The Prevalence of the EML4-ALK Fusion Gene in Cytology Specimens from Patients with Lung Adenocarcinoma

Background. Under the National Comprehensive Cancer Network (NCCN) guidelines for non-small-cell lung carcinoma (NSCLC), anaplastic lymphoma kinase (ALK) gene rearrangement is required to be assessed. However, data showing the prevalence of the ALK rearrangement is still deficient and is not yet available in Indonesia. This study used direct smear preparation from transthoracic needle specimens that are minimally invasive. The main objective of the study is to identify the prevalence of the ALK fusion rearrangement gene in cytological specimens. Materials and Methods. A total of 35 direct smear preparations diagnosed as lung adenocarcinoma and EGFR mutation negative were involved in this study. The samples were taken between 2017 and 2019. These samples were examined for EML4-ALK fusion rearrangement gene using qRT-PCR. The EML4-ALK rearrangement status was determined by qRT-PCR with high-resolution melting (HRM) analysis. Results. A total of 28 (80%) samples were from males, and 7 samples were from females. Seven (20% 95% CI: 8.4%-36.9%) samples were EML4-ALK rearrangement positive. The average age of the patients was 63.5 years old. The most common sites of metastasis in this study were pleural cavity, bone, liver, and CNS. Conclusions. qRT-PCR successfully identified EML4-ALK fusion rearrangement in direct smear preparations of lung adenocarcinoma. Direct smear samples can be used for EML4-ALK rearrangement detection using qRT-PCR. The EML4-ALK rearrangement gene has high prevalence in selected lung adenocarcinoma and EGFR mutation-negative populations. ALK inhibitors in lung cancer can be openly considered for use in Indonesian patients to improve the outcome of this subset of patients.

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Two different patterns of lung adenocarcinoma with concomitant EGFR mutation and ALK rearrangement

Tumori Journal ◽

10.1177/03008916211005546 ◽

2021 ◽

pp. 030089162110055

Author(s):

Dashi Zhao ◽

Jun Fan ◽

Li Peng ◽

Bo Huang ◽

Yili Zhu ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Egfr Mutation ◽

Growth Factor Receptor ◽

Egfr Mutations ◽

Alk Rearrangement ◽

Molecular Alterations ◽

Anaplastic Lymphoma ◽

Sporadic Cases ◽

Epidermal Growth ◽

Rare Group

Epidermal growth factor receptor ( EGFR) mutations and anaplastic lymphoma kinase ( ALK) rearrangements are considered mutually exclusive in non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma (LUAC). However, sporadic cases harboring concomitant EGFR and ALK alterations have been increasingly reported. There is no consensus opinion regarding the treatment of patients positive for both molecular alterations. NSCLC with EGFR/ ALK coalterations should be separated into two subtypes: unifocal and multifocal LUAC. Here, we present an overview of the available literature regarding this rare group of patients to provide useful suggestions for therapeutic strategies.

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Real-world evidence in the treatment of metastatic non-small cell lung cancer in a single institution of Colombia in the period August 2015 to August 2018.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e18204 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e18204-e18204

Author(s):

Luis Eduardo Pino ◽

Aylen Vanessa Ospina Serrano ◽

Ivan Camilo Triana

Keyword(s):

Lung Cancer ◽

Clinical Characteristics ◽

Egfr Mutation ◽

Small Cell Lung Carcinoma ◽

Target Therapy ◽

Stage Iv ◽

Small Cell ◽

Small Cell Lung ◽

Alk Rearrangement ◽

Cell Lung Carcinoma

e18204 Background: In Colombia, lung cancer is the first cause of mortality. However, there is a large gap in terms of the information available regarding the characteristics and survival of these patients in the country. Methods: This is an observational, descriptive study of a cohort of patients with stage IV non-small cell lung carcinoma who initiated medical treatment at Fundación Santa Fe de Bogotá, a high complexity hospital. We analyzed clinical characteristics, oncogenic addiction expression, PDL1 expression, treatments, progression free survival (PFS), overall survival (OSm) and treatment related complications. Results: Twenty-six patients were included during the 3 years. The OSm for all the cohort was 19.6 months(m). In the group without PDL-1 expression and negative for oncogenic addiction that received treatment with chemotherapy the OSm was 16.9m and the PFS 9.6m. The OSm for the group with EGFR mutation that received target therapy was 24,7m and the PFS 13.11m. The patients with ALK rearrangement treated with target therapy had an OSm 17m and PFS 5m. The group with expression greater than 50% for PDL-1 that received only immunotherapy OSm was 9.5m and PFS 9m, and in the group with expression for PDL-1 between 1-49% the median OSm and PFS has not been reached. In relation with grade 3 toxicity, 7% of patients that received chemotherapy had kidney failure, 7% emesis and 15% hyporexia. Patients that received target therapy 9% had diarrhea and 9% hepatotoxicity. 9% of patients with bevacizumab presented bleeding and 8% of patients with immunotherapy had autoimmune colitis, in all these cases the medication was suspended. Hypothyroidism was the most frequent complication with the immunotherapy, and it was resolved with substitution therapy. Conclusions: Clinical characteristics and outcomes of this cohort were similar to other lung cancer patients series. Factors like cigarette, nutritional status and ECOG were no significant in the survival. 34,6% of patients had EGFR mutation and 7% had ALK rearrangements. Related to PDL1 we found 26% expresser patients. The highest OS and PFS was for the group with the EGFR mutation and for the group with PDL-1 expression between 1-49%.

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Frequency of Anaplastic Lymphoma Kinase (ALK) Rearrangement in Turkish Patients with Non-small Cell Lung Carcinoma

International Journal of Human Genetics ◽

10.31901/24566330.2018/18.1.673 ◽

2018 ◽

Vol 18 (01) ◽

Author(s):

Kanay Yararbas

Keyword(s):

Lung Carcinoma ◽

Anaplastic Lymphoma Kinase ◽

Small Cell Lung Carcinoma ◽

Small Cell ◽

Small Cell Lung ◽

Alk Rearrangement ◽

Cell Lung Carcinoma ◽

Anaplastic Lymphoma ◽

Turkish Patients

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Efficacy and Biomarkers of Advanced Non-small Cell Lung Carcinoma (NSCLC) Patients Receiving Different PD-1 Agents in Northern China: A Real-world Clinical Study

10.21203/rs.3.rs-130708/v1 ◽

2020 ◽

Author(s):

Man Jiang ◽

Xiaochun Zhang

Keyword(s):

Real World ◽

Tp53 Mutation ◽

Small Cell Lung Carcinoma ◽

Objective Response ◽

Egfr Mutations ◽

Alk Rearrangement ◽

Cell Lung Carcinoma ◽

Anaplastic Lymphoma ◽

Potential Biomarker ◽

Nsclc Patients

Abstract Aim and Methods: From May 2019 to January 2020, 116 advanced NSCLC patients with programmed death ligand-1 (PD-L1) expression > 1% were treated with nivolumab (44), pembrolizumab (21), and toripalimab (51) as a mono-therapy, respectively. The primary endpoints were defined as the objective response rate (ORR) after 3 and 6 months of therapy, and the progression-free survival (PFS). The observed efficacy of the different PD-1 antibodies was also compared. The gene mutation statuses of tumor protein p53 (TP53), epidermal growth factor receptor ( EGFR ), and anaplastic lymphoma kinase ( ALK ), the tumor mutational burden (TMB), along with the expression of CD47 were analyzed.Results: Toripalimab had a higher ORR and a longer PFS than the other two PD-1 agents after 3 months of evaluation (P = 0.0178). Thenon-classical mutations of EGFR (EGFRG719C and EGFRE709V) did not significantly influence the efficacy of the PD-1 inhibitors, while TP53 mutation, high TMB and elevated PD-L1 expression showed benefits. EGFR co-mutated genes were enriched in the “Response to osmotic stress” , “response to oxidative stress” and “myeloid leukocyte activation” pathways. CD47 expression showed a negative correlation to the prognosis of anti-PD-1 therapy. Participants with ALK rearrangement exhibited poor clinical outcomes. Conclusions: Toripalimab seemed to have a more rapid effect and provide a longer PFS than pembrolizumab and nivolumab. The PD-1 blockade therapy was benefited by TP53 mutation, high TMB, and elevated PD-L1 expression. CD47 expression is a potential biomarker to predict the efficacy of PD-1 blockade treatment in patients with EGFR mutations.Clinical Trail : Real-World Study of Four PD-1 Agents in China(May/22/2019)Trial Registration number: NCT03966456 URL:https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0008Y4C&selectaction=Edit&uid=U00045OC&ts=3&cx=z2uldc

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A novel GHR-ALK fusion gene in a patient with metastatic lung adenocarcinoma and its response to crizotinib: a case report

Journal of International Medical Research ◽

10.1177/03000605211044652 ◽

2021 ◽

Vol 49 (9) ◽

pp. 030006052110446

Author(s):

Xue Pan ◽

Anyuan Zhong ◽

Yufei Xing ◽

Xi Li ◽

Haiwei Du ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Growth Hormone Receptor ◽

Kinase Inhibitors ◽

Fusion Gene ◽

Fusion Partner ◽

Alk Rearrangement ◽

Lung Cancers ◽

Anaplastic Lymphoma ◽

Metastatic Lung ◽

Generation Sequencing

Anaplastic lymphoma kinase ( ALK) rearrangement occurs in approximately 5% of non-small cell lung cancers (NSCLCS), and EML4-ALK is the most commonly observed ALK fusion variant in NSCLC. However, growth hormone receptor ( GHR) as the fusion partner for ALK and the clinical response to ALK tyrosine kinase inhibitors in patients with metastatic lung adenocarcinoma (LUAD) who carry the GHR-ALK variant have not been documented. This case describes a 63-year-old woman diagnosed with metastatic LUAD. Immunohistochemistry revealed positive ALK expression, and the patient was treated with crizotinib. After 3 weeks of treatment, the patient had a partial response. Because of treatment-related adverse events, the dose of crizotinib was reduced. After 3.7 months, computed tomography uncovered disease progression. Next-generation sequencing identified a novel GHR-ALK fusion in the plasma of the patient. The patient was treated again with crizotinib, but the disease progressed again 2 months later. Then, the patient received chemotherapy. She succumbed to her disease 11 months after the initial diagnosis. Our work provides evidence supporting the use of crizotinib in patients with metastatic LUAD harboring GHR-ALK.

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The Investigation of EGFR mutation and ALK gene rearrangement rates in lung adenocarcinoma patients in Mardin

Medical Science and Discovery ◽

10.36472/msd.v6i11.319 ◽

2019 ◽

Vol 6 (11) ◽

pp. 292-294

Author(s):

Aydın Aytekin

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

State Hospital ◽

Egfr Mutation ◽

Genetic Alterations ◽

Mutation Rates ◽

Categorical Variables ◽

Continuous Variables ◽

Alk Rearrangement ◽

Anaplastic Lymphoma

Objective: Non-Small Cell Lung Cancer (NSCLC) is a heterogeneous group of tumors comprising different histologic subtypes and genetic mutations. Important mutations are EGFR (Epidermal Growth Factor Receptor), ALK (Anaplastic Lymphoma Kinase) rearrangement and ROS 1 rearrangement. This study aimed to determine the mutation rates of lung adenocarcinoma patients admitted to Mardin State Hospital Oncology clinic and to review the literature on the term mutually exclusivity. Materials and Methods: The records of patients admitted to Mardin State Hospital Medical Oncology Clinic between 2014-2018 were retrospectively analyzed. The descriptive statistics for continuous variables mean/median; for categorical variables, frequency (n) and percentage (%) were shown. Results: There were 39 lung adenocarcinoma patients (30.2%) among 130 lung cancer patients. The median age of female patients was 49.31 (27-74), while the median age of male patients was 58.87 (43-78). There were 6 EGFR mutant (15.4%) patients and 2 (5.1%) patients with ALK rearrangement. There were no ROS-1 positive patients. Conclusion: This study indicates that EGFR mutation rates may be very low in Turkey compared to the literature and ALK rates may be close to the literature. To determine the actual mutation rates and factors affecting genetic alterations in Turkey, there are needed to further studies.

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EML4-ALK positive lung adenocarcinoma with skeletal muscle metastasis in the right calf which was treatable with lorlatinib after resistance to treatment with alectinib

BMJ Case Reports ◽

10.1136/bcr-2020-240295 ◽

2021 ◽

Vol 14 (4) ◽

pp. e240295

Author(s):

Hironari Matsuda ◽

Munechika Hara ◽

Shin-Ichiro Iwakami ◽

Kazuhisa Takahashi

Keyword(s):

Skeletal Muscle ◽

Lung Adenocarcinoma ◽

Kinase Inhibitor ◽

Stable Condition ◽

Japanese Woman ◽

Alk Rearrangement ◽

Anaplastic Lymphoma ◽

Resistance To Treatment ◽

Alk Positive ◽

The Right

This report concerns a patient with skeletal muscle metastases due to lung adenocarcinoma harbouring an echinoderm microtubule-associated protein-like-4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangement, who was successfully treated with lorlatinib after resistance to alectinib. A right lower lobectomy based on a diagnosis of lung adenocarcinoma was performed on a 77-year-old Japanese woman. After 7 months of surgical resection, a mass in the right calf was observed. A fine-needle aspiration biopsy from the mass was performed and the mass was diagnosed as metastatic adenocarcinoma harbouring EML4-ALK rearrangement. Alectinib was administered for 10 months. Then, administration of lorlatinib, an ALK tyrosine kinase inhibitor classified as third generation, was initiated after resistance to treatment with alectinib. After starting treatment with lorlatinib, the gastrocnemius tumour diminished and has maintained a stable condition. Our case suggests that EML4-ALK positive lung adenocarcinoma is treatable with lorlatinib after resistance to treatment with alectinib.

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Frequency of EGFR Mutation and EML4-ALK fusion gene in Arab Patients with Adenocarcinoma of the Lung

Forum of Clinical Oncology ◽

10.1515/fco-2015-0009 ◽

2015 ◽

Vol 6 (2) ◽

pp. 19-23

Author(s):

Hanan Ezzat Shafik ◽

Mohamed Ashour

Keyword(s):

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Egfr Mutation ◽

Fusion Gene ◽

Receptor Gene ◽

Growth Factor Receptor ◽

Egfr Mutations ◽

Anaplastic Lymphoma ◽

Epidermal Growth

Abstract Introduction: Improvement in the clinical outcome of lung cancer is likely to be achieved by identification of the molecular events that underlie its pathogenesis. The frequency of epidermal growth factor receptor (EGFR) mutations is ethnicity-dependent, with a higher proportion in Asian populations than in whites, while the incidence of EML4-ALK (echinoderm microtubule-associated-protein like 4-anaplastic lymphoma kinase) fusion gene ranged from 1.6% to 16.4% in patients with NSCLC and these individuals were distinct from those harbouring mutations in the epidermal growth factor receptor gene. This study was conducted to determine the frequency of EGFR mutation and EML4-ALK fusion gene in our population and to determine the effect of different clinicopathological features on the expression of those mutations in patients with lung adenocarcinoma. Results: EGFR mutations were detected in approximately 33% of our patients in this series; the most frequently detected mutation was exon 19 deletion. EML4-ALK fusion gene was detected in 7.3% of patients. Conclusion: Our population exhibited the incidence of EGFR mutation approximately similar to that reported in East Asia and Japanese patients, higher than that recorded in USA, and Australia. However, more studies with larger patients’ numbers are needed to verify this finding.

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