Dataset Information

Radiofrequency Ablation with Continued EGFR Tyrosine Kinase Inhibitor Therapy Prolongs Disease Control in EGFR-Mutant Advanced Lung Cancers with Acquired Resistance to EGFR Tyrosine Kinase Inhibitors: Two Case Reports.

ABSTRACT: Objective:Lung cancer remains the leading cause of malignant tumor-related death globally. There is mounting evidence that a large proportion of patients harboring epidermal growth factor receptor (EGFR) mutation and treated with EGFR TKI experience oligoprogressive disease. The optimal treatment strategy for these patients is undetermined. Thus, in this article, we report two cases of EGFR-mutant NSCLC patients with locally resistant lesions achieving disease control via combination therapy. Patients and Methods:We present two cases of lung adenocarcinoma patients that developed oligoprogressive disease during TKI treatment. For further treatment, the patient then received radiofrequency ablation. Results:Through follow-up observation, we found that the addition of radiofrequency ablation might provide the clinical benefit of these two NSCLC patients. Conclusion:Our two cases provide a promising treatment for oligoprogressive disease during the first-line EGFR-TKI therapy.

SUBMITTER: Shi X

PROVIDER: S-EPMC7369376 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Radiofrequency Ablation with Continued EGFR Tyrosine Kinase Inhibitor Therapy Prolongs Disease Control in EGFR-Mutant Advanced Lung Cancers with Acquired Resistance to EGFR Tyrosine Kinase Inhibitors: Two Case Reports.

Shi Xuefei X Zhou Jia J Qian Caihua C Gao Liliang L Wang Bin B Feng Xueren X

OncoTargets and therapy 20200713

<h4>Objective</h4>Lung cancer remains the leading cause of malignant tumor-related death globally. There is mounting evidence that a large proportion of patients harboring epidermal growth factor receptor (EGFR) mutation and treated with EGFR TKI experience oligoprogressive disease. The optimal treatment strategy for these patients is undetermined. Thus, in this article, we report two cases of EGFR-mutant NSCLC patients with locally resistant lesions achieving disease control via combination the ...[more]

PMID: 32764966

Similar Datasets

Project description:The non-small cell lung cancer (NSCLC) patients that experienced good clinical response to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKIs) will ultimately develop acquired resistance. This retrospective study was performed to explore the potential survival benefit of microwave ablation (MWA) therapy in epidermal growth factor receptor (EGFR)-mutant NSCLC that developed extra-central nervous system (CNS) oligoprogressive disease during TKI treatment.We retrospectively analyzed 54 NSCLC patients with EGFR mutations who showed a clinical benefit from initial EGFR-TKI therapy and developed extra-CNS oligoprogressive disease at our institutions. Twenty eight patients received MWA as a local therapy for the metastatic sites and continued on the same TKIs (MWA group). The following 26 patients received systemic chemotherapy after progression (chemotherapy group). The progression-free survival (PFS1) was calculated from initiation of targeted therapy to first progression. Progression-free survival (PFS2) was defined from first progression to second progression after MWA or chemotherapy. Overall survival (OS) was calculated from the time of diagnosis to the date of last follow-up or death.The median PFS1 for both groups was similar (median 12.6 vs. 12.9 months, HR 0.63). However, the MWA group patients had a significantly longer PFS2 (median 8.8 vs. 5.8 months, hazards ratio [HR] 0.357) and better OS (median 27.7 vs. 20.0, HR 0.238) in comparison with chemotherapy group. Multivariate analysis and the internal validation identified MWA as the main favorable prognostic factor for PFS2 and OS. In the MWA group, the median PFS2 for complete ablation was significantly longer than that for incomplete ablation (11 vs. 4.2 months, HR 0.29, P?<?0.05).MWA with continued EGFR inhibition might be associated with favorable progression-free survival (PFS) and OS in patients with extra-CNS oligometastatic disease. MWA as a local therapy for extra-CNS oligometastatic disease should be considered for NSCLC with acquired resistance to EGFR-TKIs.

Project description:BackgroundEpidermal growth factor receptor (EGFR) mutations are present in the majority of patients with non-small cell lung cancer (NSCLC) responsive to the EGFR tyrosine kinase inhibitors (TKIs) gefitinib or erlotinib. These EGFR-dependent tumors eventually become TKI resistant, and the common secondary T790M mutation accounts for half the tumors with acquired resistance to gefitinib. However, the key proapoptotic proteins involved in TKI-induced cell death and other secondary mutations involved in resistance remain unclear. The objective of this study was to identify the mechanism of EGFR TKI-induced apoptosis and secondary resistant mutations that affect this process.Methods and findingsTo study TKI-induced cell death and mechanisms of resistance, we used lung cancer cell lines (with or without EGFR mutations), Ba/F3 cells stably transfected with EGFR mutation constructs, and tumor samples from a gefitinib-resistant patient. Here we show that up-regulation of the BH3-only polypeptide BIM (also known as BCL2-like 11) correlated with gefitinib-induced apoptosis in gefitinib-sensitive EGFR-mutant lung cancer cells. The T790M mutation blocked gefitinib-induced up-regulation of BIM and apoptosis. This blockade was overcome by the irreversible TKI CL-387,785. Knockdown of BIM by small interfering RNA was able to attenuate apoptosis induced by EGFR TKIs. Furthermore, from a gefitinib-resistant patient carrying the activating L858R mutation, we identified a novel secondary resistant mutation, L747S in cis to the activating mutation, which attenuated the up-regulation of BIM and reduced apoptosis.ConclusionsOur results provide evidence that BIM is involved in TKI-induced apoptosis in sensitive EGFR-mutant cells and that both attenuation of the up-regulation of BIM and resistance to gefitinib-induced apoptosis are seen in models that contain the common EGFR T790M and the novel L747S secondary resistance mutations. These findings also suggest that induction of BIM may have a role in the treatment of TKI-resistant tumors.

Dataset Information

Radiofrequency Ablation with Continued EGFR Tyrosine Kinase Inhibitor Therapy Prolongs Disease Control in EGFR-Mutant Advanced Lung Cancers with Acquired Resistance to EGFR Tyrosine Kinase Inhibitors: Two Case Reports.

Publications

Radiofrequency Ablation with Continued EGFR Tyrosine Kinase Inhibitor Therapy Prolongs Disease Control in EGFR-Mutant Advanced Lung Cancers with Acquired Resistance to EGFR Tyrosine Kinase Inhibitors: Two Case Reports.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets