Postoperative Glioma Research Articles

BBB-penetrating magnetoelectric nanoparticles with sustainable Gel formulation for enhanced chemotherapy and reduced postoperative glioma recurrence

Overcoming blood–brain barrier (BBB), reducing drug resistance and inhibiting postoperative recurrence are the huge challenges of glioma treatment. Herein, a magnetoelectric nanoparticle, applying CoFe2O4 as magnetic core, BaTiO3 as piezoelectric shell and polyethylene glycol-connected I6P8 peptide as surface coating (CBPI), was used for glioma-targeted treatment. This nanoparticle could down-regulate tight junction proteins of BBB via magnetoelectric effect, synergized with I6P8 peptide, to achieve the enhanced BBB permeability and glioma targeting. Under magnetic field activation, this nanoparticle, after doxorubicin loading to formulate CBPID, could accomplish magnetoelectricity and pH-responsive drug release, and generate mild reactive oxygen species to sensitize the chemotherapy through c-Jun N-terminal kinase phosphorylation pathway. Importantly, CBPID facilitated intraoperative cavity administration with magnetic immobilization after easy doping to Surgiflo filler, benefiting the repeated magnetoelectric-activated therapy to inhibit glioma postoperative recurrence. Moreover, CBPID could be mostly excreted through feces after intravenous injection, which did not cause obvious blood and organ abnormalities and even improved the behavioral abnormalities caused by glioma.

Neural Progenitor Cell-Mediated Magnetic Nanoparticles for Magnetic Resonance Imaging and Photothermal Therapy of Glioma.

Glioma is the most common primary malignant tumor in the brain. The diagnostic accuracy and treatment efficiency of glioma are facing great challenges due to the presence of the blood-brain barrier (BBB) and the high infiltration of glioma. There is an urgent need to explore the combination of diagnostic and therapeutic approaches to achieve a more accurate diagnosis, as well as guidance before and after surgery. In this work, we induced human induction of pluripotent stem cell into neural progenitor cells (NPCs) and synthesized nanoprobes labeled with enhanced green fluorescent protein (EGFP, abbreviated as MFe3O4-labeled EGFP-NPCs) for photothermal therapy. Nanoprobes carried by NPCs can effectively penetrate the BBB and target glioma for the purpose of magnetic resonance imaging and guiding surgery. More importantly, MFe3O4-labeled EGFP-NPCs can effectively induce local photothermal therapy, conduct preoperative tumor therapy, and inhibit the recurrence of postoperative glioma. This work shows that MFe3O4-labeled EGFP-NPCs is a promising nanoplatform for glioma diagnosis, accurate imaging-guided surgery, and effective photothermal therapy.

Validating Brain Tumor Reporting and Data System (BT-RADS) as a Diagnostic Tool for Glioma Follow-Up after Surgery.

Gliomas are a type of brain tumor that requires accurate monitoring for progression following surgery. The Brain Tumor Reporting and Data System (BT-RADS) has emerged as a potential tool for improving diagnostic accuracy and reducing the need for repeated operations. This prospective multicenter study aimed to evaluate the diagnostic accuracy and reliability of BT-RADS in predicting tumor progression (TP) in postoperative glioma patients and evaluate its acceptance in clinical practice. The study enrolled patients with a history of partial or complete resection of high-grade glioma. All patients underwent two consecutive follow-up brain MRI examinations. Five neuroradiologists independently evaluated the MRI examinations using the BT-RADS. The diagnostic accuracy of the BT-RADS for predicting TP was calculated using histopathology after reoperation and clinical and imaging follow-up as reference standards. Reliability based on inter-reader agreement (IRA) was assessed using kappa statistics. Reader acceptance was evaluated using a short survey. The final analysis included 73 patients (male, 67.1%; female, 32.9%; mean age, 43.2 ± 12.9 years; age range, 31-67 years); 47.9% showed TP, and 52.1% showed no TP. According to readers, TP was observed in 25-41.7% of BT-3a, 61.5-88.9% of BT-3b, 75-90.9% of BT-3c, and 91.7-100% of BT-RADS-4. Considering >BT-RADS-3a as a cutoff value for TP, the sensitivity, specificity, and accuracy of the BT-RADS were 68.6-85.7%, 84.2-92.1%, and 78.1-86.3%, respectively, according to the reader. The overall IRA was good (κ = 0.75) for the final BT-RADS classification and very good for detecting new lesions (κ = 0.89). The readers completely agreed with the statement "the application of the BT-RADS should be encouraged" (score = 25). The BT-RADS has good diagnostic accuracy and reliability for predicting TP in postoperative glioma patients. However, BT-RADS 3 needs further improvements to increase its diagnostic accuracy.

Effect of Intraoperative Opioid Dose on Perioperative Neutrophil-to-Lymphocyte Ratio and Lymphocyte-to-Monocyte Ratio in Glioma.

The neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) are inflammatory biomarkers. Until now, it is unknown the impact of opioid dosage on perioperative immunity in glioma patients. The aim of this study was to explore the effect of intraoperative opioid dosage on perioperative immune perturbations using NLR and LMR as inflammatory biomarkers and evaluate the correlation between inflammatory biomarkers and pathological grade of glioma. The study included 208 patients with primary glioma who underwent glioma resection from February 2012 to November 2019 at Harbin Medical University Cancer Hospital. Complete blood count (CBC) was collected at 3 time points: one week before surgery, and 24 hours and one week after surgery. Patients were divided into high-dose and low-dose groups, based on the median value of intraoperative opioid dose. The relationships between perioperative NLR, LMR and intraoperative opioid dosage were analyzed using repeated measurement analysis of variance (ANOVA). Correlations between preoperative various factors and pathological grade were analyzed by Spearman analysis. Receiver operating characteristic (ROC) curves were performed to assess the predictive performance of the NLR and LMR for pathological grade. The NLR (P=0.020) and lower LMR (P=0.037) were statistically significant different between high-dose and low-dose groups one week after surgery. The area under the curve (AUC) of the NLR to identify poor diagnosis was 0.685, which was superior to the LMR (AUC: 0.607) and indicated a correlation between the NLR with pathological grade. The preoperative NLR (P=0.000), LMR (P=0.009), age (P=0.000) and tumor size (P=0.001) exhibited a significant correlation with the pathological grade of glioma. Intraoperative opioids in the high-dose group were associated with higher NLR and lower LMR in postoperative glioma patients. The preoperative NLR and LMR demonstrated predictive value for distinguishing between high-grade and low-grade gliomas.

Development of preoperative and postoperative models to predict recurrence in postoperative glioma patients: a longitudinal cohort study

BackgroundGlioma recurrence, subsequent to maximal safe resection, remains a pivotal challenge. This study aimed to identify key clinical predictors influencing recurrence and develop predictive models to enhance neurological diagnostics and therapeutic strategies.MethodsThis longitudinal cohort study with a substantial sample size (n = 2825) included patients with non-recurrent glioma who were pathologically diagnosed and had undergone initial surgical resection between 2010 and 2018. Logistic regression models and stratified Cox proportional hazards models were established with the top 15 clinical variables significantly influencing outcomes screened by the least absolute shrinkage and selection operator (LASSO) method. Preoperative and postoperative models predicting short-term (within 6 months) postoperative recurrence in glioma patients were developed to explore the risk factors associated with short- and long-term recurrence in glioma patients.ResultsPreoperative and postoperative logistic models predicting short-term recurrence had accuracies of 0.78 and 0.87, respectively. A range of biological and early symptomatic characteristics linked to short- and long-term recurrence have been pinpointed. Age, headache, muscle weakness, tumor location and Karnofsky score represented significant odd ratios (t > 2.65, p < 0.01) in the preoperative model, while age, WHO grade 4 and chemotherapy or radiotherapy treatments (t > 4.12, p < 0.0001) were most significant in the postoperative period. Postoperative predictive models specifically targeting the glioblastoma and IDH wildtype subgroups were also performed, with an AUC of 0.76 and 0.80, respectively. The 50 combinations of distinct risk factors accommodate diverse recurrence risks among glioma patients, and the nomograms visualizes the results for clinical practice. A stratified Cox model identified many prognostic factors for long-term recurrence, thereby facilitating the enhanced formulation of perioperative care plans for patients, and glioblastoma patients displayed a median progression-free survival (PFS) of only 11 months.ConclusionThe constructed preoperative and postoperative models reliably predicted short-term postoperative glioma recurrence in a substantial patient cohort. The combinations risk factors and nomograms enhance the operability of personalized therapeutic strategies and care regimens. Particular emphasis should be placed on patients with recurrence within six months post-surgery, and the corresponding treatment strategies require comprehensive clinical investigation.

Molecular prognostic of nine parthanatos death-related genes in glioma, particularly in COL8A1 identification.

Post-operative progression and chemotherapy resistance are the main causes of treatment failure in glioma patients. There is a lack of ideal prediction models for post-operative glioma patient progression and drug sensitivity. We aimed to develop a prognostic model of parthanatos mRNA biomarkers for glioma outcomes. A total of 11 parthanatos genes were obtained from ParthanatosCluster database. ConsensusClusterPlus and R "Limma" package were used to cluster The Cancer Genome Atlas (TCGA)-glioma cohort and analyze the differential mRNAs. Univariate Cox regression analysis, random survival forest model, and least absolute shrinkage and selection operator (LASSO) regression analysis were used to determine the nine ParthanatosScore prognostic genes combination. ParthanatosScore was verified by 656 patients and 979 patients in TCGA and CGCA-LGG/GBM datasets. Differences in genomic mutations, tumor microenvironments, and functional pathways were assessed. Drug response prediction was performed using pRRophetic. Kaplan-Meier survival analysis was analyzed. Finally, COL8A1 was selected to evaluate its potential biological function and drug sensitivity of temozolomide and AZD3759 in glioma cells. ParthanatosScore obtained a combination of nine glioma prognostic genes, including CD58, H19, TNFAIP6, FTLP3, TNFRSF11B, SFRP2, LOXL1, COL8A1, and FABP5P7. In the TCGA-LGG/GBM dataset, glioma prognosis was poor in high ParthanatosScore. Low-score glioma patients were sensitive to AZD3759_1915, AZD5582_1617, AZD8186_1918, Dasatinib_1079, and Temozolomide_1375, while high-score patients were less sensitive to these drugs. Compared with HA cells, COL8A1 was significantly over-expressed in LN229 and U251 cells. Silencing COL8A1 inhibited the malignant characterization of LN229 and U251 cells. Temozolomide and AZD3759 also promoted parthanatos gene expression in glioma cells. Temozolomide and AZD3759 inhibited COL8A1 expression and cell viability and promoted apoptosis in glioma cells and PGM cells. ParthanatosScore can accurately predict clinical prognosis and drug sensitivity after glioma surgery. Silencing COL8A1 inhibited the malignant characterization. Temozolomide and AZD3759 inhibited COL8A1 expression and cell viability and promoted apoptosis and parthanatos gene expression, which is a target to improve glioma.

Effect of Temozolomide Combined with Intensity Modulated Radiation Therapy on Serum Factor, Immune Function and Clinical Efficacy in Postoperative Glioma Patients.

To investigate the effect of Temozolomide combined with intensity modulated radiation therapy on serum factor, immune function and clinical efficacy in postoperative glioma patients. One hundred twenty-four patients with high-grade glioma admitted to the First Affiliated Hospital of Zhengzhou University were selected and randomly divided into the study group and the control group, with 62 cases in each group. The control group was given intensity modulated radiation therapy alone, and the study group was given Temozolomide combined with intensity modulated radiation therapy. The clinical efficacy, serum factor, immune function and adverse reactions were observed and compared. The overall response rate of the study group was 95.16%, which is higher than 83.87% in the control group, and the differences were significant (P < 0.05); After the treatment, the serum VEGF, EGF and HGF indicators and diverse immune function indicators were superior to those in the control group, and the differences indicated significance (P < 0.05); the incidence of adverse reactions in the study group was 37.10%, which is higher than 25.81% in the control group, but the differences showed no significance (P > 0.05). Temozolomide combined with intensity modulated radiation therapy could improve the level of serum factor in postoperative glioma patients, strengthen the immune function of the patients, and effectively facilitate the clinical comprehensive efficacy without increasing adverse reactions.

Clinical Value of a Nomogram Model Based on Apparent Diffusion Coefficient Values Within 1 cm of the Tumor Cavity to Predict Postoperative Progression of Glioma

To explore the clinical value of constructing a nomogram model based on apparent diffusion coefficient values within 1cm of the residual tumor cavity to predict the postoperative progression of gliomas. Clinical data of patients with glioma who underwent surgery were retrospectively retrieved from the First Hospital of Qinhuangdao. The mean apparent diffusion coefficient (mADC) was measured using a picture archiving and communication system. The Kaplan-Meier survival curve was constructed with the optimal mADC threshold determined by the X-tile. A nomogram was developed based on the independent risk factors determined using the Cox proportional hazards model (Cox regression model) to predict the progression of postoperative glioma. A receiver operating characteristic curve was drawn to evaluate the prediction accuracy of the model, and decision curve analysis was performed to assess the clinical value of the nomogram. There was good agreement between the mADC values of the 2 repeated measurements before and after, with a consistency correlation coefficient of 0.83. Multivariate Cox regression analysis showed that peritumoral mADC values, degree of peritumoral enhancement, age, pathological grading, and degree of tumor resection were independent risk factors for predicting postoperative progression of glioma (all P<0.05). The receiver operating characteristic curves of the nomogram predicting 1, 2, and 3years postoperative progression were 0.86, 0.82, and 0.91, respectively. The calibration curve showed good consistency between the observed and predicted values in the model. The curve showed that the nomogram model has a good clinical application value. The peritumoral mADC values, degree of peritumoral enhancement, age, pathological grade, and degree of tumor resection were independent factors affecting the postoperative progression of glioma. The nomogram model established for the first time based on mADC values within 1cm of the tumor can predict the postoperative condition of patients with glioma intuitively and comprehensively. It can provide a relatively accurate prediction tool for neurosurgeons to individualize the evaluation of survival and prognosis, and formulate treatment plans for patients.

Research Progress on Amide Proton Transfer Imaging in Preoperative and Postoperative Glioma Assessment.

Amide proton transfer (APT) imaging is a technique that reflects the level of amide proton transport of hydrogen ions in water to peptides and proteins within the tumour by using magnetic resonance imaging without contrast administration. This technique can more accurately reflect the protein level, pH value, and other relevant information within the tumour. Currently, APT is widely used in glioma research. In this paper, we briefly describe the research progress on this technique.

Multimodality MRI Radiomics Based on Machine Learning for Identifying True Tumor Recurrence and Treatment-Related Effects in Patients with Postoperative Glioma.

Conventional magnetic resonance imaging (MRI) features have difficulty distinguishing glioma true tumor recurrence (TuR) from treatment-related effects (TrE). We aimed to develop a machine-learning model based on multimodality MRI radiomics to help improve the efficiency of identifying glioma TuR. A total of 131 patients were enrolled and randomly divided into the training set (n=91) and the test set (n=40). Radiomic features were extracted from the postoperative enhancement (PoE) region and edema (ED) region from four routine MRI sequences. After analyses of Spearman's rank correlation coefficient, and least absolute shrinkage and selection operator, the key radiomic features were selected to construct support vector machine (SVM) and k-nearest neighbor (KNN) models. Decision curve analysis (DCA) and receiver operating characteristic (ROC) curves were used to analyze the performance. The PoE model had a significantly higher area under curve (AUC) than the ED model (p<0.05). Among the models constructed with a single sequence, the model using PoE regional features from CE-T1WI was superior to other models, with an AUC of 0.905 for SVM and 0.899 for KNN. In multimodality models, the PoE model outperformed the ED model with an AUC of 0.931 for SVM and 0.896 for KNN. The multimodality model, which combined routine sequences and the whole regional features, showed a slightly better performance with an AUC of 0.965 for SVM and 0.955 for KNN. Decision curve analysis showed the good clinical utility of multimodal radiomics models. Multimodality radiomics can identify glioma TuR and TrE, potentially aiding clinical decision-making for individualized treatment. And edematous regions may provide useful information for recognizing recurrence. 2021.04.15, No:2020039.

Changes and significance of serum ubiquitin carboxyl-terminal hydrolase L1 and glial fibrillary acidic protein in patients with glioma

Brain gliomas are malignant tumors with high postoperative recurrence rates. Early prediction of prognosis using specific indicators is of great significance. To assess changes in ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) levels in patients with glioma pre-and postoperatively. Between June 2018 and June 2021, 91 patients with gliomas who underwent surgery at our hospital were enrolled in the glioma group. Sixty healthy volunteers were included in the control group. Serum UCH-L1 and GFAP levels were measured in peripheral blood collected from patients with glioma before and 3 d after surgery. UCH-L1 and GFAP levels in patients with glioma with different clinicopathological characteristics were compared before and after surgery. The patients were followed-up until February 2022. Postoperative glioma recurrence was recorded to determine the serum UCH-L1 and GFAP levels, which could assist in predicting postoperative glioma recurrence. UCH-L1 and GFAP levels in patients with glioma decreased significantly 3 d after surgery compared to those before therapy (P < 0.05). However, UCH-L1 and GFAP levels in the glioma group were significantly higher than those in the control group before and after surgery (P < 0.05). There were no statistically significant differences in preoperative serum UCH-L1 and GFAP levels among patients with glioma according to sex, age, pathological type, tumor location, or number of lesions (P > 0.05). Serum UCH-L1 and GFAP levels were significantly lower in the patients with WHO grade I-II tumors than in those with grade III-IV tumors (P < 0.05). Serum UCH-L1 and GFAP levels were lower in the patients with tumor diameter ≤ 5 cm than in those with diameter > 5 cm, in which the differences were statistically significant (P < 0.05). Glioma recurred in 22 patients. The preoperative and 3-d postoperative serum UCH-L1 and GFAP levels were significantly higher in the recurrence group than these in the non-recurrence group (P < 0.05). Receiver operating characteristic curves were plotted. The areas under the curves of preoperative serum UCH-L1 and GFAP levels for predicting postoperative glioma recurrence were 0.785 and 0.775, respectively. However, the efficacy of serum UCH-L1 and GFAP levels 3 d after surgery in predicting postoperative glioma recurrence was slightly lower compared with their preoperative levels. UCH-L1 and GFAP efficiently reflected the development and recurrence of gliomas and could be used as potential indicators for the recurrence and prognosis of glioma.

Risk factors, prognostic potency, and longitudinal variation of anxiety and depression in postoperative glioma patients.

Anxiety and depression are common mental disorders in glioma patients. This study aimed to evaluate the risk factors, prognostic role, and longitudinal changes in anxiety and depression in postoperative glioma patients. Anxiety and depression were assessed by Hospital Anxiety and Depression Scale at baseline, month (M) 6, M12, M24 and M36 in 270 glioma patients after surgical resection. Furthermore, comprehensive clinic characteristics and treatment-related information were collected. Gender (female vs. male) (P = 0.014, odds ratio (OR) = 1.974), marital status (single/divorced/widowed vs. married) (P = 0.019, OR = 2.172), Karnofsky performance status (KPS) score (≤70 vs. > 70) (P = 0.002, OR = 2.556), World Health Organization (WHO) classification (high-grade glioma (HGG) vs. low-grade glioma (LGG)) (P = 0.005, OR = 2.155), and postoperative complications (yes vs. not) (P = 0.001, OR = 2.525) were independently related to anxiety occurrence. Marital status (single/divorced/widowed vs. married) (P = 0.034, OR = 2.026), KPS score (≤70 vs. > 70) (P < 0.001, OR = 3.880), WHO classification (HGG vs. LGG) (P = 0.032, OR = 1.810), and postoperative complications (yes vs. not) (P = 0.001, OR = 2.602) were independently related to depression occurrence. Besides, anxiety (P = 0.038) and depression (P = 0.013) were linked with shorter overall survival (OS), and depression was an independent risk factor for worse OS (P = 0.040, hazard ratio = 1.596). More importantly, anxiety and depression remained at a high prevalence during a 3-year follow-up. Gender, marital status, KPS score, WHO classification, and postoperative complications are risk factors for anxiety and depression; moreover, anxiety and depression are at high prevalence continuously and correlated with worse survival in postoperative glioma patients.

Retracted: Bevacizumab Combined with Intensity-Modulated Radiation Therapy on Cognitive and Coagulation Function in Postoperative Glioma Patients.

[This retracts the article DOI: 10.1155/2022/9367919.].

Dual-sensitive drug-loaded hydrogel system for local inhibition of post-surgical glioma recurrence

Local treatment after resection to inhibit glioma recurrence is thought to able to meet the real medical needs. However, the only clinically approved local glioma treatment-wafer containing bis(2-chloroethyl) nitrosourea (BCNU) showed very limited effects. Herein, in order to inhibit tumor recurrence with prolonged and synergistic therapeutic effect of drugs after tumor resection, an in situ dual-sensitive hydrogel drug delivery system loaded with two synergistic chemo-drugs BCNU and temozolomide (TMZ) was developed. The thermosensitive hydrogel was loaded with reactive oxygen species (ROS)-sensitive poly (lactic-co-glycolic) acid nanoparticles (NPs) encapsulating both BCNU and TMZ and also free BCNU and TMZ. The in vitro synergistic effect of BCNU and TMZ and in vivo presence of ROS at the residual tumor site were confirmed. The prepared ROS-sensitive NPs and thermosensitive hydrogel, as well as the long-term release behavior of drugs and NPs, were fully characterized both in vitro and in vivo. After >90% glioblastoma resection, the dual-sensitive hydrogel drug delivery system was injected into the resection cavity. The median survival time of the experimental group reached 65days which was twice as long as the Resection only group, implying that this in situ drug delivery system effectively inhibited tumor recurrence. Overall, this study provides new ideas and strategies for the inhibition of postoperative glioma recurrence.

Diagnostic Performance of Dynamic Susceptibility Contrast-Enhanced Perfusion-Weighted Imaging in Differentiating Recurrence From Radiation Injury in Postoperative Glioma: A Meta-analysis.

It is important to differentiate between radiation injury (RI) and tumor recurrence (TR) in patients with glioma after surgery and radiotherapy. Our objective was to evaluate the use of dynamic susceptibility contrast-enhanced perfusion-weighted imaging to distinguish between TR and RI in patients with glioma. Relevant studies published until October 2021 were identified in the PubMed, Embase, and Cochrane Library databases. Stata v12.0 and RevMan 5.3 were used for meta-analysis. In total, the meta-analysis incorporated 13 retrospective studies that included 513 patients with 522 lesions. Among the 522 lesions, 329 lesions were TRs and 193 lesions were RIs. The pooled relative cerebral blood volume value was significantly greater in the TR group ( P < 0.00001) with significant heterogeneity ( I2 = 88%). The pooled sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were 83% (95 confidence interval [CI], 77%-88%), 85% (95 CI, 77%-91%), 5.60 (95 CI, 3.61-8.70), and 0.20 (95% CI, 0.14-0.27), respectively. The heterogeneity of sensitivity ( I2 = 33.18%), specificity ( I2 = 24.01%), PLR ( I2 = 0.00%), and NLR ( I2 = 6.68%) is not significant. The area under the receiver operating characteristic curve was 0.91 (95% CI, 0.88-0.93). The 3.0 T magnetic resonance imaging, high-grade glioma, and Europe/America patient subgroups showed PLR greater than 5 and NLR less than 0.2. There was no significant indication of publication bias in the analysis ( P = 0.496). It is concluded that dynamic susceptibility contrast-enhanced perfusion-weighted imaging is effective for the diagnostic differentiation between TR and RI in patients with glioma.

Intracavity generation of glioma stem cell-specific CAR macrophages primes locoregional immunity for postoperative glioblastoma therapy.

Glioblastoma multiforme (GBM) remains incurable despite aggressive implementation of multimodal treatments after surgical debulking. Almost all patients with GBM relapse within a narrow margin around the initial resected lesion due to postsurgery residual glioma stem cells (GSCs). Tracking and eradicating postsurgery residual GSCs is critical for preventing postoperative relapse of this devastating disease, yet effective strategies remain elusive. Here, we report a cavity-injectable nanoporter-hydrogel superstructure that creates GSC-specific chimeric antigen receptor (CAR) macrophages/microglia (MΦs) surrounding the cavity to prevent GBM relapse. Specifically, we demonstrate that the CAR gene-laden nanoporter in the hydrogel can introduce GSC-targeted CAR genes into MΦ nuclei after intracavity delivery to generate CAR-MΦs in mouse models of GBM. These CAR-MΦs were able to seek and engulf GSCs and clear residual GSCs by stimulating an adaptive antitumor immune response in the tumor microenvironment and prevented postoperative glioma relapse by inducing long-term antitumor immunity in mice. In an orthotopic patient-derived glioblastoma humanized mouse model, the combined treatment with nanoporter-hydrogel superstructure and CD47 antibody increased the frequency of positive immune responding cells and suppressed the negative immune regulating cells, conferring a robust tumoricidal immunity surrounding the postsurgical cavity and inhibiting postoperative glioblastoma relapse. Therefore, our work establishes a locoregional treatment strategy for priming cancer stem cell-specific tumoricidal immunity with broad application in patients suffering from recurrent malignancies.

Multifunctional Hybrid Hydrogel System Enhanced the Therapeutic Efficacy of Treatments for Postoperative Glioma.

Glioma is the most lethal brain tumor with a poor prognosis, and a combination of multiple therapeutic strategies is critical for postoperative glioma treatment. Herein, a multifunctional hybrid hydrogel system (designated as CP&CL@RNPPTX-Gel) was developed for local treatment of postoperative glioma. The system was composed of self-illuminating chlorin e6 (Ce6) conjugated with luminol molecule (CL)-loaded glioma-targeting paclitaxel prodrug nanoparticles and copper peroxide nanodots (CP NDs) coembedded into a three-dimensional thermosensitive hydroxypropyl chitin hydrogel frame. After injection of CP&CL@RNPPTX-Gel into the cavity of postoperative glioma, the solution could be cross-linked into the gel as a drug reservoir under body temperature stimulation. Then, the sustained-released CP NDs decomposed into Cu2+ and H2O2 in the acidic microenvironment of the glioma cells to exert chemodynamic therapy (CDT). Meanwhile, Cu2+ could catalyze the self-luminescence of CL to induce photodynamic therapy (PDT) without external excitation light. Moreover, paclitaxel prodrug nanoparticles degraded into paclitaxel to restrain residual glioma cells in response to intracellular reduced glutathione (GSH). The in vitro and in vivo results showed that CP&CL@RNPPTX-Gel had great potential as a multifunctional hybrid hydrogel system with remarkable therapeutic effects for postoperative glioma treatment via a combination of chemotherapy, CDT, and PDT.

Bevacizumab Combined with Intensity-Modulated Radiation Therapy on Cognitive and Coagulation Function in Postoperative Glioma Patients.

To examine the influences of bevacizumab combined with intensity-modulated radiation therapy (IMRT) on postoperative brain glioma, particularly its impact on coagulation function and cognitive function, the complete clinical data of 156 patients undergoing glioma surgery in the neurosurgery department of our hospital between March 2015 and October 2018 were retrospectively analyzed. All patients underwent glioma surgery and were then assigned to the observation group (Obs group, n = 79, received bevacizumab combined with IMRT) or the control group (Con group, n = 77, received IMRT without bevacizumab) for analysis during postoperative treatment. The patients' short-term efficacy was evaluated, and their serum markers and coagulation function were compared, as well as the cognitive function, the occurrence of adverse reactions during treatment, the Karnofsky performance status (KPS) score, and quality of life after treatment. Patients' survival was followed up within 2 years after surgery. The Obs group showed a notably higher clinical remission rate and clinical control rate (DCR) than the Con group after treatment. The Obs group showed notably lower levels of interleukin-2 (IL-2), vascular endothelial growth factor (VEGF), IL-6, and epidermal growth factor (EGF), experienced notably shorter prothrombin time (PT) and activated partial thromboplastin time (APTT), and showed higher fibrinogen (FIB) and D-dimer (D-D) levels than Con group. The Obs group showed notably better cognitive function, KPS score, and quality of life than the Con group, but no notable difference was observed between them in the incidence of adverse reactions (P > 0.0500). The survival rates in the Obs group were higher than in the Con group. For patients with glioma, postoperative bevacizumab combined with IMRT delivers substantially higher clinical efficacy by lowering serum marker levels and improving cognitive function without significantly affecting coagulation function.

Development and Practical Implementation of a Deep Learning-Based Pipeline for Automated Pre- and Postoperative Glioma Segmentation.

Quantitative volumetric segmentation of gliomas has important implications for diagnosis, treatment, and prognosis. We present a deep-learning model that accommodates automated preoperative and postoperative glioma segmentation with a pipeline for clinical implementation. Developed and engineered in concert, the work seeks to accelerate clinical realization of such tools. A deep learning model, autoencoder regularization-cascaded anisotropic, was developed, trained, and tested fusing key elements of autoencoder regularization with a cascaded anisotropic convolutional neural network. We constructed a dataset consisting of 437 cases with 40 cases reserved as a held-out test and the remainder split 80:20 for training and validation. We performed data augmentation and hyperparameter optimization and used a mean Dice score to evaluate against baseline models. To facilitate clinical adoption, we developed the model with an end-to-end pipeline including routing, preprocessing, and end-user interaction. The autoencoder regularization-cascaded anisotropic model achieved median and mean Dice scores of 0.88/0.83 (SD, 0.09), 0.89/0.84 (SD, 0.08), and 0.81/0.72 (SD, 0.1) for whole-tumor, tumor core/resection cavity, and enhancing tumor subregions, respectively, including both preoperative and postoperative follow-up cases. The overall total processing time per case was ∼10 minutes, including data routing (∼1 minute), preprocessing (∼6 minute), segmentation (∼1-2 minute), and postprocessing (∼1 minute). Implementation challenges were discussed. We show the feasibility and advantages of building a coordinated model with a clinical pipeline for the rapid and accurate deep learning segmentation of both preoperative and postoperative gliomas. The ability of the model to accommodate cases of postoperative glioma is clinically important for follow-up. An end-to-end approach, such as used here, may lead us toward successful clinical translation of tools for quantitative volume measures for glioma.

The prognostic value of inflammation markers in postoperative gliomas with or without adjuvant treatments.

Recent studies have shown that some inflammatory markers are associated with the prognosis of solid tumors. This study aims to evaluate the prognosis of glioma patients with or without adjuvant treatment using the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR).All patients who were diagnosed with gliomas at the first and second affiliated hospital of Guangxi Medical University between 2011 and 2020 were included in this study. The optimal cutoff value of SII, NLR, and PLR was determined by X-tile software program. We stratified patients into several groups and evaluated the progression-free survival (PFS) and overall survival (OS) of SII, NLR, and PLR during the period of pre-surgical, con-chemoradiotherapy, and post-treatments. Multivariate Cox regression analyses were performed to detect the relationships between OS, PFS, and prognostic variables.A total of 67 gliomas patients were enrolled in the study. The cutoff values of SII, NLR, and PLR were 781.5 × 109/L, 2.9 × 109/L, and 123.2 × 109/L, respectively. Patients who are pre-SII < 781.5 × 109/L had better PFS (P = .027), but no difference in OS. In addition, patients who had low pre-NLR (<2.9 × 109/L) meant better OS and PFS. PLR after adjuvant treatments (post-PLR) was significantly higher than pre-PLR (P = .035). Multivariate analyses revealed that pre-SII, pre-NLR were independent prognostic factors for OS (pre-SII: HR 1.002, 95% CI: 1.000–1.005, P = .030 and pre-PLR: HR 0.983, 95% CI: 0.973–0.994, P = .001), while pre-PLR was an independent factor for PFS (HR 0.989, 95% CI: 0.979–1.000, P = .041).High pre-SII or high pre-NLR could be prognostic markers to identify glioma patients who had a poor prognosis.