Background: Bevacizumab is a critical anti-angiogenic therapy for glioma, but its real-world safety profile requires comprehensive characterization beyond clinical trials to effectively manage treatment risks. Methods: This pharmacovigilance study analyzed adverse event reports from the FDA Adverse Event Reporting System (FAERS) for glioma patients receiving bevacizumab. A disproportionate analysis using multiple analytical methods was conducted to identify significant safety signals. Subgroup analyses stratified by gender and age were performed to explore population heterogeneity. Results: Bevacizumab-related AEs involved multiple system organ classes, with particularly prominent disproportionality signals for vascular disorders, especially hypertension, proteinuria and thromboembolic events such as pulmonary embolism. Most AEs occurred within the early treatment period, but late-onset events, including tumor progression, still accounted for a notable proportion. Subgroup analysis indicated that male patients were at higher risk of overall bleeding and thrombotic events, whereas female patients more frequently reported cognitive impairment and showed stronger signals for severe bleeding subtypes such as intracranial hemorrhage, suggesting sex-specific heterogeneity across bleeding phenotypes. Middle-aged patients bore the greatest burden of reported AEs. Conclusion: This study delineates the adverse event spectrum of bevacizumab in patients with glioma, confirming prominent vascular and renal toxicities and revealing sex- and age-related differences in safety profiles. The findings highlight the need for heightened surveillance of vascular and renal events following bevacizumab exposure and provide hypothesis-generating evidence to inform future prospective studies.

The glioma tumor microenvironment (TME) exhibits profound heterogeneity that drives tumor progression and therapy resistance. By integrating single-cell RNA sequencing (eleven samples) and spatial transcriptomics (two samples), the cellular components of the glioma microenvironment were deconvoluted, revealing tumor-associated foam cells (TAFCs) as the most abundant and centrally connected subtype. The high expression of two prognostic candidate genes, growth differentiation factor 8 (GDF-8, also known as myostatin, MSTN) and transcription factor 12 (TCF12), in TAFCs was found to be correlated with poor overall survival. These two genes were associated with M2 macrophage infiltration, altered cholesterol homeostasis, and immunosuppressive signaling. Regulatory network and pathway analyses, based on computational motif enrichment and co-expression analysis, linked them to ribosome, Notch signaling, DNA repair, and cell-cycle pathways. Pseudotime trajectories revealed dynamic expression during differentiation. Additionally, drug sensitivity prediction analysis demonstrated that MSTN expression was significantly associated with sensitivity to paclitaxel and VE-822, while TCF12 expression showed potential associations with sensitivity to cytarabine, olaparib, Wee1 inhibitor, paclitaxel, and VE-822. Logistic regression analysis combining clinical parameters with MSTN and TCF12 expression effectively achieved risk stratification for glioma, with higher composite scores predicting worse 2- and 3-year survival outcomes. Calibration curves demonstrated high consistency between nomogram-predicted overall survival probabilities and actual observed outcomes. Immunofluorescence confirmed upregulated expression of MSTN and TCF12 in glioma tissues and their co-localization with macrophages. In conclusion, this study identified TAFCs as the central cells in the glioma microenvironment, with their signature genes MSTN and TCF12 representing candidate immunometabolic signatures associated with macrophage-mediated immunosuppression and metabolic reprogramming in glioma, suggesting their potential as biomarkers for patient stratification and as targets for immunometabolic therapies.

Background: Radiotherapy-induced severe lymphocytopenia (SL) represents a critical immune-related toxicity associated with poor oncologic outcomes. While treatment-related factors have been extensively studied, the contribution of baseline nutritional risk and cancer-related pain to immune vulnerability during radiotherapy remains insufficiently explored. This study aimed to evaluate the role of nutrition- and symptom-related factors in SL and develop a clinically applicable predictive model. Methods: A retrospective cohort of 97 cancer patients receiving radiotherapy in 2022 was analyzed. Nutritional risk was assessed using the Nutritional Risk Screening 2002 (NRS-2002) before radiotherapy and at mid-treatment; the pretreatment result was used as the baseline nutritional risk variable in the predictive analyses, whereas the mid-treatment assessment was used for nutritional monitoring. Cancer pain was evaluated using the Numeric Rating Scale. Logistic regression identified independent predictors of SL (lymphocyte count < 0.5 × 10 ⁹ /L). A nutrition-integrated nomogram was developed and internally validated using ROC analysis, calibration curves, and decision curve analysis (DCA). Results: Lymphocyte counts declined progressively during radiotherapy ( p < 0.001), with 42.3% of patients developing SL. Multivariable analysis identified nutritional risk (OR = 3.53, p = 0.016), cancer pain (OR = 3.78, p = 0.037), and radiotherapy fractions (OR = 1.11 per fraction, p = 0.006) as independent predictors. Stratified analysis suggested a stronger association between cancer pain and SL among nutritionally at-risk patients. The nomogram demonstrated good discrimination (AUC = 0.77; C-index = 0.77), adequate calibration (Hosmer–Lemeshow p = 0.45), and meaningful clinical net benefit across a threshold range of 0.18–0.90. Conclusion: Nutritional risk and cancer pain independently contribute to radiotherapy-induced immune suppression. The proposed nutrition-integrated nomogram enables personalized immune risk assessment and supports early nutritional and symptom-targeted interventions to preserve immune competence during radiotherapy.