RESUMEN
OBJECTIVE: To elucidate the potential benefits of combining radiotherapy and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) for individuals with Stage IV lung adenocarcinoma (LUAD) harboring either exon 19 deletion (19-Del) or exon 21 L858R mutation (21-L858R). METHODS: In this real-world retrospective study, 177 individuals with Stage IV LUAD who underwent EGFR-TKIs and radiotherapy at Shandong Cancer Hospital from June 2012 to August 2017 were included. The main focus of this real-world study was overall survival (OS). RESULTS: The clinical characteristics of patients with Stage IV LUAD harboring 19-Del were similar to those harboring 21-L858R (p > 0.05). Overall, the patients had a median OS (mOS) of 32.0 months (95% confidence interval [CI]: 28.6-35.5). Subsequently, multivariate analysis indicated that both EGFR mutations and thoracic radiotherapy were independent predictors of OS (p = 0.001 and 0.013). Furthermore, subgroup analysis highlighted a longer OS for the 19-Del group compared to the 21-L858R group, especially when EGFR-TKIs were combined with bone metastasis or thoracic radiotherapy (mOS: 34.7 vs. 25.1 months and 51.0 vs. 29.6 months; p = 0.0056 and 0.0013, respectively). However, no significant differences were found in OS when considering patients who underwent brain metastasis radiotherapy (mOS: 34.7 vs. 25.1 months; p = 0.088). CONCLUSIONS: Patients with Stage IV LUAD harboring 19-Del experience a notably prolonged OS following combined therapy with EGFR-TKIs and radiotherapy, while this OS benefit is observed despite the absence of substantial differences in the clinical characteristics between the 19-Del and 21-L858R groups.
Asunto(s)
Adenocarcinoma del Pulmón , Quimioradioterapia , Receptores ErbB , Neoplasias Pulmonares , Mutación , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/terapia , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/radioterapia , Adenocarcinoma del Pulmón/mortalidad , Quimioradioterapia/métodos , Receptores ErbB/genética , Receptores ErbB/antagonistas & inhibidores , Exones , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/mortalidad , Estadificación de Neoplasias , Pronóstico , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos , Eliminación de Secuencia , /uso terapéuticoRESUMEN
Background and Purpose: Epidermal growth factor receptor (EGFR)-mutant lung cancers are associated with a high risk of developing brain metastases (BM). Craniocerebral radiotherapy is a cornerstone for the treatment of BM, and EGFR-TKIs act on craniocerebral metastases". However, whether EGFR-TKIs combined with craniocerebral radiotherapy can further increase the efficacy and improve the prognosis of patients is unclear. This study aimed to evaluate the difference in efficacy between targeted-therapy alone and targeted-therapy combined with radiotherapy in EGFR-mutant lung adenocarcinoma patients with BM. Materials and Methods: A total of 291 patients with advanced non-small cell lung cancer (NSCLC) and EGFR mutations were enrolled in this retrospective cohort study. Propensity score matching (PSM) was conducted using a nearest-neighbor algorithm (1:1) to adjust for demographic and clinical covariates. Patients were divided into two groups: EGFR-TKIs alone and EGFR-TKIs combined with craniocerebral radiotherapy. Intracranial progression-free survival (iPFS) and overall survival (OS) were calculated. Kaplan-Meier analysis was used to compare iPFS and OS between the two groups. Brain radiotherapy included WBRT, local radiotherapy, and WBRT+Boost. Results: The median age at diagnosis was 54 years (range: 28-81 years). Most patients were female (55.9%) and non-smokers (75.5%). Fifty-one pairs of patients were matched using PSM. The median iPFS for EGFR-TKIs alone (n=37) and EGFR-TKIs+craniocerebral radiotherapy (n=24) was 8.9 and 14.7 months, respectively. The median OS for EGFR-TKIs alone (n=52) and EGFR-TKIs+craniocerebral radiotherapy (n=52) was 32.1 and 45.3 months, respectively. Conclusion: In EGFR-mutant lung adenocarcinoma patients with BM, targeted therapy combined with craniocerebral radiotherapy is an optimal treatment.
RESUMEN
We present an atom-based approach for determining microwave electric and magnetic fields by using a single rubidium vapor cell in a microwave waveguide. For a 87Rb cascade three-level system employed in our experiment, a weak probe laser driving the lower transition, 5S1/2â5P3/2, is first used to measure the microwave magnetic field based on the atomic Rabi resonance. When a counter-propagating strong coupling laser is subsequently turned on to drive the Rydberg transition, 5P3/2â67D5/2, the same probe laser is then used as a Rydberg electromagnetically induced transparency (EIT) probe to measure the microwave electric field by investigating the resonant microwave dressed Autler-Townes splitting (ATS). By tuning the hyperfine transition frequency of the ground state using an experimentally feasible static magnetic field, we first achieved a measurement of the microwave electric and magnetic field strength at the same microwave frequency of 6.916â GHz. Based on the ideal relationship between the electric and magnetic field components, we obtained the equivalent microwave magnetic fields by fitting the inversion to the measured microwave electric fields, which demonstrated that the results were in agreement with the experimental measurement of the microwave magnetic fields in the same microwave power range. This study provides new experimental evidence for quantum-based microwave measurements of electric and magnetic fields by a single sensor in the same system.
RESUMEN
BACKGROUND: Perfusion-weighted magnetic resonance imaging (MRI) can evaluate collateral circulation in patients with acute cerebral infarction by reflecting hemodynamic signals in the brain. The purpose of this study was to evaluate the collateral circulation and short-term prognosis of patients with acute cerebral infarction, using perfusion-weighted MRI. METHODS: The study enrolled 206 patients with acute cerebral infarction due to unilateral cerebral artery occlusion diagnosed by digital subtraction angiography (DSA) and computed tomography angiography (CTA). The relative cerebral blood volume (rCBV), relative cerebral blood flow map (rCBF), relative peak time (rTTP), and relative mean transit time (rMTT) were calculated based on the ratio of the perfusion-weighted MRI reference values of the infarcted side and the control side of the patient. According to the results of perfusion-weighted MRI, patients were divided into a high perfusion group (n=121) and a low perfusion group (n=85). The Thrombolysis in Cerebral Infarction scale proposed by Higashida et al. in 2003 (Higashida scale) was used to evaluate the establishment of collateral circulation on the day of admission and 15 days after admission. The National Institutes of Health Stroke Scale (NIHSS) score and the modified Rankin scale assessed the short-term prognosis of patients with cerebral infarction. The Spearman correlation analysis examined the correlation between the rCBV, rCBF, and NIHSS scores, and the modified Rankin scale (mRS). RESULTS: Compared with the patients in the low perfusion group, the rCBV and rCBF in the infarcted area of the patients in the high perfusion group were significantly increased and the rTTP and rMTT were significantly decreased. On day 15 after admission, the collateral circulation rate of the high perfusion group was significantly higher than that of the low perfusion group, and the NIHSS score and the mRS score were significantly lower than those scores of the low perfusion group. Perfusion-weighted MRI indexes, rCBV, and rCBF were negatively correlated with the NIHSS score and Rankin scale. CONCLUSIONS: Perfusion-weighted MRI can effectively evaluate the compensatory ability of collateral circulation and the prognosis of patients with acute cerebral infarction.
Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular , Enfermedad Aguda , Infarto Cerebral/diagnóstico por imagen , Circulación Colateral , Humanos , Imagen por Resonancia Magnética , Perfusión , Pronóstico , Estados UnidosRESUMEN
PURPOSE: Epidermal growth factor receptor (EGFR)-mutant lung cancers have a high risk of developing brain metastases (BM). Whole brain radiotherapy (WBRT), local radiotherapy, and WBRT + Boost are frequently used for treatment of BM. This retrospective study aimed to evaluate the difference in efficacy of these radiotherapy modes in patients with EGFR-mutant lung adenocarcinoma with BMs. Further, we determined the optimal radiotherapy regimen for patients based on Lung-molGPA. METHODS AND MATERIALS: We retrospectively enrolled 232 patients with EGFR-mutant lung adenocarcinoma with BMs. Patients were divided into three groups based on the different modes of brain radiotherapy: WBRT group, local radiotherapy group, and WBRT + Boost group. Graded prognostic assessment for lung cancer using molecular markers (Lung molGPA), overall survival (OS), and intracranial progression-free survival (iPFS) were calculated. Kaplan-Meier was used to compare iPFS and OS in different groups. RESULTS: The median OS for the WBRT (n = 84), local radiotherapy (n = 65), and WBRT + Boost (n = 83) cohorts was 32.8, 59.1, and 41.7 months, respectively (P = 0.0002). After stratification according to the Lung-molGPA score, the median OS for the WBRT (n = 56), local radiotherapy (n = 19), and WBRT + Boost (n = 28) cohorts was 32.5, 30.9, and 30.8 months, respectively, in subgroup with score 1-2 (P = 0.5097). In subgroup with score 2.5-4, the median OS for the WBRT (n = 26), local radiotherapy (n = 45), and WBRT + Boost (n = 54) cohorts was 32, 68.4, and 51 months, respectively (P = 0.0041). CONCLUSION: The present study showed that in patients with EGFR-mutant lung adenocarcinoma with BM, local radiotherapy and WBRT + Boost perform similarly well both in the subgroups with low and high scores of Lung-molGPA. Considering the side effect caused by whole brain radiotherapy, we recommended local radiotherapy as optimal brain radiation mode for those subtype lung cancer patients.
Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Encefálicas , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/radioterapia , Encéfalo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/radioterapia , Irradiación Craneana , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Pronóstico , Estudios RetrospectivosRESUMEN
INTRODUCTION: The aim of this study was to investigate the role of local radiotherapy in the management of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancers (NSCLCs) treated with EGFR tyrosine kinase inhibitors (TKIs). MATERIALS AND METHODS: Patients with stage IV EGFR-mutant NSCLC treated with radiotherapy concomitant to EGFR TKIs from May 2010 to December 2017 were retrospectively identified. Overall survival (OS) was the primary endpoints of the study. RESULTS: A total of 205 patients were enrolled in the study. One hundred eleven patients received one-time single-site radiotherapy (SSR), and 94 patients received multiple-site radiotherapy (MSR). Patients who received MSR had longer OS (median OS, 40.0 months; 95% confidence interval [CI], 29.6 to 50.4) than those who received SSR (median OS, 28.9 months; 95% CI, 24.3 to 33.5; P=0.031). Thoracic radiotherapy was associated with prolonged median OS (41.7 months, 95% CI, 29.0 to 54.4 vs 27.1 months, 95% CI 22.7 to 31.5; log-rank P<0.001). Multivariate analysis confirmed that thoracic radiotherapy was independently associated with improved OS (adjusted hazard ratio [HR], 0.514; 95% CI 32.3% to 81.8%; P=0.005). CONCLUSION: MSR improves survival outcomes in patients with advanced-stage, EGFR-mutant, lung adenocarcinoma, with thoracic radiotherapy having the most significant effect on prognosis.
RESUMEN
Aim: To verify the relationship between ARID1A and tumor immune microenvironment thus immune checkpoint inhibitors (ICIs) response. Material & methods: Several public databases were used to characterize the association between ARID1A gene alteration and tumor immunity. Results: The gene mutation frequency was 8.2% in all cancer types. The ARID1A-mutated cancers have higher scores of mutation count, tumor mutational burden, neoantigen load (p < 0.001) and T cell repertoire, B cell repertoire diversity (p < 0.05). The gene mutation has tight association with multiple-activated immune cells. Survival analysis suggested that patients with ARID1A mutant cancers benefit more from ICIs treatment (p = 0.013). Conclusion: The ARID1A gene mutation was correlated with higher tumor immunogenicity and activated antitumor immune microenvironment, resulting in superior cohort that respond well to ICIs.
Asunto(s)
Biomarcadores de Tumor , Proteínas de Unión al ADN/genética , Mutación , Neoplasias/etiología , Neoplasias/patología , Factores de Transcripción/genética , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Alelos , Bases de Datos Genéticas , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Frecuencia de los Genes , Humanos , Estimación de Kaplan-Meier , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Linfocitos Infiltrantes de Tumor/patología , Terapia Molecular Dirigida , Neoplasias/mortalidad , Neoplasias/terapia , Pronóstico , Receptores de Antígenos de Linfocitos B , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/metabolismoRESUMEN
This study assessed the variation in the frequency locations in the Doppler ultrasound spectra for the maximum blood flow velocities of in vessels with different degrees of bilaterally axisymmetric stenosis. This was done by comparing the relationship between the velocity distributions and corresponding Doppler power spectra. First, a geometric vessel model with axisymmetric stenosis was established. This made it possible to obtain the blood flow velocity distributions for different degrees of stenosis from the solutions of the Navier-Stokes equations. Then, the Doppler spectra were calculated for the entire segment of the vessel that was covered by the sound field. Finally, the maximum frequency locations for the spectra were determined based on the intersections of the maximum values chosen from the calculated blood flow velocity distributions and their corresponding spectra. The computational analysis showed that the maximum frequencies, which corresponded to the maximum blood flow velocities for different degrees of stenosis, were located at different positions along the spectral falling edges. The location for a normal (stenosis free) vessel was in the middle of the falling edge. For vessels with increasing degrees of stenosis, this location shifted approximately linearly downward along the falling edge. For 40% stenosis, the location reached a position at the falling edge of 0.32. Results obtained using the Field II simulation tool demonstrated the validity of the theoretical analysis and calculations, and may help to improve the maximum velocity estimation accuracy for Doppler blood flow spectra in stenosed vessels.
Asunto(s)
Velocidad del Flujo Sanguíneo , Constricción Patológica/diagnóstico por imagen , Constricción Patológica/fisiopatología , Ultrasonografía Doppler , Modelos BiológicosRESUMEN
Lettuce plants were grown at low (LL), middle (ML), and high light (HL) conditions to examine the relationship between photoacclimatory plasticity, light energy utilization, and antioxidant capacity. With the increase in light intensity from LL to ML, the energy flux via DeltapH- and xanthophylls-regulated thermal dissipation, fluorescence and constitutive thermal dissipation, and electron transport for photorespiratory carbon oxidation all increased significantly. However, plants at HL exhibited reduced electron transport for photosynthetic carbon reduction and decreased maximal photochemical efficiency of photosytem II (PSII) as compared to that at ML. Increasing light level significantly increased the alternative electron transport, O(2)(*-) production rate, and H(2)O(2) and malondialdehyde (MDA) contents followed by increased ferric reducing antioxidant power (FRAP) and activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), and glutathione reductase (GR). Moreover, plants exposed to HL showed higher nutritional value as indicated by the high contents of ascorbate, glutathione, carotenoids, and alpha-tocopherol. It was concluded that absorption of excess photon energy at high light was associated with increased antioxidant capacity and that produce quality could be improved by short-term exposure to suboptimum irradiance.