RESUMEN
Thoracic SMARCA4-deficient undifferentiated tumor is a newly recognized disease entity characterized as a high-grade malignant neoplasm with an undifferentiated or rhabdoid phenotype. The tumor was initially identified as a subtype of thoracic sarcoma with SMARCA4 loss, but further investigation resulted in its classification as a subtype of epithelial malignancies in the current World Health Organization classification. SMARCA4-deficient undifferentiated tumor is highly aggressive and has a poor prognosis. Because of its rarity, an optimal treatment strategy has not yet been identified. In this review, we summarize the literature on SMARCA4-deficient undifferentiated tumor in terms of its clinical characteristics, diagnosis, treatment strategy and future perspectives.
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Sarcoma , Neoplasias de los Tejidos Blandos , Neoplasias Torácicas , Humanos , Sarcoma/diagnóstico , Biomarcadores de Tumor/genética , Neoplasias Torácicas/genética , Neoplasias Torácicas/diagnóstico , Neoplasias Torácicas/patología , ADN Helicasas/genética , Proteínas Nucleares/genética , Factores de Transcripción/genéticaRESUMEN
The safety of osimertinib is limited in patients with severe or moderate renal impairment, or low body weight. This study aimed to investigate the safety, pharmacokinetics (PK) and recommended dose (RD) of osimertinib in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with impaired renal function and low body weight. Thirty-one eligible patients were enrolled and allocated into four cohorts: A, normal renal function (estimated glomerular filtration rate [eGFR] ≥ 50 mL/min/1.73 m2 ) and normal body weight (≥45 kg); B, moderate renal impairment (eGFR = 30-50 mL/min/1.73 m2 ); C, low body weight (<45 kg); and D, severe renal impairment (eGFR <30 mL/min/1.73 m2 or undergoing dialysis). PK parameters and safety were evaluated with a starting dose of 80 mg osimertinib administered orally once daily in cohorts A, B, and C and 40 mg once daily in cohort D. The PK parameters in cohorts A, B, and C were found to be similar. No dose-limiting toxicity was observed, and the RD was determined to be 80 mg once daily in patients with moderate renal function and low body weight. Four serious adverse events, acneiform rash, diarrhea, QTc prolongation, and interstitial lung disease, were noted. Although the PK parameters of osimertinib were similar across all cohorts, toxicity occurred more frequently in patients with impaired renal function and low body weight. Clinicians should prescribe osimertinib with caution in NSCLC patients with impaired renal function and low body weight.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Insuficiencia Renal , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Compuestos de Anilina/efectos adversos , Riñón/fisiología , Peso Corporal , Mutación , Inhibidores de Proteínas Quinasas/efectos adversosRESUMEN
BACKGROUND: Delta-like ligand 3 (DLL3) is a therapeutic target in small-cell lung cancer (SCLC). However, how DLL3 expression status affects the tumor microenvironment (TME) and clinical outcomes in SCLC remains unclear. METHODS: This retrospective study included patients with postoperative limited-stage (LS)-SCLC and extensive-stage (ES)-SCLC treated with platinum and etoposide (PE) plus anti-programmed cell death ligand 1 (PD-L1) antibody. We investigated the relationship of DLL3 expression with TME, mutation status, tumor neoantigens, and immunochemotherapy. RESULTS: In the LS-SCLC cohort (n = 59), whole-exome sequencing revealed that DLL3High cases had significantly more neoantigens (P = 0.004) and a significantly higher rate of the signature SBS4 associated with smoking (P = 0.02) than DLL3Low cases. Transcriptome analysis in the LS-SCLC cohort revealed that DLL3High cases had significantly suppressed immune-related pathways and dendritic cell (DC) function. SCLC with DLL3High had significantly lower proportions of T cells, macrophages, and DCs than those with DLL3Low. In the ES-SCLC cohort (n = 30), the progression-free survival associated with PE plus anti-PD-L1 antibody was significantly worse in DLL3High cases than in DLL3Low cases (4.7 vs. 7.4 months, P = 0.01). CONCLUSIONS: Although SCLC with DLL3High had a higher neoantigen load, these tumors were resistant to immunochemotherapy due to suppressed tumor immunity by inhibiting antigen-presenting functions.
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Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Ligandos , Microambiente Tumoral , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/patología , Etopósido/uso terapéutico , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genéticaRESUMEN
BACKGROUND: Sequential tyrosine kinase inhibitors (TKIs) following immune checkpoint inhibitors (ICIs) increases the incidence of serious adverse events (SAEs). However, the factors and the types of TKIs that affect the incidence of SAEs remain unknown. METHODS: We retrospectively reviewed advanced non-small cell lung cancer (NSCLC) patients who received sequential TKIs following ICIs between November 2015 and April 2021. All AEs were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) ver 5.0. RESULTS: Among 1,638 NSCLC patients who received ICIs, 63 patients received sequential TKIs following ICIs. The types of TKIs included EGFR-TKIs in 48 patients, ALK-TKIs in 10 patients, and others in 5 patients. The median dosing interval was 57 days (range: 7-698). Eighteen (28.6%) patients developed SAEs (Grade 3/4 or hospitalized). The incidence of SAEs and withdrawal of TKIs due to AEs were significantly higher in patients (n = 40) who initiated TKI treatment within 3 months after ICIs than in patients (n = 23) who initiated TKI treatment 3 months after ICIs (SAEs, 40.0% vs. 4.3%, p < 0.01; withdrawal rate: 57.5% vs. 21.7%, p < 0.01). There was no significant difference in the incidence of SAEs and withdrawal rate due to AEs between EGFR-TKIs and other TKIs (SAE, 22.9% vs. 40.0%, p = 0.20; withdrawal rate: 41.7% vs. 53.3%, p = 0.55). CONCLUSION: The dosing interval from last ICI to the initiation of TKI treatment can affects the incidence of SAEs and the withdrawal rate due to AEs regardless of the types of TKIs.
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Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Incidencia , Estudios Retrospectivos , Inhibidores de Proteínas Quinasas/efectos adversos , Receptores ErbB/genéticaRESUMEN
INTRODUCTION: There are two treatment strategies for non-small cell lung cancer (NSCLC) exhibiting a high expression level of programmed death-ligand 1 (tumor proportion score ≥ 50%): pembrolizumab plus chemotherapy and monotherapy. We retrospectively compared their efficacy and safety. MATERIALS AND METHODS: We reviewed the efficacy and safety of first-line pembrolizumab-containing regimens administered between 2017 and 2020 to consecutive patients. The patients were divided into a pembrolizumab plus chemotherapy group (Combo group) or monotherapy group (Mono group). To compare the efficacy, we monitored the time to failure of strategy (TFS) defined as the time from the start of treatment to the occurrence of one of the following events: the addition of any drug not included in the primary strategy, progression of cancer after complete therapy, progression and no subsequent therapy, or death, whichever occurred first. We used the propensity score matching (PSM) to reduce the bias. RESULTS: A total of 126 patients were identified (89 in the Mono group and 37 in the Combo group). PSM matched 36 individuals from each of the two groups. The overall response rate and median progression-free survival of the Combo group were better than those of the Mono group. However, the median TFS was almost the same (11.3 months vs. 14.9 months; hazard ratio 1.40 [95% confidence interval 0.62-3.15]). The frequency of all serious adverse effects was higher in the Combo group than in the Mono group. DISCUSSION: Due to similar efficacy in TFS, both pembrolizumab plus chemotherapy and monotherapy are valid options for NSCLC.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Antígeno B7-H1/genética , Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Manejo de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Terapia Molecular DirigidaRESUMEN
BACKGROUND: Cancer cachexia is a multifactorial syndrome characterized by weight loss leading to immune dysfunction that is commonly observed in patients with advanced non-small cell lung cancer (NSCLC). We examined the impact of cachexia on the prognosis of patients with advanced NSCLC receiving pembrolizumab and evaluated whether the pathogenesis of cancer cachexia affects the clinical outcome. PATIENTS AND METHODS: Consecutive patients with advanced NSCLC treated with pembrolizumab were retrospectively enrolled in the study. Serum levels of pro-inflammatory cytokines and appetite-related hormones, which are related to the pathogenesis of cancer cachexia, were analyzed. Cancer cachexia was defined as (1) a body weight loss > 5% over the past 6 months, or (2) a body weight loss > 2% in patients with a body mass index < 20 kg/m2. RESULTS: A total of 133 patients were enrolled. Patients with cachexia accounted for 35.3%. No significant difference in the objective response rate was seen between the cachexia and non-cachexia group (29.8% vs. 34.9%, P = 0.550), but the median progression-free survival (PFS) and overall survival (OS) periods were significantly shorter in the cachexia group than in the non-cachexia group (PFS: 4.2 months vs. 7.1 months, P = 0.04, and OS: 10.0 months vs. 26.6 months, P = 0.03). The serum TNF-alpha, IL-1 alpha, IL-8, IL-10, and leptin levels were significantly associated with the presence of cachexia, but not with the PFS or OS. CONCLUSION: The presence of cachexia was significantly associated with poor prognosis in advanced NSCLC patients receiving pembrolizumab, not with the response to pembrolizumab.
Asunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Caquexia/patología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/efectos adversos , Caquexia/inducido químicamente , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
PURPOSE: Aprepitant is used with dexamethasone and 5-HT3 receptor antagonists as an antiemetic treatment for chemotherapy, including cisplatin. Aprepitant is a substrate of cytochrome P450 (CYP) 3A4 and is known to cause its inhibition and induction. In addition, dexamethasone is a CYP3A4 substrate that induces CYP3A4 and CYP3A5 expression. In this study, we aimed to quantitatively evaluate the profile of CYP3A activity using its endogenous markers in non-small cell lung cancer patients receiving a standard cisplatin regimen with antiemetics, including aprepitant. METHODS: Urinary 11ß-hydroxytestosterone (11ß-OHT)/testosterone concentration ratio and plasma 4ß-hydroxycholesterol (4ß-OHC) concentrations were measured before and after cisplatin treatment (days 1, 4, and 8). CYP3A5 was genotyped, and plasma aprepitant concentrations were measured on day 4 to examine its influence on CYP3A endogenous markers. RESULTS: The urinary 11ß-OHT/testosterone concentration ratio in the 35 patients included in this study increased by 2.65-fold and 1.21-fold on days 4 and 8 compared with day 1, respectively. Their plasma 4ß-OHC concentration increased by 1.46-fold and 1.66-fold, respectively. The mean plasma aprepitant concentration on day 4 was 1,451 ng/mL, which is far lower than its inhibitory constant. The allele frequencies of CYP3A5*1 and CYP3A5*3 were 0.229 and 0.771, respectively. In patients with the CYP3A5*1 allele, the plasma 4ß-OHC concentration was significantly lower at baseline but more potently increased with chemotherapy. CONCLUSION: CYP3A activity was significantly induced from day 4 to day 8 in patients receiving cisplatin and three antiemetic drugs.
Asunto(s)
Antieméticos , Aprepitant , Carcinoma de Pulmón de Células no Pequeñas , Cisplatino , Citocromo P-450 CYP3A , Dexametasona , Neoplasias Pulmonares , Antieméticos/uso terapéutico , Aprepitant/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Carcinoma de Pulmón de Células no Pequeñas/genética , Cisplatino/efectos adversos , Cisplatino/uso terapéutico , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Dexametasona/uso terapéutico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/genética , Vómitos/inducido químicamente , Vómitos/prevención & controlRESUMEN
INTRODUCTION: The accelerated development of lung cancer treatments has resulted in a single global study that is sufficient for a new agent and indication to be approved. Not all new treatments predominate globally, and differences in standards of care may influence the efficacy of treatments in the real world. METHODS: The results from Japanese domestic trials and global trials that included a subset population of Japanese patients were evaluated for 18 genomic targeted agents and immune therapies approved after 2000. The results were collected from drug applications that were reviewed for treatment approval in Japan. RESULTS: Japan is one of the first countries to approve and fully reimburse new agents around the world. Alectinib and nivolumab, which were first developed by Japanese pharmaceutical companies, were evaluated in an independent domestic trial, which resulted in their early approval. For most other indications, 1.1-15.8% of the patients who participated in pivotal registration studies were Japanese, and their treatment results were comparable to those of the overall population. Overall survival was less likely to be improved by four agents for which the post-protocol therapy might have been different in Japan than in other countries. CONCLUSIONS: Overall, a positive result in a global trial was emulated in Japanese patients and led to the approval of a new standard treatment in Japan. Early approvals were attained by either participating in the global registrational study or conducting a domestic phase II study. The higher efficacy of new agents may be an issue in the future, as Japanese patients had early access to the new agent and may receive better treatment after the trial.
Asunto(s)
Antineoplásicos , Neoplasias Pulmonares , Antineoplásicos/uso terapéutico , Ensayos Clínicos como Asunto , Humanos , Japón , Neoplasias Pulmonares/tratamiento farmacológicoRESUMEN
Liquid biopsy analyzes the current status of primary tumors and their metastatic regions. We aimed to develop an optimized protocol for single-cell sequencing of floating tumor cells (FTCs) in pleural effusion as a laboratory test. FTCs were enriched using a negative selection of white blood cells by a magnetic-activated cell sorting system, and CD45-negative and cytokeratin-positive selection using a microfluidic cell separation system with a dielectrophoretic array. The enriched tumor cells were subjected to whole-genome amplification (WGA) followed by genome sequencing. The FTC analysis detected an EGFR exon 19 deletion in Case 1 (12/19 cells, 63.2%), and EML4-ALK fusion (17/20 cells, 85%) with an alectinib-resistant mutation of ALK (p.G1202R) in Case 2. To eliminate WGA-associated errors and increase the uniformity of the WGA product, the protocol was revised to sequence multiple single FTCs individually. An analytical pipeline, accurate single-cell mutation detector (ASMD), was developed to identify somatic mutations of FTCs. The large numbers of WGA-associated errors were cleaned up, and the somatic mutations detected in FTCs by ASMD were concordant with those found in tissue specimens. This protocol is applicable to circulating tumor cells analysis of peripheral blood and expands the possibility of utilizing molecular profiling of cancers.
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Perfilación de la Expresión Génica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Biopsia Líquida/métodos , Derrame Pleural Maligno/genética , Derrame Pleural Maligno/patología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Quinasa de Linfoma Anaplásico/genética , Antineoplásicos/uso terapéutico , Carbazoles/farmacología , Separación Celular/métodos , Crizotinib/uso terapéutico , ADN/aislamiento & purificación , Resistencia a Antineoplásicos/genética , Exones/genética , Femenino , Amplificación de Genes , Eliminación de Gen , Genes erbB-1 , Humanos , Separación Inmunomagnética/métodos , Queratinas , Antígenos Comunes de Leucocito , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Mutación , Células Neoplásicas Circulantes , Proteínas de Fusión Oncogénica/genética , Piperidinas/farmacología , Inhibidores de Proteínas Quinasas/farmacologíaRESUMEN
ALK, ROS1, and RET kinase fusions are important predictive biomarkers of tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC). Analysis of cell-free DNA (cfDNA) provides a noninvasive method to identify gene changes in tumor cells. The present study sought to use cfRNA and cfDNA for identifying fusion genes. A reliable protocol was established to detect fusion genes using cfRNA and assessed the analytical validity and clinical usefulness in 30 samples from 20 cases of fusion-positive NSCLC. The results of cfRNA-based assays were compared with tissue biopsy and cfDNA-based liquid biopsy (Guardant360 plasma next-generation sequencing [NGS] assay). The overall sensitivity of the cfRNA-based assay was 26.7% (8/30) and that of cfDNA-based assay was 16.7% (3/18). When analysis was limited to the samples collected at chemo-naïve or progressive disease status and available for both assays, the sensitivity of the cfRNA-based assay was 77.8% (7/9) and that of cfDNA-based assay was 33.3% (3/9). Fusion gene identification in cfRNA was correlated with treatment response. These results suggest that the proposed cfRNA assay is a useful diagnostic test for patients with insufficient tissues to facilitate effective administration of first-line treatment and is a useful tool to monitor the progression of NSCLC for consideration of second-line treatments.
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Quinasa de Linfoma Anaplásico/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Ácidos Nucleicos Libres de Células , Fusión Génica , Neoplasias Pulmonares/genética , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas c-ret/genética , Proteínas Proto-Oncogénicas/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Biopsia , Carbazoles/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Ácidos Nucleicos Libres de Células/aislamiento & purificación , Crizotinib/uso terapéutico , Proteínas del Citoesqueleto/genética , Progresión de la Enfermedad , Resistencia a Antineoplásicos/genética , Femenino , Gliceraldehído-3-Fosfato Deshidrogenasa (Fosforilante)/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Biopsia Líquida/métodos , Pulmón/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/aislamiento & purificación , Piperidinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , ARN Mensajero/aislamiento & purificación , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The prognostic value of the neutrophil-to-lymphocyte ratio (NLR) with large cell neuroendocrine carcinoma (LCNEC) patients remains unclear. Thus, we performed a retrospective study to examine the relationship between the pretreatment NLR and clinical outcome in advanced LCNEC patients and the impact of the immune-related tumour microenvironment (TME). METHODS: This retrospective study included 63 advanced LCNEC patients who had received chemotherapy. We collected clinical data and investigated the TME status (CD4, CD8, CD20 and FOXP3). RESULTS: The overall survival of the patients with a low NLR (<5) was significantly longer than those with a high NLR (≥5) (14.9 vs. 5.2 months; p < 0.001). A multivariate analysis identified a high NLR as a predictor of a poor prognosis (HR, 3.43; 95% CI, 1.73-6.79; p < 0.001). The NLR was inversely correlated with tumoural and stromal CD8-positive tumour-infiltrating lymphocytes (tumoural: r = -0.648, p = 0.005, stromal: r = -0.490, p = 0.046). CONCLUSIONS: A high NLR was associated with a poor prognosis in advanced LCNEC patients. Our study revealed that the NLR can reflect the TME, at least in part, suggesting that the NLR plays an important role not only as a clinical outcome predictor but also as a tumour immune status indicator.
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Carcinoma de Células Grandes/patología , Carcinoma Neuroendocrino/patología , Neoplasias Pulmonares/patología , Linfocitos/patología , Neutrófilos/patología , Microambiente Tumoral/inmunología , Adulto , Anciano , Carcinoma de Células Grandes/inmunología , Carcinoma de Células Grandes/cirugía , Carcinoma Neuroendocrino/inmunología , Carcinoma Neuroendocrino/cirugía , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: The Oncomine™ Dx Target Test based on next-generation sequencing has been approved for the screening of oncogenic mutations in advanced non-small-cell lung cancer patients. METHODS: We assessed the tissue sample factors that affect the success rate of Oncomine™ Dx Target Test companion diagnostics and the feasibility of using biopsy specimens for Oncomine™ Dx Target Test companion diagnostics in advanced non-small-cell lung cancer patients. RESULTS: Ninety-nine biopsy samples were subjected to genetic testing using the Oncomine™ Dx Target Test companion diagnostics to detect v-raf murine sarcoma viral oncogene homologue B1 mutations (Cohort 1), and 136 biopsy samples were examined using Oncomine™ Dx Target Test companion diagnostics for the detection of multiple oncogenic mutations (Cohort 2) between July 2018 and April 2020. We retrospectively collected clinical and pathological data, including tissue size and tumour cell content. The success rate was 77% (76/99) in Cohort 1 and 93% (127/136) in Cohort 2. In Cohort 1, the success rate was significantly associated with the tumour cell content: the success rate was 63% for samples with a tumour cell content of <20%, whereas it was 83% for samples with a tumour cell content of 20% or higher (P = 0.0446). The tissue size also affected the success rate: a success rate of 57% was obtained for tissue sizes <4 mm2, whereas a success rate of 95% was obtained for tissue sizes of 4 mm2 or larger (P < 0.0001). In Cohort 2, the success rate was 100% when tumour specimens with a tissue size of 4 mm2 or larger were used. CONCLUSIONS: Tissue size and tumour cell content were significantly associated with the success rate of Oncomine™ Dx Target Test companion diagnostics.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Adulto , Anciano , Anciano de 80 o más Años , Animales , Carcinoma de Pulmón de Células no Pequeñas/patología , Detección Precoz del Cáncer , Estudios de Factibilidad , Femenino , Pruebas Genéticas , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Neoplasias Pulmonares/patología , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Mutación , Estudios RetrospectivosRESUMEN
The efficacy of immune checkpoint inhibitors (ICIs) in elderly and poor performance status (PS) patients is controversial, because clinical evidence is limited. This study aimed to find a predictive biomarker for the efficacy of anti-programmed cell death 1 (PD-1) antibodies in these patient populations. We retrospectively reviewed medical records of advanced non-small-cell lung cancer (NSCLC) patients who were ≥ 75 years of age or classified as PS 2 and received anti-PD-1 antibody treatment between December 2015 and May 2018. We evaluated the association between the efficacy of the anti-PD-1 antibody in these patients and the clinical variables thought to affect ICI efficacy. A total of 235 patients with advanced NSCLC were treated with anti-PD-1 antibodies, among whom 31 patients were ≥ 75 years of age and 22 were PS 2. A Cox proportional hazard model showed that only high levels of serum vascular endothelial growth factor (VEGF) were significantly associated with a shorter progression-free survival in patients aged ≥ 75 years and those with PS 2. Among these cohorts, the overall response rate to anti-PD-1 treatment tended to be lower when serum VEGF was high compared to patients with low serum VEGF. Our results demonstrate that serum VEGF concentration may be a negative predictive biomarker in elderly and poor PS advanced NSCLC patients receiving anti-PD-1 antibody treatment. This finding may help identify patients who will not benefit from anti-PD-1 antibody therapy.
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Antineoplásicos Inmunológicos/uso terapéutico , Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Células Escamosas/sangre , Neoplasias Pulmonares/sangre , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/sangre , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
The STW-type zeolite is attractive for developing novel enantioselective syntheses/separation of chiral compounds because it is the only chiral zeolitic microporous material whose enantioenriched synthesis has been achieved. In addition to the conventional industries in which zeolites are used, STW should have diverse industrial applications in the pharmaceutical and food industries. However, the toxic and caustic fluoride required for synthesizing STW severely hinders its commercialization by mass production. Herein, we report the first example of fluoride-free STW synthesis, in which the two roles of fluoride-formation of a zeolitic framework rich in tetravalent T-atoms and promotion of double 4-membered ring unit formation-were substituted by dry gel conversion and Ge addition, respectively. The STW obtained was highly crystalline, with a similar micropore volume and thermal stability as those of original fluoride-based STW. Our approach is promising not only for the fluoride-free synthesis of enantiomeric STW but also for general fluoride-free syntheses.
RESUMEN
BACKGROUND AND OBJECTIVE: Talc pleurodesis is commonly performed to manage refractory pleural effusion or pneumothorax. It is considered as a safe procedure as long as a limited amount of large particle size talc is used. However, acute respiratory distress syndrome (ARDS) is a rare but serious complication after talc pleurodesis. We sought to determine the risk factors for the development of ARDS after pleurodesis using a limited amount of large particle size talc. METHODS: We retrospectively reviewed patients who underwent pleurodesis with talc or OK-432 at the University of Tokyo Hospital. RESULTS: Twenty-seven and 35 patients underwent chemical pleurodesis using large particle size talc (4 g or less) or OK-432, respectively. Four of 27 (15%) patients developed ARDS after talc pleurodesis. Patients who developed ARDS were significantly older than those who did not (median 80 vs 66 years, P = 0.02) and had a higher prevalence of underlying interstitial abnormalities on chest computed tomography (CT; 2/4 vs 1/23, P < 0.05). No patient developed ARDS after pleurodesis with OK-432. This is the first case series of ARDS after pleurodesis using a limited amount of large particle size talc. CONCLUSION: Older age and underlying interstitial abnormalities on chest CT seem to be risk factors for developing ARDS after talc pleurodesis.
Asunto(s)
Enfermedades Pulmonares Intersticiales/complicaciones , Pleurodesia/efectos adversos , Síndrome de Dificultad Respiratoria/etiología , Talco/efectos adversos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Tamaño de la Partícula , Picibanil/uso terapéutico , Derrame Pleural/complicaciones , Derrame Pleural/tratamiento farmacológico , Pleurodesia/métodos , Neumotórax/complicaciones , Neumotórax/tratamiento farmacológico , Estudios Retrospectivos , Factores de Riesgo , Tomografía Computarizada por Rayos XRESUMEN
AIM: We compared the nutritional and dietary intakes of users of mobile vendor vehicles and users of stores to clarify the problems in the nutritional intake of users of mobile vendor vehicles. METHODS: We conducted a questionnaire about the food accessibility among 257 elderly women (age: ≥65 years) who used mobile vendor vehicles and/or stores to shop. The nutritional intake was assessed using the 24-hour recall method. We used an analysis of covariance (ANCOVA) to calculate the age-adjusted mean values for the total nutritional intake. RESULTS: The nutritional intake among users of mobile vendor vehicles included significantly lower intakes of energy (168 kcal), green vegetables, other vegetables, and meats. Furthermore, those who only shopped at mobile vendor vehicles consumed less energy and fewer nutrients than those who shopped at places other than mobile vendor vehicles. The comparison of the shopping frequency and nutritional intake of the subjects who used mobile vendor vehicles alone revealed that the energy and protein intakes of those who shopped once per week was significantly lower in comparison to those who shopped twice per week. CONCLUSIONS: Users of mobile vendor vehicles had lower intakes of macronutrients and various minerals and vitamins. Among the food groups, intakes of vegetables, meat, and dairy products were low. These findings suggest that the lack of means of shopping other than mobile vendor vehicles and shopping once per week may be associated with an inadequate dietary intake among users of mobile vendor vehicles. It would be desirable to develop the shopping environment is desirable.
Asunto(s)
Ingestión de Energía , Anciano , Anciano de 80 o más Años , Comercio , Dieta , Femenino , Humanos , Vida Independiente , Evaluación NutricionalRESUMEN
BACKGROUND: Some case reports have found that corticosteroid treatments shrunk thymoma lesions remarkably after the failure of chemotherapy or surgery. However, few studies have comprehensibly evaluated the antitumor effects of corticosteroids in patients with invasive thymomas. METHODS: We reviewed the medical records of 13 consecutively enrolled patients with locally advanced or metastatic thymomas treated via corticosteroid monotherapies from January 2010 to March 2021 in our institute. A Cox's proportional hazard model and the Kaplan-Meier method were used to identify factors associated with survival. RESULTS: The median follow-up time was 26 months (range, 13-115 months). The median initial dose of corticosteroid was 0.90 mg/kg/day prednisolone equivalent (range, 0.4-1.1 mg/kg/day). Of the 13 cases, 7 (53.8%, 95% CI: 0.25-0.81) exhibited a partial response and 5 (38.5%, 95% CI: 0.14-0.68) stable disease. The median progression-free survival was 5.7 months [95% confidence interval (CI): 1.5-9.6 months]. The median overall survival was 25.3 months (95% CI: 7.1-not attained). The median duration of corticosteroid use was 3 months (range, 1-64 months). Patients with WHO subtype B thymomas exhibited a better overall response rate to corticosteroids than did patients with other disease subtypes (75%, 95% CI: 0.19-0.99). Adverse events of Grade 3 or more were not observed. CONCLUSIONS: Corticosteroids are clinically valuable for patients with thymomas.
Asunto(s)
Timoma , Neoplasias del Timo , Humanos , Timoma/tratamiento farmacológico , Timoma/mortalidad , Timoma/patología , Masculino , Persona de Mediana Edad , Femenino , Neoplasias del Timo/tratamiento farmacológico , Neoplasias del Timo/patología , Neoplasias del Timo/mortalidad , Anciano , Adulto , Resultado del Tratamiento , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéutico , Prednisolona/administración & dosificación , Estudios Retrospectivos , Estudios de Seguimiento , Tasa de Supervivencia , Modelos de Riesgos ProporcionalesRESUMEN
PURPOSE: The gut microbiota is hypothesized as a prognostic biomarker for cancer immunotherapy. Antibiotic-induced dysbiosis negatively affects the clinical outcomes of immunotherapy. However, the effect of dysbiosis on the efficacy and safety of Chemoimmunotherapy (chemo-IOs), the frontline standard of care, in advanced non-small cell lung cancer (NSCLC) remains unknown. We aimed to compare the efficacy and safety of chemo-IOs in patients exposed to antibiotics before treatment with those of patients who were not exposed. METHODS: We retrospectively reviewed patients with advanced NSCLC treated with first-line chemo-IOs between 2018 and 2020 at the National Cancer Center Hospital. The patients were divided into two groups: those exposed to antibiotics within 30 days before induction therapy (ABx group) and those did not antibiotics (Non-ABx group). Propensity score matching was used to control for potential confounding factors. Clinical outcomes including progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) were compared. RESULTS: Of 201 eligible patients, 21 were in the ABx group, and 42 were in the non-ABx group after propensity score matching. No differences in PFS or OS emerged between the two groups (ABx group vs. Non-ABx group) (PFS:7.0 months vs. 6.4 months, hazard ratio [HR] 0.89; 95% confidence interval [CI], 0.49-1.63, OS:20.4 months vs. 20.1 months, HR 0.87; 95% CI 0.44-1.71). The frequency of irAEs before propensity score matching was similar across any-grade irAEs (39.4% vs. 42.9%) or grade 3 or higher irAEs (9.1% vs. 11.3%). CONCLUSION: Antibiotic-induced dysbiosis may not affect the efficacy of chemo-IOs in patients with advanced NSCLC.