Journal of Neuro-Oncology最新文献

Purpose: This study aimed to describe the incidence, clinical and pathological features, and outcomes of H3 K27M- mutant Diffuse Midline Glioma (DMG) patients with leptomeningeal dissemination (LMD) and systematically investigate the predictive and prognostic factors to clarify the response to treatment after the onset of LMD.

Methods: A total of 304 patients diagnosed with DMG from October 17, 2017, to October 17, 2023, were enrolled in this study, of which 32 patients were diagnosed with LMD. Logistic regression analyses were conducted to identify the predictors of LMD, including clinical, molecular, and imaging data. Univariable and multivariable cox regression analyses were used for overall survival (OS) and post-LMD survival (PLS) analysis.

Results: The median OS and PLS were 12.5 and 8.0 months respectively. Tumor with contrast-enhanced lesions reaching ependyma (Ventricular contact type I) was the only independent risk factor for LMD. Male sex and ventricular contact type I were independent risk factors for primary LMD. In all LMD patients, Karnofsky Performance Status (KPS) of ≥ 90 and radiotherapy were statistically significantly associated with longer OS, and primary LMD was significantly associated with shorter OS. Supratentorial location and chemotherapy after LMD diagnosis were independent favorable prognostic factors on PLS. In primary LMD subgroup analysis, radiotherapy was the only independent favorable prognostic factor on OS.

Conclusions: The association between contrast-enhanced lesions and ventricular involvement is an independent predictive factor for LMD in DMG patients. Radiotherapy and preoperative KPS may contribute to improved overall survival in these patients. Chemotherapy is a potential treatment option following an LMD diagnosis.

Background: Pediatric meningiomas (PMs) are rare central nervous system tumors, accounting for 1-5% of all meningiomas, and differ from adult meningiomas in clinical, histopathological, and molecular features. Current guidelines primarily focus on adults, leaving a gap in evidence-based management for PMs. This study presents the largest meta-analysis of longitudinal individual patient data (IPD) to date, addressing progression-free survival (PFS) and overall survival (OS) in pediatric patients.

Methods: Data from 20 studies (2011-2023), including 1010 pediatric meningioma cases, were analyzed to assess PFS and OS stratified by WHO grade, NF1/NF2 status, extent of resection (EOR), and adjuvant radiotherapy. Longitudinal survival data were reconstructed from Kaplan-Meier curves using IPD extraction methods.

Results: PMs affect males and females nearly equally (52.1% vs. 47.9%). WHO grade 3 tumors had significantly shorter PFS (72.1 months) compared to grades 1 (209.8 months) and 2 (137.5 months) (p < 0.001). No significant OS difference between WHO grades 1 and 2 PMs were observed. NF1- and NF2-associated tumors showed shorter PFS (59.7 and 138.4 months) than sporadic cases (180.6 months) (p = 0.02). GTR significantly improved PFS (113.8 vs. 40.1 months, p < 0.001) and OS (602.9 vs. 173.8 months, p < 0.001). Radiotherapy enhanced PFS (72.5 vs. 23.8 months, p = 0.009) and OS (140.7 vs. 63.0 months, p = 0.002) in grade 3 tumors but not in WHO grade 2 PMs (p = 0.43).

Conclusions: This largest meta-analysis highlights the critical roles of GTR and adjuvant radiotherapy in improving outcomes for high-grade PMs and underscores the urgent need for pediatric-specific management guidelines based on robust longitudinal data.

Ependymoma is the third most common brain tumour of childhood and historically has posed a major challenge to both pediatric and adult neuro-oncologists. Ependymoma can occur anywhere in the central nervous system throughout the entire age spectrum. Treatment options have been limited to surgery and radiation, and outcomes have been widely disparate across studies. Indeed, these disparate outcomes have rendered it extraordinarily difficult to compare studies and to truly understand which patients are low and high-risk. Over the past two decades there have been tremendous advances in our understanding of the biology of ependymoma, which have changed risk stratification dramatically. Indeed, it is now well accepted that ependymoma comprises multiple distinct entities, whereby each compartment (supratentorial, posterior fossa, spinal) are distinct, and within each compartment there exist unique groups. The driver events, demographics and response to treatment vary widely across these groups and allow for a better classification of thee disease. Herein, we review the advances in the molecular stratification of ependymoma including how an improved classification and risk stratification allows for more precise therapies.

Purpose: Glioblastoma (GBM), the most common malignant tumor of the central nervous system (CNS) in adults, continues to result in poor survival rates despite standard treatment. Advancements in understanding GBM's molecular complexity have increased interest in targeted therapeutic approaches. This retrospective, single-center, single-arm study combined nimotuzumab and bevacizumab with radiotherapy (RT) and temozolomide (TMZ) for the treatment of newly diagnosed GBM. The objectives were to determine the efficacy of this treatment combination and the associated toxicity.

Methods: A retrospective analysis of clinical data of GBM patients treated at our institution from September 2021 to May 2023 with postoperative combination therapy of nimotuzumab, bevacizumab, and TMZ concurrent with RT, as well as maintenance therapy with bevacizumab and TMZ. Follow-ups were performed every 3 to 6 months via hospital visits and telephone interviews. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoint was the incidence of adverse events (AEs).

Results: A total of 18 patients were included. The median follow-up time was 23 months. The one-year PFS rate was 77.8%, and the one-year OS rate was 94.4%. The median PFS was 18 months (95%CI, 15.9-20.1), and the median OS was 28 months (95%CI, 18.9-37.1). All AEs were controllable.

Conclusion: The combination of nimotuzumab and bevacizumab with TMZ and RT appears to demonstrate efficacy and safety in newly diagnosed GBM patients, providing a reference for clinical treatment. Further prospective studies are needed to confirm our results.

Purpose: Social determinants of health including neighborhood socioeconomic status, have been established to play a profound role in overall access to care and outcomes in numerous specialized disease entities. To provide glioblastoma multiforme (GBM) patients with high-quality care, it is crucial to identify predictors of hospital length of stay (LOS), discharge disposition, and access to postoperative adjuvant chemoradiation. In this study, we incorporate a novel neighborhood socioeconomic status index (NSES) and develop three predictive algorithms for assessing post-operative outcomes in GBM patients, offering a tool for preoperative risk stratification of GBM patients.

Methods: Adult GBM patients who underwent surgical resection from a single center were identified; NSES was identified via patient street address of residence, with lower scores representing disadvantaged neighborhoods. Multivariate logistic regression analysis was used to predict high value care outcomes. The Hosmer-Lemeshow test was used to assess model calibration.

Results: A total of 467 patients were included, with a mean age of 59.85 ± 13.21 years and 58.7% being male. The mean NSES for our cohort was 63.77 ± 14.91, indicating that the majority resided in neighborhoods with a higher socioeconomic status compared to the national average NSES of 50. One hundred nine (23.3%) patients had extended LOS, 28.9% had non-routine discharge, and 19.1% did not follow the Stupp protocol following surgery. On multivariate regression, worse NSES was significantly and independently associated with extended LOS (OR = 0.981, p = 0.026), non-routine discharge disposition (OR = 0.984, p = 0.033), and non-compliance with the Stupp protocol (OR = 0.977, p = 0.014). Our three models predicting high-value care outcomes had acceptable C-statistics > 0.70, and all models demonstrated adequate calibration (p > 0.05). Final models are accessible via online calculator. https://neurooncsurgery4.shinyapps.io/GBM_NSES_Caclulator/ CONCLUSION: NSES scores are readily available and may be utilized via our open-access calculators. After external validation, our predictive models have the potential to assist in providing patients with individualized risk estimates for post-operative outcomes following GBM resection.

Purpose: This study explores the effects of mifepristone on the proliferation, motility, and invasion of malignant and benign meningioma cells, aiming to identify mifepristone-sensitive types and investigate the underlying molecular mechanisms.

Methods: IOMM-Lee and HBL-52 meningioma cells were treated with 0, vehicle control (VC), 5, 10, 20, 40, and 80 μM of mifepristone for 12, 24, 48, 72, and 96 h. Proliferation was assessed via CCK8 assay, while motility and invasion were measured using wound scratch and transwell assays. RNA sequencing and RT-PCR were used to analyze gene expression changes.

Results: Mifepristone inhibited proliferation, motility, and invasion in both IOMM-Lee and HBL-52 cells in a dose- and time-dependent manner. RNA sequencing showed up-regulated genes significantly enriched in the ferroptosis pathway in both cell lines, confirmed by increased p53 and HO1 expression, decreased GPX4 expression, lipid peroxidation, Fe²⁺ accumulation, and ROS release. Immunofluorescence staining and RT-PCR also revealed a corresponding decrease in mifepristone-related progesterone receptor expression.

Conclusion: Mifepristone induces ferroptosis in meningioma cells via the PR/p53/HO1/GPX4 axis, suggesting its potential as a treatment for ferroptosis-sensitive meningiomas. It also supplies new clues regarding ferroptosis as a treatment entry point for meningiomas.

Purpose: Spinal chordomas are aggressive tumors that rarely occur in the pediatric population. Demographics and post-treatment outcomes in this select group of patients is poorly studied. We hence aimed to analyze the clinical characteristics, demographics, and survival outcomes of pediatric patients with spinal chordomas, in contrast to the adult population. To address this, the literature was reviewed to evaluate the coverage on spinal chordomas of the pediatric population, and the National Cancer Database (NCDB) was analyzed to provide insights into the US experience over the past two decades.

Methods: A search of the literature was performed leveraging the MEDLINE and Web of Science electronic databases from inception until March 2024, using the keywords "spinal," "chordoma," and "pediatric". Additionally, the NCDB was queried for pediatric patients (≤ 21 years) with chordoma treated between 2004 and 2017. Baseline characteristics, tumor specifics, treatment details, and survival outcomes were collected and analyzed.

Results: From the literature, 45 pediatric chordoma patients were identified, with a median age of 7 years. Most chordomas were in the cervical spine (40%), and 93% of the patients received surgical treatment. Gross total resection was achieved in 59% of cases, and 49% received adjuvant radiotherapy. Recurrence, metastasis, and mortality rates were 7%, 18%, and 24%, respectively at a median follow-up of 12 months. In the NCDB cohort, 53 pediatric patients (≤ 21 years) and 980 adults (> 21 years) were compared. Despite having smaller tumors in size, pediatric patients presented with more advanced tumors with a higher proportion of stage 4 tumors. They had more mobile spine chordomas (83% vs. 51%) and traveled further for treatment (57 vs. 27 miles). Pediatric patients also received higher radiation doses (5420 vs. 5049 cGy). Surgical resection and adjuvant radiotherapy were common treatments in both groups. After matching, outcomes, including survival rates and early mortality, were similar between age groups. Kaplan-Meier analysis showed no difference in overall survival probabilities between the age groups both prior to and after matching.

Conclusion: While pediatric patients with spinal chordomas present with more advanced stage tumors, they demonstrate similar overall survival outcomes when compared to adults. The current literature is mainly composed of single cases and other reports of low evidence levels.

Purpose: Diffusing alpha-emitters Radiation Therapy ("Alpha DaRT") is a new cancer treatment modality that employs radium-224-loaded metal sources implanted in solid tumors to disperse alpha-emitting atoms within a therapeutic "kill-zone" of a few millimeters around each source. Preclinical studies have demonstrated tumor growth delay in various cancer types, including glioblastoma multiforme, and the method is used in clinical trials for patients with skin and head and neck cancer. This study aims to assess the safety and feasibility of implementing Alpha DaRT for brain tumor treatment in a large animal model.

Methods: Alpha-DaRT sources were delivered via image-guided stereotactic implantation into both hemispheres of eight swine. 1-3 layers of radial deployment of 7 sources were delivered through a single penetration point into each hemisphere. A 90-day follow-up period included clinical evaluation, brain MRI, head CT, blood, CSF, urine, and feces sampling, and an analysis of source location over time. Brain tissue pathology was performed on termination.

Results: Alpha-DaRT sources were reproducibly and efficiently delivered to the brain cortex and subcortex. No unexpected abnormalities were detected in blood or CSF samples. MRI and CT scans revealed no evidence of major bleeding or infection. Measurements of ²¹²Pb in blood and CSF exhibited the expected exponential decay from day 7 to day 14 post-source implantation. Minimal spatial and temporal movements of the sources were noted. Histopathological analysis demonstrated locally confined findings in brain parenchyma in a very close proximity to the sources.

Conclusion: Alpha-DaRT sources can be safely delivered into a large animal brain using image-guided stereotactic implantation. These findings support further exploration of Alpha DaRT as a potential treatment modality for brain tumors.

Introduction: - Accurate detection, segmentation, and volumetric analysis of brain lesions are essential in neuro-oncology. Artificial intelligence (AI)-based models have improved the efficiency of these processes. This study evaluated an AI-based module for detecting and segmenting brain metastases, comparing it with manual detection and segmentation.

Methods: - MRIs from 51 patients treated with Gamma Knife radiosurgery for brain metastases were analyzed. Manual lesion identification and contouring on Leksell Gamma Plan at the time of treatment served as the gold standard. The same MRIs were processed through an AI-based module (Brainlab Smart Brush), and lesion detection and volumes were compared. Discrepancies were analyzed to identify possible sources of error.

Results: - Among 51 patients, 359 brain metastases were identified. The AI module achieved a sensitivity of 79.2% and a positive predictive value of 95.6%, compared to a 93.3% sensitivity for manual detection. However, for lesions > 0.1 cc, the AI's sensitivity rose to 97.5%, surpassing manual detection at 93%. Volumetric agreement between AI and manual segmentations was high (Spearman's ρ = 0.997, p < 0.001). Most lesions missed by the AI (53.8%) were near anatomical structures that complicated detection.

Conclusions: - The AI module demonstrated higher sensitivity than manual detection for metastases larger than 0.1 cc, with robust volumetric accuracy. However, human expertise remains critical for detecting smaller lesions, especially near complex anatomical areas. AI offers significant potential to enhance neuro-oncology practice by improving the efficiency and accuracy of lesion management.