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Objective To investigate the imaging diagnosis and differential diagnosis methods for common tumors in the posterior fossa of children, and to propose a flow chart for the diagnosis of common tumors in the posterior fossa of children based on the limited diffusion of DWI according to the idea localization diagnosis followed by qualitative diagnosis. Methods A total of 118 pediatric patients with posterior fossa tumors who underwent surgical resection in Huashan Hospital, Fudan University from January 2021 to January 2024 were enrolled, and all of them underwent head CT and MRI examinations, and preoperative localization diagnosis and qualitative diagnosis were carried out accordingly. Then, based on whether DWI was diffusion limited, a flow chart for the diagnosis of common tumors in the posterior fossa of children was proposed. Results A total of 118 children with posterior fossa tumors were localization and qualitatively diagnosed, including 41 cases of fourth ventricular tumors, including medulloblastoma (27 cases), pilocytic astrocytoma (7 cases), ependymoma (5 cases), choroid plexus papilloma (one case), and rosette-forming glioneuronal tumor (RGNT, one case). There were 38 cases of brainstem tumors, including 24 cases of diffuse midline glioma, H3 K27 - altered, 5 cases of pilocytic astrocytoma, 3 cases of cavernous hemangioma, 2 cases of pediatric-type diffuse high-grade glioma (prone to diffuse midline glioma, H3 wild type), 2 cases of ganglio glioma, one case of atypical teratoid/rhabdoid tumor (AT/RT), and one case of pediatric - type diffuse low - grade glioma. There were 9 cases of cerebellopontine angle (CPA) tumors, including 3 cases of pilocytic astrocytoma, 2 cases of cholesteatoma, one case of medulloblastoma, one case of diffuse midline glioma, H3 K27-altered, one case of pilomyxoid astrocytoma, and one case of Ewing sarcoma. There were 30 cases of cerebellar tumors, including 15 cases of pilocytic astrocytoma, 7 cases of medulloblastoma, 2 cases of cavernous hemangioma, one case of ependymoma, one case of pediatric-type diffuse low-grade glioma, one case of pediatric-type diffuse high- grade glioma (prone to diffuse midline glioma, H3 wild type), one case of dysembryoplastic neuroepithelial tumor (DNT), one case of hamartoma, and one case of extrarenal rhabdomyomatoid tumor cerebellar metastases. Localization diagnosis, the accuracy of preoperative CT was 93.22% (110/118), while the accuracy of preoperative MRI was 100% (118/118). Qualitative diagnosis, 74 cases (62.71%) had accurate qualitative diagnosis, 23 cases (19.49%) had general diagnosis, and 21 cases (17.80%) had wrong diagnosis. The imaging differential diagnosis of posterior fossa tumors in children focuses on medulloblastoma, pilocytic astrocytoma, ependymoma, and diffuse midline glioma, H3 K27-altered. The incidence of limited diffusion of DWI in medulloblastoma, pilocytic astrocytoma and ependymoma outside the brainstem was 100% (35/35), 4% (1/25) and 5/6, and the difference among the three tumors was statistically significant (Z = - 5.601, P = 0.000). The incidence of limited diffusion of DWI in diffuse midline glioma, H3 K27- altered and pilocytic astrocytoma in the brainstem was 79.17% (19/24) and 1/5, and the difference between the two tumors was also statistically significant (Fisher's exact possibility: P = 0.038). Conclusions The early diagnosis of posterior fossa tumors in children is difficult, and DWI is an important basis for differential diagnosis. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Clinical Nursing in Practice is the property of Journal of Clinical Nursing in Practice (Editorial Board, Shanghai Jiao Tong University Press) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aquaporin-8 (AQP8) is involved in impacting glioma proliferation and can effect tumour growth by regulating Intracellular reactive oxygen species (ROS) signalling levels. In addition to transporting H2O2, AQP8 has been shown to affect ROS signaling, but evidence is lacking in gliomas. In this study, we aimed to investigate how AQP8 affects ROS signaling in gliomas. We constructed A172 and U251 cell lines with AQP8 knockdown and AQP8 rescue by CRISPR/Cas9 technology and overexpression of lentiviral vectors. We used CCK-8 and flow cytometry to test cell proliferation and cycle, immunofluorescence and Mito-Tracker CMXRos to observe the distribution of AQP8 expression in glioma cells, Amplex and DHE to study mitochondria release of H2O2, mitochondrial membrane potential (MMP) and NAD+/NADH ratio to assess mitochondrial function and protein blotting to detect p53 and p21 expression. We found that AQP8 co-localised with mitochondria and that knockdown of AQP8 inhibited the release of H2O2 from mitochondria and led to increased levels of ROS in mitochondria, thereby impairing mitochondrial function. We also discovered that AQP8 knockdown resulted in suppression of cell proliferation and was blocked at the G0/G1 phase with increased expression of mitochondrial ROS signalling-related p53/p21. This finding provides further evidence for mechanistic studies of AQP8 as a prospective target for the treatment of gliomas. [ABSTRACT FROM AUTHOR]

Background: Breast cancer has the highest incidence rate of cancer worldwide, and brain metastases (BrM) are among the most malignant cases. While some patients have benefited from immune checkpoint inhibitors (ICIs), the complex anatomical structure of the brain and the heterogeneity of metastatic tumors have made it difficult to characterize the tumor immune microenvironment (TME) of metastatic tumors. Methods: To address this, we used single‐cell RNA sequencing (scRNA‐seq) to analyze immune cells in the cerebrospinal fluid (CSF) of BrM patients with breast cancer, thereby providing a comprehensive view of the immune microenvironment landscape of BrM. Results: Based on canonical marker genes, we identified nine cell types, and further identified their subtypes through differential expression gene (DEG) analysis. We compared the changes in cells and functions in the immune microenvironment of patients with different prognoses. Our analysis revealed a series of genes that promote tumor immune function (CCR5, LYZ, IGKC, MS4A1, etc.) and inhibit tumor immune function (SCGB2A2, CD24, etc.). Conclusions: The scRNA‐seq in CSF provides a noninvasive method to describe the TME of breast cancer patients and guide immunotherapy. [ABSTRACT FROM AUTHOR]

The objective of the present study was to explore the effectiveness and safety of 'Sandwich treatment' strategy for large brain metastases (LBM) with diameter over 3 cm (minimum volume >= 15 cm3) located in motor area. Patients from four gamma knife center that received 'Sandwich treatment' were retrospectively studied from January 2016 to March 2023. The strategy was one-week treatment course including 2 stages of stereotactic radiosurgery (SRS) and using bevacizumab once during SRS gap. The tumor volume and peri-tumor edema changes were analyzed before and after 'Sandwich treatment'. Manual muscle testing (MMT) score and Barthel Index (BI) score were used to evaluate the changes of patients' movement and physical strength rehabilitation. The patients' overall survival (OS) and tumor local control (TLC) rate was calculated. Cox regression model was used to analyze the risk factors that related to TLC. 61 patients with 72 lesions received the 'Sandwich treatment'. The median prescription dose was 13.0 Gy and 12.5 Gy at the first- and second-stage SRS. The mean tumor volume at the time of 'Sandwich treatment' and 3 months later was 20.1 cm3 and 12.3, respectively (P < 0.01). The mean peri-tumor edema volume at the first- and second-stage SRS was 12.6 cm3 and 5.2 cm3, respectively (P < 0.01). Patients' median MMT score improved from 6 at the beginning to 8 at the end of 'Sandwich treatment' (P < 0.01), BI score was also greatly improved from 45 at the time of 'Sandwich treatment' to 95 after 3 months (P < 0.01). Patients' median OS was 14.0 months, and the 3, 6, 12 months OS rate was 92.0%, 86.0% and 66.0%, respectively. The TLC rate at 3, 6, 12 months was 98.4%, 93.4%, and 85.3%, respectively. Patients with lung cancer had lower risk of tumor relapse. The cumulative incidence of patient's hemorrhage and radiation necrosis was 4.92% (3/61) and 13.11% (8/61) after 'Sandwich treatment'. 'Sandwich treatment' strategy is safe and effective for LBM located in motor area. The strategy could rapidly improve the patients' movement and enhance their physical strength rehabilitation. [ABSTRACT FROM AUTHOR]

Copyright of Practical Oncology Journal is the property of Journal of Practical Oncology Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Practical Oncology Journal is the property of Journal of Practical Oncology Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Medulloblastoma (MB) is one of the most common malignant childhood brain tumors (WHO grade IV). Its high degree of malignancy leads to an unsatisfactory prognosis, requiring more precise and personalized treatment in the near future. Multi-omics and artificial intelligence have been playing a significant role in precise medical research, but their implementation needs a large amount of clinical information and biomaterials. For these reasons, it is urgent for current MB researchers to establish a large sample-size database of MB that contains complete clinical data and sufficient biomaterials such as blood, cerebrospinal fluid (CSF), cancer tissue, and urine. Unfortunately, there are few biobanks of pediatric central nervous system (CNS) tumors throughout the world for limited specimens, scarce funds, different standards collecting methods and et cl. Even though, China falls behind western countries in this area. The present research set up a standard workflow to construct the Beijing Children's Hospital Medulloblastoma (BCH-MB) biobank. Clinical data from children with MB and for collecting and storing biomaterials, along with regular follow-up has been collected and recorded in this database. In the future, the BCH-MB biobank could make it possible to validate the promising biomarkers already identified, discover unrevealed MB biomarkers, develop novel therapies, and establish personalized prognostic models for children with MB upon the support of its sufficient data and biomaterials, laying the foundation for individualized therapies of children with MB. [ABSTRACT FROM AUTHOR]

Background: Epilepsy is a prevalent comorbidity in patients with brain metastases (BM) and could result in sudden and accidental damage, as well as increased disease burden due to its rapid onset. Foreseeing the potential for the development of epilepsy may permit timely and efficient measures. This study aimed to analyze the influencing factors of epilepsy in advanced lung cancer (ALC) patients with BM and construct a nomogram model to predict the likelihood of developing epilepsy. Methods: Socio-demographic and clinical data of ALC patients with BM were retrospectively collected from the First Affiliated Hospital of Zhejiang University School of Medicine between September 2019 and June 2021. Univariate and multivariate logistic regression analyses were applied to determine the influencing factors for epilepsy in ALC patients with BM. Based on the results of the logistic regression analysis, a nomogram was built to represent the contribution of each influencing factor in predicting the probability of epilepsy development in ALC patients with BM. The Hosmer-Lemeshow test and receiver operating characteristic (ROC) curve were utilized to evaluate the goodness of fit and prediction performance of the model. Results: The incidence of epilepsy among 138 ALC patients with BM was 29.7%. On the multivariate analysis, having a higher number of supratentorial lesions (odds ratio [OR] = 1.727; p = 0.022), hemorrhagic foci (OR = 4.922; p =.021), and a high-grade of peritumoral edema (OR = 2.524; p <.001) were independent risk factors for developing epilepsy, while undergoing gamma knife radiosurgery (OR =.327; p =.019) was an independent protective factor. The p -value of the Hosmer-Lemeshow test was.535 and the area under the ROC curve (AUC) was.852 (95% CI:.807–.897), suggesting the model had a good fit and exhibited strong predictive accuracy. Conclusion: The nomogram was constructed that can predict the probability of epilepsy development for ALC patients with BM, which is helpful for healthcare professionals to identify high-risk groups early and allows for individualized interventions. [ABSTRACT FROM AUTHOR]

Background: With the continuous development of medical imaging informatics technology, radiomics has become a new and evolving field in medical applications. Radiomics aims to be an aid to support clinical decision making by extracting quantitative features from medical images and has a very wide range of applications. The purpose of this study was to perform a bibliometric and visual analysis of scientific results and research trends in the research application of radiomics in glioma. Methods: We searched the Web of Science Core Collection (WOScc) for publications related to glioma radiomics. A bibliometric and visual analysis of online publications in this field related to countries/regions, authors, journals, references and keywords was performed using CiteSpace and R software. Results: A total of 587 relevant literature published from 2012 to September 2022 were retrieved in WOScc, and finally a total of 484 publications were obtained according to the filtering criteria, including 393 (81.20%) articles and 91 (18.80%) reviews. The number of relevant publications increases year by year. The highest number of publications was from the USA (171 articles, 35.33%) and China (170 articles, 35.12%). The research institution with the highest number of publications was Chinese Acad Sci (24), followed by Univ Penn (22) and Fudan Univ (21). WANG Y (27) had the most publications, followed by LI Y (22), and WANG J (20). Among the 555 co-cited authors, LOUIS DN (207) and KICKINGEREDER P (207) were the most cited authors. FRONTIERS IN ONCOLOGY (42) was the most published journal and NEURO-ONCOLOGY (412) was the most co-cited journal. The most frequent keywords in all publications included glioblastoma (187), survival (136), classification (131), magnetic resonance imaging (113), machine learning (100), tumor (82), and feature (79), central nervous system (66), IDH (57), and radiomics (55). Cluster analysis was performed on the basis of keyword cooccurrence, and a total of 16 clusters were formed, indicating that these directions are the current hotspots of radiomics research applications in glioma and may be the future directions of continuous development. Conclusion: In the past decade, radiomics has received much attention in the medical field and has been widely used in clinical research applications. Cooperation and communication between countries/regions need to be enhanced in future research to promote the development of radiomics in the field of medicine. In addition, the application of radiomics has improved the accuracy of pre-treatment diagnosis, efficacy prediction and prognosis assessment of glioma and helped to promote the development into precision medicine, the future still faces many challenges. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ineffective effort (IE) is a frequent patient-ventilator asynchrony in invasive mechanical ventilation. This study aimed to investigate the incidence of IE and to explore its relationship with respiratory drive in subjects with acute brain injury undergoing invasive mechanical ventilation. METHODS: We retrospectively analyzed a clinical database that assessed patient-ventilator asynchrony in subjects with acute brain injury. IE was identified based on airway pressure, flow, and esophageal pressure waveforms collected at 15-min intervals 4 times daily. At the end of each data set recording, airway-occlusion pressure (P0.1) was determined by the airway occlusion test. IE index was calculated to indicate the severity of IE. The incidence of IE in different types of brain injuries as well as its relationship with P0.1 was determined. RESULTS: We analyzed 852 data sets of 71 subjects with P0.1 measured and undergoing mechanical ventilation for at least 3 d after enrollment. IE was detected in 688 (80.8%) data sets, with a median index of 2.2% (interquartile range 0.4-13.1). Severe IE (IE index ≥ 10%) was detected in 246 (28.9%) data sets. The post craniotomy for brain tumor and the stroke groups had higher median IE index and lower P0.1 compared with the traumatic brain injury group (2.6% [0.7--9.7] vs 2.7% [0.3-21] vs 1.2% [0.1--8.5], P = .002; 1.4 [1-2] cm H2O vs 1.5 [1-2.2] cm H2O vs 1.8 [1.1-2.8] cm H2O, P = .001). Low respiratory drive (P0.1 < 1.14 cm H2O) was independently associated with severe IE in the expiratory phase (IEE) even after adjusting for confounding factors by logistic regression analysis (odds ratio 5.18 [95% CI 2.69-10], P < .001). CONCLUSIONS: IE was very common in subjects with acute brain injury. Low respiratory drive was independently associated with severe IEE. [ABSTRACT FROM AUTHOR]

Aim: To review the literature related to symptom management, clinical significance and related theoretical framework systems in adult patients with brain tumours. Background: As understanding of symptoms or symptom clusters and underlying biologic mechanisms has grown, it is apparent that symptom science is moving forward. Although some progress has been made in the symptom science of solid tumours such as breast and lung neoplasms, insufficient attention has been paid to symptom management for patients suffering from brain tumours. Further research is needed to achieve effective symptom management for these patients. Design: A literature review with a systematic search of symptom management in adult brain tumours. Methods: Electronic data bases were searched to obtain relevant published literature on symptom management in adults with brain tumours. This was then analysed and a synthesis of relevant findings is presented. Findings: Four significant general themes relating to symptom management of brain tumours in adults were identified: (1) The potential theoretical foundation related to symptom management was revealed. (2) Widely accepted validated scales or questionnaires for the assessment of single symptoms or symptom clusters were recommended. (3) Several symptom clusters and the underlying biologic mechanisms have been reported. (4) Specific symptom interventions for adults with brain tumours were collected and classified as evidence‐based or insufficient evidence. Conclusion: There are still many challenges in the effective management of symptoms in adults with brain tumours. The guiding role of theoretical frameworks or models related to symptom management should be utilized in future research. Using the concept of symptom clustering for research into symptoms found in patients with brain tumours, exploring common biological mechanisms for specific symptom clusters and making full use of modern big data resources to build a strong evidence base for an effective intervention or management program may inform the management of symptoms among these patients leading to better results. No Patient or Public Contribution: This is a literature review. Implications for Symptom Management: The ultimate goal is obviously not only improving the survival rate of patients with brain tumours, but also enhancing their quality of life. Several important findings from our review include the theoretical foundations, validated assessment tools, the assessment of symptom clusters and the underlying biologic mechanism, and the identification of the evidence base for symptom interventions. These are of relevance for managers, researchers and practitioners and may function as a reference to help the effective symptom management for adults with brain tumours. [ABSTRACT FROM AUTHOR]

Background: The efficacy and safety of osimertinib combined with bevacizumab in non‐small cell lung cancer (NSCLC) patients with brain metastasis harboring epidermal growth factor receptor (EGFR) mutations have not been fully studied. Methods: Treatment‐naïve NSCLC patients with brain metastasis harboring EGFR‐activating mutations were treated with osimertinib 80 mg oral daily and bevacizumab 15 mg/kg intravenously on day 1, repeated every 21 days, until disease progression, intolerable toxicity, or death. The primary endpoint was the median progression‐free survival (mPFS), and the secondary endpoints were the median overall survival (mOS), response rates, and toxicities. This study has been registered in ClinicalTrials.gov (NCT05104281) and is ongoing. Results: A total of 52 Chinese patients were enrolled, of whom 17 harbored EGFR 19 del and 35 harbored EGFR L858R mutation. The objective response rate (ORR) was 75.0% and the disease control rate (DCR) was 96.2%; the mPFS was 17.0 months (95% CI: 11.46–22.54), while the mOS was not reached. The mPFS was 20.0 months (95% CI: 14.56–25.44) and was 17.0 months (95% CI: 13.28–20.72) for patients harboring EGFR 19 del and EGFR L858R mutation (p = 0.844), respectively. The intracranial ORR was 82.7%, and the intracranial mPFS was 22.0 months (95% CI: 2.92–41.08).The main adverse events were mild‐to‐moderate hand‐foot syndrome, diarrhea, hypertension, and proteinuria. Three patients developed grade III proteinuria, while five patients developed grade III hypertension; they permanently discontinued bevacizumab treatment. Conclusions: Osimertinib combined with bevacizumab shows promising results in EGFR‐mutated NSCLC patients with brain metastasis, and the side effects are tolerable. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma (GBM) is a common malignant brain tumor with poor prognosis and high mortality. Numerous reports have identified the correlation between aging and the prognosis of patients with GBM. The purpose of this study was to establish a prognostic model for GBM patients based on aging-related gene (ARG) to help determine the prognosis of GBM patients. Methods: 143 patients with GBM from The Cancer Genomic Atlas (TCGA), 218 patients with GBM from the Chinese Glioma Genomic Atlas (CGGA) of China and 50 patients from Gene Expression Omnibus (GEO) were included in the study. R software (V4.2.1) and bioinformatics statistical methods were used to develop prognostic models and study immune infiltration and mutation characteristics. Results: Thirteen genes were screened out and used to establish the prognostic model finally, and the risk scores of the prognostic model was an independent factor (P < 0.001), which indicated a good prediction ability. In addition, there are significant differences in immune infiltration and mutation characteristics between the two groups with high and low risk scores. Conclusion: The prognostic model of GBM patients based on ARGs can predict the prognosis of GBM patients. However, this signature requires further investigation and validation in larger cohort studies. [ABSTRACT FROM AUTHOR]

The brain tumor is an abnormal and hysterical growth of brain tissues, and the leading cause of death affected patients worldwide. Even in this technology-based arena, brain tumor images with proper labeling and acquisition still have a problem with the accurate and reliable generation of realistic images of brain tumors that are completely different from the original ones. The artificially created medical image data would help improve the learning ability of physicians and other computer-aided systems for the generation of augmented data. To overcome the highlighted issue, a Generative Adversarial Network (GAN) deep learning technique in which two neural networks compete to become more accurate in creating artificially realistic data for MRI images. The GAN network contains mainly two parts known as generator and discriminator. Commonly, a generator is the convolutional neural network, and a discriminator is the deconvolutional neural network. In this research, the publicly accessible Contrast-Enhanced Magnetic Resonance Imaging (CE-MRI) dataset collected from 2005-to 2020 from different hospitals in China consists of four classes has been used. Our proposed method is simple and achieved an accuracy of 96%. We compare our technique results with the existing results, indicating that our proposed technique outperforms the best results associated with the existing methods. [ABSTRACT FROM AUTHOR]

Periodontitis is significantly associated with the risk of cancers in the lung and the digestive system. Emerging evidence shows a plausible link between periodontitis and several types of brain diseases. However, the association between periodontal infection and glioma remains unclear. In the cultured GL261 glioma cells, P. gingivalis lipopolysaccharide (LPS) significantly promoted cell proliferation at concentrations ranging from 10 to 1000 ng/mL. It promoted cell migration at a higher concentration (100 and 1000 ng/mL). Additionally, exposure to 100 ng/mL P. gingivalis LPS induced a significant increase in the expression of TNF-α, TGF-β, MMP2, and MMP9, as well as the phosphorylation level of Akt at Ser473. These changes induced by P. gingivalis LPS were significantly antagonized by the Akt inhibitor. Furthermore, a total of 48 patients with brain tumors were enrolled to investigate their periodontal status before receiving tumor management. Poor periodontal status [probing depth (PD) ≥ 6 mm and attachment loss (AL) >5 mm] was found in 42.9% (9/21) of patients with glioma, which was significantly higher than that in patients with benign tumors and the relevant data in the 4th National Oral Health Survey in China. The glioma patients with both AL > 5 mm and PD ≥ 6 mm had a higher ki-67 labeling index than those with AL ≤ 5 mm or PD < 6 mm. These findings support the association between periodontal infection and glioma progression. [ABSTRACT FROM AUTHOR]

The precise brain tumor diagnosis is critical and shows a vital role in the medical support for treating tumor patients. Manual brain tumor segmentation for cancer analysis from many Magnetic Resonance Images (MRIs) created in medical practice is a problematic and timewasting task for experts. As a result, there is a critical necessity for more accurate computeraided methods for early tumor detection. To remove this gap, we enhanced the computational power of a computer-aided system by proposing a finetuned Block-Wise Visual Geometry Group19 (BW-VGG19) architecture. In this method, a pre-trained VGG19 is fine-tuned with CNN architecture in the block-wise mechanism to enhance the system's accuracy. The publicly accessible Contrast-Enhanced Magnetic Resonance Imaging (CE-MRI) dataset collected from 2005 to 2020 from different hospitals in China has been used in this research. Our proposed method is simple and achieved an accuracy of 0.98%. We compare our technique results with the existing Convolutional Neural network (CNN), VGG16, and VGG19 approaches. The results indicate that our proposed technique outperforms the best results associated with the existing methods. [ABSTRACT FROM AUTHOR]

Few studies focused on the incidence of brain metastasis in patients with acral and mucosal melanoma, and a better understanding of the incidences and predictors of brain metastasis is needed in these patients. A prospectively accrued cohort of 799 patients with acral and mucosal melanoma in stages I–III from July 2011 to December 2015 at Peking University Cancer Hospital were included in this study. Competing risk models (Fine and Gray) were used to estimate the cumulative incidence of brain metastasis and compare the differences in cumulative incidence curves between different primary lesions, stages, and molecular types. At a median follow-up time of 68.0 months, 60 of the 779 patients (7.7%) developed brain metastasis, and 261 (33.5%) patients developed extracranial metastasis. Considering the risk of competition, the cumulative incidence of brain metastasis at one year, two years, and five years after diagnosis were 5.1%, 10.2%, and 19.5%, respectively. Stage III, BRAF mutations, and NRAS mutations were associated with a high risk of brain metastasis in univariable analysis. Multivariate analysis showed BRAF mutations, and NRAS mutations had statistically correlated with an increased cumulative incidence of brain metastasis at diagnosis and all-time point of one year and two years after diagnosis. This study is the first to report the cumulative incidence and risk factors of brain metastasis for patients with acral and mucosal melanoma in stages I–III. Patients with BRAF and NRAS mutations had a higher incidence at diagnosis and all-time point, providing the basis for surveillance guidelines and further mechanic exploration. • Of 779 patients, 7.7% had brain metastasis with a median follow-up of 68.0 months. • Patients with BRAF and NRAS mutations an increased incidence of brain metastasis. • Patients with stage III and NRAS mutation had a high risk of extracranial metastasis. [ABSTRACT FROM AUTHOR]

Background: Previous studies have identified alterations in structural connectivity of patients with glioma. However, white matter (WM) integrity measured by diffusion kurtosis imaging (DKI) in pediatric patients with brainstem glioma (BSG) was lack of study. Here, the alterations in WM of patients with BSG were assessed through DKI analyses. Materials and methods: This study involved 100 patients with BSG from the National Brain Tumor Registry of China (NBTRC) and 50 age- and sexmatched healthy controls from social recruitment. WM tracts were segmented and reconstructed using U-Net and probabilistic bundle-specific tracking. Next, automatic fiber quantitative (AFQ) analyses of WM tracts were performed using tractometry module embedded in TractSeg. Results: WM quantitative analysis identified alterations in DKI-derived values in patients with BSG compared with healthy controls. WM abnormalities were detected in the projection fibers involved in the brainstem, including corticospinal tract (CST), superior cerebellar peduncle (SCP), middle cerebellar peduncle (MCP) and inferior cerebellar peduncle (ICP). Significant WM alterations were also identified in commissural fibers and association fibers, which were away from tumor location. Statistical analyses indicated the severity of WM abnormality was statistically correlated with the preoperative Karnofsky Performance Scale (KPS) and symptom duration of patients respectively. Conclusion: The results of this study indicated the widely distributed WM alterations in patients with BSG. DKI-derived quantitative assessment may provide additional information and insight into comprehensively understanding the neuropathological mechanisms of brainstem glioma. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with thyroid cancer have different survival rate based on their cancer type and the organs affected by the metastases. About 88% of the patients with follicular thyroid cancer are still alive 15 years after diagnosis. Still, some patients will develop metastasis, and the location of the metastases could indicate patients with more aggressive disease. We investigate the impact of lung metastasis versus metastasis of bone, brain, or liver on overall survival (OS) and thyroid cancer-specific survival (TCSS) in patients with thyroid cancer (TC). Therefore, de-identified SEER 18 registry data of primary TC patients diagnosed between 2010 and 2016 were analyzed. The primary outcome was the prognosis of TC patients with lung metastasis compared with other sites. The secondary outcomes included the prognosis comparison between patients with and without surgery and between single and multiple metastasis sites. Isolated lung metastasis was associated with worse OS and TCSS than bone metastasis (both p < 0.05) and was associated with worse OS than liver metastasis (p = 0.0467). Surgery performed either for the primary or distant site was associated with better OS and TCSS in patients with metastasis of lung or bone (p < 0.05). Isolated lung metastasis was related to better OS and TCSS than lung–liver, lung–brain, and lung–other multiple metastases. The multivariable analysis revealed that age < 55 years, surgery to the primary site, and to the distant site(s) were associated with better outcomes, while T4 and Tx were associated with worse outcomes. Nevertheless, it revealed that the other race (i.e., any race other than white, black, or unknown) and male gender were associated with better TCSS only (p < 0.05). Isolated lung metastasis is associated with a worse prognosis in TC patients compared with bone or liver metastasis. Surgery performed either for the primary or distant site(s) is associated with better survival outcomes in TC patients with metastasis of lung or bone. [ABSTRACT FROM AUTHOR]

The treatment of brain tumors, especially the malignant brain tumors, has entered in the bottleneck period at present. It is difficult for traditional molecular biology, cell and animal experiments to make a major breakthrough in the treatment of brain tumors, so researchers have turned their attention to the anatomy and pathology of human whole brain tissue. However, the human whole brain tissue which is available for research is extremely deficient. It is of great significance to encourage brain tumors patients to donate organs and establish a standard human brain tissue resource bank of brain tumors (shortened to brain bank) for the research of brain science and providing new treatment ideas for brain tumors, while the construction of brain bank in China started late, with a relatively small scale and relatively slow development. This paper intends to provide guidance for the construction and improvement of brain bank and specific brain tumors related brain bank in China by drawing on the relevant experience of the construction of brain bank in other countries. [ABSTRACT FROM AUTHOR]

The brain seems to be the most complex organ in the human body and operates as the central part of the nervous system. The classification of brain tumors is the most complicated problem which medical experts face. In our proposed work, the novelty is that we have adopted the hybridization of feature exaction techniques and a conglomerate of classification methods. The hybrid features are extracted from the tumor region using the Gray Level Co-occurrence Matrix technique and shape-based features. There are three different types of brain magnetic resonance imaging datasets used in work. For the segmentation, the Marker-controlled watershed segmentation strategy is implemented in this work. In this work, the hybrid classifier, which includes the Random Forest (RF) classifier, K-Nearest Neighbour classifier, and Decision Tree classifier, is implemented. Dataset 1 (China Hospital data) shows a better overall accuracy of 98.75%; for dataset 2, accuracy is 98.99%; and for dataset 3, the achieved accuracy is 98.92%. The other parameters that prove the overall work's efficacy include sensitivity, precision, specificity, F1-score, Cohen's kappa value, Dice coefficient, Jaccard Index, and area under the curve (AUC). The proposed work is also compared with the state-of-the-art methods and observed better one. [ABSTRACT FROM AUTHOR]

Background: To describe the epidemiological characteristics of central nervous system (CNS) tumors in children, based on the neurosurgery department of Beijing Tiantan Hospital. Methods: From January 2015 to December 2019, 3180 children were histopathologically diagnosed with CNS tumors based on the 2016 World Health Organization (WHO) classification of tumors. Patients were 0 to 15 years old. We analyzed age-related gender preferences, tumor locations, and the histological grades of the tumors. In addition, the epidemiological characteristics of the five most common intracranial tumors were compared to the previous studies. Results: In this study, intracranial and spinal tumors account for 96.4% (3066) and 3.6% (114) of all tumors, with a preponderance of supratentorial tumors (57.9%). Among all pediatric patients, low-grade tumors comprise 67.1% (2 135). The integral gender ratio of males to females is 1.47: 1 and the average age of patients is 7.59 years old. The five most common intracranial tumors are craniopharyngioma (15.4%), medulloblastoma (14.3%), pilocytic astrocytoma (11.8%), diffuse astrocytoma (9.8%), and anaplastic ependymoma (4.8%). Conclusions: Due to the lack of national data on childhood brain tumors, we used a large nationally representative population sample based on the largest pediatric neurosurgery center in China. We analyzed the data of the past 5 years, reflecting the incidence of CNS tumors in Chinese children to a certain extent, and laying a data foundation for subsequent clinical studies. [ABSTRACT FROM AUTHOR]

Background: Patients with HER2-positive metastatic breast cancer have a high risk of developing brain metastases. Efficacious treatment options are scarce. We investigated the activity and safety of pyrotinib plus capecitabine in patients with HER2-positive metastatic breast cancer and brain metastases.Methods: We did a multicentre, single-arm, two-cohort, phase 2 trial in eight tertiary hospitals in China. Patients aged 18 years or older who had radiotherapy-naive HER2-positive brain metastases (cohort A) or progressive disease after radiotherapy (cohort B), with an Eastern Cooperative Oncology Group performance status of 0-2, received pyrotinib 400 mg orally once daily, and capecitabine 1000 mg/m2 orally twice daily for 14 days, followed by 7 days off every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was confirmed intracranial objective response rate by investigator assessment according to the Response Evaluation Criteria In Solid Tumours (version 1.1). Activity and safety were analysed in patients with at least one dose of study drug. The study is ongoing, but recruitment is complete. The study is registered with ClinicalTrials.gov, NCT03691051.Findings: Between Jan 29, 2019, and July 10, 2020, we enrolled 78 women: 51 (86%) of 59 patients in cohort A and 18 (95%) of 19 patients in cohort B had previous exposure to trastuzumab. Median follow-up duration was 15·7 months (IQR 9·7-19·0). The intracranial objective response rate was 74·6% (95% CI 61·6-85·0; 44 of 59 patients) in cohort A and 42·1% (20·3-66·5; eight of 19 patients) in cohort B. The most common grade 3 or worse treatment-emergent adverse event was diarrhoea (14 [24%] in cohort A and four [21%] in cohort B). Two (3%) patients in cohort A and three (16%) in cohort B had treatment-related serious adverse events. No treatment-related deaths occurred.Interpretation: To our knowledge, this is the first prospective study showing the activity and safety of pyrotinib plus capecitabine in patients with HER2-positive breast cancer and brain metastases, especially in radiotherapy-naive population. This combination deserves further validation in a randomised, controlled trial.Funding: National Cancer Centre Climbing Foundation Key Project of China, Jiangsu Hengrui Pharmaceuticals.Translation: For the Chinese translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Background: For lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) sensitive mutation and synchronous brain metastasis (syn‐BM), when and how to apply radiotherapy (RT) during first‐line tyrosine kinase inhibitor (TKI) treatment remains debatable. Methods: From a real‐world multicenter database, EGFR‐mutant patients with syn‐BM diagnosed between 2010–2020 and treated with first‐line TKIs were enrolled and divided into upfront TKI + RT and upfront TKI groups. Median intracranial progression‐free survival (mIC‐PFS), median overall survival (mOS), and their risk factors were estimated. Results: There were 60 and 186 patients in the upfront TKI + RT group and upfront TKI group, respectively. Their mIC‐PFS were 28.9 months (m) and 17.5 m (p = 0.023), and mOS were 42.7 m and 40.1 m (p = 0.51). Upfront brain RT improved mIC‐PFS in patients ≤60‐year‐old (p = 0.035), with symptomatic BM (p = 0.002), and treated with first‐generation TKIs (p = 0.012). There was no significant difference in mOS in any subgroup. Upfront brain stereotactic radiosurgery (SRS) showed a trend of better mIC‐PFS and mOS. mIC‐PFS was independently correlated with symptomatic BM (HR = 1.54, p = 0.030), EGFR L858R mutation (HR = 1.57, p = 0.019), and upfront brain RT (HR = 0.47, p = 0.001). mOS was independently correlated with being female (HR = 0.54, p = 0.007), ECOG 3–4 (HR = 10.47, p < 0.001), BM number>3 (HR = 2.19, p = 0.002), and third‐generation TKI (HR = 0.54, p = 0.044) or antiangiogenic drugs (HR = 0.11, p = 0.005) as first/second‐line therapy. Conclusions: Upfront brain RT based on first‐line EGFR‐TKI might improve IC‐PFS but not OS in EGFR‐mutant lung adenocarcinoma patients, indicating potential survival benefit from brain SRS and early application of drugs with higher intracranial activity. [ABSTRACT FROM AUTHOR]

Objective To investigate the recurrence rate and risk factors for the patients with medulloblastoma based on the molecular subgroups. Methods A retrospective study was conducted for the clinicopathological data of 67 medulloblastoma patients who were admitted in Department of Radiotherapy and Neurosurgery, Beijing Tiantan Hospital, Capital Medical University from March 2011 to November 2013. All the cases received the MRI examinations to identify the location, aggressiveness, dissemination, stage and resection as well as the histological and molecular pathology in order to analyze the recurrence rate. The Kaplan-Meier survival curve and Cox regression were performed to detect the risk factors for medulloblastoma recurrences. Based on the recurrence, this cohort of samples were divided into recurrence group (n = 22) and non - recurrence group (n = 45). Results Among the patients, the overall survival rate was 71.64% (48/67), the progression- free survival rate was 67.16% (45/67), the recurrece rate was 32.84% (22/67), and the fatality rate was 28.36% (19/67). The fatality rate in the recurrence group was significantly higher than that in the non-recurrence group [81.82% (18/22) vs. 2.22% (1/45); χ² = 46.078, P = 0.000]. The Kaplan-Meier survival curves showed that patients with lateral medulloblastoma have a shorter median survival time than those with middle medulloblastoma (18 months vs. 51 months, P = 0.000), patients with large cell/anaplasitc medulloblastoma suffered from a poorer median survival time compared with the classic medulloblastoma, desmoplastic/nodular medulloblastoma and medulloblastoma with extensive nodularity (10 months vs. 50, 44 and 31 months; P = 0.000), median survival time of patients with SHH-activated subtype was shorter than that of patients with the other three subgroups (19 months vs. 32, 33 and 57 months; P = 0.003), and median survial time of patients with recurrence was shorter than that of patients with non - recurrence (19 months vs. 60 months, P = 0.000). The Cox regression analysis showed that lateral medulloblastoma (RR = 3.514, 95%CI: 1.262-9.781; P = 0.016), large cell/anaplasitc medulloblastoma (RR = 6.452, 95%CI: 1.320-31.537; P = 0.021) and Group 3 (RR = 4.289, 95%CI: 1.359- 13.533; P = 0.013) subtype were the risk factors for medulloblastoma recurrence. Conclusions Patients with lateral medulloblastoma, large cell/anaplasitc medulloblastoma and SHH - activated subtype suffered from a poorer survival. Patients with lateral, large cell/anaplasitc medulloblastoma and Group 3 subtype were prone to recurrence. [ABSTRACT FROM AUTHOR]

Background: There is only limited knowledge of the treatment responses and clinical outcomes of immune checkpoint inhibitors (ICIs) in driver gene‐negative non‐small cell lung cancer (NSCLC) patients with brain metastases (BM). This study aims to assess the efficacy of immunotherapy in these patients in a real world setting. Methods: NSCLC‐BM patients without driver gene mutations who received ICIs were retrospectively identified between July 2017 and December 2019. The primary observation endpoint was intracranial objective response rate (iORR), and secondary objectives were objective response rate (ORR), intracranial and systemic progression‐free survival (iPFS, PFS), and overall survival (OS). Results: We reviewed 1578 patients with lung cancer and BM. According to the exclusion criteria, 41 patients were finally enrolled. Among these 41 patients, iORR was 36.6% (95% confidence interval [CI] = 21.2%–52.0%), whereas iPFS was 6.8 (95% CI = 3.32–10.35) months. Additionally, ORR, PFS, and OS were 24.4% (95% CI = 10.7%–38.1%), 6.2 (95% CI = 4.57–7.83) months and 13.7 (95% CI = 11.20–16.26) months, respectively. ICIs combined with concurrent radiotherapy group exhibited preferred iORR (p = 0.030) compared with no radiotherapy group, and ICIs plus chemotherapy showed improved OS (p = 0.024) compared to ICI monotherapy. Moreover, the lines of ICI treatment ≥2 (p = 0.005) and derived neutrophil‐to‐lymphocyte ratio (dNLR) ≥3 (p = 0.010) were independently negative factors for OS. Conclusion: In NSCLC‐BMs patients lacking driver genes, ICIs exhibited an effective drug regime. A combination of ICIs with concurrent radiotherapy showed a better intracranial response, whereas ICIs plus chemotherapy were associated with superior OS. [ABSTRACT FROM AUTHOR]

Glioblastoma is the most common and fatal primary brain tumor in adults. Even with maximal resection and a series of postoperative adjuvant treatments, the median overall survival (OS) of glioblastoma patients remains approximately 15 months. The Huashan Hospital glioma bank contains more than 2000 glioma tissue samples with long-term follow-up data; almost half of these samples are from glioblastoma patients. Several large glioma databases with long-term follow-up data have reported outcomes of glioblastoma patients from countries other than China. We investigated the prognosis of glioblastoma patients in China and compared the survival outcomes among patients from different databases. The data for 967 glioblastoma patients who underwent surgery at Huashan Hospital and had long-term follow-up records were obtained from our glioma registry (diagnosed from 29 March 2010, through 7 June 2017). Patients were eligible for inclusion if they underwent surgical resection for newly diagnosed glioblastomas and had available data of survival and personal information. Data of 778 glioblastoma patients were collected from three separate online databases (448 patients from The Cancer Genome Atlas (TCGA, ), 191 from REpository for Molecular BRAin Neoplasia DaTa (REMBRANDT) database (GSE108476) and 132 from data set GSE16011(Hereafter called as the French database). We compared the prognosis of glioblastoma patients from records among the different databases and the changes in survival outcomes of glioblastoma patients from Huashan Hospital over an 8-year period. The median OS of glioblastoma patients was 16.3 (95% CI: 15.4–17.2) months for Huashan Hospital, 13.8 (95% CI: 12.9–14.9) months for TCGA, 19.3 (95% CI: 17.0–20.0) months for the REMBRANDT database, and 9.1 months for the French database. The median OS of glioblastoma patients from Huashan Hospital improved from 15.6 (2010–2013, 95% CI: 14.4–16.6) months to 18.2 (2014–2017, 95% CI: 15.8–20.6) months over the study period (2010–2017). In addition, the prognosis of glioblastoma patients with total resection was significantly better than that of glioblastoma patients with sub-total resection or biopsy. Our study confirms that treatment centered around maximal surgical resection brought survival benefits to glioblastoma patients after adjusting to validated prognostic factors. In addition, an improvement in prognosis was observed among glioblastoma patients from Huashan Hospital over the course of our study. We attributed it to the adoption of a new standard of neurosurgical treatment on the basis of neurosurgical multimodal technologies. Even though the prognosis of glioblastoma patients remains poor, gradual progress is being made. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii is a parasite that infects more than a third of the world's population. In recent years, some articles have been published showing association between infection with Toxoplasma gondii and brain tumors. We present the case of a male patient, aged 47 years, who was admitted in the Department of Neurosurgery, Emergency Clinical Hospital "Prof. dr. N. Oblu", presenting headache, confusion, blurred vision and loss of memory. His previous medical history revealed that the patient traveled to China, where he ate traditional food based on uncooked meat. During his two months stay in China he presented a status similar to a cold. Craniocerebral magnetic resonance imaging (MRI) took into consideration a primary brain tumor, parasitosis or tuberculoma. Laboratory analysis showed leukocytosis, granulocytosis and thrombocytopenia. Toxoplasma gondii-IgG antibodies showed values of 617.6 U / ml. anti-HIV ELISA test was negative. a biopsy was done and small fragments of pathological tissue were removed. The initial microscopical exam took into consideration a differential diagnosis of atypical toxoplasmic encephalitis versus glioblastoma. Immunohistochemical investigations diagnosed a grade IV glioblastoma based on the following aspects: the tumor cells were positive for GFAP and ATRX, but negative for IDH1. In addition, very often the tumor cells were positive for p53 and proliferative index was greater than 12%. a new MRI exam performed 6 weeks later showed a rapid increase of the tumor, so that the patient was re-operated with total excision of the tumor mass. The final pathologic diagnosis was glioblastoma associated with toxoplasmosis in evolution. The presented case is customized by the difficulty of clinical, imaging and pathological diagnosis under significantly increased titers of Toxoplasma gondii- IgG antibodies. This case also reminds the fact that this parasite may be a potential risk factor for the development of a brain glioblastoma. [ABSTRACT FROM AUTHOR]

Objective To analyze the clinical-pathological features of brain metastases of lung adenocarcinoma and detect the expressions of anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) in order to guide the targeted drug therapy of patients with advanced lung cancer. Methods A total of 86 cases of brain metastases from non-small cell lung cancer (NSCLC) in Huashan Hospital, Fudan University from January 2013 to December 2016 were selected for pathological analysis by HE staining and immunolabeling, ALK and EGFR expression were detected by immunohistochemical staining. Results Among 86 cases of brain metastases from NSCLC, 74 cases (86.05%) were adenocarcinoma, 3 cases (3.49%) of squamous cell carcinoma, and 9 cases (10.47%) of neuroendocrine tumors. Among the 74 brain metastases from lung adenocarcinoma, there were 44 cases (59.46%) of solid type, 9 cases (12.16%) of acinar type, 14 cases (18.42%) of papillary type and 7 cases (9.46%) of micropapillary type, which were significantly different from the pathological subtypes of primary lung adenocarcinoma reported in the literature (χ² = 97.858, P = 0.000). The expression rate of ALK protein was 9.46% (7/74), the expression rates were not statistically significant in different pathological types (χ² = 1.690, P = 0.639). The expression rate of EGFR non-mutant protein was 52.70% (39/74), and the expression rates were statistically significant in different pathological types (χ² = 7.938, P = 0.047). Fourteen cases (18.92%, 14/74) showed positive staining by specific mutation antibody of exon 19 of EGFR gene, while 12 cases (16.22%, 12/74) having exon 21 of EGFR gene mutation, and the total positive rate was 33.78% (25/74), the expression rates were not statistically significant in different pathological types (χ² = 1.721, P = 0.632). The expression levels of ALK and EGFR in brain metastases from lung adenocarcinoma were mutually exclusive (χ² = 12.462, P = 0.001). Conclusions Among lung adenocarcinoma, the solid lung type and the micropapillary type have higher tendencies of brain metastasis. The expression rates of ALK and EGFR in brain metastases were consistent with those of primary lung adenocarcinoma, and their expression was mutually exclusive. [ABSTRACT FROM AUTHOR]

Background and purpose: Epidemiological data on primary brain tumours (PBTs) are lacking due to the difficulty in case ascertainment among the population. Thus, we aimed to estimate mortality due to PBTs in China nationwide and the detection rate in people with suspected symptoms. Methods: A multistage, complex sampling survey regarding mortality due to PBTs in Chinese individuals was carried out by reviewing all causes of death within a year. The detection rates in people with suspected symptoms were estimated based on PBT symptom screening and neurologist reviews and compared between groups by logistic regression analysis. Results: Weighted mortality due to PBT was 1.6 (0.8–3.3) per 100,000 population in Chinese individuals, 1.8 (0.7–4.6) per 100,000 population in men, and 1.5 (0.5–4.5) per 100,000 population in women. Among 14,990 people with suspected symptoms, the PBT detection rate was 306.9 (95% CI 224.7–409.3) per 100,000 population in the total population, 233.0 (95% CI 135.7–373.1) per 100,000 population in men, and 376.9 (95% CI 252.4–546.3) per 100,000 population in women. People with an unsteady gait (OR 2.46; 95% CI 1.09–5.51; P=0.029), visual anomalies (3.84; 1.88–7.85; P<0.001), and headache (2.06; 1.10–3.86; P=0.023) were more likely to have a brain tumour than those without corresponding symptoms, while people with dizziness/vertigo were less likely to have a brain tumour than those without corresponding symptoms (0.45; 0.23–0.87; P=0.017). Conclusions: Mortality due to PBT in China was low, with a nationwide estimate of 21,215 (10,427–43,165) deaths attributable to PBTs annually. However, the detection rate of PBTs can be greatly improved based on symptom screening in the population. [ABSTRACT FROM AUTHOR]

To follow the revision of the fourth edition of WHO classification and the recent progress on the management of diffuse gliomas, the joint guideline committee of Chinese Glioma Cooperative Group (CGCG), Society for Neuro-Oncology of China (SNO-China) and Chinese Brain Cancer Association (CBCA) updated the clinical practice guideline. It provides recommendations for diagnostic and management decisions, and for limiting unnecessary treatments and cost. The recommendations focus on molecular and pathological diagnostics, and the main treatment modalities of surgery, radiotherapy, and chemotherapy. In this guideline, we also integrated the results of some clinical trials of immune therapies and target therapies, which we think are ongoing future directions. The guideline should serve as an application for all professionals involved in the management of patients with adult diffuse glioma and also a source of knowledge for insurance companies and other institutions involved in the cost regulation of cancer care in China and other countries. [ABSTRACT FROM AUTHOR]

Background: In Mainland China, advance directives (ADs) and end-of-life care for patients with tumours, especially patients with brain tumours who may have lost consciousness or the ability to speak at the early stage of their illness, have been poorly acknowledged. Thus, this study aimed to clarify the knowledge and preferences of ADs and end-of-life care in patients with brain tumours and to investigate predictors of patient preferences.Methods: This was a population-based cross-sectional survey that was conducted via face-to-face interviews. Information on sociodemographic factors, brain tumour illness, knowledge and preferences of the advanced decisions and end-of-life care of the patients was collected.Results: A total of 88.61% of participants had never heard of ADs, but 65.18% reported that they would like to make ADs. Knowledge of ADs, receiving surgical treatment or radiotherapy, being younger than 70 years old, being male, having educational qualifications of college or beyond, being childless, having medical insurance for nonworking or working urban residents and self-paying medical expenses were predictors of preference for making ADs. A total of 79.43% of participants wanted to discuss end-of-life arrangements with medical staff, and 63.29% of participants were willing to receive end-of-life care, even though it would not delay death. A total of 65.82% of patients with brain tumours wanted resuscitation, and as many as 45.45% of the patients thought that they did not need life support if they were in a persistent vegetative state. Brain primary tumours, being younger than 70 years old, male sex, educational qualification of junior middle school or below, having children, having new rural cooperative medical insurance and having medical expenses paid by children or spouses were predictors of choosing appropriate palliative care.Conclusions: ADs and end-of-life care have been poorly acknowledged among patients with brain tumours in mainland China. Additional efforts should be encouraged amongst patients with primary brain tumours, those who are undergoing surgery and radiotherapy and those who have low socioeconomic status. A longitudinal and comprehensive study is encouraged to promote disease-specific ADs among Chinese patients with brain tumours. [ABSTRACT FROM AUTHOR]

Background: Temozolomide is an alkylating agent approved by the U.S. Food and Drug Administration in 1999 for the treatment of patients with primary brain tumors. The aim of this study was to confirm the bioequivalence and safety of two strengths (20–100 mg) of generic temozolomide in the form of TOZ039 and Temodal® capsules administered to brain tumor patients. Study design: An open-label, randomized, two-phase, two-period, crossover pharmacokinetic study was performed in a single institution. The reference and test drugs were prescribed at a dose of 150 mg/m2 daily from days 1 to 5 of a 28-day cycle in the first phase; in the second phase, either a 150- or 200-mg/m2 dose was prescribed, depending on patient tolerance. On days 1 and 2 of each phase, a fixed 200-mg dose was administered either as ten 20-mg capsules in the first cycle or two 100-mg capsules in the second cycle. Drug administration in the first two days was randomized, i.e., if TOZ309 was administered on day 1, Temodal® was administered on day 2, and vice versa. The rest of the prescribed dose was administered in the form of Temodal® and spread equally over days 3–5. Blood samples were obtained for pharmacokinetic evaluation on days 1 and 2. Bioequivalence was demonstrated if the geometric means ratio of the three main pharmacokinetic parameters (mean maximum plasma concentration (Cmax), area under the concentration–time curve (AUC) 0-t, AUC 0-∞) fell within the equivalence boundary of 80–125%. Results: Twenty-nine glioblastoma multiforme or anaplastic astrocytoma patients were enrolled and dosed with the test and reference formulations under fasting conditions. The 90% confidence interval of the geometric means ratio for Cmax (91.08%, 106.18%), AUC0-t (98.62%,102.18%), and AUC0-∞ (98.65%, 102.21%) was well within the 80%–125% range for the 20-mg capsule, as was the Cmax (90.49%, 113.32%), AUC0-t (99.89%, 104.63%) and AUC0-∞ (99.99%, 104.67%) for the 100-mg capsule drug product. Additionally, all the secondary pharmacokinetic parameters were not significantly different. After two cycles of treatment, there was no mortality among the 29 patients, treatment-related severe adverse events, or events that would require study discontinuation; however, one significant adverse effect (life-threatening seizures) occurred and was related to disease progression. Adverse events were reported in 82.8% (24/29) patients, and treatment emergent adverse events were reported in 72.4% (21/29) patients. Conclusion: It can be concluded that 20-mg and 100-mg capsules of TOZ309 are bioequivalent to Temodal® capsules of the same strength under fasting conditions. Trial registration: https://www.chinadrugtrials.org.cn/index.html, CTR2017 0122. [ABSTRACT FROM AUTHOR]

Glioma is defined as a common brain tumor which causes severe disability or death. As many genes are reported to relate with glioma's occurrence and development, their prognostic and therapeutic value still remains uncertain. This study aimed at investigating the association between STAT3/p-STAT3 and glioma prognosis. Nine studies (12 trials) scored ≥5 on the Newcastle-Ottawa scale were meta-analysed from the Medline, Embase, and Web of Science databases. We found that STAT3/p-STAT3 overexpression in glioma patients was associated with worse overall survival (hazard ratio HR = 1.40 , 95 % confidence interval CI = 1.05 ~ 1.86 , P = 0.020), progression-free survival (HR = 2.05 , 95 % CI = 1.63 ~ 2.58 , P < 0.001), and better recurrence-free survival (HR = 0.37 , 95 % CI = 0.15 ~ 0.95 , P < 0.039). Subgroup analysis implied that STAT3/p-STAT3 overexpression was associated with worse OS in standard treatment (HR = 1.80 , 95 % CI = 1.06 ~ 3.04 , P = 0.030), and in China (HR = 2.18 , 95 % CI = 1.77 ~ 2.70 , P < 0.001), and metaregression analysis indicated countries (P = 0.001) may be the source of heterogeneity in our study. In conclusion, we suggested STAT3/p-STAT3 was associated with poor prognosis in patients with glioma, which indicated that STAT3/p-STAT3 might be a valuable prognostic biomarker and a promising therapeutic target for glioma. [ABSTRACT FROM AUTHOR]

Glioblastomas are high-grade brain tumors with poor prognoses, and new therapeutic approaches for these tumors are critically needed. This study revealed the underlying mechanisms of a new orphan drug, ACT001, that is currently in clinical trials for the treatment of advanced glioblastoma in Australia and China. ACT001 significantly suppressed glioma cell proliferation and induced apoptosis and cell cycle arrest in vitro, as determined by Cell Counting Kit-8 assays and flow cytometry. In addition, U-118 MG cells with high expression of p-IKKβ were sensitive to ACT001. Changes in the oxidative stress pathway in U-118 MG cells were detected with the isobaric tags for relative and absolute quantitation (iTRAQ) method. We further verified that ACT001 elevated the levels of reactive oxygen species (ROS) by regulating NF-κB-targeted MnSOD. ACT001 markedly inhibited NF-κB activation by directly binding IKKβ and inhibiting its phosphorylation. Overexpression of IKKβ markedly attenuated the changes in MnSOD and NOX1, indicating that ACT001 increased the levels of ROS by reducing the protein expression of p-IKKβ. Furthermore, ACT001 reduced cyclin B1/CDC2 expression and triggered G2/M phase arrest by increasing ROS production. ACT001 also upregulated the expression of Bax and Bim and induced apoptosis in a ROS-dependent manner. ACT001 effectively suppressed the growth of U-118 MG tumors in BALB/c nude mice and GL-261-luciferase tumors in C57BL/6 J mice. Finally, ACT001 downregulated the expression of p-p65, MnSOD, cyclin B1, CDC2, and Ki67 in U-118 MG tumor tissues. Patients with activated NF-κB signaling should thus be given priority for enrollment in future phase II clinical trials. Key messages: ACT001 directly bind to IKKβ and inhibited its phosphorylation. The inhibition of p-IKKβ induced the generation of ROS. ACT001 promoted the generation of ROS by regulating MnSOD expression to induce G2/M phase arrest. [ABSTRACT FROM AUTHOR]

Background: Tyrosine kinase inhibitors (TKIs) can significantly prolong overall survival for patients with advanced non‐small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)‐mutation or anaplastic lymphoma kinase (ALK)‐rearrangement. However, the real‐world evaluation status of ALK/EGFR in China remains unclear. Methods: We conducted a prospective study including 1134 patients with cytologically or histologically confirmed advanced NSCLC (stage IIIb–IV) at 12 Chinese hospitals. Results: The most common evaluation methods were amplification‐refractory mutation system for EGFR status and immunohistochemistry targeting D5F3 for ALK status. Among patients with non‐squamous, the EGFR mutation rate was 44.1% and the ALK rearrangement rate was 10.0%. Among patients with squamous cell carcinoma, the EGFR mutation rate was 8.3% and the ALK rearrangement rate was 3.7%. Among all patients, gender (HR = 1.7, 95%CI = 1.2–2.4, P = 0.006), smoking history (HR = 1.8, 95%CI = 1.3–2.7, P = 0.001), histology (HR = 5.0, 95%CI = 2.4–10.1, P < 0.001), and brain metastases (HR = 1.5, 95%CI = 1.1–2.2, P = 0.017) were independent predictors of EGFR mutation, while age (HR = 2.6, 95%CI = 1.7–4.1, P < 0.001) was an independent predictor of ALK rearrangement. The median time from tumor diagnosis to EGFR or ALK status confirmation was 7 and 5 days, respectively. Targeted therapy rate was 73.8% in EGFR‐positive patients and 51.4% in ALK‐positive patients. There was a negative correlation between the first‐line targeted therapy rate and the EGFR mutation detection period (r = −0.152, P = 0.02), while no significant correlation among patients with ALK rearrangement (r = −0.179, P = 0.076). Conclusion: Squamous NSCLC patients should also be routinely tested to determine their EGFR/ALK statuses. The first‐line targeted therapy rate remains low in Chinese patients with NSCLC. [ABSTRACT FROM AUTHOR]

Background: Afatinib is an irreversible ErbB family blocker that improves progression‐free survival (PFS) of advanced EGFR‐mutant lung adenocarcinoma compared to chemotherapy. However, afatinib leads to more adverse events than first‐generation EGFR inhibitors. Hence, exploration of the optimal afatinib initial dose and its efficacy and safety in Asian patients has drawn extensive attention. Methods: We retrospectively evaluated demographic and clinical information, survival data, and adverse events in advanced non‐small cell lung cancer patients treated with afatinib from 27 February 2017 to 30 October 2018. Results: A total of 60 patients were included in the study. Thirty‐nine (65%) patients received afatinib as first‐line treatment. The median PFS was 12.3 months (95% confidence internal 7.6–17.0). Multivariate Cox regression analysis revealed that age, gender, smoking history, baseline brain metastasis status, afatinib starting dose, and mutation type did not significantly influence PFS. No significant difference in median PFS between patients treated with an initial dose of afatinib of 40 mg or 30 mg, either in the first‐line (14.5 vs. 5.2 months; P = 0.101) or in a second or later‐line setting (3.0 vs. 5.0 months; P = 0.375) was observed. The incidence of all grades of rash/acne (92.5% vs. 61.1%; P = 0.011) and paronychia (82.5% vs. 50.0%; P = 0.010) in the 40 mg group was significantly higher than in the 30 mg group. Conclusion: First‐line afatinib treatment is beneficial for advanced lung adenocarcinoma patients with sensitive EGFR mutations. Initial dose and baseline brain metastasis status do not significantly impact PFS. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the differentiation efficiency of texture analysis of T1WI, T2WI and contrasted-enhanced T1WI MRI sequences in gliomas with and without IDH1 mutation based on entire tumor region.Materials and Methods: A total of 42 patients with histopathologically confirmed gliomas, including 21 patients carrying IDH1 mutation (IDH1mutation group) and 21 with wild-type IDH1 (IDH1wt group) were included in this study. The preoperative MRI and clinical data were collected. The regions of interest (ROIs) covering the entire tumor and edema were manually delineated on axial slices using O.K. (Omni Kinetics, GE Healthcare, China) software; and the histogram and GLCM features based on T1WI, T2WI and contrasted-enhanced T1WI sequences were automatically generated.Results: Based on contrasted-enhanced T1WI features, the inertia resulted as the best feature for diagnosis, with the AUC of 0.844. Furthermore, the AUC for gliomas prediction with IDH1mutation was 0.800 for cluster prominence. IDH1-mutation was differentiated on T2WI with the highest AUC of 0.848, which corresponded to GLCM Entropy. After modeling, the accuracy of the contrasted-enhanced T1WI, T1WI, and T2WI features model was 0.952, 0.857, and 0.738, respectively. The AUC of Joint VariableT1WI+C for predicting IDH1mutation was 0.984, while the AUC of Joint VariableT1WI for predicting the same mutation was 0.927. The diagnostic efficiency of Joint VariableT2WI was also desirable.Conclusion: MRI texture analysis could be used as a new noninvasive method for identification of gliomas with IDH1 mutation. The present results show that the Joint Variable derived from conventional MR imaging histogram and GLCM features is suitable for precise detection of IDH1-mutated gliomas. [ABSTRACT FROM AUTHOR]

With the health information technology being infused into clinical health, e-health is becoming a key factor in delivering improvements in the health sector. Brain tumor data feature selection is crucial for the development of a viable cancer detection system based on brain tumor data. Our study aimed to obtain an optimal feature subset through a hybrid algorithm of Simulated Annealing-Genetic Algorithms (SA-GA). Two real datasets of brain tumor Magnetic Resonance Images are used to assess the performances of the proposed approach. The first dataset was freely downloaded from the Harvard Medical School brain atlas. The second brain tumor dataset was created from Nanfang Hospital, Guangzhou, China, and General Hospital, Tianjing Medical University, China from 2005 to 2012. The proposed approach is compared to the methods of simulated annealing, genetic algorithm and with the state-of-the-art methods used separately. The obtained results show that SAGA exceeds simulated annealing and genetic algorithms when they are applied in isolation, in terms of accuracy and computing time. The evaluation shows that our method overtakes the state-of-theart methods with a segmentation accuracy rate of 97.82%±0.74 for glioma tumor and 95.12% ±3.21for pituitary tumor. [ABSTRACT FROM AUTHOR]