Neuro-oncology advances最新文献

Background: Specific herpesviruses have been implicated in glioma development. We undertook a pilot study to examine whether herpesviruses-specific human T-cell receptor (TCR) sequences in patient blood samples associate with glioma grade and survival.

Methods: The study was based on 56 pretreatment blood samples collected from both patients with glioblastoma (n = 36) with varying survival times as well as 20 lower grade glioma patients, including astrocytomas and oligodendrogliomas. Following PCR amplification and high-throughput sequencing of DNA extracted from peripheral blood, data were analyzed (AdaptiveBiotechnologies ImmunoSEQ Analyzer) to identify complementarity-determining (CDR3) regions of human TCRs specific to herpes viral antigens. We identified sequences specific for six cytomegalovirus (CMV) peptides and ten Epstein-Barr virus peptides. No CDR3 sequences specific for Varicella Zoster could be identified in the publicly available databases queried.

Results: Blood samples yielded large numbers of productive rearrangements (ie CDR3 sequences resulting in functional T-cell immunity), and one or more sequences targeting CMV and EBV were found in every patient sample. For both EBV and CMV, we observed a greater breadth (higher average number of unique CDR3 sequences) and intensity (higher average sum of all CDR3 sequences) of antiviral T-cell response in patients with lower-grade gliomas compared with glioblastoma, even after adjustment for patient age and sex in multivariate regression models.

Conclusions: Interrogation of blood samples for CDR3 sequences describing the human TCR repertoire offers a novel tool for investigating anti-viral immune response in glioma. More robust immunity to herpesviruses could result in cross-reactive, primed cyto-toxic immune responses that potentially suppress development of more aggressive tumors.

Background: Intraoperative Stimulated Raman Histology (SRH) has been reported to be fast and accurate in the assessment of neuro-oncological lesions. However, its application to spinal tumors, especially intradural extramedullary tumors (IDEM), remains underexplored. IDEM primarily include meningiomas and schwannomas, as well as less common entities such as metastases or ependymomas. Given that surgical resection is the primary treatment modality, rapid, artificial intelligence (AI)-driven intraoperative tumor classification based on SRH could enhance surgical decision-making and subsequent management.

Methods: We acquired 232 SRH images from patients with IDEM using the NIO Laser Imaging System (Invenio Imaging Inc.). We categorized images into three diagnostic classes: "Meningioma," "Schwannoma," and "Other." Images were divided into 224 × 224 pixel patches and used to train and test AI-based image classifiers employing CTransPath, ResNet, and Vision Transformer architectures.

Results: Our best-performing model, utilizing the CTransPath architecture, achieved a classification accuracy of 94.3% on the test dataset. Vision Transformer-based models also performed well, exceeding 90% accuracy, while ResNet models attained slightly lower accuracies (79.6%-88.8%). Qualitative analysis indicates that the top-performing model primarily relies on cellular morphology for classification.

Conclusions: Our findings confirm the feasibility and effectiveness of AI-assisted SRH analysis for distinguishing IDEM tumor types. This approach may complement conventional intraoperative neuropathology by providing rapid, reliable, and clinically actionable diagnostic information.

Background: Authenticated preclinical brain tumor models provide unprecedented opportunities to evaluate next-generation treatments. However, some therapies with robust anti-tumor activity in mice fail in human trials, highlighting the need to better prioritize candidates for clinical translation. Herein, we implemented a head-to-head preclinical strategy using a well-characterized murine model of NF1-optic pathway glioma (Nf1 ^OPG).

Methods: Nf1 ^OPG mice were treated with standard of care (SOC; carboplatin), clinically evaluated (everolimus, mirdametinib), and investigational (pexidartinib, HBS-101, lamotrigine) drugs during the period of most rapid tumor growth (6-12 weeks of age). Anti-tumoral efficacy was assessed by proliferation (%Ki67⁺ cells) and optic nerve (ON) volume, while vision-related outcomes were measured using retinal nerve fiber layer (RNFL) thickness and retinal ganglion cell (RGC) determinations. Tumor microenvironment (TME) soluble mediator (Ccl2, Ccl3, Ccl4, Ccl5) and tumor cell marker (NeuN, Gpr17) RNA expression was quantitated by qRT-PCR. Outcomes were compared to carboplatin-treated Nf1 ^OPG, untreated Nf1 ^OPG, and Nf1^+/- mice.

Results: While all agents restored normal tissue architecture, reduced ON proliferation, and decreased TME soluble mediator and tumor cell marker RNA expression, only lamotrigine and mirdametinib also reduced ON volume. Everolimus, lamotrigine, and HBS-101 restored RNFL thickness to wild-type levels, whereas carboplatin showed a trend towards normalization.

Conclusions: This referential preclinical study design affords direct head-to-head comparisons of investigational therapies relative to SOC treatment using clinically meaningful outcomes (OPG growth and RNFL thickness). Using this strategy, lamotrigine emerged as the most promising therapy for limiting tumor progression and vision loss in Nf1-OPG mice, relevant to clinical translation for children with NF1-OPG.

Background: Malignant gliomas are heterogeneous brain tumors with extensive neovascularization. Conventional gradient-echo dynamic susceptibility contrast (GRE-DSC) perfusion MRI may underestimate microvascular alterations. We hypothesized that a novel vascular model (NVM), based on Bayesian voxel-wise transit time distribution analysis, could yield higher perfusion metrics in untreated isocitrate dehydrogenase (IDH)-wild-type glioblastoma compared to standard vendor GRE-DSC algorithms.

Methods: In this retrospective, single-center study, 89 patients with neuropathologically confirmed glioblastoma underwent pretherapeutic GRE-DSC perfusion MRI at 1.5 or 3.0 T. Perfusion maps were generated using both the NVM and default vendor algorithms. Using co-registered T1-post-contrast and T2/FLAIR images, two neuroradiologists independently assessed perfusion conspicuity of color-coded maps for each algorithm and manually performed region-of-interest analyses within visually identified tumor hotspots for quantification. Relative values of cerebral blood flow (rCBF), cerebral blood volume (rCBV), and mean transit time (rMTT) were normalized to contralateral normal-appearing white matter. Nonparametric tests evaluated group differences.

Results: The NVM yielded enhanced hotspot delineation and significantly higher median normalized perfusion values than vendor algorithms (all P < .001), with excellent inter-rater reliability (Cohen's κ and intraclass correlation coefficients ≥0.86). At 3.0 T, NVM-derived rCBV was significantly higher than at 1.5 T (P = .008).

Conclusions: NVM post-processing yielded higher normalized CBF, CBV, and MTT values within tumor hotspots than vendor pipelines, suggesting that Bayesian model-based perfusion analysis may enhance the detection of microvascular changes in glioblastoma. As validation against a gold standard is missing, prospective multicenter studies are warranted to confirm our findings, particularly with regard to treatment monitoring and clinical decision-making.

Brain tumor registries around the world have significantly contributed to the clinical, scientific, and epidemiological understanding of brain tumors. The success of these registries has prompted many other countries to create such resources for their own populations. This narrative review compares the construction, structure, and function of brain tumor registries in the United States, China, Japan, Canada, England, Australia, Austria, Denmark, and Sweden, drawing key learnings from each. Brain tumor registries from three large, medium, and small countries were identified, and their establishment, organizational structure, and primary functions were examined. This analysis found eight key considerations for establishing a national clinical registry: (1) clearly defining the aims and objectives of the registry, (2) assessing the role of supportive legislation, (3) evaluating various registry structures, (4) assessing existing registry infrastructure, (5) weighing the benefits and drawbacks of government involvement, (6) recognizing the role of specialist centers, (7) ensuring futureproofing, and (8) prioritizing comprehensive population coverage. These findings were then applied to the New Zealand context to demonstrate how such learnings can be considered by countries wishing to establish their own registry. This review provides a practical framework for nations seeking to develop similar clinical registries.

Background: Tumor treating fields (TTFields) therapy is an important treatment for glioblastoma. However, there have been few reports showing the effectiveness thereof in clinical settings worldwide. The aim of this study was to examine the efficacy of TTFields therapy by comparing patients with compliance rates above 75% with those below 75% during the first 3 months of treatment.

Methods: Data were retrospectively collected from electronic medical records for consecutive patients with newly diagnosed World Health Organization grade 4 gliomas who received TTFields therapy at 12 institutes in Japan from January 2018 to December 2023.

Results: In total, 157 patients received TTFields therapy. We analyzed 116 patients who used TTFields for at least the first 3 months. The median age was 57 years; 67 patients were male; and the median KPS before the start of adjuvant temozolomide was 90. The average compliance rate was 78.3%. The median progression-free survival (PFS) and overall survival (OS) were 11.9 months and 23.7 months, respectively. A high compliance rate of TTFields ≥75% for the first 3 months was achieved in 67 patients and was a significant prognostic factor on PFS (P = .04). The median PFS for patients with high and low compliance rates was 12.6 and 9.0 months, respectively; the median OS was 25.3 and 21.3 months, respectively (P = .15).

Conclusions: TTFields use rate ≥75% in the first 3 months was significantly associated with improved PFS. There was a tendency for OS to be extended. Further analysis with a larger number of cases is required.

Background: Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma. Diagnosis usually requires a brain biopsy, which is associated with complications and delay of diagnosis. Cerebrospinal fluid (CSF) analysis can provide a diagnosis without the need for a biopsy, but only in a minority of PCNSL patients. The aim of this study is to identify new potential biomarkers in CSF for patients with clinical suspicion of PCNSL to improve the diagnostic yield of CSF analysis.

Methods: CSF samples were analyzed from a retrospective cohort that included patients with clinical suspicion of PCNSL. First-step analysis consisted of targeted multiplex biomarker analysis with use of a proximity extension assay (Olink), allowing the simultaneous analysis of relative expression levels of 183 protein markers in a small CSF volume (1 μl). To validate the potential identified biomarkers, a second quantitative analysis was performed in a subgroup with a bead-based multiplex immuno-assay.

Results: We included 74 patients, of whom 11 patients (15%) were diagnosed with PCNSL. In the primary analysis, 30 markers showed significant differences (P < .05) between PCNSL patients and controls. After correction for multiple testing, 6 markers remained significant. The quantitative analysis confirmed significant differences (P < .05) for 3 markers: CXCL10, programmed cell death protein 1 (PDCD1), and FAS natural ligand.

Conclusions: We identified a panel of novel potential diagnostic markers in CSF for the diagnosis of PCNSL and confirmed the value of several known markers. The diagnostic value of these markers will be validated in a multicenter prospective study.

Background: Somatostatin receptor 2 (SSTR2), a highly sensitive and specific meningioma biomarker, can be imaged with [68Ga]-DOTATATE PET, improving diagnosis and treatment. The role of postoperative radiotherapy (RT) for WHO grade 2 (WHO-2) meningiomas following gross total resection (GTR) remains controversial. We hypothesized that confirmation of GTR by DOTATATE PET/MRI followed by active surveillance would yield superior progression-free survival (PFS) compared to MRI-based GTR assessment alone.

Methods: Patients with WHO-2 meningioma enrolled in a prospective registry were included if postoperative PET/MRI showed GTR and if they were managed with surveillance alone. All patients underwent serial MRI and/or PET/MRI follow-up. Kaplan-Meier analysis was used to determine PFS. A retrospective institutional comparator cohort of patients with WHO-2 meningiomas and MRI-determined GTR managed with surveillance alone was also evaluated.

Results: Twenty-eight prospective subjects (61% women, mean age 61 years) met inclusion criteria. Meningiomas were located along the convexity (50%), falx (21%), and skull base (29%). Mean mitotic count was 5.1 per 10 high-power fields; mean follow-up was 28 months (range 5-64). In the PET/MRI cohort, PFS was 90.0% at 5 years. In comparison, the MRI-only cohort (n = 33) demonstrated a 5-year PFS of 67.0% (log-rank P = .04), despite similar clinicopathologic features.

Conclusions: DOTATATE PET/MRI-confirmed GTR followed by active surveillance yielded significantly higher PFS compared to MRI-based GTR assessment in patients with WHO-2 meningioma. DOTATATE PET/MRI increases diagnostic certainty, enabling more accurate postoperative risk stratification and potentially avoiding unnecessary RT, supporting its integration into postoperative decision-making for WHO-2 meningioma.

Background: Extensive surgical resection is associated with longer survival in patients with glioma; however, the combined impact of surgical extent and molecular pathology on prognosis remains unclear. In this study, we evaluated how molecular pathology and clinical features influence surgical outcomes in patients with World Health Organization (WHO) grade 4 gliomas, including isocitrate dehydrogenase (IDH)-mutant astrocytomas and IDH wild-type glioblastomas.

Methods: Data from 501 patients with WHO grade 4 gliomas who underwent surgery were obtained from the Chinese Glioma Genome Atlas database (2005-2019). The effect of resection extent on overall survival was analyzed and stratified using molecular pathology and clinical characteristics. Survival differences were assessed using the Kaplan-Meier method and the log-rank test, and prognostic factors were identified through univariate and multivariate analyses.

Results: The extent of resection significantly influenced survival, but its impact varied by molecular subtype. In WHO grade 4 IDH-mutant astrocytomas, gross total resection (GTR) did not confer a significant survival advantage over subtotal resection (STR). Among glioblastoma patients, those with non-methylated O-(6)-methylguanine-DNA methyltransferase promoters and preoperative Karnofsky Performance Status ≤80 showed no significant benefit from GTR compared to STR, whereas GTR substantially prolonged survival in other subgroups.

Conclusions: The survival benefits of extensive resection vary among patients with WHO grade 4 glioma. Molecular pathology and clinical characteristics should be considered in surgical planning. A conservative approach may be appropriate for some patients; nevertheless, a more aggressive strategy may optimize survival and quality of life for others.

Background: Pediatric central nervous system (CNS) tumors are the leading cause of cancer-related mortality in children, with survival outcomes significantly influenced by racial, ethnic, and socioeconomic disparities. These disparities may arise from delayed diagnosis, unequal access to care, and challenges in navigating complex treatment decisions, including clinical trial enrollment. This study explores the experiences of a diverse cohort of families from symptom onset through treatment initiation, focusing on their perspectives on diagnosis, treatment discussions, and decision-making processes.

Methods: This qualitative study involved semi-structured interviews with families of children diagnosed with pediatric CNS tumors. Transcripts were analyzed by two separate coders using thematic analysis.

Results: Four major themes were identified: Experience of diagnosis, Treatment discussion, Treatment decision, and Communication. Families described the emotional toll of diagnosis, marked by uncertainty, shock, and urgency. Many reported difficulties understanding complex medical information and accessing advanced treatment options. Treatment decisions were influenced by perceptions of therapeutic efficacy, anticipated side effects, and available family-level resources. Variations in perceived barriers to care highlighted disparities in support-seeking behaviors, emphasizing the need for personalized communication and tailored resources.

Conclusion: This study provides a nuanced understanding of pediatric CNS tumor care by centering patient and family experiences. Findings underscore the need for targeted interventions to improve access to innovative treatments, support informed decision-making, and enhance communication. Future research should incorporate quantitative methods to validate findings and develop scalable solutions that address structural and informational barriers, ultimately reducing disparities and improving family experiences in pediatric CNS tumor care.