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Boutahir A, Dalstein V, Oudart JB, Deslee G, Clavel C, Dewolf M, Durlach A, Ancel J. Unravelling the complexity of EGFR-mutated lung adenocarcinoma: a unique case report with histological transformations and co-alteration acquisition. Transl Lung Cancer Res 2025; 14:639-648. [PMID: 40114956 PMCID: PMC11921265 DOI: 10.21037/tlcr-24-707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 01/09/2025] [Indexed: 03/22/2025]
Abstract
Background Osimertinib, a third-generation tyrosine kinase inhibitor that targets epidermal growth factor receptor (EGFR), specifically inhibits both EGFR tyrosine kinase inhibitor-sensitive mutations and T790M resistance mutations. Despite initial positive responses to EGFR tyrosine kinase inhibitors, nearly all patients eventually experience disease progression. Mechanisms of resistance are classically divided into EGFR-dependent and EGFR-independent mechanisms, such as the activation of alternative pathways and histological changes. We report a case of histological transformation into large cell carcinoma associated with the subsequent acquisition of an anaplastic lymphoma kinase (ALK) rearrangement after osimertinib exposure. Case Description A 67-year-old female with no smoking history presented with supraclavicular lymphadenopathy and asthenia, which led to a diagnosis of stage IVB lung adenocarcinoma. Next generation sequencing (NGS) identified an EGFR Ex19del mutation, which suggested the use of afatinib, as it was prescribed prior to osimertinib and was covered by insurance. Initial treatment with afatinib resulted in partial remission, followed by pulmonary progression without the EGFR-T790M mutation. Moreover, ALK and ROS1 were identified through immunohistochemistry (IHC), with ROS1 expression subsequently confirmed by fluorescence in situ hybridization (FISH); this prompted a switch to crizotinib, which was discontinued owing to further disease progression. Osimertinib was then administered, which resulted in a significant positive response; however, after six months pulmonary progression was observed. A subsequent biopsy indicated a transformation to large cell neuroendocrine carcinoma, which led to treatment with platinum-etoposide chemotherapy and, later, paclitaxel and osimertinib, both of which are partially effective. Finally, a new biopsy confirmed ALK positivity in a large cell neuroendocrine carcinoma that was still harbouring an EGFR exon 19 deletion, so alectinib was introduced. Conclusions To our knowledge, this case is the first reported incidence of transformation into large cell carcinoma coupled with a second acquisition of alterations in ALK. These findings underscore the necessity of monitoring patients with oncogenic addiction through both liquid biopsy for on-target mechanism detection and tissue sampling to detect histological transformations. These mechanisms can occasionally be combined, thereby providing comprehensive panels at each stage of tumour progression.
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Affiliation(s)
- Anissa Boutahir
- Department of Pulmonology, Reims University Hospital, Reims, France
| | - Véronique Dalstein
- INSERM UMR-S 1250, P3Cell, University of Reims Champagne-Ardenne, Reims, France
- Division of Pathology, Territorial Biology Department, Reims University Hospital, Reims, France
| | - Jean Baptiste Oudart
- Department of Biochemistry-Pharmacology-Toxicology, Reims University Hospital, Reims, France
- Department of Medical Biochemistry and Molecular Biochemistry, MEDyC Unit, CNRS/URCA UMR 7369, University of Reims Champagne-Ardenne, Reims, France
| | - Gaëtan Deslee
- Department of Pulmonology, Reims University Hospital, Reims, France
- INSERM UMR-S 1250, P3Cell, University of Reims Champagne-Ardenne, Reims, France
| | - Chistine Clavel
- INSERM UMR-S 1250, P3Cell, University of Reims Champagne-Ardenne, Reims, France
- Division of Pathology, Territorial Biology Department, Reims University Hospital, Reims, France
| | - Maxime Dewolf
- Department of Pulmonology, Reims University Hospital, Reims, France
| | - Anne Durlach
- INSERM UMR-S 1250, P3Cell, University of Reims Champagne-Ardenne, Reims, France
- Division of Pathology, Territorial Biology Department, Reims University Hospital, Reims, France
| | - Julien Ancel
- Department of Pulmonology, Reims University Hospital, Reims, France
- INSERM UMR-S 1250, P3Cell, University of Reims Champagne-Ardenne, Reims, France
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Gorukmez O, Gorukmez O, Topak A. RNA-Based Next-Generation Sequencing Approach to Non-Small Cell Lung Cancer: A Single-Center Experience in Turkey. Hum Hered 2025; 90:10-17. [PMID: 39947143 DOI: 10.1159/000544697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Accepted: 02/11/2025] [Indexed: 03/22/2025] Open
Abstract
INTRODUCTION Lung cancer is a global health concern. Molecular analysis of tumor tissues, especially in non-small cell lung cancers, has become an integral part of a holistic approach to the management of the disease. Here, molecular genetic data obtained from tumor tissues collected from 373 male and 89 female patients referred to our clinic with a diagnosis of non-small cell lung cancer are presented. METHODS Patient samples (n = 462) were assessed via next-generation sequencing using an RNA-based kit containing 36 genes. Data obtained were analyzed using relevant software, and results of analysis are presented together with the demographic characteristics of the patients. RESULTS Significant somatic variations were detected in 208 of 462 patients. KRAS and EGFR had the greatest variations. Rearrangements, mostly involving ALK, were observed in 37 patients, and rare complex changes involving different genes were detected in 10 patients. CONCLUSION This study presents the comprehensive molecular data obtained using an RNA-based kit that provided information on single-nucleotide variation/insertion-deletion variants (InDel) and rearrangements in a large-patient series from a single center. Somatic variants were detected in approximately 45% of all patients. According to the Catalogue Of Somatic Mutations In Cancer (COSMIC) database, our rate of variants detected in KRAS and FGFR3 genes was higher. The rate of variants detected in other genes was lower. In addition, fusions not reported in COSMIC were detected. With the development of next-generation sequencing-based tests and an increase in their use, a broad perspective has been provided to many disease groups, including solid tissue cancers, especially non-small cell lung cancers.
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Affiliation(s)
- Orhan Gorukmez
- Department of Medical Genetics, Bursa Yüksek İhtisas Training and Research Hospital, Bursa, Turkey
| | - Ozlem Gorukmez
- Department of Medical Genetics, Bursa Yüksek İhtisas Training and Research Hospital, Bursa, Turkey
| | - Ali Topak
- Department of Medical Genetics, Bursa Yüksek İhtisas Training and Research Hospital, Bursa, Turkey
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Li L, Li W, Wu C, Xi Y, Guo L, Ji Y, Jiang L, Li J, Yun J, Chen G, Li Y, Liu Y, Mu D, Han Y, Sun L, Xia Q, Teng X, Che N, Wu W, Qiu X, Liu C, Yan X, Li D, Zhang Z, Wang Z, Li Y, Wang Z, Guo L, Nie X, Geng J, Zhou J, Ying J. Real-world data on ALK rearrangement test in Chinese advanced non-small cell lung cancer (RATICAL): a nationwide multicenter retrospective study. Cancer Commun (Lond) 2024; 44:992-1004. [PMID: 39016057 PMCID: PMC11492361 DOI: 10.1002/cac2.12593] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 06/16/2024] [Accepted: 07/09/2024] [Indexed: 07/18/2024] Open
Abstract
BACKGROUND Anaplastic lymphoma kinase (ALK) test in advanced non-small cell lung cancer (NSCLC) can help physicians provide target therapies for patients harboring ALK gene rearrangement. This study aimed to investigate the real-world test patterns and positive rates of ALK gene rearrangements in advanced NSCLC. METHODS In this real-world study (ChiCTR2000030266), patients with advanced NSCLC who underwent an ALK rearrangement test in 30 medical centers in China between October 1, 2018 and December 31, 2019 were retrospectively analyzed. Interpretation training was conducted before the study was initiated. Quality controls were performed at participating centers using immunohistochemistry (IHC)-VENTANA-D5F3. The positive ALK gene rearrangement rate and consistency rate were calculated. The associated clinicopathological characteristics of ALK gene rearrangement were investigated as well. RESULTS The overall ALK gene rearrangement rate was 6.7% in 23,689 patients with advanced NSCLC and 8.2% in 17,436 patients with advanced lung adenocarcinoma. The quality control analysis of IHC-VENTANA-D5F3 revealed an intra-hospital consistency rate of 98.2% (879/895) and an inter-hospital consistency rate of 99.2% (646/651). IHC-VENTANA-D5F3 was used in 53.6%, real-time polymerase chain reaction (RT-PCR) in 25.4%, next-generation sequencing (NGS) in 18.3%, and fluorescence in-situ hybridization (FISH) in 15.9% in the adenocarcinoma subgroup. For specimens tested with multiple methods, the consistency rates confirmed by IHC-VENTANA-D5F3 were 98.0% (822/839) for FISH, 98.7% (1,222/1,238) for NGS, and 91.3% (146/160) for RT-PCR. The overall ALK gene rearrangement rates were higher in females, patients of ≤ 35 years old, never smokers, tumor cellularity of > 50, and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup (all P < 0.05). CONCLUSIONS This study highlights the real-world variability and challenges of ALK test in advanced NSCLC, demonstrating a predominant use of IHC-VENTANA-D5F3 with high consistency and distinct clinicopathological features in ALK-positive patients. These findings underscore the need for a consensus on optimal test practices and support the development of refined ALK test strategies to enhance diagnostic accuracy and therapeutic decision-making in NSCLC.
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Affiliation(s)
- Lin Li
- Department of PathologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP. R. China
| | - Wencai Li
- Department of Pathologythe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanP. R. China
| | - Chunyan Wu
- Department of PathologyShanghai Pulmonary Hospital, School of Medicine, Tongji UniversityShanghaiP. R. China
| | - Yanfeng Xi
- Department of PathologyCancer Hospital Affiliated to Shanxi Medical UniversityShanxi Province Cancer HospitalShanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical SciencesTaiyuanShanxiP. R. China
| | - Lei Guo
- Department of PathologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP. R. China
| | - Yuan Ji
- Department of PathologyZhongshan HospitalFudan UniversityShanghaiP. R. China
| | - Lili Jiang
- Department of PathologyWest China Hospital of Sichuan UniversityChengduSichuanP. R. China
| | - Ji Li
- Department of PathologyPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP. R. China
| | - Jingping Yun
- Department of PathologySun Yat‐sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer MedicineGuangzhouGuangdongP. R. China
| | - Gang Chen
- Department of PathologyFujian Cancer HospitalFujian Medical University Cancer HospitalFuzhouFujianP. R. China
| | - Yuan Li
- Department of PathologyDepartment of OncologyFudan University Cancer CenterShanghai Medical College of Fudan UniversityShanghaiP. R. China
| | - Yueping Liu
- Department of PathologyThe Fourth Hospital of Hebei Medical UniversityShijiazhuangHebeiP. R. China
| | - Dianbin Mu
- Department of PathologyShandong Cancer HospitalJinanShandongP. R. China
| | - Yuchen Han
- Department of PathologyShanghai Chest HospitalShanghai Jiao Tong UniversityShanghaiP. R. China
| | - Leina Sun
- Department of PathologyTianjin Medical University Cancer Institute and HospitalTianjinP. R. China
| | - Qingxin Xia
- Department of Pathologythe Affiliated Cancer Hospital of Zhengzhou UniversityHenan Provincial Cancer HospitalZhengzhouHenanP. R. China
| | - Xiaodong Teng
- Department of Pathologythe First Affiliated Hospital, College of Medicine, Zhejiang UniversityHangzhouZhejiangP. R. China
| | - Nanying Che
- Department of PathologyBeijing Chest HospitalCapital Medical University, Beijing Tuberculosis and Thoracic Tumor Research InstituteBeijingP. R. China
| | - Wei Wu
- Department of PathologyCancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)HangzhouZhejiangP. R. China
| | - Xueshan Qiu
- Department of Pathologythe First Hospital of China Medical UniversityShenyangLiaoningP. R. China
| | - Chao Liu
- Department of PathologyGuangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdongP. R. China
| | - Xiaochu Yan
- Institute of PathologySouthwest HospitalThird Military Medical University (Army Medical University)ChongqingP. R. China
| | - Daiqiang Li
- Department of Pathologythe Second Xiangya Hospital of Central South UniversityChangshaHunanP. R. China
| | - Zhihong Zhang
- Department of Pathologythe First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsuP. R. China
| | - Zhe Wang
- Department of PathologyXijing HospitalFourth Military Medical UniversityXi'anShaanxiP. R. China
| | - Yujun Li
- Department of Pathologythe Affiliated Hospital of Qingdao UniversityQingdaoShandongP. R. China
| | - Zheng Wang
- Department of PathologyBeijing Hospital, National Center of GerontologyBeijingP. R. China
| | - Lingchuan Guo
- Department of Pathologythe First Affiliated Hospital of Soochow UniversitySuzhouJiangsuP. R. China
| | - Xiu Nie
- Department of PathologyUnion Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanHubeiP. R. China
| | - Jingshu Geng
- Department of PathologyHarbin Medical University Cancer HospitalHarbinHeilongjiangP. R. China
| | - Jianhua Zhou
- Department of PathologyXiangya HospitalCentral South UniversityChangshaHunanP. R. China
| | - Jianming Ying
- Department of PathologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP. R. China
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Hu H, Tan S, Xie M, Guo P, Yu Q, Xiao J, Zhao K, Liao Q, Wang Y. Case report: Concomitant EGFR mutation and ALK rearrangement in non-small cell lung cancer. Front Pharmacol 2023; 14:1167959. [PMID: 37705536 PMCID: PMC10495838 DOI: 10.3389/fphar.2023.1167959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 08/01/2023] [Indexed: 09/15/2023] Open
Abstract
In non-small cell lung cancer (NSCLC), two key genetic alterations, epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements, are commonly believed to be mutually exclusive. Studies have reported that concurrent EGFR/ALK co-mutation in non-small cell lung cancer patients is rare, with a prevalence ranging from 0.1% to 1.6%. However, the clinical and pathological characteristics of these patients are not well-defined, and the optimal treatment approach for such cases remains controversial. In this report, we present a case of stage IV lung adenocarcinoma with both epidermal growth factor receptor and anaplastic lymphoma kinase mutations, along with high PD-L1 expression. The patient initially received treatment with epidermal growth factor receptor tyrosine kinase inhibitors (TKIs), but the disease progressed. However, following a switch to ALK-TKI therapy and local radiotherapy, the lesion showed regression. Our report also provides a comprehensive summary of the clinical and pathological features, as well as treatment strategies, for non-small cell lung cancer patients with concurrent epidermal growth factor receptor mutation and anaplastic lymphoma kinase rearrangement.
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Affiliation(s)
- Haoyue Hu
- Department of Radiation Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Songtao Tan
- West China School of Medicine, Sichuan University, Chengdu, China
- Department of Cleft Lip and Palate, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shijingshan, Beijing, China
| | - Meng Xie
- Department of Pharmacy, Southwest Medical University, Luzhou, China
| | - Peng Guo
- Department of Pathology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Qiang Yu
- Department of Radiation Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
- Dazhou Quxian People’s Hospital, Dazhou, China
| | - Juan Xiao
- Department of Radiation Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Kangrui Zhao
- Department of Radiation Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Qiong Liao
- Department of Pathology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Yi Wang
- Department of Radiation Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
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Zhong WX, Wei XF. Coexistence of anaplastic lymphoma kinase rearrangement in lung adenocarcinoma harbouring epidermal growth factor receptor mutation: A single-center study. World J Clin Cases 2022; 10:12164-12174. [PMID: 36483819 PMCID: PMC9724548 DOI: 10.12998/wjcc.v10.i33.12164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Revised: 10/04/2022] [Accepted: 10/24/2022] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Accumulating evidences confirm that epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement have coexisted in lung adenocarcinoma (LUAD). However, Its biological mechanism, clinicopathological features, and optimization of targeted drugs have not yet been completely elucidated.
AIM To explore the clinical profile of LUAD patients with co-mutations of EGFR and ALK genes, with hopes of scientifically guiding similar patients towards selected, targeted drugs.
METHODS Two hundred and thirty-seven LUAD patients were enrolled. EGFR mutations were detected by the amplification refractory mutation system-peptide nucleic acid technique, while the expression of ALK rearrangement was screened by the 5′/3′ imbalance strategy for reverse transcription followed by quantitative polymerase chain reaction analysis. The clinicopathological features of these patients were analysed retrospectively, and the follow-up data were collected.
RESULTS There were six cases with co-mutations of EGFR and ALK genes, which were more common in women, non-smoking and stage IV LUAD patients with bone metastasis, hence a positive rate of 2.53% (6/237). EGFR-tyrosine kinase inhibitors (EGFR-TKIs) were their preferred drugs for targeted therapy in these patients, with progression-free survival ranging from two months to six months.
CONCLUSION In Gannan region, the positive rate of co-mutations of EGFR and ALK genes in LUAD patients is relatively high, and the co-mutations are more common in women, non-smoking and stage IV patients with bone metastasis. These patients prefer EGFR-TKIs as their preferred targeted drugs, but the therapeutic effect is not good. EGFR/ALK dual-TKIs may be more effective targeted drugs, which needs further study.
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Affiliation(s)
- Wei-Xiang Zhong
- Department of Thoracic Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
- First Clinical Medical College, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Xi-Feng Wei
- Department of Outpatient, Ganzhou Maternity and Child Health Hospital, Ganzhou 341000, Jiangxi Province, China
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Noronha V, Chougule A, Chandrani P, Kaushal RK, Patil VM, Menon N, Kapoor A, Chopade S, Singh A, Shetty O, Dutt A, Banavali S, Prabhash K. Lung cancer with dual EGFR and ALK driver alterations at baseline: a retrospective observational cohort study. Acta Oncol 2022; 61:1143-1147. [PMID: 35972844 DOI: 10.1080/0284186x.2022.2109426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Accepted: 07/30/2022] [Indexed: 11/01/2022]
Affiliation(s)
- Vanita Noronha
- Tata Memorial Center, Homi Bhabha National Institute, Mumbai, India
| | | | - Pratik Chandrani
- Tata Memorial Center, Homi Bhabha National Institute, Mumbai, India
| | | | | | - Nandini Menon
- Tata Memorial Center, Homi Bhabha National Institute, Mumbai, India
| | | | - Sunil Chopade
- Tata Memorial Center, Homi Bhabha National Institute, Mumbai, India
| | - Ajaykumar Singh
- Tata Memorial Center, Homi Bhabha National Institute, Mumbai, India
| | - Omshree Shetty
- Tata Memorial Center, Homi Bhabha National Institute, Mumbai, India
| | - Amit Dutt
- Tata Memorial Center, Homi Bhabha National Institute, Mumbai, India
| | - Shripad Banavali
- Tata Memorial Center, Homi Bhabha National Institute, Mumbai, India
| | - Kumar Prabhash
- Tata Memorial Center, Homi Bhabha National Institute, Mumbai, India
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Hung MS, Lin YC, Chen FF, Jiang YY, Fang YH, Lu MS, Lin CK, Yang TM, Lung J, Chen CC, Lee KD, Tsai YH. The potential and limitation of targeted chromosomal breakpoint sequencing for the ROS1 fusion gene identification in lung cancer. Am J Cancer Res 2022; 12:2376-2386. [PMID: 35693072 PMCID: PMC9185620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Accepted: 03/20/2022] [Indexed: 06/15/2023] Open
Abstract
ROS1 fusion genes are rare but important driver genes in lung cancer. Owing to their rarity, many clinicopathological features and treatment responses for each ROS1 fusion variant are still largely unknown and require further investigation. RNA is the preferable template for the ROS1 fusion gene screening, but deterioration of RNA in FFPE often makes the detection challenging. To resolve the difficulty, a targeted chromosomal breakpoint sequencing method was developed for searching the ROS1 fusion gene, and was compared with fluorescence in situ hybridization, immunohistochemistry, RT-qPCR using 260 lung cancer samples of Southern Taiwan. The results showed that ROS1-altered cases were present at low frequencies, did not share distinct clinicopathological features, and often carried other driver mutations. The performance of the targeted sequencing assay was superior to the RT-qPCR in ROS1 fusion gene identification when the cDNAs were from FFPE samples, but long-read DNA sequencing and fresh-frozen samples would be better to revolve all fusion genes. Precise determination of all ROS1 fusion variants and concomitant driver mutations using both genomic DNA and RNA would be required to help improve the treatment of patients with ROS1 alterations.
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Affiliation(s)
- Ming-Szu Hung
- Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi BranchTaiwan
- Department of Medicine, College of Medicine, Chang Gung UniversityTaoyuan, Taiwan
- Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi CampusChiayi, Taiwan
| | - Yu-Ching Lin
- Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi BranchTaiwan
- Department of Medicine, College of Medicine, Chang Gung UniversityTaoyuan, Taiwan
- Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi CampusChiayi, Taiwan
| | - Fen-Fen Chen
- Department of Pathology, Chang Gung Memorial Hospital, Chiayi BranchTaiwan
| | - Yuan-Yuan Jiang
- Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi BranchTaiwan
| | - Yu-Hung Fang
- Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi BranchTaiwan
| | - Ming-Shian Lu
- Department of Surgery, Division of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Chiayi BranchTaiwan
| | - Chin-Kuo Lin
- Department of Medicine, College of Medicine, Chang Gung UniversityTaoyuan, Taiwan
| | - Tsung-Ming Yang
- Department of Medicine, College of Medicine, Chang Gung UniversityTaoyuan, Taiwan
| | - Jrhau Lung
- Department of Medical Research and Development, Chang Gung Memorial Hospital, Chiayi BranchTaiwan
| | - Chih-Cheng Chen
- Department of Medicine, College of Medicine, Chang Gung UniversityTaoyuan, Taiwan
- Department of Hematology and Oncology, Chang Gung Memorial Hospital, Chiayi BranchTaiwan
| | - Kuan-Der Lee
- Department of Hematology and Oncology, Taipei Medical University HospitalTaipei 110, Taiwan
| | - Ying-Huang Tsai
- Department of Respiratory Care, College of Medicine, Chang Gung UniversityTaoyuan, Taiwan
- Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Linkou BranchTaiwan
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Behel V, Noronha V, Patil V, Menon N, Chandrani P, Kumar R, Rastogi S, Mahajan A, Chougule A, Dutt A, Prabhash K. Molecular tumor board–guided treatment of non-small-cell lung cancer with dual driver (ALK and EGFR) alterations. CANCER RESEARCH, STATISTICS, AND TREATMENT 2022; 5:312-316. [DOI: 10.4103/crst.crst_114_22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Yin Q, Guo T, Zhou Y, Sun L, Meng M, Ma L, Wang X. Effectiveness of alectinib and osimertinib in a brain metastasized lung adenocarcinoma patient with concurrent
EGFR
mutations and
DCTN1‐ALK
fusion. Thorac Cancer 2021; 13:637-642. [PMID: 34964276 PMCID: PMC8841708 DOI: 10.1111/1759-7714.14291] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 12/06/2021] [Accepted: 12/08/2021] [Indexed: 12/17/2022] Open
Abstract
The echinoderm microtubule associated protein‐like 4 gene (EML4) encodes the predominant anaplastic lymphoma kinase (ALK) fusion partner in non‐small‐cell lung cancer (NSCLC); however, the dynactin subunit 1 (DCTN1)‐ALK rearrangement is extremely rare. The co‐occurrence of primary epidermal growth factor receptor (EGFR) T790M mutation with EGFR exon 19 deletion (del) in patients with NSCLC is uncommon. Here we report a female lung adenocarcinoma patient with brain metastases and possible coexistence of primary EGFR T790M mutation/EGFR exon 19 del/DCTN1‐ALK translocation. The patient received multiline treatment including chemotherapy, antivascular, and targeted therapies. To overcome developed resistance to chemotherapy or targeted therapy to prolong overall survival, the patient's circulating tumor DNA (ctDNA) was dynamically monitored. The patient responded to successive osimertinib and alectinib treatment, and alectinib achieved a nearly complete response for lung and brain lesions after she acquired osimertinib resistance. Furthermore, we summarize 22 published cases of patients with lung adenocarcinoma with concurrent EGFR mutation and ALK rearrangement, including details of clinical characteristics, natural history, and pertinent therapy of this uncommon tumor subtype. This literature review shows that EGFR inhibition was an indispensable aspect of the treatment of patients with EGFR/ALK co‐alterations in the pre‐alectinib era and that ALK inhibition with crizotinib did not show more eye‐catching therapeutic results. Considering the effectiveness achieved by alectinib, this case study provides a new perspective for the treatment of lung cancer brain metastasis patients with concurrent EGFR/ALK mutations.
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Affiliation(s)
- Qiang Yin
- Department of Neurosurgery and Neuro‐Oncology Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin's Clinical Research Center for Cancer Tianjin China
| | - Taiyan Guo
- The Medical Department Nanjing Simcere Medical Laboratory Science Co., Ltd, The State Key Lab of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd Nanjing China
| | - Yangyang Zhou
- Division of Pulmonary Medicine Tianjin Institute of Respiratory Diseases, Tianjin Haihe Hospital Tianjin China
| | - Leina Sun
- Department of Pathology Tianjin Medical University Cancer Institute & Hospital Tianjin China
| | - Maobin Meng
- Department of Radiotherapy Tianjin Medical University Cancer Institute & Hospital Tianjin China
| | - Li Ma
- Department of Neurosurgery and Neuro‐Oncology Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin's Clinical Research Center for Cancer Tianjin China
| | - Xiaoguang Wang
- Department of Neurosurgery and Neuro‐Oncology Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin's Clinical Research Center for Cancer Tianjin China
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Lu Z, Wang X, Luo Y, Wei J, Zeng Z, Xiong Q, Cai J, Liu A. EGFR (p. G719A+L747V)/EML4-ALK Co-alterations in Lung Adenocarcinoma with Leptomeningeal Metastasis Responding to Afatinib Treatment: A Case Report. Onco Targets Ther 2021; 14:2823-2828. [PMID: 33935502 PMCID: PMC8079359 DOI: 10.2147/ott.s294635] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Accepted: 04/06/2021] [Indexed: 11/29/2022] Open
Abstract
Leptomeningeal metastasis (LM) is a disastrous complication of advanced lung adenocarcinoma (LAC) associated with poor prognosis and rapid deterioration of performance status. The prevalence of epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) co-alterations in patients with LAC was low. Herein, we report a patient with alterations in both EGFR (p. G719A+L747V) and echinoderm microtubule-associated protein-like ALK (EML4-ALK) fusion and LM who was treated with afatinib. The patient’s clinical symptoms improved, and imaging examination revealed reduced intracranial and extracranial lesions. The progression-free survival (PFS) using afatinib for LM was 25 months, and no severe adverse events occurred.
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Affiliation(s)
- Zhiqin Lu
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People's Republic of China
| | - Xia Wang
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People's Republic of China.,Jiangxi Key Laboratory of Clinical Translational Cancer Research, Nanchang, Jiangxi Province, People's Republic of China
| | - Yuxi Luo
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People's Republic of China
| | - Jianping Wei
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People's Republic of China
| | - Zhimin Zeng
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People's Republic of China.,Jiangxi Key Laboratory of Clinical Translational Cancer Research, Nanchang, Jiangxi Province, People's Republic of China
| | - Qiang Xiong
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People's Republic of China.,Jiangxi Key Laboratory of Clinical Translational Cancer Research, Nanchang, Jiangxi Province, People's Republic of China
| | - Jing Cai
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People's Republic of China.,Jiangxi Key Laboratory of Clinical Translational Cancer Research, Nanchang, Jiangxi Province, People's Republic of China
| | - Anwen Liu
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People's Republic of China.,Jiangxi Key Laboratory of Clinical Translational Cancer Research, Nanchang, Jiangxi Province, People's Republic of China
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Noronha V, Talreja V, Joshi A, Patil V, Mahajan A, Prabhash K. Coexistence of epidermal growth factor receptor mutation and anaplastic lymphoma kinase translocation in non-small cell lung cancer: Do we know the treatment sequence? CANCER RESEARCH, STATISTICS, AND TREATMENT 2019; 2:119. [DOI: 10.4103/crst.crst_26_19] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
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