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The diagnosis and treatment of brain metastases in EGFR mutant lung cancer.

ABSTRACT: The epidemiology of non-small-cell lung cancer (NSCLC) has changed with a new pattern of disease emerging - a form of adenocarcinoma in mostly younger female patients, who are never or light smokers and more frequently in East Asian populations. Description of EGF receptor (EGFR) mutations has allowed new management strategies to evolve. Oral targeted therapies have broadened the treatment options in the advanced setting with the potential for periods of long term response. The brain is a common site of metastases with EGFR mutated lung cancer typically displaying asymptomatic, small volume, multiple lesions that respond to treatment. We explore the role of local and system therapies for brain metastases in this disease including the role of EGFR inhibitors.

SUBMITTER: Minchom A

PROVIDER: S-EPMC6124369 | biostudies-other | 2014 May

REPOSITORIES: biostudies-other

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The diagnosis and treatment of brain metastases in EGFR mutant lung cancer.

Minchom Anna A Yu Ken C KC Bhosle Jaishree J O'Brien Mary M

CNS oncology 20140501 3

The epidemiology of non-small-cell lung cancer (NSCLC) has changed with a new pattern of disease emerging - a form of adenocarcinoma in mostly younger female patients, who are never or light smokers and more frequently in East Asian populations. Description of EGF receptor (EGFR) mutations has allowed new management strategies to evolve. Oral targeted therapies have broadened the treatment options in the advanced setting with the potential for periods of long term response. The brain is a common ...[more]

PMID: 25055129

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Cranial irradiation in patients with EGFR-mutant non-small cell lung cancer brain metastases.

Project description:The most effective treatment approach for brain metastases in patients with non-small cell lung cancer (NSCLC) and activating epidermal growth factor receptor (EGFR) mutations is a current subject of investigation. Cranial irradiation is the standard treatment for brain metastases, but tyrosine kinase inhibitors (TKIs) such as erlotinib have also activity against brain metastases in this subset of patients. The combination of TKI and radiotherapy is a promising one, but data is lacking to indicate whether this is superior to erlotinib or whole brain radiation therapy (WBRT) alone. Retrospective data suggest that WBRT achieves more durable intracranial control compared to erlotinib alone. Randomized, prospective studies will be necessary to determine whether TKI, cranial irradiation, or both is the optimal initial treatment for brain metastases in EGFR-mutant NSCLC.

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Detection of EGFR Mutations in Cerebrospinal Fluid of EGFR-Mutant Lung Adenocarcinoma With Brain Metastases.

Project description:BackgroundWe aimed to investigate the feasibility of detecting epidermal growth factor receptor (EGFR) mutations in cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) and plasma of advanced lung adenocarcinoma (LADC) with brain metastases (BMs) by droplet digital polymerase chain reaction (ddPCR).MethodsThirty advanced LADC patients with BMs were enrolled, and their matched CSF and plasma samples were collected. Droplet digital PCR was used to test cfDNA in CSF and plasma for EGFR mutation status. The clinical response and prognosis were evaluated.ResultsOut of 30 patients, there were 21 females and 9 males, aged 34-75 years. In all of the cases, CSF cytology were negative. In ddPCR assays, 10 patients (33.3%) had EGFR mutation in CSF, including 3 cases of EGFR T790M mutation, and 16 patients (53.3%) had EGFR mutation in plasma, including 6 cases of EGFR T790M mutation. Five patients with activating EGFR mutations in CSF achieved an intracranial partial response (iPR) after combination treatment with the first-generation EGFR-tyrosine kinase inhibitors. Three patients with EGFR T790M mutations in CSF achieved iPR after second-line osimertinib treatment. The median overall survival and intracranial progression-free survival were 17.0 months and 11.0 months, respectively.ConclusionIt was feasible to test EGFR mutation in cerebrospinal fluid and plasma. In LADC patients with brain metastasis, cerebrospinal fluid can be used as a liquid biopsy specimen to guide treatment strategy by monitoring EGFR mutation status.

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Erlotinib versus radiation therapy for brain metastases in patients with EGFR-mutant lung adenocarcinoma.

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Clinical factors associated with treatment outcomes in EGFR mutant non-small cell lung cancer patients with brain metastases: a case-control observational study.

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Neurological Death is Common in Patients With EGFR Mutant Non-Small Cell Lung Cancer Diagnosed With Brain Metastases.

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Radiotherapy in brain metastases from EGFR-mutated non-small cell lung cancer.

Project description:Epidermal growth factor receptor (EGFR) mutations are present in 20-40% of non-small cell lung cancers (NSCLCs). Brain metastasis (BM) is more common in EGFR-mutated NSCLC (25-45%) compared to EGFR wild-type (15-30%). First and second-generation tyrosine kinase inhibitors (TKIs), such as erlotinib and afatinib have proven to be superior to chemotherapy in the front-line treatment of EGFR-mutated NSCLC. Osimertinib, a third-generation EGFR TKI, has demonstrated better blood brain barrier (BBB) penetration, higher rate of intracranial response (66% vs. 43%) and a lower rate of CNS progression when compared to first generation EGFR TKI. Evidence on upfront radiation vs. upfront osimertinib is limited, but rapidly evolving and being tested in ongoing comparative trials. Stereotactic radiation (SRS) is very effective in the control of BMs and has been increasingly used and consequently replacing resection of BMs. SRS also has been increasingly used in the treatment of multiple BMs. Considering the effectiveness of targeted agents such as third generation EGFR inhibitors clinicians now are more frequently faced with the decision, if systemic therapy is safe and effective enough to withhold SRS. Third generation EGFR inhibitors also have fewer adverse events as previous generations. This review discusses the current literature available for management of BM in EGFR-mutated NSCLC.

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Effects of icotinib with and without radiation therapy on patients with EGFR mutant non-small cell lung cancer and brain metastases.

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| S-EPMC5362911 | biostudies-literature

Efficacy of nano-particulated, water-soluble erlotinib against intracranial metastases of EGFR-mutant lung cancer.

Project description:Central nervous system (CNS) metastasis is one of the serious complications of epidermal growth factor receptor (EGFR)-mutant lung cancer, which arises due to poor penetration of the brain-blood barrier by EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Although osimertinib, a third-generation EGFR-TKI, has efficacy against CNS metastases, further treatment modalities are still needed as some of these lesions do not respond to osimertinib, or undergo progression after an initial response to this drug if radiotherapy has already been conducted. Here, we investigated the efficacy of water-soluble erlotinib (NUFS-sErt) against these metastases. This agent was synthesized using a nano-particulation platform technology utilizing fat and supercritical fluid (NUFS™) to resolve the low solubility problem that typically prevents the creation of injectable forms of EGFR-TKIs. The average NUFS-sErt particle size was 236.4 nm, and it showed time-dependent dissolution in culture media. The effects of NUFS-sErt were similar to those of conventional erlotinib in terms of inhibiting the proliferation of EGFR-mutant lung cancer cells and suppressing EGFR signaling. In an intraperitoneal xenograft model of HCC827 cells, intraperitoneal administration of NUFS-sErt produced a dose-dependent inhibition of tumor growth and enhanced survival rate. Notably, the injection of NUFS-sErt into the brain ventricle caused significant tumor growth inhibition in an intracranial xenograft model. Hence, our current findings indicate that NUFS-sErt is a novel, water-soluble form of erlotinib that can be administered using intraventricular or intrathecal injections. The target cases would be patients with a progressive CNS metastasis and no other therapeutic options. This drug could also be given intravenously to patients with swallowing difficulties or an inability to ingest due to a medical condition.

| S-EPMC6275278 | biostudies-literature

Radiomic Signatures for Predicting <i>EGFR</i> Mutation Status in Lung Cancer Brain Metastases.

Project description:BackgroundLung cancer is the most common primary tumor metastasizing to the brain. A significant proportion of lung cancer patients show epidermal growth factor receptor (EGFR) mutation status discordance between the primary cancer and the corresponding brain metastases, which can affect prognosis and therapeutic decision-making. However, it is not always feasible to obtain brain metastases samples. The aim of this study was to establish a radiomic model to predict the EGFR mutation status of lung cancer brain metastases.MethodsData from 162 patients with resected brain metastases originating from lung cancer (70 with mutant EGFR, 92 with wild-type EGFR) were retrospectively analyzed. Radiomic features were extracted using preoperative brain magnetic resonance (MR) images (contrast-enhanced T1-weighted imaging, T1CE; T2-weighted imaging, T2WI; T2 fluid-attenuated inversion recovery, T2 FLAIR; and combinations of these sequences), to establish machine learning-based models for predicting the EGFR status of excised brain metastases (108 metastases for training and 54 metastases for testing). The least absolute shrinkage selection operator was used to select informative features; radiomics models were built with logistic regression of the training cohort, and model performance was evaluated using an independent test set.ResultsThe best-performing model was a combination of 10 features selected from multiple sequences (two from T1CE, five from T2WI, and three from T2 FLAIR) in both the training and test sets, resulting in classification area under the curve, accuracy, sensitivity, and specificity values of 0.85 and 0.81, 77.8% and 75.9%, 83.7% and 73.1%, and 73.8% and 78.6%, respectively.ConclusionsRadiomic signatures integrating multi-sequence MR images have the potential to noninvasively predict the EGFR mutation status of lung cancer brain metastases.

| S-EPMC9334014 | biostudies-literature

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