Neuro-oncology advances最新文献

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: 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.

Background: Approximately 60% of pediatric central nervous system (CNS) tumors originate within the posterior fossa. Posterior Fossa Syndrome (PFS), also known as Cerebellar Mutism Syndrome, is a major and sometimes devastating complication of posterior fossa surgery. The incidence of posterior fossa syndrome varies from 10%-48% in reported studies. This study aims to report the incidence and risk factors of PFS along with the role of occupational therapy, speech therapy, and zolpidem in alleviating the symptoms.

Methods: Patients were included if they were ≤ 18 years old, developed PFS after posterior fossa tumor resection, and were treated between 2014 and 2023 at Aga Khan University Hospital. Data was collected retrospectively by chart review and included symptoms, radiological findings, histopathology, management, and outcomes.

Results: One hundred and sixty-eight patients with posterior fossa tumors were identified; 116 were males with a median age of 8 years. Tumor location was cerebellar hemisphere in 78 (46.4%) patients, fourth ventricle in 76 (45.2%), cerebellar peduncle in 8 (4.8%), and pons in 6 (3.6%). Medulloblastoma was the most common tumor (37.5%). Of the 168 patients, 63 (37.5%) developed PFS, and the incidence was higher in male patients (P = .001), IV^th ventricular tumors (P < .001), and medulloblastomas (P < .001). There was a greater likelihood of improved speech in those treated with speech therapy along with zolpidem (P < .001).

Conclusion: The incidence of PFS after tumor resection is high in our setting. Patients treated with zolpidem showed significant improvement. The role of this medication should be confirmed in prospective clinical trials.

Abstract: BackgroundGlioma patients may require long-term anticoagulation for comorbidities, including arrhythmias or venous thromboembolism (VTE). While direct oral anticoagulants (DOACs) have demonstrated safety in general cancer populations, safety data for glioma patients remains limited. The aim of this study was to assess intracerebral hemorrhage (ICH) risk with DOAC compared to low molecular weight heparin (LMWH) in glioma patients.

Methods: We reviewed adult patients with primary glioma who received DOAC and/or LMWH for at least 10 days between 2008 and 2023 across Cleveland Clinic Health System hospitals. ICH rates and severity were compared between treatment groups.

Results: Among 277 patients (147 DOAC, 130 LMWH), median time from tumor diagnosis to first VTE was 70 days, with 32% experiencing VTE within six months of glioma diagnosis. Of these, 74% had glioblastoma. No statistically significant difference in ICH risk was found between DOAC and LMWH groups (P = .3) or across tumor grades (P = .6). Six ICH events occurred: three trace/minor, one subdural, and two major/fatal (both in LMWH patients). Five events occurred in glioblastoma patients and one in a patient with oligodendroglioma.

Conclusions: This observational study suggests DOACs are relatively safe in glioma patients given the low ICH risk. While most ICH events occurred in glioblastoma patients, no significant difference in risk was found across tumor grades. Prospective studies will establish anticoagulation risks in this population.

Background: People with neurofibromatosis type 1 (NF1) have an 8%-13% lifetime risk of developing malignant peripheral nerve sheath tumors (MPNST). Atypical neurofibromas (AN) and atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP) have been described as precursors to MPNST. AN/ANNUBP often appear as distinct nodular lesions (DNL) that are ≥3 cm in longest diameter. To assess the hypothesis that most MPNST originate in preexisting DNL, we performed a retrospective review of MRIs obtained prior to the MPNST diagnosis in people with NF1.

Methods: Study subjects were identified at two NF centers, University Hospital Hamburg-Eppendorf in Germany and the National Cancer Institute in Bethesda, Maryland, USA. We confirmed the location of MPNST on the MRI performed at the time of histopathological diagnosis and analyzed distinguishing imaging features at the site of MPNST on prior MRIs.

Results: Thirty subjects with NF1 and 35 histologically confirmed MPNST were included in the analysis. Twenty-six MPNST (74%) were detected incidentally on surveillance MRI. In 32 of 35 MPNST (91%), a pre-existing DNL could be detected at the site of subsequent malignancy on prior MRIs. Thirteen DNL gradually emerged within a plexiform neurofibroma (PN) during observation, and 19 DNL were already established on the first available scan. The median time from DNL detection to MPNST diagnosis was 5.1 years (range 0.5-15.7).

Conclusions: Most NF1-related MPNST develop from preexisting DNL. However, we cannot estimate what percentage of DNL will transform to MPNST. Assessing the risk of malignant transformation of DNL in NF1 requires prospective studies.

Glioblastoma (GBM) presents significant therapeutic challenges due to the limited efficacy of current treatments. This resistance is multifactorial, stemming from tumor heterogeneity, an immunosuppressive tumor microenvironment, and the restrictive blood-brain barrier, which limits therapeutic access. In response, immunotherapies, particularly tumor vaccines, have emerged as strategies to harness the immune system against these tumors. This review provides an overview of recent advancements and notable clinical trials in tumor vaccine development for GBM. Additionally, it discusses recent preclinical advancements focused on enhancing immune recruitment and response. Identified strategies include peptide, cellular, and nucleic acid vaccines targeting tumor-specific antigens to induce antitumor T-cell responses. Clinical data and preclinical studies exploring various vaccine candidates, adjuvants, and delivery methods demonstrate encouraging results, with some showing improved progression-free and overall survival rates. Despite these advancements, it is clear that further research into personalized vaccines and combination therapies is necessary to enhance immune responses and improve clinical outcomes.

Background: We evaluated the amino acid PET-based response assessment criteria (PET RANO 1.0) for their proficiency in predicting longer survival in patients with gliomas undergoing adjuvant temozolomide chemotherapy.

Methods: In a previous study, 38 patients with newly diagnosed grade 4 gliomas according to the World Health Organisation classification underwent O-(2-[¹⁸F]fluoroethyl)-l-tyrosine (¹⁸F-FET) PET at baseline and after the second cycle of adjuvant temozolomide chemotherapy. The ability of PET parameter changes to predict favorable progression-free and overall survival (PFS, OS) of ≥9 and ≥15 months was evaluated. Here, we performed a post hoc analysis of these PET data to evaluate the PET RANO 1.0 criteria. In addition, the value of the RANO 2.0 criteria for MRI to predict response was evaluated and compared with the PET RANO 1.0 criteria.

Results: According to the PET RANO 1.0 criteria, patients with Stable Disease (n = 16), Partial Response (n = 9), or Complete Response (n = 0) had a significantly longer OS than patients with Progressive Disease (n = 13) (16.8 vs 12.0 months; P = .016). This difference remained significant in the multivariate survival analysis (HR, 4.185; 95% CI, 1.715-10.530, P = .002). In contrast, PFS was not significantly different between the two groups (9.7 vs 8.1 months; P = .147). PET RANO 1.0 criteria could not identify patients with a PFS ≥ 9 months (P = .503) or OS ≥ 15 months (P = .722). RANO 2.0 criteria for MRI were unable to predict a longer PFS (8.8 vs 9.8 months; P = .565) or OS (16.4 vs 16.8 months; P = .625).

Conclusions: Our data suggest that PET RANO 1.0 criteria identify survival differences between predefined groups.

Background: Diffuse midline gliomas, H3 K27-altered (DMG), are rare CNS WHO grade 4 tumors characterized by the global loss of K27me3 on histone H3. DMGs cannot be safely resected and are associated with poor outcomes in children, though relatively few DMGs have undergone extensive molecular and clinical profiling. Herein, we describe the clinical and molecular profiles of 36 pediatric DMGs as they relate to patient outcomes.

Methods: Pediatric patients (<18 y/o) between 2015 and 2024 with biopsy-proven DMGs and next-generation sequencing (NGS) panels of 86 hotspot genes were reviewed for clinicopathologic characteristics and survival outcomes. Gene Ontology (GO) enrichment analysis was performed. Progression-free survival (PFS) and overall survival (OS) were calculated according to the Kaplan-Meier method. Multivariate Cox regression analysis was performed.

Results: Thirty-six patients were included (median age = 9 y/o). Patients <10 y/o at diagnosis (n = 24) progressed significantly earlier and experienced significantly greater mortality than patients ≥10 y/o at diagnosis (n = 11); PFS and OS at 12 months were 9.0% and 26% for <10 y/o and 36% and 64% for ≥10 y/o (PFS: P ≤ .03, OS: P < .03). NGS findings revealed PIK3CA mutations occurred only in patients <10 y/o (10/25), and GO analysis revealed patients <10 y/o were significantly more enriched for PI3K/AKT signaling pathway alterations than patients ≥10 y/o (P ≤ .03).

Conclusion: We present findings that suggest "adolescent" DMGs carry more favorable prognosis and are molecularly distinct from earlier onset pediatric DMGs. These findings have implications in the design and interpretation of clinical trials, in addition to informing clinical practice.