Testing for EGFR Mutations and ALK Rearrangements in Advanced Non-Small-Cell Lung Cancer: Considerations for Countries in Emerging Markets

The treatment of patients with advanced non-small-cell lung cancer (NSCLC) in recent years has been increasingly guided by biomarker testing. Testing has centered on driver genetic alterations involving the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) rearrangements. The presence of these mutations is predictive of response to targeted therapies such as EGFR tyrosine kinase inhibitors (TKIs) and ALK TKIs. However, there are substantial challenges for the implementation of biomarker testing, particularly in emerging countries. Understanding the barriers to testing in NSCLC will be key to improving molecular testing rates worldwide and patient outcomes as a result. In this article, we review EGFR mutations and ALK rearrangements as predictive biomarkers for NSCLC, discuss a selection of appropriate tests and review the literature with respect to the global uptake of EGFR and ALK testing. To help improve testing rates and unify procedures, we review our exp..... READ ARTICLE

OncoTargets and Therapy DOI:10.2147/OTT.S313669

Authors: Mercedes L Dalurzo, Alejandro Avilés-Salas, Fernando Augusto Soares, Yingyong Hou, Yuan Li, Anna Stroganova, Büge Öz, Arif Abdillah, Hui Wan and Yoon-La Choi

ALK Gene Rearrangements in Lung Adenocarcinomas: Concordance of Immunohistochemistry, Fluorescence In Situ Hybridization, RNA In Situ Hybridization, and RNA Next-Generation Sequencing Testing

The 2018 updated molecular testing guidelines for patients with advanced lung cancer incorporated ALK immunohistochemistry (IHC) analysis as an equivalent to fluorescence in situ hybridization (FISH) method recommended in 2013. Nevertheless, no specific recommendation for alternative methods was proposed owing to insufficient data. The aim of this study was to compare the results of ALK IHC, FISH, RNA next-generation sequencing (NGS), and RNA in situ hybridization (ISH) with available clinical data. Our results reveal high concordance among IHC, RNA NGS, and RNA ISH. In cases of discordance with available RNA NGS, FISH result was positive whereas IHC and ISH results were negative. On the basis of our data, multimodality testing is recommended to identify discrepant results and patients (un)likely to respond to tyrosine kinase inhibitors. READ ARTICLE

JTO Clinical and Research Reports DOI:0.1016/j.jtocrr.2021.100223

Authors: Carleigh R. Canterbury, Helen Fernandes, John P. Crapanzano, Vundavalli V. Murty, Mahesh M.Mansukhani, Catherine A. Shu, Matthias Szabolcs, Anjali Saqi

Genomic characteristics of driver genes in Chinese patients with non-small cell lung cancer

Background: The aim of this study was to determine the demographic prole ofdriver gene alterations, especially low-frequency gene alterations in Chinesepatients with non-small cell lung cancer (NSCLC).Methods: A total of 7395 Chinese patients with NSCLC were enrolled in thestudy. Next-generation sequencing (NGS) was performed on formalin-xedparafn-embedded specimens collected via either surgical resection or biopsy.Results: The frequent genomic alteration s found in the study were EGFR muta-tions (51.7%), KRAS mutations (13.1%), MET alterations (5.6%; 3.2% copy num-ber gains and 0.5% exon 14 skipping mutation), HER2 alterations (7.0%; 2.0%copy number gains and 5.4% mutations), ALK alterations (7.2%; 3.9%rearrangements), RET rearrangements (1.4%), ROS1 rearrangements (0.9%), andNTRK rearrangements (0.6%). The EGFR mutation rate was found to be signi-cantly higher in women than in men (69.1% vs. 38.5%, P < 0.001), while theKRAS mutation (17.5% vs. 7.3%, P < 0.001) and MET alteration ..... READ ARTICLE

Thoracic Cancer DOI:10.1111/1759-7714.13757

Authors: Xiaoyan Si, Ruili Pan, Shaohua Ma, Lin Li, Li Liang, Ping Zhang, Yuping Chu, Hanping Wang, Mengzhao Wang, Xiaotong Zhang, Li Zhang

Comparison of EML4-ALK fusion gene positive rate in different detection methods and samples of non-small cell lung cancer

Objective: To evaluate differences of EML4-ALK positive rates in tissues samples between immunohistochemistry, reverse transcriptase polymerase chain reaction and the next-generation sequencing method. Besides, to compare the differences of EML4-ALK positive rates in blood samples and tissue samples by next-generation sequencing. The results provide a basis for the selection of a suitable EML4-ALK fusion gene detection method. Conclusion: Among the three methods for detecting EML4-ALK, reverse transcription polymerase chain reaction has the highest positive rate, followed by immunohistochemistry, and next-generation sequencing has the lowest positive rate. The positive detection rate of EML4-ALK in tissue samples by next-generation sequencing was higher than that in blood samples. READ ARTICLE

Journal of Cancer DOI:10.7150/jca.36580

Authors: Shan Lu, Can Lu, YuXuan Xiao, Wei Zhu, QiuYan He, Bin Xie, JianHua Zhou, YongGuang Tao, Shuang Liu, DeSheng Xiao