many advances in molecular cytopathology and the suitability and utility of cytology samples in molecular and genetic testing of NSCLC. Data Sources.— Data sources comprised published peer-reviewed literature and personal experience of the authors. Conclusions.— Molecular testing can be performed on cytologic specimens, especially on direct smears. Rapid on-site evaluation by cytopathologists has improved the adequacy and the management of cytology samples for molecular testing. Mutational profiling of NSCLC using next-generation sequencing can be performed on cytology samples from very small amounts of DNA. Fluorescence in situ hybridization assays on cytology specimens, including stained direct smear, offer some distinct advantages over their histologic counterpart, and are used to detect ALK and ROS1 rearrangements in NSCLC. Cytology specimens allow assessment of the entire tumor cell nucleus, avoiding signal loss from truncation artifacts. The use of cytology samples for assessing programmed death ligand-1 protein expression is currently being developed. Protocols for bisulfite conversion and DNA droplet digital polymerase chain reaction assays have been optimized for cytology smear to investigate aberrant DNA methylation of several NSCLC-related genes.

Reflex Testing for Epidermal Growth Factor Receptor Mutation and Anaplastic Lymphoma Kinase Fluorescence In Situ Hybridization in Non–Small Cell Lung Cancer

2011 ◽  
Vol 135 (5) ◽  
pp. 655-664
Author(s):  
Mari Mino-Kenudson ◽  
Eugene J. Mark
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Molecular Testing ◽  
Small Cell Lung ◽  
Alk Rearrangement ◽  
Anaplastic Lymphoma ◽  
Epidermal Growth

Abstract Context.—Non–small cell lung cancer (NSCLC) is a poor-prognosis malignancy for which more effective treatments are needed, with accumulating clinical experiences supporting benefits of receptor tyrosine kinase inhibitors for patients with tumors harboring an epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement. Objective.—To review completed and ongoing clinical trials of EGFR tyrosine kinase inhibitors for EGFR mutation–positive NSCLC and an ALK inhibitor for those with ALK rearrangement, while also exploring practical issues surrounding the implementation of molecular testing as a routine component of the diagnostic workup of NSCLC in the United States. Data Sources.—Published biomedical literature, abstracts presented at recent major oncology meetings, and ClinicalTrials.gov. Conclusions.—Continually evolving evidence indicates the possible efficacy of molecularly targeted agents for the treatment of advanced NSCLC, especially adenocarcinoma. To identify patients who will most likely benefit from the targeted therapy, routine determination of the corresponding genetic alterations after histologic diagnosis of NSCLC (reflex molecular testing for EGFR mutations and ALK rearrangement) should be considered.

scholarly journals Molecular Testing Guideline for Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors

2013 ◽  
Vol 15 (4) ◽  
pp. 415-453 ◽  
Author(s):  
Neal I. Lindeman ◽  
Philip T. Cagle ◽  
Mary Beth Beasley ◽  
Dhananjay Arun Chitale ◽  
Sanja Dacic ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Cancer Patients ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Molecular Testing ◽  
Lung Cancer Patients ◽  
Selection Of

Advances in the Treatment of Non-Small Cell Lung Cancer

2014 ◽  
Vol 12 (5S) ◽  
pp. 764-767 ◽  
Author(s):  
Leora Horn
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Acquired Resistance ◽  
Small Cell ◽  
Driver Mutations ◽  
Annual Conference ◽  
Small Cell Lung ◽  
Nccn Guidelines

Clinical trial data continue to emerge on treatments in advanced non-small cell lung cancer (NSCLC), supporting the strategy that histology and molecular driver mutations should guide treatment selection. During her presentation at the NCCN 19th Annual Conference, Dr. Leora Horn highlighted 3 specific areas in which the 2014 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for NSCLC focus attention: updates on the assortment of chemotherapy options, targeted therapies and how acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors appears to have become the catalyst of the development of newer-generations of agents, and the revisited role of newer immunotherapeutic options.

scholarly journals Molecular Testing for Selection of Patients With Lung Cancer for Epidermal Growth Factor Receptor and Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitors: American Society of Clinical Oncology Endorsement of the College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology Guideline

2014 ◽  
Vol 32 (32) ◽  
pp. 3673-3679 ◽  
Author(s):  
Natasha B. Leighl ◽  
Natasha Rekhtman ◽  
William A. Biermann ◽  
James Huang ◽  
Mari Mino-Kenudson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitors ◽  
International Association ◽  
Growth Factor Receptor ◽  
Molecular Testing ◽  
Review Panel ◽  
Anaplastic Lymphoma ◽  
Epidermal Growth ◽  
American Society ◽  
Selection Of

Purpose The College of American Pathologists (CAP), the International Association for the Study of Lung Cancer (IASLC), and the Association for Molecular Pathology (AMP) guideline on molecular testing for the selection of patients with lung cancer for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors was considered for endorsement. Methods American Society of Clinical Oncology (ASCO) staff reviewed the CAP/IASLC/AMP guideline for developmental rigor; an ASCO ad hoc review panel of experts reviewed the guideline content. Results The ASCO panel concurred that the recommendations are clear, thorough, and based on the most relevant scientific evidence in this content area and present options that will be acceptable to patients. The CAP/IASLC/AMP guideline comprises 37 recommendations (evidence grade A or B), expert consensus opinions, or suggestions that address the following five principal questions: (1) When should molecular testing be performed? (2) How should EGFR testing be performed? (3) How should ALK testing be performed? (4) Should other genes be routinely tested in lung adenocarcinoma? (5) How should molecular testing be implemented and operationalized? Conclusion The ASCO review panel endorses the CAP/IASLC/AMP guideline. This guideline represents an important advance toward standardization of EGFR and ALK testing practices and is of major clinical relevance in advancing the care of patients with lung cancer. In the Discussion section, the ASCO review panel highlights three evolving areas: advances in ALK testing methodology, considerations for selecting appropriate populations for molecular testing, and emergence of other targetable molecular alterations.

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