Genetic alteration and PD-L1 expression profiles of Chinese patients with lung squamous cell carcinoma

Backgrounds: Despite the achievements made in treating lung cancer during the past decades, lung cancer still leads in cancer incidence and mortality worldwide. Compared to lung adenocarcinoma, the gene mutation profiles of Chinese lung squamous cell carcinoma (SQCC) have not been well established yet... Conclusion: Our study identified unique genomic profiles of Chinese SQCC patients and provided novel insights into the detection of additional actionable genes and ctDNA in further genotyping. Genetic testing on expanded panel merits further study to comprehensive understanding the therapeutic value of targetable alterations in Chinses SQCC patients. READ ARTICLE

Pathology - Research and Practice DOI:10.1016/j.prp.2022.153761

Authors: Ying Chen, Wencui Kong, Zongyang Yu, Zhongquan Zhao

Short communication: The activity of brigatinib in patients with disease progression after next generation anaplastic lymphoma tyrosine kinase inhibitors...

Highlights:
- Brigatinib demonstrated activity in patients with disease progression after next-generation anaplastic lymphoma (ALK) tyrosine kinase inhibitors (TKI’s).
- The objective response was similar in patients who received next generation ALK inhibitors as first-line or second line therapy, and patients with and without brain metastases at baseline.
- Circulating tumor DNA testing (ctDNA) for ALK resistance mutations is feasible; however, a number of patients did not have detectable ctDNA or an ALK resistance mutations. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2021.12.019

Authors: Thomas E. Stinchcombe, Xiaofei Wang, Robert C. Doebele, Leylah M. Drusbosky, David E. Gerber, Leora Horn, Erin M. Bertino, Geoff Liu, Liza C. Villaruz, D. Ross Camidge

Clinical TrialsKirk SmithJanuary 3, 2022Targeted therapy, biomarker, ctDNA, liquid biopsy

Early identification of disease progression in ALK-rearranged lung cancer using circulating tumor DNA analysis

Targeted kinase inhibitors improve the prognosis of lung cancer patients with ALK alterations (ALK+). However, due to the emergence of acquired resistance and varied clinical trajectories, early detection of disease progression is warranted to guide patient management and therapy decisions. We utilized 343 longitudinal plasma DNA samples from 43 ALK+ NSCLC patients receiving ALK-directed therapies to determine molecular progression based on matched panel-based targeted next-generation sequencing (tNGS), and shallow whole-genome sequencing (sWGS). ALK-related alterations were detected in 22 out of 43 (51%) patients. Among 343 longitudinal plasma samples analyzed, 174 (51%) were ctDNA-positive. ALK variant and fusion kinetics generally reflected the disease course. Evidence for early molecular progression was observed in 19 patients (44%). Detection of ctDNA at therapy baseline indicated shorter times to progression compared to cases without mutations at baseline. In patients who succumb..... READ ARTICLE

Nature Profolio Journal: Precision Oncology DOI:10.1038/s41698-021-00239-3

Authors: Angeles, A.K., Christopoulos, P., Yuan, Z., Bauer, S., Janke, F., Ogrodnik, S.J., Reck, M., Schlesner, M., Meister, M., Schneider, M.A., Dietz, S., Stenzinger, A., Thomas, M. and Sültmann, H.

Circulating tumor DNA to investigate resistance mechanism and clone evolution of ALK TKI treated lung adenocarcinoma

Conference PaperKirk SmithMay 28, 2021ctDNA, resistance mechanism, ALK, TKI sequence, lung adenocarcinoma

Circulating tumor DNA to investigate resistance mechanism and clone evolution of ALK TKI treated lung adenocarcinoma.

Genotyping of sequential post-progression plasma specimens reveals that treatment with sequential first-, second-, and third-generation ALK inhibitors can accelerate the accumulation of ALK resistance mutations and may lead to treatment-refractory compound ALK mutations. The selection for optimal first-line TKI is very important to achieve a more efficacious long-term strategy and prevent the emergence of on-target resistance. READ ARTICLE

Journal of Clinical Oncology DOI: 10.1200/JCO.2021.39.15_suppl.3011

Authors: Gang Hua, Xiaoxi Chen, Ruoying Yu, Hua Bao, Xue Wu and Yang Shao

Case StudyKirk SmithMay 6, 2021ALK, ctDNA

Decoding the Evolutionary Response to Ensartinib in Patients With ALK-Positive NSCLC by Dynamic Circulating Tumor DNA Sequencing

By implementing dynamic circulating tumor DNA (ctDNA) analysis, we explored the impact of TP53 mutations on tumor evolution and resistance mechanisms to ensartinib in patients with ALK-positive NSCLC. Our study highlighted the advantage of ctDNA analysis for monitoring tumor evolution. TP53 mutations promoted genetic evolution and accelerated occurrence of resistance. We also unveiled ALK-dependent resistance mechanisms, mainly by G1269A, G1202R, and E1210K mutations, and ALK-independent resistance mechanisms to ensartinib. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2021.01.1615

Authors: Yunpeng Yang, Jie Huang, Tao Wang, Jianya Zhou, Jing Zheng, Jifeng Feng, Wu Zhuang, Jianhua Chen, Jun Zhao, Wei Zhong, Yanqiu Zhao, Yiping Zhang, Yong Song, Yi Hu, Zhuang Yu, Youling Gong, Yuan Chen, Feng Ye, Shucai Zhang, Lejie Cao, Yun Fan, Gang Wu, Yubiao Guo, Chengzhi Zhou, Kewei Ma, Jian Fang, Weineng Feng, Yunpeng Liu, Zhendong Zheng, Gaofeng Li, Huijie Wang, Shundong Cang, Ning Wu, Wei Song, Xiaoqing Liu, Shijun Zhao, Lieming Ding, Li Mao, Giovanni Selvaggi, Larry Zhu, Shanshan Xiao, Xiaobin Yuan, Zhilin Shen, Li Zhang

Pre-ClinicalKirk SmithMay 1, 2021ALK+, NSCLC, ctDNA, TP53, Resistance mechanism

Early circulating tumor (ct) DNA dynamics and efficacy of lorlatinib: Analysis from the CROWN study.

Early ctDNA dynamics may predict lorlatinib efficacy in pts with previously untreated ALK-positive NSCLC. The magnitude of reduction in ctDNA at 4 weeks may be associated with better responses and potentially longer PFS. These findings further support the utility of dynamic ctDNA monitoring in ALK-positive NSCLC. READ ARTICLE

Journal of Clinical Oncology DOI:10.1200/JCO.2021.39.15_SUPPL.9011

Authors: Ross A. Soo, Jean-Francois Martini, Anthonie J. van der Wekken, Shunsuke Teraoka, Alice T. Shaw, Deborah Shepard, Anna Maria Calella, Anna Polli, Francesca Toffalorio, Pascale Tomasini, Chao-Hua Chiu, Dariusz Kowalski, Hye Ryun Kim, Benjamin J. Solomon

Review PaperKirk SmithMay 1, 2021lorlatinib, CROWN study, ctDNA

The role of plasma genotyping in ALK- and ROS1-rearranged lung cancer

Review discusses technical aspects of plasma genotyping strategies and summarize findings from studies exploring plasma genotyping (including ctDNA analysis and profiling of nucleic acids contained in other plasma components) in two rearrangement-driven NSCLC subsets (ALK-rearranged and ROS1-rearranged). READ ARTICLE

Translational Lung Cancer Research DOI: 10.21037/tlcr-2019-cnsclc-09

Authors: Dagogo-Jack I, Ritterhouse LL.

Review PaperKirk SmithDecember 9, 2020ctDNA, next-generation sequencing, NGS, ALK, liquid biopsy

Humanistic burden of living with anaplastic lymphoma kinase-positive non-small-cell lung cancer: findings from the ALKConnect patient insight network and research platform

ALKConnect demonstrated that disease progression, HRQoL, fatigue/sleep, ALK TKIs and employment matter in ALK+ NSCLC. READ ARTICLE

Lung Cancer Management DOI: 10.2217/lmt-2020-0018

Authors: Lin HM, Pan X, Biller A, J Covey K, Huang H, Sugarman R, Scipione F, West H.

Case StudyKirk SmithNovember 20, 2020ctDNA, ALK, liquid biopsy, next-generation sequencing (NGS)

STRN-ALK Fusion in Lung Adenocarcinoma with Excellent Response Upon Alectinib Treatment: A Case Report and Literature Review

More than 90 fusion partners of ALK have been reported in NSCLC patients.
Striatin gene (STRN)-ALK fusion has rarely been reported. Case study of NSCLC patient harboring an STRN-ALK fusion and exhibiting an excellent response to alectinib treatment. READ ARTICLE

OncoTargets and Therapy DOI: 10.2147/OTT.S282933

Authors: Su C, Jiang Y, Jiang W, Wang H, Liu S, Shao Y, Zhao W, Ning R, Yu Q.

Case StudyKirk SmithNovember 6, 2020lung adenocarcinoma, STRN-ALK fusion, ctDNA, alectinib, targeted NGS

Circulating Tumor DNA Analysis for Patients with Oncogene-Addicted NSCLC With Isolated Central Nervous System Progression

Introduction: In patients with oncogene-addicted NSCLC and isolated central nervous system progression (iCNS), tissue biopsy is challenging, and the clinical utility of plasma liquid biopsy (i.e., circulating tumor DNA [ctDNA]) is unknown... Conclusions: Although tagged amplicon-based next-generation sequencing has high detection rates of GA in plasma ctDNA in patients with NSCLC with extra-CNS disease, detection rate of GAs (52%) is lower in the subset of patients with iCNS disease. Complementary tests such as cerebrospinal fluid cell-free DNA may be useful. Further evidence would be beneficial to understand the genomic landscape in patients with NSCLC and iCNS. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.11.024

Authors: Mihaela Aldea, Lizza Hendriks, Laura Mezquita, Cécile Jovelet, David Planchard, Edouard Auclin, Jordi Remon, Karen Howarth, Jose Carlos Benitez, Anas Gazzah, Pernelle Lavaud, Charles Naltet, Ludovic Lacroix, Frankde Kievit, Clive Morris, Emma Green, Maud Ngo-Camus, Etienne Rouleau, … , Benjamin Besse

Review PaperKirk SmithMarch 1, 2020Liquid biopsy, ctDNA, NSCLC, Brain, Leptomeningeal

P103-15 Non-Invasive Detection of Secondary Resistance Mutations in ALK-Positive NSCLC Patients by Next-Generation Sequencing

Remarkably different mutations can confer different sensitivities to different ALK inhibitors. However, 2nd and 3rd line treatment is often prescribe empirically without knowing the molecular mechanism underlying treatment failure.21 samples from ALK-positive NSCLC patients were collected at disease progression. Circulating Nucleic Acids were isolated from platelets, exosomes and plasma. Libraries were prepared using 20ng of template and Oncomine™ Pan-Cancer Cell-Free Assay. Samples were sequenced on an Ion GeneStudio S5 Plus System. Sequencing data was first analyzed using Torrent Suite software. Subsequently variant calling, annotation and filtering was performed on the Ion Reporter (v5.10) platform using the Oncomine TagSeq Pan-Cancer Liquid Biopsy w2.1 workflow. The results show that secondary ALK-TKI resistance mutations could be detected using liquid biopsies in a high proportion of patients. Non-invasive molecular profiling of samples collected at disease progression is feasible being useful for further treatment selection in ALK-positive NSCLC patients.
READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.867

Authors: E. Sánchez Herrero, M. Barquin, V. Calvo De Juan, M. Auglyte, R. Garcia Campelo, J.M. Sánchez, M. Domine, B. Massuti, E. Jantus, C. Camps, N. Reguart, M. Provencio, A. Romero

Conference PaperKirk SmithOctober 1, 2019ctDNA, liquid biopsy, ALK

P114-47 ctDNA NGS for Guiding Crizotinib Treatment in ALK-Rearranged Advanced NSCLC Patients (Pts)

Background: FISH and IHC are commonly used and the golden standard for testing ALK rearrangement. However, they provide no information on fusion types or mutation status of other genes, which could be important prognostic factors. In addition, a tissue biopsy is not always applicable/preferred by pts. Conclusion: Information on ALK fusion types, concomitant mutations, and mutation frequencies provided by NGS could be valuable prognostic factors and deserves further investigation. ctDNA NGS could be used as an effective alternative to identify ALK+ pts, especially for elderly pts, when tissue biopsy is inapplicable or not preferred. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.1198

Authors: Y. He, J. Zhao, C. Liu, R. Chen, X. Xia

Conference PaperKirk SmithOctober 1, 2019ALK, crizotinib, ctDNA

Monitoring therapeutic response and resistance: analysis of circulating tumor DNA in patients with ALK+ lung cancer

Clinical utility of ctDNA was shown, both at pre-treatment by identifying a potential subgroup of ALK+ NSCLC patients who may derive more benefit from ensartinib and longitudinally by tracking resistance. Prospective application of this technology may translate to improved outcomes for NSCLC patients treated with ALK TKIs. READ ARTICLE

Journal of Thoracic Oncology DOI: 10.1016/j.jtho.2019.08.003

Authors: Leora Horn MD, Jennifer G. Whisenant PhD, Heather Wakelee MD, Karen L. Reckamp MD, Huan Qiao, MD PhD, Ticiana A. Leal MD, Liping Du PhD, Jennifer Hernandez BS, Vincent Huang BS, George R. Blumenschein MD, Saiama N. Waqar MD, Sandip P. Patel MD, Jorge Nieva MD, Geoffrey R. Oxnard MD, Rachel E. Sanborn MD, Tristan Shaffer, Kavita Garg, Allison Holzhausen MS, Kimberly Harrow MBA, Chris Liang PhD, Lee P. Lim PhD, Mark Li, Christine M. Lovly MD, PhD

Pre-ClinicalKirk SmithAugust 22, 2019ctDNA, ALK, next-generation sequencing (NGS), liquid biopsy