Novel MRPS9-ALK Fusion Mutation in a Lung Adenocarcinoma Patient: A Case Report

Anaplastic lymphoma kinase (ALK) rearrangements account for approximately 5–6% of non–small-cell lung cancer (NSCLC) patients. In this study, a case of lung adenocarcinoma harboring a novel MRPS9-ALK fusion is reported. The patient responded well to the first and second generation of ALK-tyrosine kinase inhibitors (ALK-TKIs) (crizotinib then alectinib), as her imaging findings and clinical symptoms significantly improved. At last follow-up, over 21 months of overall survival (OS) has been achieved since ALK-TKI treatment. The progression-free survival (PFS) is already ten months since alectinib. The adverse effects were manageable. The case presented here provides first clinical evidence of the efficacy of ALK-TKIs in NSCLC patients with MRPS9-ALK fusion.

Download Full-text

Case Report: Detection of Double ROS1 Translocations, SDC4-ROS1 and ROS1-GK, in a Lung Adenocarcinoma Patient and Response to Crizotinib

Frontiers in Medicine ◽

10.3389/fmed.2021.649177 ◽

2021 ◽

Vol 8 ◽

Author(s):

Long Xu ◽

Xiaoxia Chen ◽

Hong Huo ◽

Yongye Liu ◽

Xiaodan Yang ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Large Scale ◽

Molecular Subtype ◽

Brain Lesion ◽

Progression Free Survival ◽

Free Survival ◽

Highly Sensitive ◽

Duration Of Response ◽

Lung Adenocarcinoma Patient ◽

Nsclc Patients

ROS1 rearrangement, identified in ~2% of non-small cell lung cancer (NSCLC), has defined a distinctive molecular subtype. Patients with ROS1 fusion have been shown to be highly sensitive to treatment with crizotinib. However, the efficacy of crizotinib in NSCLC patients with double ROS1 fusions remains to be elucidated. Here, we report a 40-year-old male diagnosed with stage IIIA lung adenocarcinoma. Two ROS1 fusions [SDC4-ROS1 (EX2:EX32) and ROS1-GK (EX31:EX13)] were detected simultaneously in tumor tissue of this patient by next-generation sequencing. Crizotinib was administered, and the patient showed a partial response in lung lesions. Nevertheless, a brain lesion was found at 8 months after treatment. The slightly short duration of response may be related to the presence of ROS1-GK rearrangement. This case proved that patients with SDC4-ROS1 and ROS1-GK fusions may be sensitive to crizotinib, but short progression-free survival of this case showed that the presence of ROS1-GK rearrangement may affect the efficacy of crizotinib. A large-scale investigation on the efficacy of ROS1 inhibitors in patients with complex ROS1 fusions should be conducted in the future.

Download Full-text

Future Perspectives in Detecting EGFR and ALK Gene Alterations in Liquid Biopsies of Patients with NSCLC

International Journal of Molecular Sciences ◽

10.3390/ijms22083815 ◽

2021 ◽

Vol 22 (8) ◽

pp. 3815

Author(s):

Daniela Ferreira ◽

Juliana Miranda ◽

Paula Martins-Lopes ◽

Filomena Adega ◽

Raquel Chaves

Keyword(s):

Kinase Inhibitors ◽

Liquid Biopsies ◽

Assay Sensitivity ◽

Non Invasive ◽

Tki Treatment ◽

Nsclc Patients ◽

Next Generation Sequencing Ngs ◽

Routine Procedures ◽

The Impact

Non-small-cell lung cancer (NSCLC) is a major cause of death worldwide. Alterations in such genes as EGFR and ALK are considered important biomarkers in NSCLC due to the existence of targeted therapies with specific tyrosine kinase inhibitors (TKIs). However, specific resistance-related mutations can occur during TKI treatment, which often result in therapy inefficacy. Liquid biopsies arise as a reliable tool for the early detection of these types of alterations, allowing a non-invasive follow-up of the patients. Furthermore, they can be essential for cancer screening, initial diagnosis and to check surgery success. Despite the great advantages of liquid biopsies in NSCLC and the high input that next-generation sequencing (NGS) approaches can provide in this field, its use in oncology is still limited. With improvement of assay sensitivity and the establishment of clinical guidelines for liquid biopsy analysis, it is expected that they will be used in routine procedures. This review focuses on the usefulness of liquid biopsies of NSCLC patients as a means to detect alterations in EGFR and ALK genes and in disease management, highlighting the impact of NGS methods.

Download Full-text

Neoadjuvant EGFR-TKI Therapy for EGFR-Mutant NSCLC in Traditionally Unresectable Patients

10.21203/rs.3.rs-578508/v1 ◽

2021 ◽

Author(s):

Ke-Cheng Chen ◽

Shuenn-Wen Kuo ◽

Chen-Hao Hsiao ◽

Jing-Shing Chen

Keyword(s):

Thoracic Surgery ◽

Lung Adenocarcinoma ◽

Surgical Resection ◽

Kinase Inhibitors ◽

Growth Factor Receptor ◽

Progression Free Survival ◽

Egfr Mutations ◽

Multidisciplinary Management ◽

Advanced Stage ◽

Nsclc Patients

Abstract IntroductionAdvanced stage non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations may have benefit from tyrosine kinase inhibitors (TKI). However, the role of multidisciplinary management including neoadjuvant TKI therapy and thoracic surgery is uncertain. This study assessed the possible impact of neoadjuvant TKI therapy and thoracic surgery in selected advanced stage patients.MethodsAdvanced stage of IIIB and IVA NSCLC patients were retrospectively reviewed from 2010 to 2013. Patients with EGFR mutations who received neoadjuvant TKI followed by surgical resection were included. All patients were followed up for 5 years or until death.ResultsThere were total 15 advanced stage lung adenocarcinoma patients in the study. 8 patients were stage IIIB and 7 were stage IVA. All tumor sizes significantly decreased after neoadjuvant TKI therapy (p value = 0.0002). 11 patients received adjuvant TKI therapy after surgical resection and others received adjuvant cisplatin-based chemotherapy. Progression-free survival was superior in the group of adjuvant TKI therapy than in the group of adjuvant chemotherapy (median 14 months versus 5.9 months, p value = 0.016). Overall survival (OS) was not different between two groups (p value = 0.755). In the group of adjuvant TKI therapy, median OS in patients harboring exon 19 deletion and exon 21 L858R was 60 months and 44.9 months, respectively (p value = 0.078). ConclusionTKI may decrease the size of EGFR mutation lung adenocarcinoma. A multidisciplinary management including neoadjuvant TKI therapy and thoracic surgery may be discussed in selected advanced stage lung adenocarcinoma.

Download Full-text

Detection of TP53 Mutations in Tissue or Liquid Rebiopsies at Progression Identifies ALK+ Lung Cancer Patients with Poor Survival

Cancers ◽

10.3390/cancers11010124 ◽

2019 ◽

Vol 11 (1) ◽

pp. 124 ◽

Cited By ~ 9

Author(s):

Petros Christopoulos ◽

Steffen Dietz ◽

Martina Kirchner ◽

Anna-Lena Volckmar ◽

Volker Endris ◽

...

Keyword(s):

Lung Cancer ◽

Kinase Inhibitors ◽

Stage Iv ◽

Progression Free Survival ◽

Resistance Mechanisms ◽

Wild Type ◽

Tp53 Mutations ◽

Lung Cancer Patients ◽

Anaplastic Lymphoma ◽

Nsclc Patients

Anaplastic lymphoma kinase (ALK) sequencing can identify resistance mechanisms and guide next-line therapy in ALK+ non-small-cell lung cancer (NSCLC), but the clinical significance of other rebiopsy findings remains unclear. We analysed all stage-IV ALK+ NSCLC patients with longitudinally assessable TP53 status treated in our institutions (n = 62). Patients with TP53 mutations at baseline (TP53mutbas, n = 23) had worse overall survival (OS) than patients with initially wild-type tumours (TP53wtbas, n = 39, 44 vs. 62 months in median, p = 0.018). Within the generally favourable TP53wtbas group, detection of TP53 mutations at progression defined a “converted” subgroup (TP53mutconv, n = 9) with inferior OS, similar to that of TP53mutbas and shorter than that of patients remaining TP53 wild-type (TP53wtprogr, 45 vs. 94 months, p = 0.043). Progression-free survival (PFS) under treatment with tyrosine kinase inhibitors (TKI) for TP53mutconv was comparable to that of TP53mutbas and also shorter than that of TP53wtprogr cases (5 and 8 vs. 13 months, p = 0.0039). Fewer TP53wtprogr than TP53mutbas or TP53mutconv cases presented with metastatic disease at diagnosis (67% vs. 91% or 100%, p < 0.05). Thus, acquisition of TP53 mutations at progression is associated with more aggressive disease, shorter TKI responses and inferior OS in ALK+ NSCLC, comparable to primary TP53 mutated cases.

Download Full-text

Emerging a Novel VOPP1-EGFR Fusion Coexistent With T790M as an Acquired Resistance Mechanism to Prior Icotinib and Sensitive to Osimertinib in a Patient With EGFR L858R Lung Adenocarcinoma: A Case Report

Frontiers in Oncology ◽

10.3389/fonc.2021.720819 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xia Wang ◽

Weiwei Peng ◽

Zhimin Zeng ◽

Jing Cai ◽

Anwen Liu

Keyword(s):

Case Report ◽

Lung Adenocarcinoma ◽

Kinase Inhibitors ◽

Fusion Gene ◽

Acquired Resistance ◽

Resistance Mechanism ◽

Growth Factor Receptor ◽

Progression Free Survival ◽

Egfr Tyrosine Kinase Inhibitors ◽

Nsclc Patients

BackgroundEpidermal growth factor receptor (EGFR) fusions are rare genomic events in non-small-cell lung cancer (NSCLC). Clinical support and evidence to guide management are absent for NSCLC patients harboring EGFR fusion.Case PresentationIn this case report, we describe a 69-year-old female who received right lobectomy and was diagnosed with pathological stage IIIA lung adenocarcinoma harboring EGFR L858R. Twenty months later he had recurrent disease in the liver, lung, and bone, and was treated with icotinib. A novel vesicular overexpressed in cancer pro-survival protein 1 (VOPP1)-EGFR fusion gene coexistent with T790M were identified by next-generation sequencing using pericardial effusion and blood samples after icotinib treatment, which led to progression after icotinib six months and suggested a potential resistance mechanism. Subsequently, the patient was switched to osimertinib treatment, which resulted in a progression-free survival interval of more than 11 months.ConclusionsThe present results suggested that acquired VOPP1-EGFR fusion gene with T790M potentially serve an additional resistance mechanism to first-generation EGFR tyrosine kinase inhibitors in EGFR-mutated NSCLC. And the present case increases the evidence supporting use of osimertinib for treatment of NSCLC patients harboring EGFR fusion.

Download Full-text

Efficacy of Osimertinib in NSCLC Harboring Uncommon EGFR L861Q and Concurrent Mutations: Case Report and Literature Review

Frontiers in Oncology ◽

10.3389/fonc.2021.731572 ◽

2021 ◽

Vol 11 ◽

Author(s):

Ruiting Lin ◽

Ruilian Chen ◽

Zhiqiang Chen ◽

Leihao Hu ◽

Wei Guo ◽

...

Keyword(s):

Kinase Inhibitors ◽

Growth Factor Receptor ◽

Progression Free Survival ◽

Free Survival ◽

First Line Therapy ◽

Epidermal Growth ◽

Good Treatment Option ◽

Nsclc Patients ◽

First And Second Generation ◽

Egfr Tkis

The efficacy of first-and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in NSCLC patients with the EGFR L861Q mutation has been studied previously. However, there is little evidence on the efficacy of osimertinib in NSCLC patients with uncommon mutations. Here, we report the case of a 68-year-old man with advanced NSCLC with concurrent EGFR L861Q mutation as well as TP53 and RB1 mutations. The patient was treated with osimertinib as first-line therapy and achieved a remarkable progression-free survival of 15 months. His symptoms were significantly alleviated and the dose was well tolerated. The findings of the present study indicate that osimertinib might be a good treatment option for NSCLC patients with the L861Q mutation.

Download Full-text

A Lung Adenocarcinoma Patient With a Rare EGFR E709_T710delinsD Mutation Showed a Good Response to Afatinib Treatment: A Case Report and Literature Review

Frontiers in Oncology ◽

10.3389/fonc.2021.700345 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yu Wei ◽

Yueli Cui ◽

Yao Guo ◽

Lei Li ◽

Liang Zeng

Keyword(s):

Lung Adenocarcinoma ◽

Kinase Inhibitors ◽

Growth Factor Receptor ◽

Progression Free Survival ◽

Insertion Mutation ◽

Lung Cancer Patients ◽

First Line Therapy ◽

Lung Adenocarcinoma Patient ◽

Epidermal Growth ◽

L858r Mutation

For advanced lung adenocarcinoma patients with common epidermal growth factor receptor (EGFR) mutations (exon 19 deletions or the exon 21 L858R mutation), tyrosine kinase inhibitors (TKIs) are the standard therapies, and achieve favorable responses. However, for the rare EGFR deletion-insertion mutation of exon 18, there is no evidence of the efficacy of EGFR TKIs. Herein, we report a lung adenocarcinoma patient harboring a rare EGFR E709_T710delinsD mutation who was treated with afatinib as the first-line therapy and achieved a progression-free survival of 23 months. After the disease progressed, the patient received almonertinib treatment and exhibited a stable disease. This case indicated that non-small cell lung cancer patients harboring the EGFR E709_T710delinsD mutation could benefit from afatinib treatment, followed with almonertinib treatment, as a potential therapeutic strategy.

Download Full-text

The combination of fibrinogen concentrations and the platelet-to-lymphocyte ratio predicts survival in patients with advanced lung adenocarcinoma treated with EGFR-TKIs

Journal of International Medical Research ◽

10.1177/03000605211004021 ◽

2021 ◽

Vol 49 (4) ◽

pp. 030006052110040

Author(s):

Qiong He ◽

Yamin Li ◽

Xihong Zhou ◽

Wen Zhou ◽

Chunfang Xia ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Kinase Inhibitors ◽

Characteristic Curve ◽

Performance Status ◽

Univariate Analysis ◽

Progression Free Survival ◽

Platelet To Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Egfr Mutant ◽

Egfr Tkis

Objective This study aimed to identify a predictive marker of response to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR-mutant advanced lung adenocarcinoma. Methods A cohort of 190 patients with EGFR-mutant advanced lung adenocarcinoma was analyzed. Receiver operating characteristic curve analysis was used to evaluate the optimal cutoffs for fibrinogen levels, the neutrophil-to-lymphocyte ratio (NLR), and the platelet-to-lymphocyte ratio (PLR) for predicting progression-free survival (PFS). Univariate and multivariate survival analyses were performed to identify factors correlated with PFS and overall survival (OS). Results High NLR was associated with worse performance status. In univariate analysis, fibrinogen levels, NLR, and PLR were correlated with OS and PFS. In multivariate analysis, all three variables remained predictive of OS, whereas only fibrinogen levels and PLR were independent prognostic factors for PFS. Furthermore, the combination of fibrinogen levels and PLR (F-PLR score) could stratify patients into three groups with significantly different prognoses, and the score was independently predictive of survival. Conclusion The F-PLR score predicted the prognosis of patients with EGFR-mutant advanced lung adenocarcinoma who received EGFR-TKIs, and this score may serve as a convenient blood-based marker for identifying high-risk patients.

Download Full-text

Better Progression-Free Survival in Elderly Patients with Stage IV Lung Adenocarcinoma Harboring Uncommon Epidermal Growth Factor Receptor Mutations Treated with the First-line Tyrosine Kinase Inhibitors

Cancers ◽

10.3390/cancers10110434 ◽

2018 ◽

Vol 10 (11) ◽

pp. 434 ◽

Cited By ~ 4

Author(s):

Ming-Ju Tsai ◽

Jen-Yu Hung ◽

Mei-Hsuan Lee ◽

Chia-Yu Kuo ◽

Yu-Chen Tsai ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Kinase Inhibitors ◽

Growth Factor Receptor ◽

Stage Iv ◽

Progression Free Survival ◽

Egfr Mutations ◽

First Line ◽

Free Survival ◽

Younger Patients ◽

Epidermal Growth

Patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutations usually have a good response rate (RR) and longer progression-free survival (PFS) to EGFR tyrosine kinase inhibitors (TKIs). However, the treatment efficacy to uncommon EGFR mutations remains controversial. We, therefore, performed a retrospective study, screening 2958 patients. A total of 67 patients with lung adenocarcinoma harboring uncommon EGFR mutations were enrolled and 57 patients with stage IV diseases receiving a first-line EGFR TKI were included for further analyses. The patients were classified into 27 (47%) “a single sensitizing uncommon mutation”, 7 (12%) “multiple sensitizing mutations”, 5 (9%) “a sensitizing mutation and a resistant uncommon mutation”, and 18 (32%) “other resistant uncommon mutations”. No significant difference was noted in PFS or overall survival (OS) between groups. Patients receiving different first-line EGFR TKIs had similar PFS and OS. The elder patients had a significantly poorer performance status than the younger patients but a significantly longer PFS than the younger patients (median PFS: 10.5 vs. 5.5 months, p = 0.0320). In conclusion, this is the first study to identify that elderly patients with stage IV lung adenocarcinoma harboring uncommon EGFR mutation might have a longer PFS. Large-scale prospective studies are mandatory to prove our findings.

Download Full-text

Durable Response to the Combination of Atezolizumab With Platinum-Based Chemotherapy in an Untreated Non-Smoking Lung Adenocarcinoma Patient With BRAF V600E Mutation: A Case Report

Frontiers in Oncology ◽

10.3389/fonc.2021.634920 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xiaomin Niu ◽

Yingjia Sun ◽

David Planchard ◽

Luting Chiu ◽

Jian Bai ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Nsclc Patient ◽

Braf Inhibitor ◽

Progression Free Survival ◽

Braf V600e ◽

First Line ◽

Liquid Biopsies ◽

Durable Response ◽

Platinum Based Chemotherapy ◽

Lung Adenocarcinoma Patient

BackgroundImmune checkpoint inhibitor (ICPi) has become a major treatment in advanced non-small cell lung cancer (NSCLC) and demonstrated a clinical benefit for NSCLC patients with high programmed death ligand-1 (PD-L1) expression without EGFR/ALK/ROS1 drivers; however, the benefit in BRAF V600E NSCLC is so far unknown. Here, we report a case of prolonged tumor response to the combination of immunotherapy with chemotherapy in a non-smoking BRAF V600E NSCLC patient.Materials and MethodsWe verify a co-expression of BRAF V600E mutation and PD-L1 high expression more than 50% on formalin-fixed paraffin-embedded tumor sample of a newly diagnosed lung adenocarcinoma patient by immunohistochemistry and BRAF V600E/EGFR/ALK/ROS1 Mutations Detection Kit. The tissue and liquid biopsies were further subjected to next-generation sequencing (NGS) for identification of mutations with progression on immunotherapy and BRAF inhibitor (BRAFi). The patient had provided written informed consent and authorized the publication of clinical case.ResultsWe demonstrate the case of 62-year-old female non-smoker with high PD-L1 expression and BRAF V600E mutated NSCLC. The progression-free survival (PFS) of first-line combination of atezolizumab with platinum-based chemotherapy and sequential second-line treatment with BRAFi Vemurafenib are 20 and 5.5 months, respectively.ConclusionThis case shows a durable response to ICPi in BRAF V600E non-smoking lung adenocarcinoma with PFS of 20 months under first-line atezolizumab plus chemotherapy treatment. The case supports the idea that the combination immunotherapy may be an attractive option for BRAF V600E mutated non-smoking NSCLC with high PD-L1 expression.

Download Full-text