Journal of Neuro-Oncology最新文献

Glioblastoma (GBM), the most common and aggressive primary central nervous system (CNS) tumor in adults, continues to have a dismal prognosis. Across hundreds of clinical trials, few novel approaches have translated to clinical practice while survival has improved by only a few months over the past three decades. Randomized controlled trials of immune checkpoint inhibitors (ICIs), which have seen impressive success for advanced or metastatic extracranial solid tumors, have so far failed to demonstrate a clinical benefit for patients with GBM. This has been secondary to GBM heterogeneity, the unique immunosuppressive CNS microenvironment, immune-evasive strategies by cancer cells, and the rapid evolution of tumor on therapy. This review aims to summarize findings from major clinical trials of ICIs for GBM, review historic failures, and describe currently promising avenues of investigation. We explore the biological mechanisms driving ICI responses, focusing on the role of the tumor microenvironment, immune evasion, and molecular biomarkers. Beyond conventional monotherapy approaches targeting PD-1, PD-L1, CTLA-4, we describe emerging approaches for GBM, such as dual-agent ICIs, and combination of ICIs with oncolytic virotherapy, antigenic peptide vaccines, chimeric antigenic receptor (CAR) T-cell therapy, along with nanoparticle-based delivery systems to enhance ICI efficacy. We highlight potential strategies for improving patient selection and treatment personalization, along with real-time, longitudinal monitoring of therapeutic responses through advanced imaging and liquid biopsy techniques. Integrated radiomics, tissue, and plasma-based analyses, may potentially uncover immunotherapeutic response signatures, enabling early, adaptive therapeutic adjustments. By specifically targeting current therapeutic challenges, outcomes for GBM patients may potentially be improved.

Objective: The presence of multiple localizations (ML) in glioblastoma is rare and associated with perceived poor prognosis. The aim of this study is to evaluate the impact of a multimodal treatment on progression-free survival (PFS) and overall survival (OS) in ML glioblastoma.

Methods: Patients presenting with CNS WHO grade 4 glioblastoma with ML to 2 major German Departments of Neurosurgery between January 1st, 2008, to December 31st, 2020 were included in this study. Primary outcome parameters were extent of resection (EOR) using the 2021 RANO criteria, progression free- and overall survival.

Results: A total of 483 patients with newly diagnosed glioblastoma (CNS WHO grade 4) were assessed. 134 patients presented with ML (72 multifocal (MF), 62 multicentric (MC)). The median PFS and OS did not differ among MC and MF glioblastomas. The EOR was a significant predictor of PFS and OS in ML glioblastoma. complete-, near total-, and subtotal resection significantly prolonged PFS (p < 0.0001) and OS (p < 0.0001) compared to biopsy alone. Standard radiotherapy (p = 0.045) and hypofractionated (p < 0.0001) radiotherapy and adjuvant treatment (Stupp protocol) prolonged PFS (p = 0.0012) and OS (p < 0.0001). In multivariate analysis Karnfosky performance score, EOR, and concomitant adjuvant treatment remained significant factors influencing OS. Propensity score matching of patients with ML and solitary lesion tumors showed similar PFS and OS (p = 0.08).

Conclusion: The presented data suggests that glioblastomas with multiple lesions treated with multimodal therapy equal survival rates compared to patients with solitary lesion tumors can be achieved. The results reflect the importance of an equally aggressive maximal treatment effort in this particular and often marginalized group of patients.

Purpose: We assess the efficacy of different surgical resection types, radiotherapy, systemic therapy on overall survival in very elderly patients (age > 80) with intracranial atypical meningioma in contrast with their elderly (65-80) counterparts.

Methods: Patients > 65 years old with intracranial atypical meningiomas surgically resected and catalogued via the National Cancer Database were included. Cox proportional hazards models were developed to assess the association between surgical resection type, radiotherapy and systemic therapy with OS while controlling for sex, race, ethnicity, facility type, income, tumor size and CDCC score.

Results: 1747 elderly patients and 382 very elderly patients were included. 61.70% elderly patients and 58.90% very elderly patients received GTR. 26.50% elderly patients and 14.13% very elderly patients received radiotherapy. In multivariate analysis, subtotal resection is associated with worse survival (HR 1.28, p < 0.01) and radiotherapy is associated with improved survival (HR 0.76, p < 0.01). Systemic therapy was not associated with changes in survival outcomes (HR 1.17, p = 0.79). Using subgroup analysis, gross total resection is associated with better survival outcomes in both elderly and very elderly cohorts. Radiotherapy was not associated with improved survival (HR 0.85, p = 0.11) for patients between 65 and 80 years old, but was associated with improved survival (HR 0.51, p < 0.01) for patients > 80 years old.

Conclusion: GTR provides survival advantage in both elderly and very elderly cohorts. Radiotherapy provides survival benefits for very elderly patients even though very elderly patients are less likely to received radiotherapy. Very elderly patients may benefit from more aggressive management in the treatment of atypical meningiomas.

Purpose: Lower-grade gliomas typically exhibit 5-aminolevulinic acid (5-ALA)-induced fluorescence in only 20-30% of cases, a rate that can be increased by doubling the administered dose of 5-ALA. Fluorescence can depict anaplastic foci, which can be precisely sampled to avoid undergrading. We aimed to analyze whether a deep learning model could predict intraoperative fluorescence based on preoperative magnetic resonance imaging (MRI).

Methods: We evaluated a cohort of 163 glioma patients categorized intraoperatively as fluorescent (n = 83) or non-fluorescent (n = 80). The preoperative MR images of gliomas lacking high-grade characteristics (e.g., necrosis or irregular ring contrast-enhancement) consisted of T1, T1-post gadolinium, and FLAIR sequences. The preprocessed MRIs were fed into an encoder-decoder convolutional neural network (U-Net), pre-trained for tumor segmentation using those three MRI sequences. We used the outputs of the bottleneck layer of the U-Net in the Variational Autoencoder (VAE) as features for classification. We identified and utilized the most effective features in a Random Forest classifier using the principal component analysis (PCA) and the partial least square discriminant analysis (PLS-DA) algorithms. We evaluated the performance of the classifier using a tenfold cross-validation procedure.

Results: Our proposed approach's performance was assessed using mean balanced accuracy, mean sensitivity, and mean specificity. The optimal results were obtained by employing top-performing features selected by PCA, resulting in a mean balanced accuracy of 80% and mean sensitivity and specificity of 84% and 76%, respectively.

Conclusions: Our findings highlight the potential of a U-Net model, coupled with a Random Forest classifier, for pre-operative prediction of intraoperative fluorescence. We achieved high accuracy using the features extracted by the U-Net model pre-trained for brain tumor segmentation. While the model can still be improved, it has the potential for evaluating when to administer 5-ALA to gliomas lacking typical high-grade radiographic features.

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.

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: Toxicities associated with stereotactic radiosurgery (SRS) are important when considering treatment and supportive management for patients with brain metastases. We herein assessed the association between brain metastasis location and risk of toxicity after SRS.

Methods: We conducted a retrospective institutional review of patients treated with SRS for brain metastases between 2008 and 2023. Outcomes included radiation necrosis, seizure, local failure, and overall survival (OS).

Results: We reviewed 215 patients treated to 605 metastases (median diameter 10 mm, IQR 5-17 mm), in the frontal (34%), cerebellar (19%), parietal (16%), temporal (13%), and occipital (13%) regions. Median follow-up was 16 months (IQR 7-36). New-onset seizures developed in 11% (19/174) of patients without prior seizure and was higher in patients with motor or sensory cortex lesions (12/48, 25%) on multivariate analysis (MVA, P = 0.02). SRS-related grade ≥ 2 symptomatic radionecrosis occurred in 6% (33/605) of lesions and correlated with larger metastasis volume (P < 0.001) and renal cell carcinoma histology (P < 0.05), while supratentorial location was nearly significant (MVA, P = 0.06). Median OS across all patients was 16 months (95% CI 12-20). Patients with symptomatic radiation necrosis had a longer median survival compared to those who did not (43 vs. 14 months, P = 0.002), which remained significant alongside Karnofsky performance status and extracranial disease on MVA.

Conclusion: Brain metastasis location in the motor or sensory cortex is associated with increased risk of new-onset seizure following SRS and may warrant consideration of steroid and/or anti-epileptic prophylaxis. Symptomatic radiation necrosis is uncommon in the cerebellum and may be increasing with improvements in survival.

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.

Background and aim: Elevated lactate dehydrogenase (LDH), a marker of tumor aggressiveness and metabolic alterations, may predict treatment response and overall survival across various tumors. This study investigates the correlation between serum LDH levels and clinical outcomes in glioblastoma patients treated with radiotherapy (RT) and temozolomide (TMZ).

Materials and methods: This retrospective study analysed patients with IDH wild-type glioblastoma (IDH-wt GB) treated at the Radiotherapy Department of Azienda Ospedaliero-Universitaria Senese from 2018 to 2023. Clinical data, including hematologic parameters (e.g., LDH), imaging (MRI), and MGMT promoter methylation status, were collected. All patients received RT and TMZ following the Stupp protocol. Serum LDH levels were measured one week before RT, and Radiological Response (RR) was assessed using RANO criteria. Overall survival (OS), progression-free survival (PFS), and RR were primary endpoints. Statistical analyses included Kaplan-Meier, Cox regression, and decision tree analysis for LDH cut-off determination.

Results: In a cohort of 147 IDH wild-type glioblastoma patients treated with the Stupp protocol, the median OS was 14 months and median PFS was 8 months. Elevated baseline LDH levels were associated with significantly poorer outcomes, showing a median OS of 9 months versus 20 months and a median PFS of 6 months versus 13 months for lower LDH levels (p < 0.001 and p = 0.0001, respectively). LDH levels also correlated with RR (p = 0,001), Multivariate analysis confirmed high LDH as an independent predictor of worse OS (HR = 2.31) and PFS (HR = 2.60), suggesting its utility as a prognostic biomarker.

Conclusions: Elevated LDH levels before starting the Stupp protocol are clinically significant as they predict poorer overall survival and progression-free survival in glioblastoma patients and worse RR. Incorporating LDH measurements into treatment planning can help identify patients at higher risk of poor outcomes, allowing for more tailored and potentially aggressive treatment strategies to improve management and therapeutic responses in glioblastoma.