This study aimed to describe the incidence, clinical and pathological features, and outcomes of H3 K27M- mutant Diffuse Midline Glioma (DMG) patients with leptomeningeal dissemination (LMD) and systematically investigate the predictive and prognostic factors to clarify the response to treatment after the onset of LMD. A total of 304 patients diagnosed with DMG from October 17, 2017, to October 17, 2023, were enrolled in this study, of which 32 patients were diagnosed with LMD. Logistic regression analyses were conducted to identify the predictors of LMD, including clinical, molecular, and imaging data. Univariable and multivariable cox regression analyses were used for overall survival (OS) and post-LMD survival (PLS) analysis. The median OS and PLS were 12.5 and 8.0 months respectively. Tumor with contrast-enhanced lesions reaching ependyma (Ventricular contact type I) was the only independent risk factor for LMD. Male sex and ventricular contact type I were independent risk factors for primary LMD. In all LMD patients, Karnofsky Performance Status (KPS) of ≥ 90 and radiotherapy were statistically significantly associated with longer OS, and primary LMD was significantly associated with shorter OS. Supratentorial location and chemotherapy after LMD diagnosis were independent favorable prognostic factors on PLS. In primary LMD subgroup analysis, radiotherapy was the only independent favorable prognostic factor on OS. The association between contrast-enhanced lesions and ventricular involvement is an independent predictive factor for LMD in DMG patients. Radiotherapy and preoperative KPS may contribute to improved overall survival in these patients. Chemotherapy is a potential treatment option following an LMD diagnosis.

Target populationAdults with imaging suggestive of a WHO grade II diffuse gliomas (oligodendrogliomas or astrocytomas)QuestionIn adults with imaging suggestive of a WHO grade II diffuse gliomas (oligodendrogliomas or astrocytomas), does surgical resection improve overall survival compared to observation or biopsy?Updated Recommendation from the Prior Version of These Guidelines:Level III: In adults with imaging suggestive of a WHO grade II diffuse gliomas (oligodendrogliomas or astrocytomas), surgical resection is suggested over observation or biopsy to improve overall survival.Question Q2In adults with imaging suggestive of a WHO grade II diffuse gliomas (oligodendrogliomas or astrocytomas), does maximal surgical resection improve progression free survival (PFS) and overall survival (OS) compared to subtotal resection/biopsy?Unchanged Recommendations from the Prior Version of These GuidelinesLevel II It is recommended that GTR or STR be accomplished instead of biopsy alone when safe and feasible so as to decrease the frequency of tumor progression recognizing that the rate of progression after GTR is fairly high.Level III Greater extent of resection can improve OS in WHO grade II diffuse gliomas patients. New RecommendationsLevel III: It is suggested that extent of resection be maximized as is safely possible for IDH mutant and IDHwt WHO grade II diffuse gliomas. to improve PFS and OS. Level III: There is insufficient evidence that greater extent of resection of 1p19q codeleted oligodendrogliomas (WHO grade II diffuse gliomas) improves OS Question Q3In adults with imaging suggestive of a WHO grade II diffuse gliomas (oligodendrogliomas or astrocytomas), does the addition of intraoperative MRI and/or intraoperative ultrasound during surgery improve extent of resection?Unchanged Recommendation from the Prior Version of These GuidelinesLevel III: The use of intraoperative MRI is suggested to increase the extent of resection for adults with WHO grade II diffuse glioma.New RecommendationLevel III: The use of intraoperative ultrasound is suggested to increase the extent of resection compared to conventional surgery for adults with WHO grade II diffuse glioma.Question 4In adults with imaging suggestive of a WHO grade II diffuse glioma (oligodendrogliomas or astrocytomas) with seizures, does maximal surgical resection improve seizure control compared to observation or subtotal resection/biopsy?Updated Recommendation from the Prior Version of These GuidelinesLevel III: In adults with imaging consistent with a WHO Grade II diffuse glioma who present with seizure activity, surgical resection of greater than 90% of the lesion, when it can be accomplished safely, is suggested over observation or lesser extent of resection/biopsy to improve seizure control.New Questions and RecommendationsQuestion 5In adults with imaging suggestive of a WHO grade II diffuse glioma (oligodendrogliomas or astrocytomas), does use of intraoperative fluorescent guided surgery improve extent of resection?RecommendationLevel III: Intraoperative fluorescent guided surgery with 5-ALA is not suggested to improve the extent of resection for WHO grade II gliomas.Question 6In adults with imaging suggestive of a WHO grade II diffuse glioma (oligodendrogliomas or astrocytomas) in eloquent brain cortex, does awake craniotomy or other methods of intraoperative mapping increase extent of resection compared to conventional surgery without these techniques?RecommendationLevel III: It is suggested that awake craniotomy and other methods of intraoperative mapping can be used to increase the extent of resection for adults with WHO grade II diffuse glioma.Question 7In adults with imaging suggestive of a WHO grade II diffuse glioma (oligodendrogliomas or astrocytomas) in eloquent brain cortex, does use of advanced preoperative imaging modalities in the form of fMRI and/or DTI decrease surgical morbidity?RecommendationLevel III: The use of functional MRI and DTI related modalities are suggested to decrease surgical morbidity in adults with WHO grade II diffuse glioma.

Pediatric meningiomas (PMs) are rare central nervous system tumors, accounting for 1-5% of all meningiomas, and differ from adult meningiomas in clinical, histopathological, and molecular features. Current guidelines primarily focus on adults, leaving a gap in evidence-based management for PMs. This study presents the largest meta-analysis of longitudinal individual patient data (IPD) to date, addressing progression-free survival (PFS) and overall survival (OS) in pediatric patients. Data from 20 studies (2011-2023), including 1010 pediatric meningioma cases, were analyzed to assess PFS and OS stratified by WHO grade, NF1/NF2 status, extent of resection (EOR), and adjuvant radiotherapy. Longitudinal survival data were reconstructed from Kaplan-Meier curves using IPD extraction methods. PMs affect males and females nearly equally (52.1% vs. 47.9%). WHO grade 3 tumors had significantly shorter PFS (72.1months) compared to grades 1 (209.8months) and 2 (137.5months) (p < 0.001). No significant OS difference between WHO grades 1 and 2 PMs were observed. NF1- and NF2-associated tumors showed shorter PFS (59.7 and 138.4months) than sporadic cases (180.6months) (p = 0.02). GTR significantly improved PFS (113.8 vs. 40.1months, p < 0.001) and OS (602.9 vs. 173.8months, p < 0.001). Radiotherapy enhanced PFS (72.5 vs. 23.8months, p = 0.009) and OS (140.7 vs. 63.0months, p = 0.002) in grade 3 tumors but not in WHO grade 2 PMs (p = 0.43). This largest meta-analysis highlights the critical roles of GTR and adjuvant radiotherapy in improving outcomes for high-grade PMs and underscores the urgent need for pediatric-specific management guidelines based on robust longitudinal data.

Glioblastoma (GBM), the most common malignant tumor of the central nervous system (CNS) in adults, continues to result in poor survival rates despite standard treatment. Advancements in understanding GBM's molecular complexity have increased interest in targeted therapeutic approaches. This retrospective, single-center, single-arm study combined nimotuzumab and bevacizumab with radiotherapy (RT) and temozolomide (TMZ) for the treatment of newly diagnosed GBM. The objectives were to determine the efficacy of this treatment combination and the associated toxicity. A retrospective analysis of clinical data of GBM patients treated at our institution from September 2021 to May 2023 with postoperative combination therapy of nimotuzumab, bevacizumab, and TMZ concurrent with RT, as well as maintenance therapy with bevacizumab and TMZ. Follow-ups were performed every 3 to 6months via hospital visits and telephone interviews. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoint was the incidence of adverse events (AEs). A total of 18 patients were included. The median follow-up time was 23months. The one-year PFS rate was 77.8%, and the one-year OS rate was 94.4%. The median PFS was 18months (95%CI, 15.9-20.1), and the median OS was 28months (95%CI, 18.9-37.1). All AEs were controllable. The combination of nimotuzumab and bevacizumab with TMZ and RT appears to demonstrate efficacy and safety in newly diagnosed GBM patients, providing a reference for clinical treatment. Further prospective studies are needed to confirm our results.

Irinotecan demonstrates anti-tumor efficacy in preclinical glioma models but clinical results are modest due to drug delivery limitations. Convection enhanced delivery (CED) improves drug delivery by increasing intratumoral drug concentration. Real-time magnetic resonance imaging of infusate delivery during CED may optimize tumor coverage. This phase 1 trial examines the safety and tolerability of liposomal irinotecan and gadolinium delivered via CED using real-time MRI guidance in recurrent high-grade glioma patients. Initially, a 3 + 3 dose-escalating, single dose trial was planned with 4 cohorts based on a fixed drug dose and volume. After 9 patients, a protocol amendment allowed for variable volume and dose of the study agent based on tumor size. The amended design specified 'personalized' drug volume but fixed concentration of 20mg/mL of liposomal irinotecan in the first cohort escalating to 40mg/mL in the second cohort. Eighteen patients with recurrent WHO grade 3 or 4 gliomas (diameter 1-4cm) were treated. Based on the tumor volume, the total dose of liposomal irinotecan was 20-680mg in a total volume of 2-17ml. Technical challenges were overcome by real-time MRI guidance and protocol amendment. The only dose-limiting toxicity (DLT) was a grade 3 stroke. Safety and survival information is presented. CED of liposomal irinotecan using real-time MRI in patients with recurrent high-grade glioma is feasible. Image-guidance allowed for improved placement of CED cannulas and optimal tumor coverage. Our results warrant further study with repeat CED dosing.

Ependymoma is the third most common brain tumour of childhood and historically has posed a major challenge to both pediatric and adult neuro-oncologists. Ependymoma can occur anywhere in the central nervous system throughout the entire age spectrum. Treatment options have been limited to surgery and radiation, and outcomes have been widely disparate across studies. Indeed, these disparate outcomes have rendered it extraordinarily difficult to compare studies and to truly understand which patients are low and high-risk. Over the past two decades there have been tremendous advances in our understanding of the biology of ependymoma, which have changed risk stratification dramatically. Indeed, it is now well accepted that ependymoma comprises multiple distinct entities, whereby each compartment (supratentorial, posterior fossa, spinal) are distinct, and within each compartment there exist unique groups. The driver events, demographics and response to treatment vary widely across these groups and allow for a better classification of thee disease. Herein, we review the advances in the molecular stratification of ependymoma including how an improved classification and risk stratification allows for more precise therapies.