Journal of Neuro-Oncology最新文献

Purpose: Extent of brain tumor resection continues to be one of the central decisions taken during standard of care in glioma patients. Here, we aimed to evaluate the most essential molecular factors, such as IDH (isocitrate dehydrogenase) mutation in gliomas classification with patient-derived glioma organoids (PGOs) using differential mobility spectrometry (DMS).

Methods: we prospectively recruited 12 glioma patients, 6 IDH-mutated and 6 IDH wild-type tumors, from which PGOs were generated ex-vivo. Altogether, 320 PGOs DMS spectra were analyzed with a classifier algorithm based on linear discriminant analysis (LDA).

Results: LDA model classification accuracy (CA) obtained between IDH-mutant and IDH wild-type PGOs was 90% (91% sensitivity and 89% specificity). Furthermore, 1p/19q codeletion classification within IDH mutant PGOs reached 98% CA (93% sensitivity and 99% specificity), while CDKN2A/B homozygous loss status had 86% CA (63% sensitivity 93% specificity).

Conclusion: DMS suitability to differentiate IDH-mutated PGOs was thus validated in ex vivo cultured samples, PGOs. Preliminary results regarding 1p/19q codeleted PGOs and CDKN2A/B loss PGOs identification endorse testing in a prospective intraoperative glioma patient cohort. Our results reveal a sample classification set-up that is compatible with real-time intraoperative surgery guidance.

Purpose: High-grade gliomas (HGG) represent the most aggressive primary brain tumors in adults, characterized by high recurrence rates due to incomplete resection. This review explores the effectiveness of emerging intraoperative therapies that may extend survival by targeting residual tumor cells. The main research question addressed is: What recent intraoperative techniques show promise for complementing surgical resection in HGG treatment?

Methods: A comprehensive literature review was conducted, examining recent studies on intraoperative therapeutic modalities that support surgical resection of HGG. Techniques reviewed include laser interstitial thermal therapy (LITT), intraoperative brachytherapy, photodynamic therapy (PDT), sonodynamic therapy (SDT), and focused ultrasound (FUS). Each modality was evaluated based on clinical application, evidence of effectiveness, and potential for integration into standard HGG treatment protocols.

Results: Findings indicate that these therapies offer distinct mechanisms to target residual tumor cells: LITT provides localized thermal ablation; intraoperative brachytherapy delivers sustained radiation; PDT and SDT activate cytotoxic agents in tumor cells; and FUS enables precise energy delivery. Each method has shown varying levels of clinical success, with PDT and LITT currently more widely implemented, while SDT and FUS are promising but under investigation.

Conclusion: Intraoperative therapies hold potential to improve surgical outcomes for HGG by reducing residual tumor burden. While further clinical studies are needed to optimize these techniques, early evidence supports their potential to enhance the effectiveness of surgical resection and improve patient survival in HGG management.

Purpose: Meningiomas are the most frequent primary intracranial malignancy. While surgical resection can confer long term tumor control, stereotactic radiosurgery (SRS) is often used for small, asymptomatic tumors in the adjuvant setting. Frailty has been associated with increased rates of peri-operative morbidity but has yet to be defined in the setting of SRS for meningiomas. We therefore sought to examine the relationship between frailty and clinical/radiographic outcomes of patients with meningiomas who have undergone SRS.

Methods: A single-center, retrospective cohort study classified patients by their 5-factor modified frailty index (mFI-5) score into pre-frail (0-1) and frail (2-5) at the time of SRS treatment. Evaluations of overall survival (OS), progression free survival (PFS), local control (LC), and distant control (DC) were performed using Kaplan-Meier analysis. Cox proportional hazards regression analysis was used to further define factors associated with OS/PFS.

Results: 94 patients met inclusion criteria and underwent SRS for meningioma treatment from 2019 to 2023. Analyses compared prefrail (0-1) and frail (2-5) individuals. Kaplan-Meier analysis demonstrated a near significant association between frailty and OS (HR 3.66, 95% CI 0.49-26.8 p = 0.05) with 3-year OS rates of 75.4% in the pre-frail versus 36.6% in the frail group. However, a significant relationship was demonstrated between frailty and PFS (HR: 2.95 95% CI 1.12-7.81, p = 0.02) with 3-year PFS rates of 90.5% in the pre-frail group versus 49.2% in the frail group. Univariable regression analysis demonstrated that frailty, prior surgical excision, and cumulative tumor volume predicted PFS.

Conclusion: Frailty, as assessed by the mFI-5, did not independently predict OS but did predict PFS in individuals with meningioma undergoing SRS.

Background: The incidence of glioblastoma in the elderly population is increasing as the worldwide population ages. The differential and poorer survival in the elderly population compared to younger patients is partially explained. The present study aimed to investigate the clinical impact of epidermal growth factor receptor EGFR-altered glioblastoma in a real-life elderly glioblastoma population.

Patients and methods: A bicentric and retrospective study was conducted. Patients were 70 years or older and suffering from histomolecularly confirmed glioblastoma. Single nucleotide variants (SNV), amplification, or chromosome 7 polysomy were sought. The primary endpoint was the comparison of overall survival (OS) in patients with or without EGFR alteration. Secondary objectives were to determine other clinical parameters correlated with EGFR alteration status.

Results: Seventy-three patients were analyzed: 41.1% had at least one EGFR alteration. The presence of EGFR alteration did not impact overall survival: HR 0.97 [0.6-1.57], p = 0.9; the median overall survival was 6.5 months [5.3-9.3] in the EGFR-altered group versus 7 months [4.5-10] in the EGFR wild-type group, p = 0.75. In multivariate analysis, tumor resection was associated with a significant overall survival improvement: the median OS in the resected group (n = 20) was 11 months [95% CI 7.8-22] versus a median OS of 5.5 months [4.6-7.8] in the unresected group (n = 53), without correlation to EGFR alteration status.

Conclusion: In the modern era of molecular characterization and improved treatment modalities, the presence of at least one EGFR alteration did not influence survival outcomes in an elderly population of glioblastoma patients.

Purpose: Glioblastoma multiforme (GBM) poses significant challenges in treatment due to its aggressive nature and immune escape mechanisms. Despite recent advances in immune checkpoint blockade therapies, GBM prognosis remains poor. The role of bromodomain and extraterminal domain (BET) protein BRD4 in GBM, especially its interaction with immune checkpoints, is not well understood. Our study aimed to explore the role of BRD4 in GBM, especially the immune aspects.

Methods: In this study, we performed bioinformatics gene expression and survival analysis of BRD4 using TCGA and CGGA databases. In addition, we investigated the effects of BRD4 on glioma cell proliferation, invasion and migration by clone formation assay, Transwell assay, CCK8 assay and wound healing assay. Chromatin immunoprecipitation (ChIP) assay was conducted to confirm BRD4 binding to the programmed death ligand 1 (PD-L1) promoter. GL261 cells with BRD4 shRNA and/or PD-L1 cDNA were intracranially injected into mice to investigate tumor growth and survival time. Tumor tissue characteristics were analyzed using H&E and IHC staining and immune cell infiltration were assessed by flow cytometry.

Results: The results showed that elevated expression of BRD4 in high-grade gliomas was associated with poor patient survival. In addition, we validated the promotional effects of BRD4 on glioma cell proliferation, invasion and migration. The results of ChIP experiments showed that BRD4 is a regulator of PD-L1 at the transcriptional level, implying that it is involved in the immune escape mechanism of glioma cells. In vivo studies showed that BRD4 knockdown inhibited tumor growth and reduced immunosuppression, improving prognosis.

Conclusion: BRD4 has the capability to regulate the growth of glioblastoma and enhance immune suppression by promoting PD-L1 expression. Targeting BRD4 represents a promising direction for future research and treatment.

Purpose: Length of stay (LOS) is a critical metric of healthcare delivery. Prolonged LOS is associated with a heightened risk of adverse complications. We aimed to provide a comprehensive evaluation of LOS, specifically identifying variables associated with extended LOS (eLOS), in children and young adults following elective craniotomy for tumor resection.

Methods: All elective craniotomies for tumor resection performed at our tertiary care children's hospital from January 2010 to December 2022 were included for review, excluding patients > 21 years of age. Demographic, clinical, and procedural variables for each craniotomy were collected. LOS was defined as the interval in days from index surgery to discharge. eLOS was defined as greater than 7 days.

Results: 1,276 patients underwent a total of 1,497 elective craniotomies for tumor resection. The median age was 9.45 years old, with the most common age group being > 10 years (45.6%). Most patients had supratentorial tumors (63.4%) and underwent de novo surgery (60.7%). Patients with an eLOS experienced longer ICU admissions, longer surgical times, and were younger. Variables found to be significantly associated with eLOS were posterior fossa resection (OR = 2.45), de novo craniotomy (OR = 0.49), prior shunt or ETV (OR = 1.80), tumor type (craniopharyngioma (OR = 3.74) and medulloblastoma (OR = 0.51)), and the presence of at least one postoperative event (POE) (OR = 29.85).

Conclusion: This is the largest study evaluating factors (patient, tumor, surgical) associated with eLOS after elective craniotomy for tumor resection in children and young adults. The findings of this clinical study are important for preoperative counseling, neurosurgical team preparedness, and healthcare delivery optimization.

Purpose: This study aimed to identify variables that portend early construct failure requiring surgical revision in patients undergoing instrumented fusion for spine metastases.

Methods: A detailed retrospective chart review was performed. Demographic, surgical, and oncologic variables were collected and analyzed via independent samples t-testing, chi-square testing, and Kaplan-Meier method with log-rank testing. Significance was determined as p < 0.05.

Results: 482 spinal fusion operations for solid tumor metastases were performed between 2012 and 2022. Of these, 24 (5.0%) required revision surgery for construct failure. There were no major differences between the revision and non-revision patients in terms of several surgical characteristics. Thirteen (54.1%) were revised within 3 months of index surgery. These early construct failures were more likely to have functional neurological deficits at surgery (6/13 vs. 0/11 [p = 0.009]), longer constructs (mean 6.4±2.4 vs. 4.2 ± 1.4 levels [p = 0.015]), and cement-augmented pedicle screws (4/13 vs. 0/11 [p = 0.044)) compared to late construct failures (> 3 months after index surgery). Additionally, 17 symptomatic failures were identified, compared to 7 asymptomatic failures which were identified incidentally with routine follow-up imaging. All 7 asymptomatic construct failures occurred in the early revisions group [p = 0.004]. Revision surgery for early construct failure was associated with significantly reduced median overall survival compared to late failure (p = 0.010).

Conclusion: Construct failures in our cohort were not associated with any classical characteristics of patients undergoing revision spine surgery. Early revision (< 3 months) portends a reduction in overall survival when compared with late revisions, and early revised patients were more likely to have had more extensive surgery and poorer neurological status at the time of index cases.

Purpose: Existing literature on adjuvant radiation after subtotal resection (STR) of WHO II meningiomas is limited by heterogenous patient cohorts, combining adjuvant and salvage radiation, gross total resection (GTR) and STR, primary radiation treatment vs. re-treatment, or grade II and III meningiomas, all of which have different expected outcomes. Tumor control estimates in a large homogenous patient cohort are needed to accurately counsel patients.

Methods: A retrospective review of patients that had immediate post-operative imaging-confirmed residual WHO grade II meningioma followed by either adjuvant intensity-modulated radiation therapy (IMRT) or stereotactic radiosurgery (SRS) between 1996 and 2020 was conducted. Kaplan-Meier survival analysis and log-rank test was used to assess progression-free survival (PFS).

Results: Thirty-nine patients met inclusion criteria (IMRT = 32; SRS = 7). Overall, the 3-, 5-, and 10-year PFS was 81.1%, 61.2%, and 44.6%, respectively. Median follow-up time was 37 months. When comparing IMRT and SRS cohorts, baseline characteristics did not differ significantly between groups, but significantly larger residual tumor volumes were treated with IMRT (22.2 cm³ vs. 6.3 cm³, p = 0.004). PFS was not significantly different between IMRT and SRS at 3 years (81.1% vs. 80.0%) or 5 years (65.5% vs. 40%) (p = 0.19). There was no significant difference in radiation necrosis between groups (IMRT = 3/32 patients vs. SRS = 0/7 patients, p = 0.32).

Conclusion: Our homogenous patient cohort displayed acceptable control rates at 3 years using SRS or IMRT as adjuvant therapy. No significant difference in PFS or radiation necrosis was noted between patients treated with adjuvant IMRT versus SRS.

Purpose: Previous evidence suggests that glioma re-resection can be effective in improving clinical outcomes. Furthermore, the use of mapping techniques during surgery has proven beneficial for newly diagnosed glioma patients. However, the effects of these mapping techniques during re-resection are not clear. This systematic review aimed to assess the evidence of using these techniques for recurrent glioma patients.

Methods: A systematic search was performed to identify relevant studies. Articles were eligible if they included adult patients with recurrent gliomas (WHO grade 2-4) who underwent re-resection. Study characteristics, application of mapping, and surgical outcome data on survival, patient functioning, and complications were extracted.

Results: The literature strategy identified 6372 articles, of which 125 were screened for eligibility. After full-text evaluation, 58 articles were included in this review, comprising 5311 patients with re-resection for glioma. Of these articles, 17% (10/58) reported the use of awake or asleep intraoperative mapping techniques during re-resection. Mapping was applied in 5% (280/5311) of all patients, and awake craniotomy was used in 3% (142/5311) of the patients.

Conclusion: Mapping techniques can be used during re-resection, with some evidence that it is useful to improve clinical outcomes. However, there is a lack of high-quality support in the literature for using these techniques. The low number of studies reporting mapping techniques may, next to publication bias, reflect limited application in the recurrent setting. We advocate for future studies to determine their utility in reducing morbidity and increasing extent of resection, similar to their benefits in the primary setting.

Purpose: Meningiomas are central nervous system tumors whose incidence increases with age. Benign meningioma pathogenesis involves germline or somatic mutation of target genes, such as NF2, leading to clonal expansion. We used an established cancer epidemiology model to investigate the number of rate-limiting steps sufficient for benign meningioma development.

Methods: Incidence data was obtained from the Surveillance, Epidemiology and End Results Program (SEER) for nonmalignant meningioma from 2004 to 2020. Age-adjusted incidence rates per 100,000 person-years were divided into 5-year bands. This was repeated for vestibular schwannomas as a negative control. The Armitage-Doll methodology was applied. Mathematical solutions correcting for volatile tumor microenvironments were applied to fit higher-order models using polynomial regression when appropriate. A 75:25 training:test split was utilized for validation.

Results: 222,509 cases of benign meningiomas were identified. We noted strong linear relationships between log-transformed incidence and age across the cohort and multiple subpopulations: male, white, black, Hispanic, Asian/Pacific Islander, and American Indian subpopulations all demonstrated R² = 0.99. Slopes were between 3.1 and 3.4, suggesting a four-step process for benign meningioma development. Female patients exhibited nonlinear deviations, but the corrected model demonstrated R² = 0.99 with a four-hit pathway. This model performed robustly on test data with R² = 0.99. Vestibular schwannomas demonstrated a slope of 2.1 with R² = 0.99, suggesting a separate three-step process.

Conclusion: Four mutations are uniquely required for the development of benign meningiomas. Correcting for volatile tumor microenvironments reliably accounted for nonlinear deviations in behavior. Further studies are warranted to elucidate genomic findings suggestive of key mutations in this pathway.