Neuro-oncology advances最新文献

Immunotherapies have thus far proved of limited efficacy against glioblastoma. Failures can be attributed to a host of immunosuppressive mechanisms that are either directly employed by the tumor or are instead a convenient feature of the intracranial environment. This review aims to categorize glioblastoma immune-evasive tendencies, provide an update on our understanding of etiologies, and describe newer approaches to improving therapeutic responses.

Recent studies have highlighted the therapeutic potential of targeting tumor antigens (TAs) in glioblastoma (GBM). Several classes of TAs, such as tumor-associated, cancer testis, and tumor-specific antigens, have proven to be immunogenic and used safely in vaccines. Many of these vaccines have focused on tumor-associated or cancer testis antigens. However, tumor-specific antigens (TSA) present an ideal target due to the lack of tolerance and exclusive tumor expression, mitigating the risk of off-target effects. Most research on TSAs in GBM has aimed to uncover neoantigens, yet the dearth of shared neoantigens as well as the cost and labor-intensive process of identifying personal neoantigens have acted as barriers to treatment. A better understanding of the individual antigens spanning all three TA classes is important to improve the design of GBM antigen therapies and understand, fundamentally, the nature of immunologic specificity in glioma. We review the antigen classes in all cancers and how TAs are discovered. Then, we focus on the unique properties of GBM and the antigens that have been identified and used for therapy in GBM. Finally, we discuss translational considerations for future antigen-targeted treatments.

Background: Among diffuse midline gliomas with H3K27-altered with MAPK pathway mutations, those with BRAF V600E mutations show the most histologic variability and potential for targeted therapy, yet remain incompletely characterized. We present a series of such tumors, focusing on imaging, histologic, molecular, and therapeutic features.

Methods: Pathology archives from 2016 to 2025 at our institution were searched for gliomas with H3K27M/BRAF V600E mutations. Clinical history, imaging, histology, molecular findings, therapy, and outcomes were reviewed.

Results: Eight patients were identified (6 males, 2 females; age 3-18 years, average 11). Six tumors were thalamic, one cervical, and one suprasellar. Histology fell into three categories: low-grade glioma-like (n = 3), ganglioglioma-like (n = 3), and high-grade glioma-like (n = 2). Tumors with low-grade morphology had no additional clinically significant mutations, while high-grade tumors had co-occurring variants including TERT, 1q/5q gains, and polysomy 7. Two tumors had no methylation class match; two clustered with diffuse midline glioma, and one clustered with high-grade glioma with piloid features. Six patients had maximal safe resections, and two had biopsies (1 low-grade, 1 high-grade). All received BRAF/MEK inhibitors; six also had radiation, and two had chemotherapy. The two patients with high-grade tumors had outcomes similar to classic H3K27M diffuse midline gliomas (both deceased at 17 and 12 months). Patients with low-grade glioma or ganglioglioma-like tumors had better outcomes (all alive, average 38-month follow-up, range 6-80 months).

Conclusion: H3K27M/BRAF V600E-mutant gliomas may represent a distinct subgroup, with outcomes linked to histologic and co-occurring molecular features. Targeted therapy and a surgical approach may support long-term survival in low-grade cases.

Background: Advances in multi-omic studies have improved medulloblastoma (MB) characterization, yet novel molecular biomarkers are needed to refine tumor biology and therapeutic strategies. Current profiling mainly targets the protein-coding genome, while the potential of noncoding regions remains unexplored. This study aims to identify long noncoding RNAs (lncRNAs), emerging as crucial regulators in MB, as potential key biomarkers specific to molecular group, enhancing understanding of MB's genomic landscape.

Methods: RNA-seq data from 54 Spanish MB patients (C1) and 207 public samples (C2) were analyzed to profile lncRNAs. Expression and Weighted Gene Coexpression Network (WGCNA) analyses were performed to identify lncRNA-oncogene interactions. Group-specific interactions were examined to infer their role in MB pathogenesis and highlight potential lncRNA involvement in disease mechanisms.

Results: LncRNA expression profiles identified 4 clusters corresponding to the MB molecular groups, confirming their potential as biomarkers. Expression and WGCNA analyses revealed group-specific lncRNAs for Sonic hedgehog (SHH), Group 3 (Gr3), and Group 4 (Gr4) MB. Lnc-SMARCA2 was exclusively upregulated in SHH MB, and associated with ATOH1 and PDLIM3, key cilium regulators of this group's cell of origin. In Gr4 MB, MGC32805 and LOC107986446 were upregulated and linked to SNCAIP, potentially influencing PRDM6 activation via enhancer hijacking. Additionally, a 5-lncRNA signature linked to phototransduction was exclusive to Gr3, offering insights into its lineage switch and molecular regulation.

Conclusions: Lnc-SMARCA2 and, MGC32805 and LOC107986446, are exclusively deregulated in SHH and Gr4 MB, respectively, and directly associated with group-specific MB oncogenes, representing promising novel biomarkers and therapeutic targets in MB.

Background: Intracranial neoplasms, encompassing benign and malignant tumors, remain a significant health concern worldwide. This review systematically examines hospital-based reports of intracranial neoplasms in Nigeria from 1960 to July 2024, highlighting their distribution, demographics, and temporal trends.

Methods: Following PRISMA guidelines, studies published from 1960 onward were identified through PubMed, Google Scholar, and African Journals Online. Eligible studies reported incidence, prevalence, or demographic data of intracranial neoplasms in Nigeria. Extracted data were pooled for meta-analysis to estimate aggregated incidence and prevalence.

Results: Forty-five studies comprising 3517 cases were included. Pooled extrapolated prevalence was 3.22 (95% CI: 1.66-5.22), while compounded 10 yearly incidence was 3.66 (95% CI: 1.67-6.32). Reported incidence increased from 2.18% (1960-1969) to 4.08% (2000-2009) and 4.84% (2010-2019). Gliomas, meningiomas, and pituitary adenomas were the most frequent tumors. Among adults, meningioma predominated, followed by glioma and pituitary adenoma, whereas in children, gliomas were most common, followed by medulloblastoma and craniopharyngioma. Male predominance was observed (male-to-female ratio 1.17:1), with peak cases in the fourth to sixth decades. Regionally, southern Nigeria (southeast and southwest) showed higher incidence, reflecting disparities in diagnostic capacity and reporting compared with the north.

Conclusion: Reported intracranial neoplasms in Nigeria have increased over the decades, with a prevalence of 3.22 and distinct demographic and geographic patterns. Strengthening diagnostic infrastructure, improving reporting systems, and establishing a national registry are essential for better understanding and management.

Background: Neurocognitive decline in patients with primary brain tumors is associated with alterations in the functional connectome and reduced independence in daily living. This study explores postoperative connectomic changes associated with functional independence outcomes in patients with eloquent glioma, and how these associations differ from neurocognitive-connetcomic relationships.

Methods: Fifteen patients with left perisylvian glioma underwent resting-state functional magnetic resonance imaging (fMRI) and neuropsychological evaluation within 2 weeks before and on average 1 month after resection. Functional independence was measured with the Physical Self-Maintenance Scale (PSMS) and the Instrumental Activities of Daily Living scale (IADL). Graph theoretical analysis quantified functional brain network properties.

Results: Postoperative need for assistance in at least 1 activity on the IADL increased in 80% of patients with Total scores significantly increasing at the group level (Mdn change = 4.0, P = .006). In contrast, need for assistance on the PSMS increased in less than 30% of patients and Total scores were unchanged. Connectomic changes in Local Efficiency, Clustering Coefficient, Path Length, and Betweenness Centrality showed significant associations with need for assistance on the IADL (ρ = 0.63 to.72, all P < .01) but few activities on the PSMS. Functional independence ratings were not associated with Karnofsky Performance Status, manual dexterity, tumor volume, or extent of resection.

Conclusions: Alterations in functional connectomic properties after eloquent glioma resection are associated with early postoperative need for assistance in instrumental activities. Changes in connectomics are also associated with cognitive outcome in this population, though properties most involved appear to differ from those underlying changes in independence.

Background: Early after surgery and completion of first-line radiotherapy with concomitant temozolomide, the prediction of progression-free and overall survival (PFS, OS) is of considerable interest for managing patients with glioblastoma.

Methods: Sixty-three newly diagnosed patients with glioblastoma (age range, 19-82 years) who received PET imaging using the radiolabeled amino acid O-(2-[¹⁸F]fluoroethyl)-L-tyrosine (FET) after surgery or biopsy and completion of radiotherapy with concomitant temozolomide were evaluated. Static FET PET parameters, that is, maximum and mean tumor-to-brain ratios (TBR_max, TBR_mean), metabolic tumor volumes (MTV), and the dynamic FET PET parameters time-to-peak (TTP) and slope were obtained. Additionally, n = 1,303 FET PET radiomics features were extracted per patient, of which 15 robust features were selected for further evaluation based on test-retest analysis. The prognostic values of FET PET parameters and radiomics features were evaluated using receiver-operating-characteristic (ROC) analyses regarding a favorable PFS and OS. Subsequently, univariate and multivariate survival estimates were performed to assess the prognostic value of these parameters in predicting a significantly longer PFS and OS.

Results: ROC analyses revealed that static parameters (ie, TBR_max, MTV) and one radiomics feature were the most powerful parameters to predict a significantly longer PFS (all P = .002) and OS (all P ≤ .02). In addition, the dynamic parameter TTP predicted a significantly longer OS (P ≤ .03) but not PFS (P > .05). TBR_max, MTV, and one radiomics feature remained significant in multivariate survival analysis (all P ≤ .03).

Conclusion: Our results suggest that FET PET parameters, including radiomics, are highly prognostic in patients with glioblastoma at an early stage of first-line therapy.