Secondary Brain Tumors Research Articles

LSTM-NAS-Net: Enhanced Brain Tumor Segmentation in MRI and CT Images using LSTM-Autoencoder-based Neural Architecture Search

Brain Tumour (BT) a mass or a lump or a growth which occurs due to abnormal cell division or unusual growth of cells in the brain tissue. Initially, the two major types of BT are Primary BT and Secondary BT, the tumour that originate from brain is known as Primary BT and it may be cancerous or non-cancerous. The tumour the initiates from other part of the body and spreads to the brain is stated as secondary BT. Diagnosing BT generally involves a multiple investigation method, such as MRI, CT, PET, SPECT as well as the neurological examinations and blood investigations, whereas some of the patients may need biopsies to evaluate the tumour size and stage. Here we use MRI and CT images for BT segmentation whereas these modalities play a major role in diagnosing, treating, planning and monitoring the BT patients. Moreover, the multimodal data can provide a quantitative information’s about the tumour size, shape, volume and texture. While segmenting the BT the lack of segmentation methods and the interpretability of the segmented regions are limited. To overcome this, we propose a novel LSTM autoencoder bas NAS method which is used for the extracting the BT features and these features can be fused using Contextual Integration Module (CIM) and segmented using the Segmentation Guided Regulizer (SGR) which helps to overcome the stated issues. Finally, the performance metrices are calculated by comparing with the state-of -the -art methods and our method achieves a best segmenting metrices.

Brain tumours in the Western Cape Province of South Africa: A plea for a dedicated brain tumour registry in Africa

Abstract Background: Epidemiological data on brain tumours provides valuable insight into risk factors, treatment modalities and prognoses of these tumours. Despite abundant epidemiological data from brain tumour registries in high-income countries, a critical data gap persists in low- and middle-income countries. Aim: The aim of this study was to report on the epidemiology of brain tumours in South Africa's Western Cape province. Methods: This retrospective study collected data from the National Health Laboratory Services database housed in the public healthcare sector in the Western Cape Province of South Africa. All pathology reports over 2 years (January 2018 to December 2019) that included the term “brain” or equivalent terms were analyzed to compile the epidemiological dataset. Results: The dataset yielded 505 patients with brain tumours, with a mean age at diagnosis of 44 years (range: 0–82 years). A noteworthy subset (16%) of primary tumours occurred in individuals under 20 years of age. The top three primary tumour diagnoses in the study were gliomas, glioneuronal and neuronal tumours, meningiomas and pituitary tumours. Secondary brain tumours (18%) constituted a significant proportion of brain tumours, with lung and breast being the most common primary sites. Comparison with registries and audits from both high- and low-income countries revealed South Africa's unique landscape; ependymal tumours exhibited a substantial proportion, while nerve sheath tumours displayed a reduced proportion. Conclusion: This study offers a unique perspective on brain tumour epidemiology in South Africa's Western Cape Province. It reports on unique trends and emphasizes the feasibility and necessity of establishing a dedicated brain tumour registry.

Evaluation of the Effect of Radiosurgery for Target and Non-Target Lesions in Patients with Brain Metastases Using RANO-BM Criteria.

The current therapeutic indications of radiosurgery are constantly expanding. Magnetic resonance imaging (MRI) has an important role in the diagnostic and post-therapeutic period of primary and secondary brain tumor formations. A total of 66 patients with verified cancer disease and brain metastases were separated into two groups. The first group includes 34 patients with primary non-small cell lung cancer and the second one 32 patients with other types of primary cancer. All of them received high-dose radiotherapy in 1-5 fractions. The number, size, and location of the treated lesions responded to robotic stereotactic radiosurgery criteria. The Response Assessment Criteria for Brain Metastases (RANO-BM) is an international multidisciplinary group of experts who developed acceptable criteria for assessing brain metastases. Before treatment and on the first, third, sixth month after radiosurgery, a MRI and blood tests were performed. Treated lesions were separated into four groups depending on the results - complete response, partial response, progressive disease, and stable disease. In both groups of patients, the percentage of complete or partial response had increased in the third and sixth months. The results give us a reason not to recommend an MRI 1 month after treatment if the patient doesn't have any new neurological symptoms, because there may be a pseudo-progression. MRI results valued by RANO-BM criteria give us a good option to evaluate brain metastases on the third and sixth month after after stereotactic radiosurgery.

Focused ultrasound combined with radiotherapy for malignant brain tumor: a preclinical and clinical study.

Blood-brain barrier (BBB) remains to be the major obstacle to conquer in treating patients with malignant brain tumors. Radiation therapy (RT), despite being the mainstay adjuvant modality regardless of BBB, the effect of radiation induced cell death is hindered by the hypoxic microenvironment. Focused ultrasound (FUS) combined with systemic microbubbles has been shown not only to open BBB but also potentially increased regional perfusion. However, no clinical study has investigated the combination of RT with FUS-BBB opening (RT-FUS). We aimed to provide preclinical evidence of RT-FUS combination in GBM animal model, and to report an interim analysis of an ongoing single arm, prospective, pilot study (NCT01628406) of combining RT-FUS for recurrent malignant high grade glioma patients, of whom re-RT was considered for disease control. In both preclinical and clinical studies, FUS-BBB opening was conducted within 2h before RT. Treatment responses were evaluated by objective response rate (ORR) using magnetic resonance imaging, progression free survival, and overall survival, and adverse events (AE) in clinical study. Survival analysis was performed in preclinical study and descriptive analysis was performed in clinical study. In mouse GBM model, the survival analysis showed RT-FUS (2Gy) group was significantly longer than RT (2Gy) group and control, but not RT (5Gy) group. In the pilot clinical trial, an interim analysis of six recurrent malignant high grade glioma patients underwent a total of 24 RT-FUS treatments was presented. Three patients had rapid disease progression at a mean of 33days after RT-FUS, while another three patients had at least stable disease (mean 323days) after RT-FUS with or without salvage chemotherapy or target therapy. One patient had partial response after RT-FUS, making the ORR of 16.7%. There was no FUS-related AEs, but one (16.7%) re-RT-related grade three radiation necrosis. Reirradiation is becoming an option after disease recurrence for both primary and secondary malignant brain tumors since systemic therapy significantly prolongs survival in cancer patients. The mechanism behind the synergistic effect of RT-FUS in preclinical model needs further study. The clinical evidence from the interim analysis of an ongoing clinical trial (NCT01628406) showed a combination of RT-FUS was safe (no FUS-related adverse effect). A comprehensive analysis of radiation dosimetry and FUS energy distribution is expected after completing the final recruitment.

Preclinical Characterization of AZD9574, a Blood-Brain Barrier Penetrant Inhibitor of PARP1.

We evaluated the properties and activity of AZD9574, a blood-brain barrier (BBB) penetrant selective inhibitor of PARP1, and assessed its efficacy and safety alone and in combination with temozolomide (TMZ) in preclinical models. AZD9574 was interrogated in vitro for selectivity, PARylation inhibition, PARP-DNA trapping, the ability to cross the BBB, and the potential to inhibit cancer cell proliferation. In vivo efficacy was determined using subcutaneous as well as intracranial mouse xenograft models. Mouse, rat, and monkey were used to assess AZD9574 BBB penetration and rat models were used to evaluate potential hematotoxicity for AZD9574 monotherapy and the TMZ combination. AZD9574 demonstrated PARP1-selectivity in fluorescence anisotropy, PARylation, and PARP-DNA trapping assays and in vivo experiments demonstrated BBB penetration. AZD9574 showed potent single agent efficacy in preclinical models with homologous recombination repair deficiency in vitro and in vivo. In an O6-methylguanine-DNA methyltransferase (MGMT)-methylated orthotopic glioma model, AZD9574 in combination with TMZ was superior in extending the survival of tumor-bearing mice compared with TMZ alone. The combination of three key features-PARP1 selectivity, PARP1 trapping profile, and high central nervous system penetration in a single molecule-supports the development of AZD9574 as the best-in-class PARP inhibitor for the treatment of primary and secondary brain tumors. As documented by in vitro and in vivo studies, AZD9574 shows robust anticancer efficacy as a single agent as well as in combination with TMZ. AZD9574 is currently in a phase I trial (NCT05417594). See related commentary by Lynce and Lin, p. 1217.

Dark Blood Contrast-Enhanced Brain MRI Using Echo-uT1RESS.

The widely used magnetization-prepared rapid gradient-echo (MPRAGE) sequence makes enhancing lesions and blood vessels appear bright after gadolinium administration. However, dark blood imaging using T1-weighted Sampling Perfection with Application optimized Contrast using different flip angle Evolution (T1 SPACE) can be advantageous since it improves the conspicuity of small metastases and leptomeningeal disease. As a potential alternative to T1 SPACE, we evaluated a new dark blood sequence called echo-uT1RESS (unbalanced T1 Relaxation-Enhanced Steady-State). We compared the performance of echo-uT1RESS with Dixon fid-uT1RESS, MPRAGE, and T1 SPACE. Retrospective, IRB approved. Phantom to assess flow properties of echo-uT1RESS. Twenty-one patients (14 female, age range 35-82 years) with primary and secondary brain tumors. 3 Tesla/MPRAGE, T1 SPACE, Dixon fid-uT1RESS, echo-uT1RESS. Flow phantom signal vs. velocity as a function of flip angle and sequence. Qualitative image assessment on 4-point scale. Quantitative evaluation of tumor-to-brain contrast, apparent contrast-to-noise ratio (aCNR), and vessel-to-brain aCNR. Friedman and Mann-Whitney U tests. A P value <0.05 was considered statistically significant. In the phantom, echo-uT1RESS showed greater flow-dependent signal loss than fid-uT1RESS. In patients, blood vessels appeared bright with MPRAGE, gray with fid-uT1RESS, and dark with T1 SPACE and echo-uT1RESS. For MPRAGE, Dixon fid-uT1RESS, echo-uT1RESS, and T1 SPACE, respective tumor-to-brain contrast values were 0.6 ± 0.3, 1.3 ± 0.5, 1.0 ± 0.4, and 0.6 ± 0.4, while normalized aCNR values were 68.9 ± 50.9, 128.4 ± 59.2, 74.2 ± 42.1, and 99.4 ± 73.9. Volumetric dark blood contrast-enhanced brain MRI is feasible using echo-uT1RESS. The dark blood effect was improved vs. fid-uT1RESS, while both uT1RESS versions provided better tumor-to-brain contrast than MPRAGE. Whereas T1 SPACE provided better tumor aSNR, echo-uT1RESS provided better Weber contrast, lesion sharpness and a more consistent dark blood effect. 3 TECHNICAL EFFICACY: Stage 1.

Urgent necessity for structured screening for symptoms and distress in patients with primary and secondary brain tumors

Urgent necessity for structured screening for symptoms and distress in patients with primary and secondary brain tumors

The Incidence and Location of Different Types of Ring Enhancing Lesion of Brain

Background: Ring-enhancing lesions are one of the most common types of neuroimaging abnormalities. Many different primary and secondary brain tumors, including glioblastomas, low-grade gliomas, and brain metastases, can also manifest as ring-enhancing lesions. Aim of the study: The objective of this study is to assess the incidence and location of different types of ring enhancing lesion of brain. Methods: This prospective observational study was carried out from January 2012 to December 2013 at the Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, Department of Radiology and Imaging, in collaboration with the Department of Neurosurgery. 56 cases total were randomly chosen for the study population based on clinical and brain CT results. First, all the pertinent information was gathered on a master chart, after which it was arranged using a scientific calculator and the proper statistical formulas. Finally, using MS Office and SPSS programs as necessary, all data were processed, examined, and disseminated. Results: The present study was found that among the ring enhancing lesions of brain patients, highest percentage were in the range of 31-40 years (35.7%). Clinical features of different etiologies headache emerged as the most common complaint that the patients presented. Out of 56 patients, 45 (80.4%) complained of headache. Parietal was observed as the most common site of lesion of 31 (57.1%). Parenthesis indicates percentage out of 21 diagnosed Glioma patients, 20 (95.2%) were single number of lesion and the rest 1 (4.8%) was multiple number of lesion. Perilesional Parenchymal changes were observed 45 (80.3%) patients. Conclusion: The present study was designed and attempted to find out the incidence and location of different types of ring enhancing lesion of brain. This was a single centre study and may limit the ability to reflect the generalized population in our country.

Proteomic landscape of primary and metastatic brain tumors for heterogeneity discovery.

Despite recent advancements in our understanding of driver gene mutations and heterogeneity within brain tumors, whether primary or metastatic (also known as secondary), our comprehension of proteomic changes remains inadequate. The aim of this study is to provide an informative source for brain tumor researches, and distinguish primary brain tumors and secondary brain tumors from extracranial origins based on proteomic analysis. We assembled the most frequent brain tumors as follows: gliomas from WHO grade 2 to 4, with IDH1 mutations and wildtypes; brain metastases (BrMs) originating from lung cancer (LC), breast cancer (BC), ovarian cancer (OC), and colorectal cancer (CC). A total of 29 tissue samples were analyzed by label free quantitative mass spectrometry-based proteomics. In total, 8165 protein groups were quantified, of which 4383 proteins were filtered at 50% valid intensity values for downstream analysis. Proteomic analysis of BrMs reveals conserved features shared among multiple origins. While proteomic heterogeneities were found for discriminating different grades of gliomas, as well as IDH1 mutant and wildtype gliomas. In addition, notable distinctions were observed at the pathway level between BrMs and gliomas. Specifically, BrMs exhibited characteristic pathways focused on proliferation and immunomodulation after colonizing the brain, whereas gliomas primarily engaged in invasion processes. We characterized an extensive proteomic landscape of BrMs and gliomas. These findings have promising implications for the development of targeted therapies for BrMs and gliomas.

P15.12.A BIUX2X2

Abstract BACKGROUND Brain metastases occur in 20-40% of cancer patients. In connection with the development of radiosurgical treatment, the problem of differential diagnosis of continued tumor growth and post-radiation changes becomes relevant. The main method of radiosurgical treatment of secondary lesions is the Gamma-Knife. Positron emission tomography with 11C-Meth and 18F-FET is an important method in monitoring the treatment of patients with secondary brain tumors. MATERIAL AND METHODS We examined 73 patients with brain metastases. Of these, 36.36% were patients with breast cancer, 39.39% were patients with lung cancer, 9.00% were patients with melanoma, 6.06% were patients with kidney cancer, 9.09% were other nosology, which corresponds to the data on the frequency of metastasis to the brain of various types of cancers. All patients underwent MRI with standard sequences (T1, T2, FLAIR, T1+C) and PET-CT with 18F-FET. PET-CT was performed according to the standard protocol: scanning 20 minutes after the INTRODUCTION of the radiopharmaceutical, scanning time 20 minutes. The evaluation of PET images was carried out by a semi-quantitative method - TBR max. RESULTS The mean age of patients with breast cancer was 54.5 ± 10.4, which significantly differs from the mean age of patients with lung cancer (65.9 ± 8.7) and the mean age of patients with other primary cancers (62.8 ± 8, 8) (Kruskal-Wallis test: H(2, N=66)=13.99052 p=.0009). Differences in TBR max and the number of metastases in these groups are not significant, as well as, according to the Kaplan-Meier analysis, differences in the duration of the relapse-free period. However, differences in the duration of the relapse-free period in the groups after a single ( Median, Q1; Q3) (12.9, 10.5; 24.4) or multiple (7.5, 3.5; 10.5) radiosurgical treatment are significant ( Gehan's Wilcoxon Test, Test statistic = 2.063905 p = .03903). Based on the analysis of the data obtained, it was found that the threshold value TBR max &amp;gt;=2.8 in 100% of cases indicates progression, TBR max &amp;lt;=1.7 indicates a stable course. Whereas TBR max in the range from 1.7 to 2.8 (in 33 people from the examined group, i.e. in 50% of all cases) may indicate both progression and post-radiation changes, as well as confirmed positive dynamics. CONCLUSION Thus, we confirmed that the numerical value of TBR max is a relative indicator. And when interpreting PET data, we cannot rely only on the TBR max value in the range from 1.7 to 2.8 for a confident judgment about the genesis of increased RP uptake in tumors. In the absence of other markers of the development of progression (for example, the appearance of new pathological foci), to assess the dynamics and confidently identify post-radiation changes, a repeat PET study should be prescribed after 2-3 months with a preliminary MRI with contrast enhancement.

P11.69.B INTRAVENOUS THROMBOLYSIS WITH OR WITHOUT ENDOVASCULAR TREATMENT FOR SUSPECTED ISCHEMIC STROKE IN PATIENTS WITH INTRACRANIAL TUMORS

Abstract BACKGROUND: AND OBJECTIVES Intravenous thrombolysis (IVT) for suspected ischemic stroke in patients with intracranial neoplasms is off-label. However, data on risks of intracranial hemorrhage (ICH) is scarce. METHODS In a multicenter registry-based analysis within the European Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration, we assessed frequencies of symptomatic and fatal ICH after IVT for suspected ischemic stroke in patients with intracranial tumors by descriptive statistics and analyzed associations with clinical and imaging characteristics by binary logistic regression. Definition of symptomatic ICH was based on the clinical criteria of the European Cooperative Acute Stroke-II trial including hemorrhage at any site in cranial imaging and concurrent clinical deterioration. RESULTS Screening data of 21,289 patients from 14 centers, we identified 105 patients receiving IVT, among them 29 patients (28%) with additional endovascular treatment, with suspected, i.e. imaging-based, or histologically confirmed diagnosis of intracranial tumors. Among 104 patients with CT or MRI after IVT available, symptomatic and fatal ICH were observed in nine and four patients (9% and 4%). Among 82 patients with suspected or confirmed meningioma, symptomatic and fatal ICH occurred in six and three patients (7% and 4%). In 18 patients with intra-axial suspected or confirmed primary or secondary brain tumors, there was one symptomatic nonfatal ICH (6%). Out of four patients with tumors of the pituitary region, two patients (50%) had symptomatic ICH including one fatal ICH (25%). Tumor size was not associated with occurrence of symptomatic ICH (Odds ratio 2.8, 95% CI 0.3-24.8, p=0.34). CONCLUSION In our dataset from routine clinical care, we provide insights on the safety of IVT for suspected ischemic stroke in patients with intracranial tumors, a population that is commonly withheld thrombolysis in clinical practice and prospective trials. Except for a potential high risk of symptomatic ICH after IVT in patients with tumors of the pituitary region, frequencies of symptomatic ICH in patients with intracranial tumors in our cohort appear to be in the upper range of rates observed in previous studies within the TRISP cooperation. These results may guide individual treatment decisions in patients with acute stroke and intracranial tumors with potential benefit of IVT.

P11.68.A INTRA-ARTERIAL ADMINISTRATION OF [68GA]GA-PSMA-11 IN MALIGNANT PRIMARY AND SECONDARY BRAIN TUMOURS; A NOVEL APPROACH THAT SIGNIFICANTLY INCREASES TUMOUR UPTAKE AND POTENTIAL OF/FOR THERANOSTIC STRATEGIES

Abstract BACKGROUND Primary and secondary brain tumours carry a dismal prognosis and require new treatment strategies. First studies into novel radionuclide therapies have thus far yielded little success, potentially because of limitary uptake in tumour upon intravenous (IV) administration. The aim of the present study was to show that intra-arterial (IA) administration of radiopharmaceuticals will lead to much higher uptake and, consequently, to higher delivered dose to the tumour, which convincingly outweighs the systemic non-target uptake. MATERIAL AND METHODS Ten patients with malignant brain tumours (n=5 high-grade glioma (HGG), n=5 brain metastasis (BM)) twice received 1.5 MBq/kg [68Ga]Ga-PSMA-11 followed by PET-MRI at 90, 165 and 240 minutes post-administration, first upon IV and subsequently upon selective IA administration, with a median interval time of 5 days. Standardised uptake values (SUVs) were calculated for tumour, and non-target sites (contralateral healthy brain, salivary glands and liver) using volumes of interest (VOIs). Tumour-to-liver (T/L), tumour-to-salivary gland (T/SG) uptake-ratios and simulated achievable tumour doses with either [177Lu]Lu- or [225Ac]Ac-PSMA were calculated for each patient. Paired T-test and Wilcoxon signed rank-test were performed to compare outcomes. RESULTS All patients showed significantly higher uptake in tumour following IA administration compared to IV administration, with a median SUVmax of 142.8 (range: 31.3-336.8) versus 10.5 (range: 5.1-17.1, P=0.005). Healthy brain showed no significant uptake, independent of the route of administration (SUVmean range: &amp;lt;0.1-0.1). Uptake at non-target sites was comparable following IA and IV administration, resulting in more favourable T/SG-ratios of 8.4 (median, range: 1.8-18.9) for IA versus 1.8 (0.9-7.0) for IV; P=0.005 and T/L-ratios of 26.5 (7.4-68.7) for IA versus 1.8 (0.9-7.0) for IV; P=0.005. Simulations showed a maximum delivered dose to the tumours for a single treatment cycle to be 68 Gy (median, range: 5-282) for [177Lu]Lu- and 78 Gy (5-174) for [225Ac]Ac-PSMA when administered intra-arterially, versus 10 Gy (1-37) and 18 Gy (1-49), when administered intra-venously. CONCLUSION Selective IA administration of radiopharmaceuticals in malignant brain tumours leads to a significant and therapeutically relevant increase in target to non-target uptake ratios. This observation opens new avenues for the development of theranostic strategies for patients with HGG and BM whom we, to date, have no curative treatment to offer.

Risk of intracranial hemorrhage with direct oral anticoagulation versus low molecular weight heparin in the treatment of brain tumor-associated venous thromboembolism: A meta-analysis

ObjectivesDirect oral anticoagulants (DOACs) are effective in treating cancer-related thrombosis and are superior to low molecular weight heparin (LMWH) in terms of efficacy. The effects of DOACs or LMWH on intracranial hemorrhage (ICH) remain uncertain in individuals with brain tumors. We conducted a meta-analysis to compare the frequency of ICH in individuals with brain tumors treated with DOACs or LMWH. MethodsTwo independent investigators reviewed all studies that compared the frequency of ICH in patients with brain tumors who received DOACs or LMWH. The primary outcome was the incidence of ICH. We used the Mantel-Haenszel method to estimate the combined effect and calculated 95% confidence intervals (CI). ResultsThis study encompassed six articles. The results indicated that cohorts treated with DOAC experienced much fewer instances of ICH compared to the LMWH cohorts (relative risk [RR] 0.39; 95% CI 0.23-0.65; P = 0.0003; I2 = 0%). The same effect was observed for the prevalence of major ICH (RR 0.34; 95% CI 0.12-0.97; P = 0.04; I2 = 0%), but there was no difference for fatal ICH. Subgroup analysis indicated that DOACs had a substantially reduced incidence of ICH in primary brain tumors (RR 0.18; 95% CI 0.06-0.50; P = 0.001; I2 = 0%), but had no impact on ICH with secondary brain tumors. ConclusionsThis meta-analysis showed that DOACs are associated with a lower risk of ICH than LMWH therapy in treating venous thromboembolism associated with brain tumors, especially in patients with primary brain tumors.

Complement Activation and Up-Regulated Expression of Anaphylatoxin C3a/C3aR in Glioblastoma: Deciphering the Links with TGF-β and VEGF.

The complement (C) innate immune system has been shown to be activated in the tumor microenvironment of various cancers. The C may support tumor growth by modulating the immune response and promoting angiogenesis through the actions of C anaphylatoxins (e.g., C5a, C3a). The C has important double-edged sword functions in the brain, but little is known about its role in brain tumors. Hence, we analyzed the distribution and the regulated expression of C3a and its receptor C3aR in various primary and secondary brain tumors. We found that C3aR was dramatically upregulated in Grade 4 diffuse gliomas, i.e., glioblastoma multiforme, IDH-wildtype (GBM) and astrocytoma, IDH-mutant, Grade 4, and was much less expressed in other brain tumors. C3aR was observed in tumor-associated macrophages (TAM) expressing CD68, CD18, CD163, and the proangiogenic VEGF. Robust levels of C3a were detected in the parenchyma of GBM as a possible result of Bb-dependent C activation of the alternative C pathway. Interestingly, in vitro models identified TGF-β1 as one of the most potent growth factors that upregulate VEGF, C3, and C3aR in TAM (PMA-differentiated THP1) cell lines. Further studies should help to delineate the functions of C3a/C3aR on TAMs that promote chemotaxis/angiogenesis in gliomas and to explore the therapeutic applications of C3aR antagonists for brain tumors.

Develop Model for Detection and Localization of Brain Tumor

Abstract: A brain tumor is growth of damaged cells in your brain. There are many different types of brain tumors. Some brain tumors are non-cancerous (benign) and some brain tumors are cancerous (malignant). Brain tumors can start in your brain (primary brain tumors), or cancer can start in other parts of your body and spread to your brain as secondary (metastatic) brain tumors. The rate at which a brain tumor grows can vary widely. Brain tumor growth rate and location determine how your nervous system functions. One of the most important and useful tests performed on the brain is an MRI, which is magnetic resonance imaging. All images are tested and analyzed by a radiologist, due to the rapid development in neural networks and machine learning techniques of high performance systems for detecting the diseased part of a person. Machine learning and neural network models play an important role in computer vision. In this revive paper, we did an analysis on many object detection model and summarize the research done on this domain.

Understanding the activity of antibody–drug conjugates in primary and secondary brain tumours

Antibody-drug conjugates (ADCs), a class of targeted cancer therapeutics combining monoclonal antibodies with a cytotoxic payload via a chemical linker, have already been approved for the treatment of several cancer types, with extensive clinical development of novel constructs ongoing. Primary and secondary brain tumours are associated with high mortality and morbidity, necessitating novel treatment approaches. Pharmacotherapy of brain tumours can be limited by restricted drug delivery across the blood-brain or blood-tumour barrier, although data from phase II studies of the HER2-targeted ADC trastuzumab deruxtecan indicate clinically relevant intracranial activity in patients with brain metastases from HER2+ breast cancer. However, depatuxizumab mafodotin, an ADC targeting wild-type EGFR and EGFR variant III, did not provide a definitive overall survival benefit in patients with newly diagnosed or recurrent EGFR-amplified glioblastoma in phase II and III trials, despite objective radiological responses in some patients. In this Review, we summarize the available data on the central nervous system activity of ADCs from trials involving patients with primary and secondary brain tumours and discuss their clinical implications. Furthermore, we explore pharmacological determinants of intracranial activity and discuss the optimal design of clinical trials to facilitate development of ADCs for the treatment of gliomas and brain metastases.

474 Incidence and Risk Factors for Perioperative Stroke Following Resection of Intracranial Tumors: A Nationwide Analysis of 30,951 Cases

INTRODUCTION: Perioperative cerebrovascular accidents (CVA) in neurosurgical patients is a serious complication that may result in permanent neurological deficits. Establishment of associated risk factors allows for mitigation of CVA risk and sequelae. METHODS: The National Surgical Quality Improvement Program (NSQIP) database was queried for cranial tumor excision cases (2015-2019, N = 30,951). Univariate and multivariable analysis of demographic data and comorbidities was used to assess predictive strength of these factors on postoperative CVA. RESULTS: CVA occurred in 1.7% of cases (N = 532). Patients with CVA, on average, were older, frailer, with increased rates of diabetes mellitus, hypertension, and weight loss. In multivariable analysis, predictors of CVA included advanced age (≥75th percentile in cohort)(OR: 1.9, 95% CI: 1.4-2.5), diabetes mellitus (OR: 1.4, 95% CI: 1.1-1.8), hypertension (OR: 1.4, 95% CI: 1.1-1.7), and weight loss (OR: 1.9, 95% CI: 1.1-3.2). Increased proportions of CVA were found among patients with primary malignant brain tumors (46.1%) and meningiomas (32.9%) when compared to all other benign brain tumors (6.6%) and secondary metastatic brain tumors (14.5%)(all p &lt; .001). Elective surgery status was associated with decreased likelihood of CVA (OR: .74, 95% CI: .60-.91). In multivariable analysis, increasing frailty (as measured by mFI-5 and RAI-revised) was associated with increasing likelihood of CVA. CONCLUSIONS: The current study was the largest to identify preoperative risk factors for perioperative stroke after resection of intracranial tumors. Patients with advanced age, multiple comorbidities, and higher frailty scores were significantly more likely to suffer CVA. Frailty (as measured by mFI- and RAI-revised) is a valuable tool for preoperative risk stratification.

The progress of microenvironment-targeted therapies in brain metastases.

The incidence of brain metastases (BrM) has become a growing concern recently. It is a common and often fatal manifestation in the brain during the end-stage of many extracranial primary tumors. Increasing BrM diagnoses can be attributed to improvements in primary tumor treatments, which have extended patients' lifetime, and allowed for earlier and more efficient detection of brain lesions. Currently, therapies for BrM encompass systemic chemotherapy, targeted therapy, and immunotherapy. Systemic chemotherapy regimens are controversial due to their associated side effects and limited efficacy. Targeted and immunotherapies have garnered significant attention in the medical field: they target specific molecular sites and modulate specific cellular components. However, multiple difficulties such as drug resistance and low permeability of the blood-brain barrier (BBB) remain significant challenges. Thus, there is an urgent need for novel therapies. Brain microenvironments consist of cellular components including immune cells, neurons, endothelial cells as well as molecular components like metal ions, nutrient molecules. Recent research indicates that malignant tumor cells can manipulate the brain microenvironment to change the anti-tumoral to a pro-tumoral microenvironment, both before, during, and after BrM. This review compares the characteristics of the brain microenvironment in BrM with those in other sites or primary tumors. Furthermore, it evaluates the preclinical and clinical studies of microenvironment-targeted therapies for BrM. These therapies, due to their diversity, are expected to overcome drug resistance or low permeability of the BBB with low side effects and high specificity. This will ultimately lead to improved outcomes for patients with secondary brain tumors.

Assessing the reporting quality of adult neuro-oncology protocols, abstracts, and trials: Adherence to the SPIRIT and CONSORT statements.

Comprehensive and transparent reporting of clinical trial activity is important. The Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 and Consolidated Standards of Reporting Trials (CONSORT) 2010 statements define the items to be reported in clinical trial protocols and randomized controlled trials, respectively. The aim of this methodological review was to assess the reporting quality of adult neuro-oncology trial protocols and trial result articles. Adult primary and secondary brain tumor phase 3 trial protocols and result articles published after the introduction of the SPIRIT 2013 statement, were identified through searches of 4 electronic bibliographic databases. Following extraction of baseline demographic data, the reporting quality of independently included trial protocols and result articles was assessed against the SPIRIT and CONSORT statements respectively. The CONSORT-A checklist, an extension of the CONSORT 2010 statement, was used to specifically assess the abstract accompanying the trial results article. Percentage adherence (standard deviation [SD]) was calculated for each article. Seven trial protocols, and 36 trial result articles were included. Mean adherence of trial protocols to the SPIRIT statement was 79.4% (SD: 0.11). Mean adherence of trial abstracts to CONSORT-A was 75.3% (SD: 0.12) and trial result articles to CONSORT was 74.5% (SD: 0.10). The reporting quality of adult neuro-oncology trial protocols and trial result articles requires improvement to ensure comprehensive and transparent communication of planned neuro-oncology clinical trials and results within the literature. Raising awareness by clinical triallists and implementing mandatory evidence of proof of adherence by journals should improve reporting quality.

Prospective Evaluation of CD45RA+/CCR7- Effector Memory T (TEMRA) Cell Subsets in Patients with Primary and Secondary Brain Tumors during Radiotherapy of the Brain within the Scope of the Prospective Glio-CMV-01 Clinical Trial.

Radiotherapy (RT) of the brain is a common treatment for patients with high-grade gliomas and brain metastases. It has previously been shown that reactivation of cytomegalovirus (CMV) frequently occurs during RT of the brain. This causes neurological decline, demands antiviral treatment, and is associated with a worse prognosis. CMV-specific T cells are characterized by a differentiated effector memory phenotype and CD45RA+ CCR7- effector memory T (TEMRA) cells were shown to be enriched in CMV seropositive individuals. In this study, we investigated the distribution of TEMRA cells and their subsets in the peripheral blood of healthy donors and, for the first time, prospectively within the scope of the prospective Glio-CMV-01 clinical trial of patients with high-grade glioma and brain metastases during radiation therapy as a potential predictive marker. First, we developed a multicolor flow cytometry-based assay to monitor the frequency and distribution of TEMRA cells in a longitudinal manner. The CMV serostatus and age were considered as influencing factors. We revealed that patients who had a reactivation of CMV have significantly higher amounts of CD8+ TEMRA cells. Further, the distribution of the subsets of TEMRA cells based on the expression of CD27, CD28, and CD57 is highly dependent on the CMV serostatus. We conclude that the percentage of CD8+ TEMRA cells out of all CD8+ T cells has the potential to serve as a biomarker for predicting the risk of CMV reactivation during RT of the brain. Furthermore, this study highlights the importance of taking the CMV serostatus into account when analyzing TEMRA cells and their subsets.