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1.
BMC Cancer ; 22(1): 580, 2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35614407

RESUMO

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) provide a better prognosis in EGFR-mutant non-small cell lung cancer (NSCLC). Nevertheless, the outcome of leptomeningeal metastasis (LM) remains poor. In addition, due to limited access to intracranial tumour tissue, gene alterations associated with leptomeningeal metastasis from lung adenocarcinoma (LM-LUAD) are unclear. METHODS: Forty-five patients with LM-LUAD from May 2019 to June 2021 in Guangdong Sanjiu Brain Hospital were enrolled in this study. Seventy-five percent (34/45) of patients with LM harbored EGFR mutations, and patients with progressive disease (PD) of LM had 3rd-generation EGFR-TKI therapy and were defined as Cohort 1; those without 3rd-generation EGFR-TKI therapy were defined as Cohort 2. Next-generation targeted panel sequencing (NGS) was performed in each cerebrospinal fluid (CSF) sample of the two cohorts, and 9/45 LM-LUAD patients had matched plasma (PLA). RESULTS: The common gene alterations discovered in the CSF of LM-LUAD were EGFR mutation (34/45, 75%), TP53 (25/45, 56%), CDKN2A (9/45, 20%), ALK (7/45, 16%), CTNNB1 (6/45, 13%), MET (5/45, 11%), APC (4/45, 9%), FGF4 (4/45, 9%), FGF3 (4/45, 9%), ERBB2 (4/45, 9%), and PIK3CG (4/45, 9%). Cooccurring mutations of TP53 and EGFR were found in 49% (22/45) of patients and correlated with poor prognosis. CDKN2A was identified in 20% (9/45) of patients and presented slightly shorter overall survival (OS) than those without (7.1 versus 8.8 months, p = 0.2). Cohort 1 had more genes associated with poor prognosis, consisting of CDK4, CDKN2A, PIK3CG, or PIK3CA, and YES1 and MET were more likely to be detected in cohort 2. The alteration of EGFR was comparable between CSF and matched PLA. Incidences of gene alterations such as CDK4, CDKN2A, MET, SOX2, JAK2, BRAF, and PIK3CG were more likely to be identified in CSF. All mutant allele frequencies (MAF) were much higher in CSF than in matched PLA. CONCLUSIONS: CSF could be a potential candidate for the genetic profiling of LM-LUAD, demonstrating the genetic characteristics of LM in EGFR-mutated lung adenocarcinoma on diverse EGFR-TKI therapies.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Líquido Cefalorraquidiano , Neoplasias Pulmonares , Carcinomatose Meníngea , Adenocarcinoma de Pulmão/complicações , Adenocarcinoma de Pulmão/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Líquido Cefalorraquidiano/química , Líquido Cefalorraquidiano/metabolismo , Receptores ErbB/líquido cefalorraquidiano , Receptores ErbB/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/patologia , Carcinomatose Meníngea/complicações , Carcinomatose Meníngea/secundário , Mutação , Inibidores de Proteínas Quinases
2.
Medicine (Baltimore) ; 99(43): e22851, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120820

RESUMO

RATIONALE: Liquid biopsy of cerebrospinal fluid (CSF) and sequencing of cell-free DNA has rarely been used to identify epidermal growth factor receptor (EGFR) mutations, which can guide the design of precise, personalized treatment for patients with leptomeningeal metastasis from lung adenocarcinoma. PATIENT CONCERNS: A 42-year-old woman with lung adenocarcinoma and leptomeningeal metastasis was admitted to our hospital on March 31, 2019. She exhibited no response to treatment with gefitinib, osimertinib, or chemoradiotherapy and was in critical condition, with an expected survival of <4 weeks. DIAGNOSIS: Next-generation sequencing of CSF and peripheral blood samples identified an EGFR complex mutation (exon19del+K754E). INTERVENTIONS: On April 10, 2019, the patient started oral afatinib (40 mg po qd), but she developed a grade III oral mucosal reaction 1 week later. The afatinib dose was reduced to 30 mg po qd. OUTCOMES: At the follow-up examination on May 15, 2019, the patient reported relief from headaches. Enhanced magnetic resonance imaging revealed a reduction in abnormal leptomeningeal enhancement, and the CSF pressure and carcinoembryonic antigen levels were also reduced. The patient continued to respond to afatinib treatment (30 mg once daily) with minimal adverse effects. LESSONS: This is the first case report of clinical improvement after afatinib treatment in a patient with lung adenocarcinoma and leptomeningeal metastasis harboring an EGFR complex mutation (exon19del+K754E), and thus provides a clinical reference for treatment with afatinib of cancers harboring EGFR compound mutations.


Assuntos
Afatinib/administração & dosagem , Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Meníngeas/secundário , Administração Oral , Adulto , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/líquido cefalorraquidiano , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Meníngeas/tratamento farmacológico , Neoplasias Meníngeas/patologia , Mutação
3.
Mol Oncol ; 13(12): 2633-2645, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31529604

RESUMO

Many advanced cases of cancer show central nervous system, pleural, or peritoneal involvement. In this study, we prospectively analyzed if cerebrospinal fluid (CSF), pleural effusion (PE), and/or ascites (ASC) can be used to detect driver mutations and guide treatment decisions. We collected 42 CSF, PE, and ASC samples from advanced non-small-cell lung cancer and melanoma patients. Cell-free DNA (cfDNA) was purified and driver mutations analyzed and quantified by PNA-Q-PCR or next-generation sequencing. All 42 fluid samples were evaluable; clinically relevant mutations were detected in 41 (97.6%). Twenty-three fluids had paired blood samples, 22 were mutation positive in fluid but only 14 in blood, and the abundance of the mutant alleles was significantly higher in fluids. Of the 34 fluids obtained at progression to different therapies, EGFR resistance mutations were detected in nine and ALK acquired mutations in two. The results of testing of CSF, PE, and ASC were used to guide treatment decisions, such as initiation of osimertinib treatment or selection of specific ALK tyrosine-kinase inhibitors. In conclusion, fluids close to metastatic sites are superior to blood for the detection of relevant mutations and can offer valuable clinical information, particularly in patients progressing to targeted therapies.


Assuntos
Acrilamidas/administração & dosagem , Quinase do Linfoma Anaplásico , Compostos de Anilina/administração & dosagem , Líquido Ascítico , Neoplasias Pulmonares , Mutação , Proteínas de Neoplasias , Derrame Pleural Maligno , Idoso , Quinase do Linfoma Anaplásico/genética , Quinase do Linfoma Anaplásico/metabolismo , Líquido Ascítico/metabolismo , Líquido Ascítico/patologia , Carcinoma Pulmonar de Células não Pequenas/líquido cefalorraquidiano , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/líquido cefalorraquidiano , Receptores ErbB/genética , Feminino , Células HT29 , Humanos , Neoplasias Pulmonares/líquido cefalorraquidiano , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/líquido cefalorraquidiano , Proteínas de Neoplasias/genética , Derrame Pleural Maligno/líquido cefalorraquidiano , Derrame Pleural Maligno/tratamento farmacológico , Derrame Pleural Maligno/genética , Estudos Prospectivos
4.
BMC Cancer ; 19(1): 702, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315676

RESUMO

BACKGROUND: The epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer has been successfully treated with tyrosine kinase inhibitors (TKIs). Acquired resistance becomes a tough issue when patients fail to respond to the third-generation TKI osimertinib. This study aimed to report a case baring acquired EGFR L858R/L718Q mutation in the central nervous system induced by osimertinib, which was successfully overcome using afatinib. CASE PRESENTATION: A 65-year-old female patient was diagnosed with stage IV non-small-cell lung adenocarcinoma with synchronic brain metastasis in February 2015. Before and during treatment, 416 tumor-related genes were monitored dynamically by liquid biopsies using next-generation sequencing, and the treatment strategy was decided according to the gene status. At baseline, an EGFR L858R mutation in exon 21 was detected, so treatment with icotinib was started. After 8 months, she experienced disease progression with leptomeningeal metastasis and switched to osimertinib based on an acquired EGFR T790 M mutation. After 9 months, her disease progressed and an EGFR L718Q mutation was found in the cerebrospinal fluid. The patient was then challenged with afatinib, and her disease was under control for 4 months. In January 2017, the patient passed away, with an overall survival time of 23 months, 15 months after leptomeningeal metastasis. CONCLUSION: The acquired EGFR L718Q mutation in the cerebrospinal fluid resulted in subsequent resistance to osimertinib and could be partly overcome using afatinib, indicating a promising treatment option in the clinic.


Assuntos
Acrilamidas/efeitos adversos , Afatinib/uso terapêutico , Compostos de Anilina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Carcinomatose Meníngea/secundário , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Acrilamidas/administração & dosagem , Acrilamidas/uso terapêutico , Afatinib/administração & dosagem , Idoso , Compostos de Anilina/administração & dosagem , Compostos de Anilina/uso terapêutico , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/genética , Éteres de Coroa/administração & dosagem , Éteres de Coroa/efeitos adversos , Progressão da Doença , Receptores ErbB/líquido cefalorraquidiano , Receptores ErbB/genética , Evolução Fatal , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/genética , Carcinomatose Meníngea/genética , Inibidores de Proteínas Quinases/administração & dosagem , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos
5.
Cancer Biother Radiopharm ; 34(2): 128-133, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30452286

RESUMO

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations are associated with leptomeningeal metastases (LM) of nonsmall cell lung cancer and sensitivity to tyrosine kinase inhibitor (TKI) treatment. Owing to the difficulty of obtaining carcinomatous meningeal tissue for analysis, cerebrospinal fluid (CSF) might be an alternative. OBJECTIVE: To investigate the EGFR mutation detection in the CSF of lung adenocarcinoma patients with LM. METHODS: Twenty-five lung adenocarcinoma patients with LM diagnosed by CSF cytology were retrospectively evaluated. The results of EGFR mutation detection in CSF, the treatment plan, and clinical outcome information were recorded. RESULTS: Nineteen patients had a known EGFR status in their primary tumors. Twenty patients received EGFR mutation analysis in CSF after LM diagnosis and 14 of them with a known EGFR mutation status of both primary tumors and CSF. Ten (71.4%) had the same EGFR gene status. In primary tumors, no T790M mutations were detected, whereas in CSF, 2 L858R cases and 1 19del case had T790M mutations at the same time. The detection rate of T790M mutations in CSF was 18.1% (2 of 11) in all cases with EGFR-sensitive mutations in the primary lesion. CONCLUSIONS: EGFR mutation detection in CSF of lung adenocarcinoma patients with LM might be an alternative when leptomeningeal biopsy cannot be applied and may help to guide TKI treatments.


Assuntos
Adenocarcinoma de Pulmão/genética , Líquido Cefalorraquidiano/química , Neoplasias Pulmonares/genética , Carcinomatose Meníngea/secundário , Mutação , Adenocarcinoma de Pulmão/líquido cefalorraquidiano , Adenocarcinoma de Pulmão/enzimologia , Adenocarcinoma de Pulmão/patologia , Receptores ErbB/líquido cefalorraquidiano , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/líquido cefalorraquidiano , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Masculino , Carcinomatose Meníngea/líquido cefalorraquidiano , Carcinomatose Meníngea/enzimologia , Carcinomatose Meníngea/genética , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos , Resultado do Tratamento
6.
Cytopathology ; 30(2): 144-149, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30471155

RESUMO

BACKGROUND: The cobas® epidermal growth factor receptor (EGFR) Mutation Test v2 designed for cell-free DNA (cfDNA) is approved as a companion diagnostic for osimertinib therapy. The aim of this study was to evaluate the concordance of EGFR mutation detection between paired primary or recurrent samples, and cerebrospinal fluid (CSF) cytology samples of lung cancer patients. METHODS: In total, 26 lung cancer patients with supernatant cytology cfDNA in CSF were analysed for EGFR mutations using the cobas® EGFR Mutation Test v2.0 designed for cfDNA, and the concordance rates between CSF cfDNA and primary or recurrent samples were investigated. RESULTS: Of the 26 CSF cytology cfDNA samples, 46.1% (12/26) were valid and 53.9% (14/26) were invalid. Sensitivity, specificity and accuracy between the valid CSF cfDNA samples and primary or recurrent samples for detection of EGFR mutation, including T790M were 87.5%, 100.0% and 91.7%, respectively. Amounts of both inflammatory cells and tumour cells in CSF cytology were higher in the valid evaluation samples than in the invalid samples (P < .05), and mutant EGFR was detected in 80.0% (4/5) of the valid CSF cytology cfDNA samples with a negative cytology diagnosis. CONCLUSIONS: The cobas® EGFR Mutation Test v2.0 can accurately detect EGFR mutations, including T790M, from supernatant cfDNA of CSF cytology samples. Utilisation of supernatant cytology cfDNA in CSF will allow us to perform both EGFR mutation analysis and cytopathological diagnosis at the same time. This represents a new role of cytology in patient treatment, based on assured sample quality.


Assuntos
Ácidos Nucleicos Livres/líquido cefalorraquidiano , Citodiagnóstico , Neoplasias Pulmonares/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Receptores ErbB/líquido cefalorraquidiano , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação/genética
7.
Intern Med ; 57(23): 3423-3427, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30101917

RESUMO

A 53-year-old man with advanced lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) exon 19 deletion received erlotinib. After 12 months of disease control with erlotinib monotherapy, leptomeningeal metastases (LM) occurred. A cerebrospinal fluid examination demonstrated a pre-existing EGFR exon 19 deletion. Bevacizumab was combined with erlotinib, and the LM improved. After six months of combination therapy, however, the LM was exacerbated. A re-examination of the cerebrospinal fluid revealed a T790M mutation and exon 19 deletion. Osimertinib was administered, and the LM improved. The combination of bevacizumab and erlotinib was effective for erlotinib-resistant LM and resulted in the expression of a newly acquired T790M mutation, which enabled successful treatment with osimertinib.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Deleção de Genes , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Carcinomatose Meníngea/secundário , Acrilamidas , Adenocarcinoma de Pulmão/patologia , Compostos de Anilina , Bevacizumab/uso terapêutico , Receptores ErbB/líquido cefalorraquidiano , Receptores ErbB/genética , Cloridrato de Erlotinib/uso terapêutico , Éxons , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Piperazinas/uso terapêutico , Resultado do Tratamento
9.
Br J Cancer ; 118(1): 32-37, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29190637

RESUMO

BACKGROUND: Osimertinib demonstrated promising efficacy for refractory leptomeningeal metastases (LM) in preclinical data and a clinical study at 160 mg, but there is limited data for the standard 80 mg dose. METHODS: T790M-positive patients with suspected LM after classical epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) failure were enroled. RESULTS: We investigated 13 patients (5 definitive and 8 possible LM cases). In two of the five definitive cases with T790M in and outside the central nervous system (CNS), osimertinib was effective for both lesions, with cerebrospinal fluid (CSF) clearance of cancer cells and sensitive/T790M mutations. In three definitive cases with extra-CNS T790M without CSF T790M, cancer cells and sensitive mutations in the CSF persisted after osimertinib initiation. The median progression-free survival of all 13 patients was 7.2 months. Osimertinib was generally well-tolerated despite poor performance status, but interstitial lung disease (grade 2) was confirmed in one patient. Based on 25 samples from 13 patients, the osimertinib CSF penetration rate was 2.5±0.3%. CONCLUSIONS: Osimertinib 80 mg is a useful therapeutic option for refractory LM after classical EGFR-TKI failure. It appears more effective in CSF T790M-positive cases.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Meníngeas/tratamento farmacológico , Neoplasias Meníngeas/secundário , Piperazinas/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Acrilamidas , Idoso , Compostos de Anilina , Carcinoma Pulmonar de Células não Pequenas/líquido cefalorraquidiano , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/líquido cefalorraquidiano , Receptores ErbB/genética , Humanos , Doenças Pulmonares Intersticiais/induzido quimicamente , Doenças Pulmonares Intersticiais/epidemiologia , Neoplasias Pulmonares/líquido cefalorraquidiano , Neoplasias Pulmonares/genética , Neoplasias Meníngeas/líquido cefalorraquidiano , Neoplasias Meníngeas/genética , Pessoa de Meia-Idade , Mutação , Projetos Piloto , Piperazinas/efeitos adversos , Piperazinas/líquido cefalorraquidiano , Intervalo Livre de Progressão , Estudos Prospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/líquido cefalorraquidiano , Resultado do Tratamento
10.
Respir Investig ; 54(1): 14-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26718140

RESUMO

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been successfully used to treat patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations. However, despite an initial excellent response, recurrence within one or two years is common. Diagnosis and treatment of leptomeningeal metastasis (LM), a form of NSCLC recurrence, remains particularly difficult. Here, we analyzed the EGFR mutation status of cerebrospinal fluid (CSF) directly using real-time polymerase chain reaction (PCR) and evaluated the efficacy of therapy with erlotinib, an EGFR TKI. PATIENTS AND METHODS: Seven NSCLC patients harboring activating EGFR mutations who had developed LM during or after therapy with gefitinib, an EGFR TKI, were retrospectively analyzed. CSF was obtained and subjected to cytological examination and EGFR mutation analysis, including detection of the resistance-associated T790M mutation, using real-time PCR. RESULTS: In all seven cases, the EGFR mutation detected in the CSF was the same as that detected in the primary tumor (sensitivity, 100%). Conversely, cytology results were positive in only two patients (sensitivity, 28.6%). No additional T790M mutations were detected. Erlotinib was efficacious in all cases, and improved performance status was achieved for five of the seven patients. The effect of erlotinib treatment was temporary, however, with time to treatment failure (TTF) ranging from 29 to 278 days (median, 65 days) and the interval between commencement of erlotinib treatment and death ranging from 45 to 347 days (median, 168 days). CONCLUSIONS: Analysis of EGFR mutations in CSF using a highly sensitive real-time PCR assay is a potentially powerful diagnostic method for LM.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Neoplasias Meníngeas/secundário , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/secundário , Análise Mutacional de DNA , Receptores ErbB/líquido cefalorraquidiano , Cloridrato de Erlotinib/uso terapêutico , Feminino , Gefitinibe , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Tirosina Quinases/antagonistas & inibidores , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Fatores de Tempo , Falha de Tratamento , Resultado do Tratamento
11.
Zhongguo Fei Ai Za Zhi ; 19(1): 52-6, 2016 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-26805738

RESUMO

BACKGROUND AND OBJECTIVE: One of the most often distance metastasis site of non-small cell lung cancer (NSCLC) is brain and the standard treatment of brain metastasis was radiotheraphy including whole brain irradiation (WBI) and stereotactic radiotherapy (SRT). It has been reported that epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) had the active response in brain metastasis of lung cancer. In the present study, we reported one case of EGFR 19el in cerebrospinal fluid tested by ARMS got partial response given erlotinib. METHODS: Cerebrospinal fluid was collected through lumbar puncture, then cast-off cells and EGFR mutation was analysed. Erlotinib was given with dose of 150 mg, qd. Objective response was evaluated by Response Evaluation Criteriation in Solid Tumours (RECIST) v1.1 and adeverse events were evaluated according to Common Terminology Criteria for Adverse Events v4.0 (CTC AE v4.0). RESULTS: Heterocyst cells were found in cerebrospinal fluid and EGFR mutation was tested as 19del. The patient achieved partial response (PR) of brain metastasis and the effective response in lung was stable disease (SD) after 4 weeks of erlotinib. The progression-free survival (PFS) and overall survival (OS) of brain metastasis was 10.5 months and 11 months respectively. The main adverse event was rash (Grade I). CONCLUSIONS: It was feasible to test EGFR mutation in cerebrospinal fluid and the combination of erlotinib with chemotheraphy would be an appropriate choice to those lung cancer patients who had brain metastasis harboring EGFR sensitive mutation.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/administração & dosagem , Receptores ErbB/líquido cefalorraquidiano , Receptores ErbB/genética , Cloridrato de Erlotinib/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Adenocarcinoma/líquido cefalorraquidiano , Adenocarcinoma/genética , Adenocarcinoma de Pulmão , Adulto , Feminino , Humanos , Neoplasias Pulmonares/líquido cefalorraquidiano , Neoplasias Pulmonares/genética , Mutação , Resultado do Tratamento
12.
J Thorac Oncol ; 6(7): 1215-20, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21610522

RESUMO

BACKGROUND: Neoplastic meningitis (NM) is a devastating neurological complication of cancer that needs to be diagnosed in the early stages of disease. Polymerase chain reaction detection of epithelial growth factor receptor (EGFR) mutations in cerebrospinal fluid (CSF), which are predictive markers for EGFR tyrosine kinase inhibitor therapy in lung cancer, might be important to diagnose and to treat NM in patients with lung cancer. In this study, we attempted to detect EGFR mutations in CSF and to compare EGFR status between CSF and primary or metastatic lesions in patients with lung adenocarcinoma suspected of NM. METHODS: Twenty-nine patients with lung adenocarcinoma suspected of having NM underwent lumbar puncture. EGFR status of CSF was analyzed by direct DNA sequencing. EGFR mutations of primary or metastatic lesions (lymph nodes and bones) were analyzed in 20 cases. RESULTS: EGFR mutations were detected in CSF of 13 (45%) of 29 patients. In 5 (31%) of 16 patients with negative CSF cytology, EGFR mutations were detected. In four patients, EGFR mutations were shown in CSF, but not in primary or metastatic lesions. Conversely, in two patients, EGFR mutations were shown in primary or metastatic lesions, but not in CSF despite positive CSF cytology. CONCLUSIONS: EGFR mutations, suggesting the existence of malignant cells, were detected in CSF, even in patients with non-small cell lung cancer with negative cytological results. EGFR mutations in CSF do not always reflect the same status as in primary or metastatic lesions.


Assuntos
Adenocarcinoma/complicações , Biomarcadores Tumorais/líquido cefalorraquidiano , Carcinoma Pulmonar de Células não Pequenas/complicações , Receptores ErbB/líquido cefalorraquidiano , Neoplasias Pulmonares/complicações , Meningite/diagnóstico , Mutação/genética , Adenocarcinoma/genética , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/secundário , DNA de Neoplasias/líquido cefalorraquidiano , DNA de Neoplasias/genética , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Imageamento por Ressonância Magnética , Masculino , Meningite/líquido cefalorraquidiano , Meningite/etiologia , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real
13.
J Neurooncol ; 99(2): 283-6, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20146086

RESUMO

Leptomeningeal metastases (LM) occur in 5-10% of patients with solid tumors and are associated with a dismal prognosis. We describe LM from lung adenocarcinoma harboring a mutation in the epidermal growth factor receptor (EGFR) gene that confers sensitivity to the EGFR tyrosine kinase inhibitors (EGFR-TKIs) erlotinib and gefitinib. The CSF concentration of EGFR-TKIs achieved by standard daily dosing may be insufficient for therapeutic effect. However, intermittent (pulsatile) high dose administration (1000-1500 mg/week) achieves a higher CSF concentration than standard dosing, and successfully controlled LM in this patient.


Assuntos
Adenocarcinoma/tratamento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Meníngeas/tratamento farmacológico , Mutação/genética , Inibidores de Proteínas Quinases/administração & dosagem , Quinazolinas/administração & dosagem , Adenocarcinoma/genética , Adenocarcinoma/secundário , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/líquido cefalorraquidiano , Cloridrato de Erlotinib , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/secundário , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/sangue , Inibidores de Proteínas Quinases/líquido cefalorraquidiano , Quinazolinas/sangue , Quinazolinas/líquido cefalorraquidiano , Resultado do Tratamento
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