搜索结果：Brain tumor pathology

Atypical teratoid rhabdoid tumor (ATRT) is the most common malignant brain tumor in infants. ATRT is associated with inactivation/deletion of SMARCB1, a member of the SWI/SNF chromatin remodeling complex. SMARCB1 loss contributes to tumorigenicity by compromising SWI/SNF activity at specific loci associated with the CoREST repressor complex, which regulates transcription at critical gene promoters and enhancers. We therefore explored the role of the CoREST repressor complex in ATRT. We evaluated the effects of the bifunctional LSD1/HDAC1/2 small molecule CoREST inhibitor, corin, on ATRT tumor cell growth, apoptosis, differentiation, gene expression and chromatin accessibility. Corin inhibited the growth of ATRT cells regardless of their epigenetic subgroup. Corin caused increased tumor cell apoptosis and differentiation. ATAC-seq showed increased chromatin accessibility in corin-treated ATRT cells, with changes seen at genes associated with neuronal differentiation and synaptic function. RNA-seq confirmed increased expression of neuronal differentiation genes in ATRT cells treated with corin. Knockdown of RCOR2 phenocopied the effects of corin, and desensitized the cells to the drug, confirming corin specificity to the CoREST complex. Corin suppressed orthotopic ATRT tumor growth, leading to significant extension of lifespan in ATRT mouse models. Corin caused increased histone acetylation (H3K9ac) and methylation (H3K4Me1) in ATRT orthotopic xenografts, consistent with on-target pharmacodynamics. The CoREST inhibitor, corin, suppressed tumor growth, induced differentiation, and promoted apoptosis in ATRT leading to significantly increased survival of mice bearing ATRT orthotopic xenografts. Our results suggest a potential application of CoREST complex inhibitors in patients with ATRT. Atypical teratoid rhabdoid tumor (ATRT) is the most common malignant brain tumor of babies. The DNA change that is found in most ATRT tumors prevents the tumor cells from maturing into neurons, the thinking cells of the brain. A new drug, called corin, unblocks maturation programs. Corin forces tumor cells out of their immature state and causes them to stop growing. Corin treatment of mice that had human ATRT tumors implanted into their brains led to maturation of tumor cells and longer survival of mice. These results tell us that corin could be a useful treatment for children with ATRT.

Gallium-68 fibroblast activation protein inhibitor-04 PET-computed tomography (68Ga-FAPi-04 PET-CT) imaging is a promising modality with higher tumor affinity and lower background activity than 18F-fluorodeoxyglucose, especially for brain imaging, which has no significant physiological uptake. This study aimed to determine the uptake of high-grade glioma lesions in correlation with histopathological FAP expression and to assess the contribution of imaging accordingly. Fifteen patients with high-grade gliomas (WHO grade 3 and 4) were the subjects of this study. The patients presented with suspicion of recurrent tumors, which were determined by MRI imaging. 68Ga-FAPi-04 PET-CT was performed on all subjects. The images were analyzed by visual and quantitative evaluation, which was compared with FAP expression determined from the pathology specimens, and all results were compared with the follow-up results (progression) at 12.2 ± 14.6 months. PET-CT imaging revealed an area under the curve of 0.97 for the tumor-to-background ratio of 14.3, with 100% sensitivity and 88.9% specificity for predicting progression in this small patient cohort (Fig. 1). In addition, whole-body imaging revealed suspicion of bone metastasis in three patients and liver metastasis in one patient, but validation was not possible because of short survival after imaging. Although the sample size is limited, Ga-FAPi-04 PET-CT imaging showed high diagnostic value for recurrent tumors, as tumor-to-background ratio values correlate with prognosis. In addition, a theranostic approach using these radiopharmaceuticals might yield favorable results in further studies.

Precise segmentation of brain tumors from MRI remains a challenging problem in medical image analysis because tumor regions exhibit substantial size variability, diffuse and infiltrative boundaries, and severe foreground-background imbalance. To address these challenges, we propose MamNet-PT, a hybrid segmentation architecture that integrates efficient long-range dependency modeling, multi-resolution feature aggregation, and uncertainty-aware prediction within a unified framework. First, a selective state-space model is embedded into the U-Net-based feature pathway to capture long-range spatial dependencies with linear computational complexity, which is particularly important for irregular and spatially extended tumor regions. Second, a pre-trained ResNet-50 encoder is used to improve feature robustness under limited annotated medical data. Third, a gated feature interaction mechanism adaptively balances Mamba-derived global contextual features and CNN-derived local boundary features, avoiding simple feature concatenation or uncontrolled module stacking. In addition, a multi-resolution pyramid fusion module strengthens scale-aware representation of small enhancing foci and extensive edema, while Monte Carlo Dropout-based uncertainty estimation provides spatial confidence maps for retrospective confidence characterization and failure-mode analysis. On the BraTS2020 benchmark, MamNet-PT achieves a Dice score of 96.7% and an Intersection over Union of 95.4%, outperforming representative CNN-Transformer and Mamba-based segmentation baselines. Ablation experiments further confirm that the performance gain is attributable to the complementary effects of selective state-space modeling, gated global-local fusion, multi-resolution aggregation, and uncertainty-aware inference. These results suggest that MamNet-PT is a promising research framework for accurate and efficient brain tumor segmentation under retrospective benchmark evaluation.

Central nervous system lymphoma (CNSL) is difficult to treat owing to the blood-brain barrier and limited efficacy of conventional chemotherapy. Herein, we report a bioinspired cisplatin-based nanomedicine that exploits gut-derived macrophages as endogenous carriers for brain-targeted delivery. Single-cell transcriptomic analyses of human and murine CNSL samples revealed a previously unrecognized enrichment of intestinal macrophages within tumor lesions, suggesting a gut-immune-brain trafficking route. Guided by this insight, a hierarchical nanostructure (Cdp NM) wasconstructed, consisting of a cisplatin-pyrazinoquinoxaline core enabling controlled drug release and a trehalose shell that promotes macrophage uptake via organic anion transport pathways while inducing autophagy. Following oral administration, Cdp NMs are internalized by intestinal macrophages and transported to brain tumors. Under laser irradiation, a slow-light effect triggers localized cisplatin release, resulting in efficient tumor cell ablation. Concurrently, autophagy activation in macrophages enhances antitumor immune responses. In both primary and secondary CNSL models, this system achieved significant tumor suppression and prolonged survival. This work establishes a chemically programmable strategy that leverages endogenous immune cells for noninvasive brain-targeted chemotherapy, offering a new paradigm for treating intracranial malignancies.

Primary central nervous system tumors (PCNST) are rare, understudied tumors for which knowledge of their clinical course, biology, physical, and psychological impact is limited. The National Cancer Institute's Neuro-Oncology Branch Natural History Study was developed to better understand the long-term disease course and outcomes experienced by these patients. Past medical histories, tumor tissue (if available), and patient-reported outcomes assessing symptom burden, general health status, anxiety, depression, and perceived cognitive deficits were collected at study enrollment. Sociodemographic, clinical, molecular, and patient-reported outcome data were analyzed descriptively. Among the first 1000 participants, 796 had primary brain tumors (PBT) and 92 had primary spine tumors (PST); 88 were excluded. The cohort was predominantly male (56%), White (81%), and non-Hispanic (89%). Based on advanced molecular testing at enrollment, 190 (21%) patients had a change in diagnosis or subclassification since their initial diagnosis. Meningioma cases reported family brain tumor history more frequently than others. Most PBTs were diagnosed within 6 months of symptoms, while most PSTs were diagnosed ≥1 year after. Patients with PBT and PST reported an average of 10 symptoms, with 4 and 5 symptoms rated as moderate/severe, respectively. Nearly half of PBT participants reported anxiety or depression (46%) and difficulty with usual activities (48%). PST participants reported higher functional impairment and worse general health status. These findings underscore the substantial burden of PCNSTs and highlight the value of longitudinal, tumor-agnostic data in generating real-world insights into the disease trajectories of these rare and heterogeneous tumors to inform clinical research.

BeadChip array-based DNA methylation profiling has been recognized by the World Health Organization (WHO) as a key diagnostic tool for brain tumor classification. While its diagnostic utility has been well established, data on technical reproducibility, interlaboratory comparability, and data interpretation under real-world diagnostic conditions remain limited. Bridging this gap, we here report the results of an international proficiency test using the Infinium MethylationEPIC v2.0 platform and the corresponding Brain Tumor Classifier version 12.8. Tissue slides of eight FFPE brain tumor samples, covering a representative range of CNS tumor entities, were distributed among 24 laboratories in 10 different countries. Participants were asked to report methylation classes and copy number variation (CNV) profiles. Pre-array workflows were left to local procedures and results had to be submitted within 15 working days. Technical data reproducibility was high with a median pairwise beta-value correlation of 0.99 (range 0.93-1.0). In general, participating centers generated high-quality data, reflected by consistently low detection p-values (<0.01). Eighteen of the 24 participating centers (75%) successfully passed the test. Of the six centers that failed the test, two laboratories experienced technical issues that led to misclassification of individual cases and contributed to incorrect CNV reporting. Four additional centers showed substantial discrepancies in the interpretation of diagnostically highly relevant CNVs, whereas methylation classification was not impaired. While accurate DNA quantification proved to be an important pre-array step, the use of the DNA restoration kit had only minor influence on overall results. Taken together, our interlaboratory performance testing on EPIC v2.0 CNS tumor profiling confirms high reproducibility of tumor classification but reveals the need for harmonized CNV reporting.

In this study, a new series of (E)-4-((2-(2-(4-amino-3-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)acetyl)hydrazono)methyl)phenyl 4-halogenobenzenesulfonates (3a-3d), where 3a = F, 3b = Cl, 3c = Br, and 3d = I, were successfully synthesized via a straightforward synthetic route. The structures of the obtained compounds were fully characterized and confirmed by spectroscopic techniques, including FT-IR, 1H NMR, and 13C NMR, as well as LC-MS/MS analysis. 1,2,4-triazole-based hydrazone derivatives (3a-3d) were investigated using IR and NMR spectroscopy and DFT calculations. Intermolecular interactions, HOMO-LUMO, dipole moment, polarization, first-order hyperpolarizability, and molecular electrostatic potential studies on the molecules were examined. The HOMO and LUMO energy gap study supports the charge transfer probability in the molecules. These were conducted to investigate the reactivity and stability of heterocyclic molecules in bioactivity analysis. Electron density mapping within the molecular electrostatic potential plot and electrostatic potential representation within the iso-surface plot evaluated the concept of charge distribution in the molecule as nucleophilic reactions and electrophilic regions. The predicted nonlinear optical (NLO) properties of the molecules are much greater than those of urea. The results obtained from these investigations collectively provide evidence that the molecules possess nonlinear optical applications. Novel triazole-hydrazone-functionalized aryl sulfonate derivatives (3a-3d) were evaluated for their anticancer potential against a panel of brain and non-brain cancer cell lines. Compound 3b exhibited the most favorable overall biological profile, displaying potent activity against SH-SY5Y neuroblastoma (GI = 7.59 &#x3bc;M) and U87MG glioblastoma cells (GI = 13.85 &#x3bc;M), together with the lowest toxicity toward normal FL fibroblasts (GI = 62.02 &#x3bc;M). Compounds 3c and 3d demonstrated remarkable potency against IDHmut-U87 glioma cells (GI = 3.87 and 3.27 &#x3bc;M, respectively), although their selectivity toward cancer cells was limited. DNA degradation studies revealed substantial fragmentation, particularly in C6 and SH-SY5Y cells, while migration assays indicated reduced cellular motility. Molecular docking studies identified compound 3b as the strongest PI3K&#x3b1; binder, supporting a possible. In addition, the antimicrobial activities of compounds 3a-3d were evaluated against selected Gram-positive and Gram-negative bacteria as well as Candida species using the broth microdilution method. The compounds exhibited measurable antimicrobial effects with MIC values ranging from 156 to 625 &#xb5;g/mL, showing moderate growth inhibition against the tested microorganisms. Although the observed activity was lower than that of the reference antimicrobial agents, the results indicate that these triazole-hydrazone derivatives possess a detectable level of antimicrobial activity and provide a basis for further structural optimization. Collectively, the results suggest that compound 3b represents the most promising lead structure due to its balanced combination of potency, selectivity, and predicted target engagement. Molecular docking was performed to evaluate the binding potential of newly synthesized triazole derivatives (3a-3d) against PI3K&#x3b1;. The docking protocol was validated by re-docking alpelisib, yielding an RMSD of 0.64 &#xc5;. Among the tested compounds, 3b showed the most favorable binding energy (-9.94 kcal/mol) and estimated Ki value (52.13 nM), consistent with its superior in vitro activity. Its interactions with key PI3K&#x3b1; residues, including Val851, Ser854, Met922, and Asp933, support a stable binding mode within the ATP-binding pocket. In silico ADME and toxicity analyses suggested acceptable drug-likeness characteristics, absence of major hepatotoxic, mutagenic, and carcinogenic liabilities, and moderate predicted acute toxicity profiles. These findings suggest that 3b is the most promising derivative for further validation.

BACKGROUND A durable complete response, or sustained disappearance of measurable malignancy, can occur in selected patients with metastatic renal cell carcinoma after systemic therapy. Clear cell renal cell carcinoma is the most common renal cell carcinoma subtype. Lenvatinib is a multikinase inhibitor with antiangiogenic activity, and pembrolizumab is an anti-programmed death-1 immune checkpoint inhibitor. Although this combination can induce deep extracranial responses, central nervous system relapse after prolonged complete response remains incompletely characterized. This report describes a 73-year-old man with late isolated brain metastasis of clear cell renal cell carcinoma after durable complete response to lenvatinib-pembrolizumab and deferred cytoreductive nephrectomy. CASE REPORT A 73-year-old man presented with right flank pain. Computed tomography showed a right renal tumor, level II inferior vena cava tumor thrombus, and multiple pulmonary metastases. Baseline brain computed tomography showed no intracranial metastasis. He received lenvatinib plus pembrolizumab, resulting in marked regression of the primary tumor, inferior vena cava thrombus, and lung metastases. Deferred cytoreductive nephrectomy with thrombectomy was then performed, and pathology confirmed clear cell renal cell carcinoma with extensive treatment effect. Lenvatinib was discontinued because of renal dysfunction, and pembrolizumab monotherapy was continued. The patient maintained complete extracranial radiographic remission for more than 2 years. He later developed headache, and brain magnetic resonance imaging revealed a solitary left occipital metastasis without systemic recurrence. Stereotactic body radiotherapy achieved local control. CONCLUSIONS This case shows that late isolated central nervous system relapse can occur despite durable extracranial complete response after lenvatinib-pembrolizumab and deferred cytoreductive nephrectomy. New neurological symptoms in long-term responders should prompt brain magnetic resonance imaging, because intracranial progression may occur even when systemic imaging remains negative.

Glioblastoma (GBM) remains resistant to therapy due to cellular heterogeneity and adaptive stress responses, yet the role of tumor-intrinsic Toll-like receptor 4 (TLR4) signaling in this process remains unresolved. This review addresses a central inconsistency in the field by defining tumor-intrinsic TLR4 as a context-dependent signaling rheostat that generates distinct biological outcomes rather than a uniform tumor-promoting pathway. Across experimental systems, TLR4 signaling produces divergent effects that range from mesenchymal transition, invasion, and adaptive survival under chronic or therapy-associated conditions, to differentiation, apoptosis, and increased treatment sensitivity under specific cellular and temporal contexts. These opposing outputs are not contradictory but arise from defined determinants, including ligand environment, signaling dynamics, tumor cell state, and metabolic conditions. This framework explains previously discordant findings and establishes that the functional role of tumor-intrinsic TLR4 cannot be inferred from receptor activation alone. Instead, its impact is conditional and state-dependent. This perspective defines a clear experimental and translational priority: to identify the contexts in which tumor-intrinsic TLR4 signaling sustains tumor persistence versus exposes therapeutic vulnerability, thereby enabling rational and stratified intervention strategies in GBM.

Fluorescence-guided surgery improves intraoperative brain tumor visualization, but currently available agents remain unreliable for several common entities, particularly lower-grade gliomas and lesions without visible 5-aminolevulinic acid (5-ALA)-induced fluorescence. We prospectively analyzed 69 surgically obtained tumor specimens from 61 patients with WHO grade 4 gliomas, WHO grade 2/3 gliomas, meningiomas, and brain metastases before and after ex vivo incubation in 4 &#xb5;M water-soluble high-load hypericin-polyvinylpyrrolidone complex (HHL-PVP). Fluorescence lifetime and intensity were quantified using a dual-tap CMOS camera system with a hypericin-specific 575-615&#xa0;nm bandpass filter. HHL-PVP incubation significantly increased both fluorescence intensity and lifetime in all tumor entities, including specimens without visible 5-ALA fluorescence. An independently derived combined lifetime/intensity regression model discriminated pre- from post-incubation measurements with an area under the receiver operating characteristic curve of 0.975, sensitivity of 98.6%, and specificity of 82.6%; entity-specific areas under the curve ranged from 0.933 to 1.000. These findings support robust hypericin-associated signal detection across major brain tumor entities after ex vivo incubation and provide a rationale for future in vivo evaluation of HHL-PVP in fluorescence-guided neuro-oncological surgery.

Combination therapies involving vascular targeting drugs have shown promise in overcoming resistance to immunotherapy. However, the prerequisite for vascular modulation to evoke an effective antitumor T-cell response remains elusive. Tracing the transcriptional response of liver metastasis-associated peritumoral and tumor endothelial cells (TEC) to T-cell intervention, we discovered an immunomodulatory TEC subpopulation that highly expressed lipoprotein lipase (LPL). LPL+ TECs facilitated intratumoral homing of activated antitumor CD8+ T cells driving liver metastatic regression. Mechanistically, LPL enhanced MHC-I-dependent cross-presentation of tumor antigens on TECs for T-cell trafficking. Consequently, LPL+ TECs were recognized and targeted by T cells, further aiding antitumor response. Corresponding analyses of human liver metastasis samples identified a significant correlation between the presence of intratumoral LPL+ blood vessels and the accumulation of T cells. Altogether, the study identifies a decisive role of TECs in orchestrating an effective T-cell response by overcoming tumor's intrinsic insufficient antigen presentation. The study identifies LPL+ TECs as orchestrators of activated CD8+ T-cell homing into immunologically cold tumors with low baseline MHC-I expression. Enhancing tumor antigen exposure by MHC-I cross-presentation in TECs presents a promising approach to compensate the intrinsic inability of tumor cells and boost antitumor immunotherapy.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, characterized by favorable prognosis and low incidence of distant metastasis. However, brain metastasis from PTC is rare, and its development years after the initial diagnosis is even more uncommon. Given the potential clinical implications of late metastasis, there is a need to reconsider follow-up strategies for high-risk PTC patients. A 54-year-old woman with a history of PTC diagnosed 8 years earlier presented with progressive headaches and mild left-sided hemiparesis. She had previously undergone multiple surgeries and radioiodine therapy after the initial diagnosis and had a history of childhood neck irradiation. Imaging revealed a brain mass, which was confirmed as isolated brain metastasis from PTC following biopsy after surgical resection. Despite persistently undetectable serum thyroglobulin (Tg) levels and no lymph node metastasis at the time of primary surgery, this patient developed isolated brain metastasis 8 years after initial treatment. The patient underwent craniotomy to remove the metastatic brain lesion. No adjuvant radiotherapy was given postoperatively. The patient recovered well after surgery, with mild left-sided hemiparesis (4/5 muscle strength). At the most recent follow-up, no additional distant metastases were detected. This case highlights the importance of extending the follow-up period for high-risk PTC patients, including those with prior neck irradiation or aggressive tumor features. Late metastasis can occur even in patients with initially favorable prognoses and normal biochemical markers. Imaging-based surveillance is necessary to detect late metastasis early. The findings support extended follow-up strategies to enable timely intervention and improve outcomes in high-risk patients with PTC.

Ependymoma-like tumor with mesenchymal differentiation (ELTMD) is a recently proposed, but not yet formally defined, entity that is not recognized in the 2021 World Health Organization (WHO) classification of central nervous system tumors. Although it shares molecular features, such as ZFTA fusion, with ependymomas, it exhibits distinct histopathological and epigenetic profiles. Herein, we report the case of a 5-year-old girl with a supratentorial tumor harboring the ZFTA::NCOA2 fusion. Histopathology revealed atypical features including mesenchymal and undifferentiated components, which overlapped with those of ependymomas. DNA methylation profiling using two independent classifiers (DKFZ and NIH) yielded no matches, indicating that the tumor did not belong to any recognized CNS class. The failure of subclass assignment by both classifiers suggests that ELTMD represents a potentially epigenetically distinct subgroup. Despite being unclassifiable by the current WHO criteria, the tumor shared features with previously reported ELTMDs, supporting its recognition as an emerging tumor. This highlights the need for additional cases to refine the diagnosis, classification, and future therapeutic strategies.

Posterior pituitary and hypothalamic neuronal tumors are uncommon sellar and suprasellar neoplasms that can mimic pituitary neuroendocrine tumors clinically and radiologically. The 5th edition World Health Organization classifications (Endocrine and Neuroendocrine Tumors) reinforce a lineage-based framework that separates anterior pituitary tumors from posterior pituitary and hypothalamic neuronal lineages, which is particularly important in hormone-negative lesions and limited tissue samples. This narrative review provides a practical, pathology-centered approach to classification by integrating key anatomic and radiologic clues with histomorphology and targeted immunohistochemistry. We highlight the value and limitations of thyroid transcription factor 1, outline a stepwise workflow incorporating anterior pituitary transcription factors and neuronal differentiation markers, and discuss when vasopressin immunostaining is informative. We also summarize selected molecular insights and clinical management considerations relevant to surgical planning and follow-up.

Glioblastoma (GBM) remains one of the most lethal primary brain tumors, with limited therapeutic improvement despite maximal surgical resection, radiotherapy, and temozolomide. A major barrier to durable treatment response is the profoundly immunosuppressive tumor microenvironment, which is characterized by immune exclusion, defective antigen presentation, myeloid dominance, and severe T-cell dysfunction. Tumor-associated macrophages, resident microglia, myeloid-derived suppressor cells, neutrophils, regulatory T cells, and glioma-derived extracellular vesicles collectively establish a suppressive niche through cytokine signaling, metabolic restriction, checkpoint ligand expression, impaired phagocytosis, and extracellular matrix remodeling. Key pathways, including TGF-&#x3b2;/SMAD, IL-10/STAT3, IDO-kynurenine metabolism, arginase-1-mediated amino acid depletion, adenosine signaling, hypoxia-HIF-1&#x3b1; activation, and VEGF-driven vascular dysfunction, converge to prevent effective antitumor immunity. This review summarizes the cellular and molecular mechanisms underlying immune suppression in GBM and discusses emerging therapeutic strategies, including myeloid reprogramming, phagocytosis checkpoint blockade, neutrophil and NET targeting, cellular immunotherapy, checkpoint blockade combinations, and metabolic intervention. Understanding these interconnected barriers may guide rational multimodal strategies to convert immune-excluded GBM into immune-responsive disease.

The optimal sequencing of brain-directed radiation and systemic therapy in stage IV non-small cell lung cancer (NSCLC) with brain metastases remains uncertain in the era of CNS-active systemic agents. We evaluated survival outcomes using national real-world data. We conducted a retrospective cohort study of adults diagnosed between 2010 and 2022 with stage IV NSCLC and brain metastases in the National Cancer Database who received both brain-directed radiation and systemic therapy. Treatment sequence was classified as radiation-first or systemic-first based on initiation dates. Multivariable Cox proportional hazards models, stratified by treatment era (pre-2015 vs. 2015+), assessed associations with overall survival (OS), adjusting for demographic, clinical, tumor, and treatment factors. Propensity score matching and delayed-entry sensitivity analyses were performed to address confounding and immortal time bias. Among 45&#x2009;577 patients, 78.3% received radiation-first and 21.7% received systemic therapy first. Unadjusted Kaplan-Meier analysis showed no significant difference in OS (log-rank p&#x2009;=&#x2009;0.624). In multivariable analysis, systemic-first sequencing was associated with a modest increase in mortality (adjusted hazard ratio [aHR] 1.06; 95% CI: 1.04-1.09), which was consistent in propensity-matched (HR 1.07; 95% CI: 1.04-1.11) and delayed-entry analyses (aHR 1.09; 95% CI: 1.07-1.12). The use of systemic-first therapy increased over time. Established prognostic factors demonstrated larger effect sizes. Systemic-first sequencing was associated with a modest increase in adjusted mortality; however, the effect size was small relative to established prognostic factors and likely influenced by residual confounding and selection bias. These findings support individualized, multidisciplinary treatment decisions rather than a uniform sequencing strategy.

Surgical decision making in patients with brain metastasis is complex, particularly for patients with melanoma brain metastasis (MBM). Few studies specifically address neurosurgical outcomes based on histology. This study aims to identify clinical factors associated with early mortality and overall survival (OS) after tumor resection in patients with MBM. Patients diagnosed with MBM from 2009 to 2018 at our institution who underwent surgical resection as their first-line therapy were included in the study. The primary outcomes were postoperative OS, 90-day mortality, and leptomeningeal disease (LMD) incidence. Associations between OS and postoperative 90-day mortality with demographic/clinical factors were assessed using Cox proportional hazards regression models and logistic regression models, respectively. The cumulative incidence of LMD was determined using competing risks, and associations with demographic/clinical factors were assessed using proportional subdistribution hazards regression models. A total of 103 patients with MBM were included. Ninety-day mortality occurred in 18% (n = 19). Elevated lactate dehydrogenase at MBM diagnosis (odds ratio [OR] [95% CI]: OR = 7.17 [1.50-34.25]; P = .013) was associated increased odds of early mortality in multivariable analysis. Postoperative Karnofsky Performance Scale &#x2265;80 (OR = 0.13 [0.03-0.62]; P = .010) and MBM at stage 4 diagnosis (OR = 0.11 [0.02-0.67]; P = .016) were associated with reduced odds of early mortality. Factors associated with better postoperative OS (hazard ratio [HR] [95% CI]) included synchronous diagnosis of MBM and stage 4 disease (HR = 0.59 [0.36-0.95]; P = .032), preoperative Karnofsky Performance Scale &#x2265;80 (HR = 0.46 [0.27-0.80]; P = .006), adjuvant stereotactic radiosurgery (HR = 0.55 [0.32-0.93]; P = .026), and surgical reduction of volumetric intracranial tumor burden &#x2265;95.6% (HR = 0.47 [0.28-0.80]; P = .005). No factors were significantly associated with cumulative incidence of LMD. This is the largest analysis of patients with MBM who underwent surgery as first-line therapy. We identified clinical factors associated with early postoperative mortality and survival including surgical reduction of intracranial tumor burden.

Albumin-bound paclitaxel (Abraxane) exhibits potent antitumor activity, but its suboptimal pharmacokinetics and the restrictive blood-brain barrier (BBB) greatly limit the broader application of albumin-based paclitaxel formulations in intracranial tumors. In this work, we engineered size-uniform (~&#x2009;160&#xa0;nm) paclitaxel-albumin nanoparticles (Fe3+@SA-PTX) via simple one-step nano-precipitation method guided by a "protein corona intervention" strategy. During nanoparticle fabrication, tannic acid-Fe3+ (TA-Fe3+) were strategically introduced. On the one hand, the introduction of TA-Fe3+ shell could slow down the leakage of paclitaxel and improving the stability and pharmacokinetic profile of the nanoparticles. On the other hand, the presence of Fe3+ enabled the nanoparticles to interact with unsaturated transferrin in plasma, forming a stable transferrin protein corona. This endowed the nanoparticles with enhanced tumor-targeting capability and the ability to penetrate the BBB. The Fe3+@SA-PTX exhibited superior pharmacokinetics and therapeutic efficacy against intracranial tumors via intravenous administration.

Brain metastasis (BM) in small cell lung cancer (SCLC) is typically associated with poor survival rates and quality of life, making the timely identification of patients with a high likelihood of BM at diagnosis crucial. To develop and validate a machine learning (ML) prediction model for BM in the overall SCLC population and provide an interpretable and clinically accessible risk assessment tool. Univariate and multivariate logistic regression analyses were performed to identify BM-associated factors. Eight ML algorithms were applied to build the model. The model performance was quantified using the area under the curve (AUC), area under the precision-recall curve (AUPRC), and Matthews correlation coefficient (MCC). SHapley Additive exPlanations (SHAP) was used to interpret the best-performing model. A web calculator was developed to facilitate individualized BM risk estimation. Multivariate logistic regression revealed that age, T stage, tumor size, bone metastasis, lung metastasis, and distant lymph node metastasis were independently associated with BM. Extreme Gradient Boosting (XGB) achieved the best discrimination in the validation cohort, with an AUC of 0.8762, AUPRC of 0.9025, accuracy of 0.7974, precision of 0.8009, recall of 0.7974, specificity of 0.8516, MCC of 0.5983, F1-score of 0.7968, and Brier score of 0.1377. Cross-validation demonstrated similarly strong performance. SHAP analysis identified age, tumor size, T stage, distant lymph node metastasis, bone metastasis, and lung metastasis as the strongest contributors to BM risk. A web-based risk calculator was developed to facilitate exploratory risk stratification and individualized BM risk estimation. We created and internally validated an interpretable ML model to identify brain metastasis at diagnosis in SCLC, with XGB showing the best performance. Its web-based tool may assist in identifying patients with a higher likelihood of brain metastasis at diagnosis and provide supplementary risk stratification information for exploratory clinical assessment. Further prospective validation is required before routine clinical implementation of this model.