RESUMEN
BACKGROUND Brigatinib is used for anaplastic lymphoma kinase (ALK)-positive lung cancer treatment, and some research showed it was useful in treating triple-mutant epidermal growth factor receptor lung cancer. Clinical trials have shown some potential pulmonary toxicities of brigatinib. The early-onset pulmonary events (EOPEs) of brigatinib are associated with high dosage and older age. The successful treatment of EOPEs with steroids was reported. We present the case of a patient with epidermal growth factor receptor L858R/cis-T790M/cis-C797S triple mutations who developed EOPEs after using brigatinib together with afatinib, and the patient was successfully treated with high-dose steroids. CASE REPORT A 54-year-old woman with underlying stage IV lung adenocarcinoma, ECOG score of 0, was treated with brigatinib and afatinib due to disease progression secondary to L858R/cis-T790M/cis-C797S triple mutations. After starting brigatinib and afatinib, she developed dyspnea and dry cough within 2 days and was intubated due to hypercapnic respiratory failure. The chest X-ray showed bilateral interstitial infiltrates while chest computed tomography (CT) showed bilateral ground-glass opacities. EOPEs were suspected and methylprednisolone was prescribed. The oxygenation of the patient improved and her chest CT showed complete resolution after 2 weeks of steroid treatment. CONCLUSIONS This is the first reported case in which brigatinib combined with afatinib induced EOPEs in a patient with triple-mutant epidermal growth factor receptors of lung cancer. Use of doubled tyrosine kinase inhibitors may result in increased risk of pulmonary toxicities that require high alertness, and the respiratory symptoms should be monitored closely after prescription. The early treatment of EOPEs with high-dose steroids resulted in remarkable improvement.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Afatinib/uso terapéutico , Quinasa de Linfoma Anaplásico/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Familia de Proteínas EGF/genética , Familia de Proteínas EGF/uso terapéutico , Receptores ErbB/genética , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Mutación , Compuestos Organofosforados , Inhibidores de Proteínas Quinasas/uso terapéutico , PirimidinasRESUMEN
BACKGROUND/PURPOSE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been gradually introduced in the diagnosis of mediastinal tuberculous (TB) lymphadenitis. The purposes of this study were to evaluate the utility of polymerase chain reaction for Mycobacterium tuberculosis (TB-PCR) using EBUS-TBNA rinse fluid and to explore the factors that influence the accuracy of EBUS-TBNA. METHODS: A retrospective study with prospective data collection was carried out with patients with unselected mediastinal lymphadenopathy who underwent EBUS-TBNA and a TB-PCR study from April 2010 to July 2017. Patients without TB were excluded. The diagnostic accuracy rate for each diagnostic modality (pathology, smear, culture, and TB-PCR) was calculated respectively. The characteristics of the lymph node (LN) and the pathologic findings were analyzed as possible impact factors. RESULTS: 240 consecutive patients who received EBUS-TBNA were enrolled, and in the end, 21 patients with a diagnosis of TB lymphadenitis were included. When combined with histologic results and traditional microbiologic studies, the diagnostic accuracy of EBUS-TBNA was 57.1%. If TB-PCR was also utilized, the diagnostic accuracy would significantly increase to 71.4% (p < 0.001). Univariate and multivariate regression analysis revealed that pathology showing necrosis had a higher positive microbiologic result when using EBUS-TBNA rinse fluid. CONCLUSION: EBUS-TBNA is a valuable tool for diagnosis of mediastinal TB lymphadenitis. Using TB-PCR assay and targeting LNs with a necrotic component would improve the diagnostic performance of EBUS-TBNA.
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Enfermedades del Mediastino/diagnóstico , Enfermedades del Mediastino/patología , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis Ganglionar/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Reacción en Cadena de la Polimerasa , Análisis de Regresión , Estudios Retrospectivos , TaiwánRESUMEN
INTRODUCTION: Non-small cell lung cancer (NSCLC) harbouring EGFR exon 19 deletions or L858R mutation usually respond to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), whereas T790M mutation and exon 20 insertion are frequently resistant to EGFR-TKIs. EGFR mutations other than those above are seldom investigated. METHODS: In this multicentre, retrospective study, we enrolled NSCLC patients with non-resistant uncommon EGFR mutations, which were defined as mutations other than L858R, exon 19 deletions, exon 20 insertions and T790M. The mutation patterns, clinical data and treatment outcomes were analysed. Patients were classified as gefitinib/erlotinib and afatinib groups according to the EGFR-TKIs received as the first-line therapy. RESULTS: A total of 177 patients were identified (177/1983, 8.9%). Sixty-six patients had more than one EGFR mutation, including those coexisting with exon 19 deletion or L858R mutation. In treatment-naïve patients with advanced stages (n = 72), the objective response rate was 35.8% for gefitinib/erlotinib group and 60.6% for afatinib group (p = 0.036). In multivariate analysis, no significant differences were found between gefitinib/erlotinib and afatinib groups in median progression-free survival (PFS) and overall survival (OS). Brain metastasis at diagnosis was associated with a shorter PFS (hazard ratio [HR] = 2.49, 95% confidence interval [CI] = 1.29-4.83) and OS (HR = 3.22, 95% CI = 1.41-7.35). CONCLUSIONS: For patients with NSCLC harbouring non-resistant uncommon EGFR mutations, afatinib use as the first-line therapy may provide a better treatment response but no survival benefit, as compared with gefitinib or erlotinib. Brain metastasis at diagnosis is associated with a poor prognosis.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB/antagonistas & inhibidores , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Afatinib/uso terapéutico , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/genética , Clorhidrato de Erlotinib/uso terapéutico , Femenino , Gefitinib/uso terapéutico , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Mutación , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: As the first-line treatment, afatinib is commonly used in patients with EGFR-mutated non-small-cell lung cancer (NSCLC). However, dose adjustments are frequently required. The optimal dose of afatinib for brain metastasis has seldom been investigated. PATIENTS AND METHODS: From May 2014 to March 2017, treatment-naive patients with advanced EGFR-mutated NSCLC and brain metastases at diagnosis who received afatinib therapy were retrospectively enrolled. Clinical data was reviewed and analyzed, including age, gender, performance status, smoking history, EGFR mutation status, initial doses of afatinib, average daily doses of afatinib, and best intracranial treatment responses. RESULTS: A total of 74 patients were included for analysis. The overall intracranial objective response rate (IORR) and intracranial disease control rate (IDCR) were 81.1% and 95.9%, respectively. For patients treated with afatinib alone (N = 45), no significant difference between an initial daily dose of 30 mg (N = 15) and 40 mg (N = 30) (30 mg vs. 40 mg, IORR: 86.7% vs. 80.0%; P = .581 and IDCR: 93.3% vs. 93.3%; P = 1.000, respectively). The IORRs were 75.0%, 91.7%, 80.0%, and 85.7% (P = .707), and the IDCRs were 93.8%, 100.0%, 90.0%, and 85.7% (P = .638) in patients with an average daily dose of 40 mg (N = 16), < 40 mg and > 30 mg (N = 12), 30 mg (N = 10), and < 30 mg and > 20 mg (N = 7), respectively. No significant differences in intracranial treatment responses between groups treated with afatinib alone or afatinib plus local treatments. CONCLUSION: Dose reduction may not affect intracranial treatment responses to afatinib therapy, either alone or combined with local treatments, in patients with advanced EGFR-mutated NSCLC and brain metastases.
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Afatinib/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Encéfalo/patología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Afatinib/provisión & distribución , Encéfalo/efectos de los fármacos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/secundario , Cálculo de Dosificación de Drogas , Receptores ErbB/genética , Femenino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Mutación/genética , Resultado del TratamientoRESUMEN
INTRODUCTION: Afatinib is commonly used as the first-line treatment for EGFR-mutated lung adenocarcinoma. However, dose adjustments are frequently required. This study aimed to investigate the treatment effectiveness of afatinib administered at different doses to patients with EGFR-mutated lung adenocarcinoma. METHODS: Treatment-naïve patients with advanced EGFR-mutated lung adenocarcinoma who received afatinib therapy between May 2014 and September 2016 were enrolled retrospectively. Collected clinical data included age, sex, smoking history, performance status, disease stages, EGFR mutation status, initial doses of afatinib, dose adjustments, treatment responses, progression-free survival and treatment-associated adverse events. The average daily dose was calculated by dividing the summation of all doses of prescribed tablets during the treatment period by the total days of afatinib use. The patients were classified into five treatment groups based on average daily doses: 40 mg, <40 and >30 mg, 30 mg, <30 and ≥ 20 mg and <20 mg. RESULTS: A total of 254 patients were included. No significant differences were found among these five treatment groups with respect to response rates (69.3%, 68.3%, 70.5%, 77.8% and 66.7%, respectively, p = 0.920) and disease control rates (97.4%, 95.2%, 97.7%, 100% and 100%, respectively, p = 0.749). However, the treatment group with an average daily dose of <20 mg had a significant shorter progression-free survival as compared with the other groups (16.8, 12.4, 13.9, 17.0 and 5.3 months, respectively, p = 0.049). CONCLUSIONS: Dose reduction may not affect the treatment effectiveness until the average daily dose is below 20 mg. Further prospective studies of afatinib therapy at different daily doses are warranted.
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Adenocarcinoma del Pulmón/tratamiento farmacológico , Afatinib/uso terapéutico , Antineoplásicos/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Adenocarcinoma del Pulmón/patología , Afatinib/farmacología , Antineoplásicos/farmacología , Receptores ErbB , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/farmacologíaRESUMEN
HER2 is a major proliferative driver in lung cancer. HER2 gene aberrations impact the prognosis of lung adenocarcinoma (ADC). A one-step reverse transcription-polymerase chain reaction was performed using RNA samples from 888 Asian lung cancer patients to detect HER2, EGFR, KRAS, ALK, and ROS1 mutations. The demographic data and treatment outcomes of HER2 mutation-positive lung ADC patients were analyzed and compared to those with HER2 mutation-negative tumors. HER2 mutation was identified in 40 (4.5%) lung ADC patients. HER2 mutations tended to occur in male patients with advanced-stage disease and never-smokers. A775_G776insYVMA (n = 22, 55%) was the most prevalent HER2 mutation, followed by P780_Y781insGSP (n = 4, 10%). For patients diagnosed with stage-IIIB/IV disease, HER2-mutant patients showed clinical outcomes comparable to EGFR-mutant patients (P = 0.721, log-rank test) and a better overall survival (OS) compared to patients lacking driver mutations in the investigated genes (P = 0.033, Breslow test). Specifically, lung ADC patients with stage-IV HER2-mutant tumors treated with chemotherapy or targeted agents, even without afatinib or anti-HER2 targeted therapy, showed similar clinical outcomes to lung ADC patients harboring EGFR exon 19 deletion or L858R mutations (P = 0.870). In addition, multivariate analysis indicated that HER2 mutation status was not a major risk factor for diminished OS in stage-IV lung cancer. In conclusion, lung ADC harboring HER2 mutations showed distinct characteristics from other driver mutations, including increased chemosensitivity with in advanced stage disease.
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Adenocarcinoma/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Receptores ErbB/genética , Neoplasias Pulmonares/patología , Mutación/genética , Receptor ErbB-2/genética , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Ultrasound elastography has shown promising result in the diagnosis of various diseases; however, its application for pulmonary diseases has yet to be clarified. This study aimed to assess the application and feasibility of ultrasound elastography in various pulmonary lesions and diseases. We enrolled 45 patients with radiographic evidence of pneumonia, tumors or obstructive pneumonitis, and 70 ultrasonic lesions were identified (eight necrosis, 17 atelectasis, seven consolidation and 38 tumors). Ultrasound elastography was performed and the strain ratio, which is the ratio of strain of the reference tissue to an equally measuring region of interest of a lesion, was measured. The strain ratio was significantly different among lesions with different ultrasound morphologies (1.03 ± 0.71 [necrosis] vs. 2.51 ± 1.14 [atelectasis] vs. 19.98 ± 15.59 [consolidation] vs. 36.19 ± 20.18 [tumor]; p < 0.05). The strain ratio of primary lung cancer was also significantly different from pneumonia (p = 0.023) and metastatic lung cancer (p = 0.015). In conclusion, transthoracic ultrasound elastography can differentiate pulmonary lesions with different ultrasound morphologies. ClinicalTrials.gov Identifier: NCT02636985.
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Diagnóstico por Imagen de Elasticidad/métodos , Enfermedades Pulmonares/diagnóstico por imagen , Diagnóstico Diferencial , Femenino , Humanos , Pulmón/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND AND OBJECTIVE: Weaning parameters are commonly measured through an endotracheal tube in mechanically ventilated patients recovering from acute respiratory failure, however this practice has rarely been evaluated in tracheostomized patients. This study aimed to investigate changes in weaning parameters measured before and after tracheostomy, and to explore whether the data measured after tracheostomy were associated with weaning outcomes in difficult-to-wean patients. METHODS: In a two-year study period, we enrolled orotracheally intubated patients who were prepared for tracheostomy due to difficult weaning. Weaning parameters were measured before and after the conversion to tracheostomy and compared, and the post-tracheostomy data were tested for associations with weaning outcomes. RESULTS: A total of 86 patients were included. After tracheostomy, maximum inspiratory pressure (mean difference (Δ) = 4.4, 95% CI, 2.7 to 6.1, P<0.001), maximum expiratory pressure (Δ = 5.4, 95% CI, 2.9 to 8.0, P<0.001) and tidal volume (Δ = 33.7, 95% CI, 9.0 to 58.5, P<0.008) significantly increased, and rapid shallow breathing index (Δ = -14.6, 95% CI, -25.4 to -3.7, P<0.009) and airway resistance (Δ = -4.9, 95% CI, -5.8 to -4.0, P<0.001) significantly decreased. The patients who were successfully weaned within 90 days of the initiation of mechanical ventilation had greater increments in maximum inspiratory pressure (5.9 vs. 2.4, P = 0.04) and maximum expiratory pressure (8.0 vs. 2.0, P = 0.02) after tracheostomy than those who were unsuccessfully weaned. CONCLUSIONS: In conclusion, the conversion from endotracheal tube to tracheostomy significantly improved the measured values of weaning parameters in difficult-to-wean patients who subsequently weaned successfully from the mechanical ventilator. The change was significant only for airway resistance in patients who failed weaning. TRIAL REGISTRATION: ClinicalTrials.gov NCT01312142.