Anlotinib in patients with relapsed or refractory thymic epithelial tumors: a study of 50 cases.

The optimal pharmaceutical regimen for advanced thymic epithelial tumors (TETs) remains controversial when first-line chemotherapy fails. This retrospective study aims to evaluate the efficacy and safety of anlotinib treatment for patients with relapsed and refractory TETs. Patients with progressive disease after failure of platinum-based chemotherapy were enrolled in this study. Anlotinib was orally taken once a day at an initial dose of 12 mg (10 mg when body weight <60 kg). The cycle was repeated every 3 weeks (2 weeks of treatment followed by 1-week rest). Objective response rate (ORR) and progression-free survival (PFS) were recorded as primary endpoints. There were 50 patients enrolled in this study from October 2018 to June 2021 at a median age of 50 (range 23-79) years old. Patients with thymoma and thymic carcinoma were 33 (66%) and 17 (34%), respectively. The ORR in thymoma and thymic carcinoma patients were 33% (11/33) and 41% (7/17), respectively. The median PFS (mPFS) was 7 (95% CI, 5.9-10.2) months in thymoma patients and 6 (95% CI, 4.6-9.3) months in the thymic carcinoma group. Eleven patients experienced dose reduction due to toxicities, among whom, eight patients discontinued treatment even after dose reduction. Six patients with thymoma showed myasthenia gravis deterioration during treatment, and two of them died of myasthenia gravis crisis. Anlotinib is active in patients with advanced TETs refractory to routine chemotherapy. Prescription of anlotinib to patients with myasthenia gravis should be made cautiously.

Anaphylactic shock in a small cell lung cancer patient receiving atezolizumab therapy: a rare but potentially fatal complication.

Immunotherapy has been a revolutionary innovation in cancer therapy in recent years, but it is accompanied by various unique immune-related adverse events (irAEs). Among these irAEs, anaphylactic shock is very rare. Here, we report a case of a patient who developed anaphylactic shock after receiving one dose of atezolizumab. A 74-year-old male patient with small cell lung cancer experienced recurrence 10 years after surgery. After one cycle of treatment, the patient developed a grade 2 rash and recovered after receiving oral methylprednisolone tablets. In the second cycle, atezolizumab was discontinued. Then, the patient was scheduled to receive atezolizumab plus carboplatin and etoposide again after three weeks, but approximately three minutes after an intravenous infusion of atezolizumab, the patient developed signs and symptoms of anaphylactic shock, such as dyspnea, cold limbs, and loss of consciousness. At this point, the infusion was immediately stopped, and a normal saline infusion was administered. Meanwhile, ECG monitoring, supplemental humidified high-flow supplemental 100% oxygen, epinephrine, dopamine, hormone treatment with methylprednisolone, and other anti-shock treatments were carried out. For better recuperation, this patient was transferred to the intensive care unit for further treatment and was discharged two days later. Anaphylactic shock develops rapidly and is also a very severe complication. Prompt detection, diagnosis, and therapeutic intervention are the basics for survival.

Genomic Landscape Survey Identifies SRSF1 as a Key Oncodriver in Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is an aggressive disease with poor survival. A few sequencing studies performed on limited number of samples have revealed potential disease-driving genes in SCLC, however, much still remains unknown, particularly in the Asian patient population. Here we conducted whole exome sequencing (WES) and transcriptomic sequencing of primary tumors from 99 Chinese SCLC patients. Dysregulation of tumor suppressor genes TP53 and RB1 was observed in 82% and 62% of SCLC patients, respectively, and more than half of the SCLC patients (62%) harbored TP53 and RB1 mutation and/or copy number loss. Additionally, Serine/Arginine Splicing Factor 1 (SRSF1) DNA copy number gain and mRNA over-expression was strongly associated with poor survival using both discovery and validation patient cohorts. Functional studies in vitro and in vivo demonstrate that SRSF1 is important for tumorigenicity of SCLC and may play a key role in DNA repair and chemo-sensitivity. These results strongly support SRSF1 as a prognostic biomarker in SCLC and provide a rationale for personalized therapy in SCLC.

Anlotinib as a third-line therapy in patients with refractory advanced non-small-cell lung cancer: a multicentre, randomised phase II trial (ALTER0302).

BACKGROUND: Anlotinib (AL3818) is a novel multitarget tyrosine kinase inhibitor, inhibiting tumour angiogenesis and proliferative signalling. The objective of this study was to assess the safety and efficacy of third-line anlotinib for patients with refractory advanced non-small-cell lung cancer (RA-NSCLC). METHODS: Eligible patients were randomised 1 : 1 to receive anlotinib (12 mg per day, per os; days 1-14; 21 days per cycle) or a placebo. The primary end point was progression-free survival (PFS). RESULTS: A total of 117 eligible patients enrolled from 13 clinical centres in China were analysed in the full analysis set. No patients received immune check-point inhibitors and epidermal growth factor receptor status was unknown in 60.7% of the population. PFS was better with anlotinib compared with the placebo (4.8 vs 1.2 months; hazard ratio (HR)=0.32; 95% confidence interval (CI), 0.20-0.51; P<0.0001), as well as overall response rate (ORR) (10.0%; 95% CI, 2.4-17.6% vs 0%; 95% CI, 0-6.27%; P=0.028). The median overall survival (OS) was 9.3 months (95% CI, 6.8-15.1) for the anlotinib group and 6.3 months (95% CI, 4.3-10.5) for the placebo group (HR=0.78; 95% CI, 0.51-1.18; P=0.2316). Adverse events were more frequent in the anlotinib than the placebo group. The percentage of grade 3-4 treatment-related adverse events was 21.67% in the anlotinib group. CONCLUSIONS: Anlotinib as a third-line treatment provided significant PFS benefits to patients with RA-NSCLC when compared with the placebo, and the toxicity profiles showed good tolerance.

Prognostic value of pretreatment procalcitonin and neutrophil-lymphocyte ratio in extensive-stage small-cell lung cancer.

BACKGROUND: To investigate the influence of pretreatment neutrophil-to-lymphocyte ratio (NLR) and procalcitonin (PCT) on progression-free survival (PFS) in extensive-stage small-cell lung cancer (SCLC) patients. METHOD: A total of 100 extensive-stage SCLC patients were enrolled in our study. Patients were stratified according to the median values of pretreatment NLR and PCT levels: low NLR group (NLR ≤3.17), high NLR group (NLR＞3.17), low PCT group (PCT ≤0.06; ng/ml), high PCT group (PCT＞0.06; ng/ml). The Kaplan-Meier method and multivariable Cox regression model were used to reveal the prognostic effects of pretreatment NLR and PCT on PFS. RESULTS: The median PFS of the total extensive-stage SCLC patients was 6.0 months. The median PFS of low pretreatment NLR group (NLR ≤3.17) was not significantly different from that of high pretreatment NLR group (6.2 months vs 5.8 months; p = .675). Patients with low pretreatment PCT (PCT ≤0.06; ng/ml) had significantly better PFS than patients with high pretreatment PCT (PCT＞0.06; ng/ml) (6.9 months vs 5.7 months; p = .043). With the multivariable Cox regression analysis, the response to first-line chemotherapy (p ≤ .001) and pretreatment PCT (HR = 0.516; 95%CI 0.326-0.817; p = .005) were identified as independent factors associated with PFS. CONCLUSION: Pretreatment PCT is an independent factor associated with PFS in extensive-stage SCLC patients treated with first-line chemotherapy, but pretreatment NLR reflects no significant prognostic value in our study.

A Re-Examination of Neoadjuvant Therapy for Thymic Tumors: A Long and Winding Road.

For most patients with advanced thymic epithelial tumors (TETs), a complete resection is a strong indicator of a better prognosis. But sometimes, primary surgery is unsatisfactory, and preoperative therapy is needed to facilitate complete resection. Neoadjuvant chemotherapy is the most used form of preoperative therapy. But studies on neoadjuvant chemotherapy have included mainly patients with thymoma; its efficacy in patients with thymic carcinoma is less known. Neoadjuvant chemoradiation has also been explored in a few studies. Novel therapies such as immunotherapy and targeted therapy have shown efficacy in patients with recurrent/metastatic TETs as a second-line option; their role as preoperative therapy is still under investigation. In this review, we discuss the existing evidence on preoperative therapy and the insight it provides for current clinical practice and future studies.

Ambient Air Pollution and Vision Disorder: A Systematic Review and Meta-Analysis.

The effects of air pollution on physical health are well recognized, with many studies revealing air pollution's effects on vision disorder, yet no relationship has been established. Therefore, a meta-analysis was carried out in this study to investigate the connection between vision disorder and ambient particles (diameter ≤ 2.5 µm (PM2.5), diameter ≤ 10 µm (PM10)) and gaseous pollutants (nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), Ozone (O3)). Twelve relevant studies published by 26 February 2024 were identified in three databases. A pooled odds ratios (ORs) of 95% confidence intervals (CIs) were obtained using random-effects meta-analysis models. Meta-analysis results revealed that for every 10 µg/m3 increase in PM2.5 and NO2 exposure, a substantially higher incidence of vision disorder was observed (OR = 1.10; 95% CI: 1.01, 1.19; OR = 1.08, 95% CI: 1.00, 1.16). No significant correlation existed between exposure to PM10, SO2 and CO and vision disorder. However, O3 exposure was negatively associated with vision disorder. In addition, subgroup analyses revealed that PM2.5 exposure was significantly correlated with the risk of glaucoma and age-related macular degeneration and that children and adolescents were more susceptible to NO2 and PM2.5 than adults. Overall, exposure to air pollutants, especially PM2.5 and NO2, may increase the incidence of vision disorder.

Telehealth With Comprehensive Live-Fed Real-World Data as a Patient Care Platform for Lung Cancer: Implementation and Evaluation Study.

BACKGROUND: Telehealth has emerged as a popular channel for providing outpatient services in many countries. However, the majority of telehealth systems focus on operational functions and offer only a sectional patient journey at most. Experiences with incorporating longitudinal real-world medical record data into telehealth are valuable but have not been widely shared. The feasibility and usability of such a telehealth platform, with comprehensive, real-world data via a live feed, for cancer patient care are yet to be studied. OBJECTIVE: The primary purpose of this study is to understand the feasibility and usability of cancer patient care using a telehealth platform with longitudinal, real-world data via a live feed as a supplement to hospital electronic medical record systems specifically from physician's perspective. METHODS: A telehealth platform was constructed and launched for both physicians and patients. Real-world data were collected and curated using a comprehensive data model. Physician activities on the platform were recorded as system logs and analyzed. In February 2023, a survey was conducted among the platform's registered physicians to assess the specific areas of patient care and to quantify their before and after experiences, including the number of patients managed, time spent, dropout rate, visit rate, and follow-up data. Descriptive and inferential statistical analyses were performed on the data sets. RESULTS: Over a period of 15 months, 16,035 unique users (13,888 patients, 1539 friends and family members, and 174 physician groups with 608 individuals) registered on the platform. More than 382,000 messages including text, reminders, and pictures were generated by physicians when communicating with patients. The survey was completed by 78 group leaders (45% of the 174 physician groups). Of the participants, 84% (65.6/78; SD 8.7) reported a positive experience, with efficient communication, remote supervision, quicker response to questions, adverse event prevention, more complete follow-up data, patient risk reduction, cross-organization collaboration, and a reduction in in-person visits. The majority of the participants (59/78, 76% to 76/78, 97.4%) estimated improvements in time spent, number of patients managed, the drop-off rate, and access to medical history, with the average ranging from 57% to 105%. When compared with prior platforms, responses from physicians indicated better experiences in terms of time spent, the drop-off rate, and medical history, while the number of patients managed did not significantly change. CONCLUSIONS: This study suggests that a telehealth platform, equipped with comprehensive, real-world data via a live feed, is feasible and effective for cancer patient care. It enhances inpatient management by improving time efficiencies, reducing drop-off rates, and providing easy access to medical history. Moreover, it fosters a positive experience in physician-patient interactions.

Prognosis of different extrathoracic metastasis patterns in patients with M1c lung adenocarcinoma receiving immunotherapy.

INTRODUCTION: Lung cancer with extrathoracic metastases is classified as M1c. However, extrathoracic metastases can be further classified into different patterns. The purpose of this study was to analyze the survival differences between different patterns of extrathoracic metastases in patients with stage M1c lung adenocarcinoma after receiving immunotherapy. MATERIALS AND METHODS: This study included 160 stage M1c lung adenocarcinoma patients and treated with immunotherapy. The enrolled patients were divided into two groups: those with multiple extrathoracic metastases alone (EM group) and those with simultaneous multiple extrathoracic and intrathoracic metastases (EIM group). Progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS: The median PFS and OS in the whole group were 7.7 months and 25.4 months, respectively. The patients in the EM group show better PFS (13.0 months vs. 5.0 months; hazard ratio [HR] = 0.462, 95% confidence interval [CI] 0.317-0.673, P < 0.0001) and OS (35.0 months vs. 18.9 months; HR 0.592, 95% CI 0.380-0.922, P = 0.019) compared with the EIM group. Furthermore, in patients with lung adenocarcinoma with simultaneous extrathoracic and intrathoracic metastases who received immunotherapy, immunotherapy combined with chemotherapy has better PFS and OS than immunotherapy alone. There was no difference between immunotherapy alone or combined with chemotherapy in patients with lung adenocarcinoma with extrathoracic metastasis alone. CONCLUSION: The different patterns of extrathoracic metastasis were related to the efficacy and prognosis of immunotherapy in M1c cohort. In addition, patients with simultaneous extrathoracic and intrathoracic metastases were more recommended to choose immunotherapy in combination with chemotherapy rather than immunotherapy alone.

miR-135a Regulates Atrial Fibrillation by Targeting Smad3.

Background: Atrial fibrillation (AF) is the most common arrhythmia in clinical. Atrial fibrosis is a hallmark feature of atrial structural remodeling in AF, which is regulated by the TGF-ß1/Smad3 pathway. Recent studies have implicated that miRNAs are involved in the process of AF. However, the regulatory mechanisms of miRNAs remain largely unknown. This study is aimed at investigating the function and regulatory network of miR-135a in AF. Methods: In vivo, the plasma was collected from patients with AF and non-AF subjects. Adult SD rats were induced by acetylcholine (ACh) (66 µg/ml)-CaCl2 (10 mg/ml) to establish an AF rat model. In vitro, atrial fibroblasts (AFs), isolated from adult SD rats, were treated with high-frequency electrical stimulation (HES) (12 h) and hypoxia (24 h) to mimic the AF and atrial fibrosis, respectively. miR-135a expression was detected through quantitative real-time polymerase chain reaction (qRT-PCR). The association between miR-135a and Smad3 was speculated by the TargetScan database and confirmed by the luciferase reporter assay. Fibrosis-related genes, Smad3, and TRPM7 were all assessed. Results: The expression of miR-135a was markedly decreased in the plasma of AF patients and AF rats, which was consistent with that in HES-treated and hypoxia-treated AFs. Smad3 was identified as a target of miR-135a. the downregulation of miR-135a was associated with the enhancement of Smad3/TRPM7 expressions in AFs. Additionally, the knockdown of Smad3 significantly reduced the expression of TRPM7 and further inhibited atrial fibrosis. Conclusions: Our study demonstrates that miR-135a regulates AF via Smad3/TRPM7, which is a potential therapeutic target for AF.

Clinical predictors of treatment efficacy and a prognostic nomogram in patients with lung adenocarcinoma receiving immune checkpoint inhibitors: a retrospective study.

Background: At present, there is no accurate biomarker for immune checkpoint inhibitors (ICIs). Since the efficacy of ICIs is associated with a variety of indicators, establishing a model to predict its efficacy is more clinically significant and in line with clinical needs. Methods: We collected and retrospectively analyzed the relationship between immunotherapy efficacy and clinicopathologic features in lung adenocarcinoma patients treated with ICIs. Progression-free survival (PFS) and overall survival (OS) were analyzed. Univariate and multivariate Cox proportional hazards regression analyses were conducted to identify prognostic factors associated with PFS. Besides, a clinical prediction model was established based on the results of the multivariate Cox regression analyses to predict PFS. Results: A total of 201 lung adenocarcinoma patients treated with ICIs were assessed. Univariate analysis showed that male gender [hazard ratio (HR) =0.521, 95% confidence interval (CI): 0.356-0.761, P=0.001], smoking (HR =0.595, 95% CI: 0.420-0.843, P=0.003), epidermal growth factor receptor (EGFR) wild type (HR =2.766, 95% CI: 1.719-4.452, P<0.001), Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation (HR =0.449, 95% CI: 0.271-0.743, P=0.001), positive programmed death ligand 1 (PD-L1) expression (HR =0.527, 95% CI: 0.336-0.825, P=0.004), early tumor node metastasis (TNM) stage (HR =0.581, 95% CI: 0.344-0.983, P=0.039), no liver metastasis (HR =1.801, 95% CI: 1.046-3.102, P=0.031), ICIs combined with chemotherapy (HR =0.560, 95% CI: 0.384-0.815, P=0.002), having immune-related adverse effects (HR =0.354, 95% CI: 0.228-0.511, P<0.001) and first-line immunotherapy (HR =0.596, 95% CI: 0.420-0.845, P=0.003) were significantly associated with better PFS in patients with lung adenocarcinoma receiving immunotherapy. Multivariate analysis showed that smoking status, KRAS mutation, PD-L1 expression, line of immunotherapy and immune-related adverse effects were independent prognostic factors affecting PFS. A clinical prediction model was established to predict the PFS of lung adenocarcinoma patients treated with ICIs. The model showed good predictive ability via C-index, calibration curve and receiver operating characteristic (ROC) curve validation. Conclusions: The clinical prediction model developed in this study can be used to some extent to predict PFS after immunotherapy in lung adenocarcinoma patients. However, the model still needs to be validated in studies with large sample size.

The efficacy of anlotinib as third-line treatment for non-small cell lung cancer by EGFR mutation status: a subgroup analysis of the ALTER0303 randomized phase 3 study.

Background: Anlotinib demonstrated improved overall survival (OS) and progression-free survival (PFS) compared with placebo as a third-line or subsequent therapy in patients with non-small cell lung cancer (NSCLC) in the ALTER0303 trial. The status of epidermal growth factor receptor (EGFR) mutation, different previous treatment may affect the efficacy of subsequent therapy, and we did this subgroup analysis to characterize the efficacy of anlotinib in patients with and without EGFR mutation. Methods: The ALTER0303 trial was a randomized, double-blind, phase 3 study of anlotinib in patients with NSCLC who failed at least 2 lines of treatment. In the study, 138 of 437 randomized patients were EGFR mutation positive. A Cox model was used to examine the influence of previous treatment on the efficacy of anlotinib according to EGFR mutation status. Results: For patients with EGFR mutation, the OS was 10.7 and 6.3 months (HR 0.59; 95% CI: 0.38-0.94, P=0.025) in the anlotinib and placebo group, respectively. The PFS was 5.6 and 0.8 months (HR 0.21; 95% CI: 0.13-0.32, P<0.0001) in the anlotinib and placebo group, respectively. For patients without EGFR mutation, the OS was 8.9 months for anlotinib and 6.5 months for placebo (HR 0.73; 95% CI: 0.55-0.97, P=0.029), and the PFS was 5.4 months for anlotinib and 1.6 months for placebo (HR 0.29; 95% CI: 0.22-0.39, P<0.0001). In the anlotinib group, the OS and PFS for patients with and without EGFR mutation was 10.7 and 8.9 months (HR 0.69; 95% CI: 0.50-0.95, P=0.021), 5.6 and 5.4 months (HR 1.00; 95% CI: 0.75-1.34, P=1.000), respectively. The incidence of adverse events was similar in subgroups. Conclusions: This analysis demonstrated that the benefit of anlotinib as a third-line therapy for patients with NSCLC was independent of EGFR mutation status.

Expert consensus on multi-disciplinary treatment, whole-course pulmonary rehabilitation management in patients with lung cancer and chronic obstructive lung disease.

Comorbidity of lung cancer and chronic obstructive pulmonary disease (COPD) is very common. Surgical operation is the initial treatment of lung cancer. But surgery operation will aggravate the symptoms of COPD, such as shortness of breath, chest tightness. On the other side, the COPD also increase the perioperative complications. Besides, the COPD may also influence the anti-cancer treatment and long-term survival of lung cancer patients. At present, there are guidelines for pulmonary rehabilitation (PR) of COPD or lung cancer respectively, but there is no reference expert consensus on the PR of patients with lung cancer who are comorbidity of COPD. Primary care has to satisfy the patient's complex needs holistically, and single-disease guidelines are unsuitable. In view of this, we organized experts from respiratory department, thoracic surgery department, oncology department, nursing department, etc., to write the expert consensus. We discussed the contents of the expert consensus through literature review, expert correspondence, expert meeting and discussion. This expert consensus contain five parts: introduction, respiratory assessment, timing of PR, PR strategies, perioperative PR management strategies in lung cancer patients with COPD. This expert consensus focuses on patients with COPD comorbid lung cancer and undergoing surgery operation, highlighting the concept of whole process management. For clinical medical staff, this expert consensus will promote the practice of PR in and out the hospital for this specific patient; for patients, this expert consensus is helpful to better understand PR and improve the enthusiasm of participating in PR in the whole process.

[A multicenter, randomized, double-blind, placebo-controlled safety study to evaluate the clinical effects and quality of life of paclitaxel-carboplatin (PC) alone or combined with endostar for advanced non-small cell lung cancer (NSCLC)].

OBJECTIVE: To analyze the efficacy and quality of life and safety for paclitaxel and carboplatin (TC) and TC combined with endostar in the treatment of advanced non-small cell lung cancer (NSCLC). METHODS: This is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical study. A total of 126 cases of untreated advanced NSCLC were enrolled in this study. There were 63 patients in the TC control arm and TC combined endostar arm, respectively. All enrolled patients were continuously followed-up for disease progression and death. RESULTS: The objective response rate (ORR) of TC combined with endostar arm was 39.3%, and that of TC control arm was 23.0%, P = 0.078. The progression-free survival rates for TC combined with endostar arm and TC control arm were 78.3% and 58.8%, respectively, in 24 weeks (P = 0.017). The hazard ratio for the risk of disease progression was 0.35 (95%CI 0.13 to 0.90, P = 0.030). The median time to progression (TTP) of the TC combined with endostar arm was 7.1 months and TC arm 6.3 months (P > 0.05). The follow-up results showed that the median survival time (mOS) of the TC + Endostar arm was 17.6 months; (95%CI 13.4 to 21.7 months), and the TC + placebo arm 15.8 months (95%CI 9.4 to 22.9 months) (P > 0.05). The quality of life scores (LCSS patient scale) after treatment of the TC combined with endostar arm was improved, and that of the TC group was improved after completion of two cycles and three cycles of treatment. The quality of life scores compared with baseline after the completion of one cycle treatment was significantly improved for both the TC combined with endostar arm (P = 0.028 and), and TC arm (P = 0.036). It Indicated that TC combined with endostar treatment improved the patient's quality of life in the early treatment. The difference of adverse and serious adverse event rates between the two groups was not significant (P > 0.05). CONCLUSIONS: Compared with TC alone treatmrnt, TC combined with endostar treatment can reduce the risk of disease progression at early time (24 weeks), increase the ORR, and can be used as first-line treatment for advanced NSCLC. The TC combined with endostar treatment has good safety and tolerability, improves the quality of life, and not increases serious adverse effects and toxicity for patients with advanced NSCLC.

Utility and Safety of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in the Diagnosis of Isolated Mediastinal Masses.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a valuable tool for diagnosing pulmonary disease due to its efficiency and safety. We retrospectively analyzed patients with mediastinal masses who underwent diagnostic EBUS-TBNA at Shanghai Chest Hospital, and evaluated the clinical accuracy of EBUS-TBNA in the diagnosis mediastinal masses. METHOD: From 2009 and 2014, patients who received EBUS-TBNA to diagnose a isolated mediastinal mass were enrolled. Clinical follow-up was performed to ascertain the patient's final diagnosis. RESULTS: Forty-six patients were enrolled in this study. Thirty-seven were diagnosed with an oncologic disease, 3 were diagnosed with a mediastinal infection, and 2 were found to have a mediastinal goiter. The overall sensitivity, specificity, positive predictive value, negative predictive value, diagnostic yield was 63.6%, 100%, 100%, 42.9%, and 71.4%, respectively. CONCLUSION: EBUS-TBNA is a safe and effective means of diagnosing mediastinal masses.

EGFR Tyrosine Kinase Inhibitor (TKI) Combined With Concurrent or Sequential Chemotherapy for Patients With Advanced Lung Cancer and Gradual Progression After First-Line EGFR-TKI Therapy: A Randomized Controlled Study.

INTRODUCTION: Continuing tyrosine kinase inhibitor (TKI) therapy may be beneficial when patients with non-small-cell lung cancer and EGFR mutations experience gradual disease progression after initial EGFR-TKI treatment. We aimed to compare the efficacy of simultaneous EGFR-TKI and chemotherapy with that of sequential treatment after patients' disease gradually progressed after first-line EGFR-TKI treatment. PATIENTS AND METHODS: Patients with gradual progression who were EGFR-T790M mutation negative were randomly divided into two groups. In the concurrent group, patients were treated with pemetrexed plus cisplatin along with the same EGFR-TKI. In the sequential group, patients continued with EGFR-TKI until the disease progressed again, according to RECIST, then switched to chemotherapy. We evaluated the patients' progression-free survival (PFS) and overall survival times. RESULTS: Ninety-nine patients were enrolled: 49 in the concurrent group and 50 in the sequential group. The median PFS (mPFS) was 7.7 months (95% confidence interval [CI], 3.6-11.7) in the concurrent group and 5.7 months (95% CI, 3.5-7.9) in the sequential group (hazard ratio = 0.66; 95% CI, 0.44-1.00; P = .026), respectively. For the sequential group, the mPFS1 and mPFS2 were 1.8 months (95% CI, 1.4-2.3) and 3.8 months (95% CI, 3.1-4.5), respectively. The median overall survival of the concurrent group was longer than that of the sequential group (20.0 vs. 14.7 months; hazard ratio = 0.52; 95% CI, 0.32-0.85; P = .038). CONCLUSION: For patients with advanced non-small-cell lung cancer and gradual progression who are EGFR-T790M mutation negative after initial EGFR-TKI therapy, EGFR-TKI combined with chemotherapy confers longer PFS and overall survival than sequential EGFR-TKI and chemotherapy does.

Detection of Genetic Mutations by Next-Generation Sequencing for Predicting Prognosis of Extensive-Stage Small-Cell Lung Cancer.

Some studies have revealed that specific genetic mutations could be associated with chemotherapy response or even survival in small-cell lung cancer (SCLC). Our retrospective study aimed to identify the correlation between genetic mutations and progression-free survival (PFS) in extensive-stage SCLC after first-line chemotherapy. A total of 75 patients with extensive-stage SCLC confirmed by histopathology from February 2018 to February 2019 were retrospectively analyzed. The biopsy specimens of all patients were analyzed by Next-Generation Sequencing (NGS). All patients received first-line chemotherapy and follow-up at Shanghai Chest Hospital. Eleven genes were mutated in, at least, 10% of the 75 patients, including TP53 (96%), RB1 (77%), SMAD4 (32%), NOTCH1 (21%), PTEN (16%), FGFR1 (16%), KDR (15%), PIK3CA (15%), ROS1 (15%), BRCA2 (13%), and ERBB4 (10%). The median number of mutated genes among all patients was 5. Patients with more than 5 mutated genes (PFS = 6.7 months, P=0.004), mutant TP53 (PFS = 5.0 months, P=0.011), and mutant BRCA2 (PFS = 6.7 months, P=0.046) had better PFS after first-line chemotherapy than other patients. Multivariate Cox regression analysis showed that patients who achieved a PR (HR 3.729, 95% CI 2.038-6.822), had more than 5 mutated genes (HR 1.929, 95% CI 1.096-3.396), had BRCA2 mutations (HR 4.581, 95% CI 1.721-12.195), and had no liver metastasis (HR 0.415, 95% CI 0.181-0.951) showed improvements in PFS after first-line chemotherapy. In conclusion, the number of mutated genes and BRCA2 mutation status in extensive-stage SCLC were significantly related to PFS after first-line chemotherapy.

Astragaloside IV inhibits cardiac fibrosis via miR-135a-TRPM7-TGF-ß/Smads pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiac fibrosis is a common characteristic of many cardiac diseases. Our previous results showed that TRPM7 channel played an important role in the fibrosis process. MicroRNA-135a was reported to get involved in the fibrotic process. Astragalus membranaceus (Fisch.) Bunge was widely used in Chinese traditional medicine and showed cardiac protective effects in previous researches. Astragaloside IV(ASG), which is regarded as the most important ingredient of Astragalus, has been showed the effect of cardiac protection via various mechanisms, while no data suggested its action related to miRNAs regulation. AIM OF THE STUDY: The objective of this article is to investigate the inhibition effect of ASG on cardiac fibrosis through the miR-135a-TRPM7-TGF-ß/Smads pathway. MATERIALS AND METHODS: We extracted the active components from herb according to the paper and measured the content of ASG from the mixture via HPLC. The inhibition potency of cardiac hypertrophy between total extract of Astragalus and ASG was compared. SD rats were treated with ISO (5 mg/kg/day) subcutaneously (s.c.) for 14 days, ASG (10 mg/kg/d) and Astragalus extract (AE) (4.35 g/kg/d, which contained about ASG 10 mg) were given p.o. from the 6th day of the modeling. Cardiac fibroblasts (CFs) of neonatal rats were incubated with ISO (10 µM) and treated with ASG (10 µM) simultaneously for 24 h. RESULTS: The results showed that both AE and ASG treatment reduced the TRPM7 expression from the gene level and inhibited cardiac fibrosis. ASG group showed similar potency as the AE mixture. ASG treatment significantly decreased the current, mRNA and protein expression of TRPM7 which was one of targets of miR-135a. The activation of TGF-ß/Smads pathway was suppressed and the expression of α-SMA and Collagen I were also decreased obviously. In addition, our results showed that there was a positive feedback between the activation of TGF-ß/Smads pathway and the elevation of TRPM7, both of which could promote the development of myocardial fibrosis. CONCLUSIONS: AE had the effect of cardiac fibrosis inhibition and decreased the mRNA expression of TRPM7. ASG, as one of the effective ingredients of AE, showed the same potency when given the same dose. ASG inhibited cardiac fibrosis by targeting the miR-135a-TRPM7-TGF-ß/Smads pathway.

Prognostic value of tumor cavitation in extensive-stage small-cell lung cancer patients treated with anlotinib.

PURPOSE: Anlotinib is a novel multi-target tyrosine kinase inhibitor (TKI) for tumor angiogenesis and tumor cell proliferation. The efficacy of anlotinib as a third-line or beyond therapy for SCLC was confirmed in the ALTER1202 trial. For lung cancer patients treated with antiangiogenesis agents, the phenomenon of cavitation is commonly seen in the lung target lesions. The impact of tumor cavitation on survival in lung cancer patients treated with vascular-targeted therapy remains controversial. Our retrospective study was to investigate the prognostic value of tumor cavitation in extensive-stage SCLC patients treated with anlotinib. METHODS: A total of 73 extensive-stage SCLC patients confirmed by histopathology from January 2018 to January 2019 were retrospectively analyzed. All patients received anlotinib therapy at Shanghai Chest Hospital. We defined tumor cavitation of the lung target lesions as that part of solid component was changed to air-filled area according to chest CT. Progression-free survival (PFS) was calculated from the beginning of anlotinib therapy to the disease progression or the last follow-up visit. RESULTS: Eleven (15.0%) patients had tumor cavitation during anlotinib therapy. The ORR of the 73 patients was 15.1%. Multivariate logistic regression analysis showed that tumor cavitation during anlotinib therapy was not associated with gender (P = 0.630), age (P = 0.190), smoking status (P = 0.165), anatomy type (P = 0.641), and the line of anlotinib therapy (P = 0.302). The median PFS of all patients was 2.6 months (95%CI 2.1-3.2). According to the univariate analysis, the median PFS in patients with and without tumor cavitation was 5.0 months and 2.2 months, respectively, and the difference was statistically significant (P = 0.041). According to the multivariate analysis, tumor cavitation was an independent factor for PFS after adjusting gender, age, smoking status, anatomy type, the line of anlotinib therapy, tumor cavitation, and response to anlotinib (adjusted HR 0.316, 95%CI 0.142-0.702; P = 0.005). CONCLUSIONS: In 73 extensive-stage SCLC patients treated with anlotinib, no demographic/clinical characteristic was related to tumor cavitation, and tumor cavitation was an independent factor in predicting better PFS.