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Medulloblastomas (MBs) associated with the Wnt activation represent a subgroup with a favorable prognosis, but it remains unclear whether Wnt activation confers a less aggressive phenotype and/or enhances radiosensitivity. To investigate this issue, we evaluated the biological behavior of an MB cell line, UW228-1, stably transfected with human β-catenin cDNA encoding a nondegradable form of β-catenin (UW-B) in standard culture conditions and after radiation treatment. We evaluated the expression, transcriptional activity, and localization of β-catenin in the stably transfected cells using immunofluorescence and WB. We performed morphological analysis using light and electron microscopy. We then analyzed changes in the invasiveness, growth, and mortality in standard culture conditions and after radiation. We demonstrated that (A) Wnt activation inhibited 97 % of the invasion capability of the cells, (B) the growth of the UW-B cells was statistically significantly lower than that of all the other control cells ( p < 0.01), (C) the mortality of irradiated UW-B cells was statistically significantly higher than that of the controls and their nonirradiated counterparts ( p < 0.05), and (D) morphological features of neuronal differentiation were observed in the Wnt-activated cells. In tissue samples, the Ki-67 labeling index (LI) was lower in β-catenin-positive samples compared to non-β-catenin positive ones. The Ki-67 LI median (LI = 40) of the nuclear β-catenin-positive tumor samples was lower than that of non-nuclear β-catenin-positive samples (LI = 50), but the difference was not statistically significant. Overall, our data suggest that activation of the Wnt pathway reduces the proliferation and invasion of MBs and increases the tumor's radiosensitivity. [ABSTRACT FROM AUTHOR]

Papillary glioneuronal tumor is a recently described neoplasm composed of gliovascular pseudopapillae associated with intervening neuronal cells ranging from neurocytes to ganglion cells. This tumor is not currently included in the WHO classification of tumors of the central nervous system. We describe a new case of papillary glioneuronal tumor and analyze the data for a series of further 15 patients from international literature. A 27-year-old man presented to us for generalized seizure. CT and MRI showed a cystic tumor with mural nodule in the left frontal lobe. Frontal craniotomy with gross total removal of the tumor was performed. Histopathological examination was positive for papillary glioneuronal tumor. The clinical, radiologic, and pathological features of our case are strikingly similar to those of the previous reported cases. A review of the literature disclosed only 15 other cases of these tumors. It is important that every new case of PGNT is reported to allow its recognition and classification. [ABSTRACT FROM AUTHOR]

Summary There are conflicting reports regarding gliosarcomas. The goal of this study is to examine clinical, radiological, surgical and therapeutic aspects of 11 patients with gliosarcoma. Between 1993 and 2001, 11 patients with cerebral gliosarcoma were treated at our Institute. Ten patients underwent surgery and one patient had stereotactic biopsy. Four patients received whole brain radiotherapy with 60Co, five underwent radiotherapy with LINAC extended 2 cm beyond the edema margins. One patient refused any additional treatment after surgery and one patient was not treated postoperatively for poor clinical conditions (KPS 40). Chemotherapy (temozolomide) was administered to four patients. Four patients had a prevalence of sarcomatous component that corresponded to surgical and radiological aspects similar to meningioma while six patients showed a prevalence of gliomatous component and radiological and surgical aspects similar to those of glioblastomas. Surgical resection was total in six and subtotal in four patients. Patients with prevalent sarcomatous component showed median survival time more prolonged than patients with prevalent gliomatous component (71 ± 6 weeks vs. 63 ± 6; P=0.0417). Moreover, the survival rate differed in relation to the therapy: patients treated with multimodality therapy (surgery, radiotherapy and chemotherapy) had a longer survival time than patients treated in single or bimodality. Despite prognosis of gliosarcomas remains poor, a multidisciplinary approach (surgery, radiotherapy and chemotherapy) seems to be associated with slight more prolonged survival times. [ABSTRACT FROM AUTHOR]

Purpose: Although pediatric low-grade gliomas (pLGG) are the most common pediatric brain tumors, patient-derived cell lines reflecting pLGG biology in culture are scarce. This also applies to the most common pLGG subtype pilocytic astrocytoma (PA). Conventional cell culture approaches adapted from higher-grade tumors fail in PA due to oncogene-induced senescence (OIS) driving tumor cells into arrest. Here, we describe a PA modeling workflow using the Simian Virus large T antigen (SV40-TAg) to circumvent OIS. Methods: 18 pLGG tissue samples (17 (94%) histological and/or molecular diagnosis PA) were mechanically dissociated. Tumor cell positive-selection using A2B5 was perfomed in 8/18 (44%) cases. All primary cell suspensions were seeded in Neural Stem Cell Medium (NSM) and Astrocyte Basal Medium (ABM). Resulting short-term cultures were infected with SV40-TAg lentivirus. Detection of tumor specific alterations (BRAF-duplication and BRAF V600E-mutation) by digital droplet PCR (ddPCR) at defined time points allowed for determination of tumor cell fraction (TCF) and evaluation of the workflow. DNA-methylation profiling and gene-panel sequencing were used for molecular profiling of primary samples. Results: Primary cell suspensions had a mean TCF of 55% (+/− 23% (SD)). No sample in NSM (0/18) and ten samples in ABM (10/18) were successfully transduced. Three of these ten (30%) converted into long-term pLGG cell lines (TCF 100%), while TCF declined to 0% (outgrowth of microenvironmental cells) in 7/10 (70%) cultures. Young patient age was associated with successful model establishment. Conclusion: A subset of primary PA cultures can be converted into long-term cell lines using SV40-TAg depending on sample intrinsic (patient age) and extrinsic workflow-related (e.g. type of medium, successful transduction) parameters. Careful monitoring of sample-intrinsic and extrinsic factors optimizes the process. [ABSTRACT FROM AUTHOR]

Background: Extensive surgical resection has been found to be associated with longer survival in patients with gliomas, but the interactive prognostic value of molecular pathology of the surgical resection is unclear. This study evaluated the impact of molecular pathology and clinical characteristics on the surgical benefit in WHO grade 3 IDH-mutant gliomas. Methods: Clinical and pathological information of 246 patients with WHO grade 3 IDH-mutant gliomas were collected from the Chinese Glioma Genome Atlas database (2006–2020). The role of the extent of resection on overall survival, stratified by molecular pathology and clinical characteristics, was investigated. We then assessed prognostic factors using a univariate log-rank test and multivariate Cox proportional hazards model in the subgroups. Results: The extent of resection was an independent prognostic factor in the entire cohort, even when adjusted for molecular pathology. Gross total resection was found to be associated with longer survival in all patients and in the astrocytoma group but not in the oligodendroglioma group. Compared with subtotal resections, gross total resections resulted in a longer survival time for astrocytoma patients aged ≤ 45 years. However, there was no survival benefit from total resection in patients with astrocytoma aged > 45 years. Conclusions: Extensive resection benefits only a proportion of patients with WHO grade 3 IDH-mutant gliomas. Younger patients with astrocytomas had survival benefits from extensive resection. In addition to clinical characteristics (especially age), molecular pathology impacted prognosis in patients with gliomas. Our findings provide guiding information to neurosurgeons while planning surgeries. [ABSTRACT FROM AUTHOR]

Despite aggressive management consisting of surgery, radiation therapy (RT), and systemic therapy given alone or in combination, a significant proportion of patients with brain tumors will experience tumor recurrence. For these patients, no standard of care exists and management of either primary or metastatic recurrent tumors remains challenging. Advances in imaging and RT technology have enabled more precise tumor localization and dose delivery, leading to a reduction in the volume of health brain tissue exposed to high radiation doses. Radiation techniques have evolved from three-dimensional (3-D) conformal RT to the development of sophisticated techniques, including intensity modulated radiation therapy (IMRT), volumetric arc therapy (VMAT), and stereotactic techniques, either stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT). Several studies have suggested that a second course of RT is a feasible treatment option in patients with a recurrent tumor; however, survival benefit and treatment related toxicity of reirradiation, given alone or in combination with other focal or systemic therapies, remain a controversial issue. We provide a critical overview of the current clinical status and technical challenges of reirradiation in patients with both recurrent primary brain tumors, such as gliomas, ependymomas, medulloblastomas, and meningiomas, and brain metastases. Relevant clinical questions such as the appropriate radiation technique and patient selection, the optimal radiation dose and fractionation, tolerance of the brain to a second course of RT, and the risk of adverse radiation effects have been critically discussed. [ABSTRACT FROM AUTHOR]

Purpose: The aims of our retrospective study investigated the role of immune system in glioblastoma (GBM), which is the most aggressive primary brain tumor in adults characterized by a poor prognosis. The recurrence rate remains high, probably due to "immune-desert" tumor microenvironment (TME) making GBM hidden from the anti-tumoral immune clearance. Considering this, we aimed to create a panel of prognostic markers from blood and tumor tissue correlating with overall survival (OS) and progression-free survival (PFS). Methods: Firstly, we analyzed the inflammatory markers NLR and PLR as the ratio of the absolute neutrophil count and absolute platelet count by the absolute lymphocyte count respectively, collected at different time points in the peripheral blood of 95 patients. Furthermore, in 31 patients of the same cohort, we analyzed the formalin-fixed paraffin embedded samples to further compare the impact of circulating and inflammatory markers within the TME. Results: Patients aged < 60 years and with methylated MGMT showed better OS. While, pre-chemotherapy Systemic Inflammatory Index (SII) < 480 was related to a better OS and PFS, we observed that only CD68+macrophage and CD66b+neutrophils expressed in vascular/perivascular area (V) showed a statistically significant prognostic role in median OS and PFS. Conclusions: Thus, we underscored a role of SII as predictive value of response to STUPP protocol. Regarding the TME-related markers, we suggested to take into consideration for future studies with new immunotherapy combinations, each component relating to expression of immune infiltrating subsets. [ABSTRACT FROM AUTHOR]

Purpose: We and others have demonstrated that MYC-amplified medulloblastoma (MB) cells are susceptible to class I histone deacetylase inhibitor (HDACi) treatment. However, single drug treatment with HDACi has shown limited clinical efficacy. We hypothesized that addition of a second compound acting synergistically with HDACi may enhance efficacy. Methods: We used a gene expression dataset to identify PLK1 as a second target in MB cells and validated the relevance of PLK1 in MB. We measured cell metabolic activity, viability, and cycle progression in MB cells after treatment with PLK1-specific inhibitors (PLK1i). Chou–Talalay synergy calculations were used to determine the nature of class I HDACi entinostat and PLK1i interaction which was validated. Finally, the clinical potential of the combination was assessed in the in vivo experiment. Results: MYC-amplified tumor cells are highly sensitive towards treatment with ATP-competitive PLK1i as a monotherapy. Entinostat and PLK1i in combination act synergistically in MYC-driven MB cells, exerting cytotoxic effects at clinically relevant concentrations. The downstream effect is exerted via MYC-related pathways, pointing out the potential of MYC amplification as a clinically feasible predictive biomarker for patient selection. While entinostat significantly extended survival of mice implanted with orthotopic MYC-amplified MB PDX, there was no evidence of the improvement of survival when treating the animals with the combination. Conclusion: The combination of entinostat and PLK1i showed synergistic interaction in vitro, but not in vivo. Therefore, further screening of blood–brain barrier penetrating PLK1i is warranted to determine the true potential of the combination as no on-target activity was observed after PLK1i volasertib treatment in vivo. [ABSTRACT FROM AUTHOR]

Purpose: The WHO classification of Tumors of the Central Nervous System represents the international standard classification for brain tumors. In 2021 the 5th edition (WHO CNS5) was published, and this review summarizes the changes regarding IDH-mutant gliomas and discusses unsolved issues and future perspectives. Methods: This review is based on the 5th edition of the WHO Blue Book of CNS tumors (WHO CNS5) and relevant related papers. Results: Major changes include taxonomy and nomenclature of IDH-mutant gliomas. Essential and desirable criteria for classification were established considering technical developments. For the first time molecular features are not only relevant for the classification of IDH-mutant gliomas but may impact grading as well. Conclusion: WHO CNS5 classification moves forward towards a classification which is founded on tumor biology and serves clinical needs. The rapidly increasing knowledge on the molecular landscape of IDH-mutant gliomas is expected to further refine classification and grading in the future. [ABSTRACT FROM AUTHOR]

Purpose: According to the presence or absence of isocitrate dehydrogenase (IDH) mutation, the 2021 WHO classification system bisected diffuse gliomas into IDH-mutant tumors and IDH-wildtype tumors. This study was aimed to evaluate the outcomes of proton radiotherapy treating IDH-mutant diffuse gliomas. Patients and Methods: Between May 2015 and May 2022, a total of 52 consecutive patients with IDH-mutant diffuse gliomas were treated at Shanghai Proton and Heavy Ion Center. Tumor histologies were 33 cases of astrocytoma and 19 cases of oligodendroglioma. Tumor classified by WHO grade 2, 3 and 4 were 22, 25, and 5 cases, respectively. All 22 patients with WHO grade 2 tumors and one patient with brain stem WHO grade 4 tumor were irradiated with 54GyE. The other 29 patients with WHO grade 3 and 4 tumors were irradiated with 60GyE. Temozolomide was recommended to all patients, and was eventually conducted in 50 patients. Results: The median follow-up time was 21.7 months. The 12/24-month progression-free survival (PFS) and overall survival (OS) rates for the entire cohort were 97.6%/78.4% and 100%/91.0% group. Examined by both univariate and multivariate analysis, WHO grade of tumor were of the most significant impact for both PFS and OS. No severe acute toxicity (grade 3 or above) was found. In terms of late toxicity, grade 3 radio-necrosis was developed in one case of oligodendroglioma, WHO grade 3. Conclusion: Proton radiotherapy produced a favorable outcome with acceptable adverse-effects in patients with IDH-mutant diffuse gliomas. [ABSTRACT FROM AUTHOR]

Purpose: As there is no standard of care treatment for recurrent/progressing pediatric high-grade gliomas (pHGG), we aimed to gain an overview of different treatment strategies. Methods: In a web-based questionnaire, members of the SIOPE-BTG and the GPOH were surveyed on therapeutic options in four case scenarios (children/adolescents with recurrent/progressing HGG). Results: 139 clinicians with experience in pediatric neuro-oncology from 22 European countries participated in the survey. Most respondents preferred further oncological treatment in three out of four cases and chose palliative care in one case with marked symptoms. Depending on the case, 8–92% would initiate a re-resection (preferably hemispheric pHGG), combined with molecular diagnostics. Throughout all case scenarios, 55–77% recommended (re-)irradiation, preferably local radiotherapy > 20 Gy. Most respondents would participate in clinical trials and use targeted therapy (79–99%), depending on molecular genetic findings (BRAF alterations: BRAF/MEK inhibitor, 64–88%; EGFR overexpression: anti-EGFR treatment, 46%; CDKN2A deletion: CDK inhibitor, 18%; SMARCB1 deletion: EZH2 inhibitor, 12%). 31–72% would administer chemotherapy (CCNU, 17%; PCV, 8%; temozolomide, 19%; oral etoposide/trofosfamide, 8%), and 20–69% proposed immunotherapy (checkpoint inhibitors, 30%; tumor vaccines, 16%). Depending on the individual case, respondents would also include bevacizumab (6–18%), HDAC inhibitors (4–15%), tumor-treating fields (1–26%), and intraventricular chemotherapy (4–24%). Conclusion: In each case, experts would combine conventional multimodal treatment concepts, including re-irradiation, with targeted therapy based on molecular genetic findings. International cooperative trials combining a (chemo-)therapy backbone with targeted therapy approaches for defined subgroups may help to gain valid clinical data and improve treatment in pediatric patients with recurrent/progressing HGG. [ABSTRACT FROM AUTHOR]

Purpose: Review of the clinicopathologic and genetic features of early ependymal tumor with MN1-BEND2 fusion (EET MN1-BEND2), classical astroblastomas, and recently described related pediatric CNS tumors. I also briefly review general mechanisms of gene expression silencing by DNA methylation and chromatin remodeling, and genomic DNA methylation profiling as a powerful new tool for CNS tumor classification. Methods: Literature review and illustration of tumor histopathologic features and prenatal gene expression timelines. Results: Astroblastoma, originally descried by Bailey and Cushing in 1926, has been an enigmatic tumor. Whether they are of ependymal or astrocytic derivation was argued for decades. Recent genetic evidence supports existence of both ependymal and astrocytic astroblastoma-like tumors. Studies have shown that tumors exhibiting astroblastoma-like histology can be classified into discrete entities based on their genomic DNA methylation profiles, gene expression, and in some cases, the presence of unique gene fusions. One such tumor, EET MN1-BEND2 occurs mostly in female children, and has an overall very good prognosis with surgical management. It contains a gene fusion comprised of portions of the MN1 gene at chromosomal location 22q12.1 and the BEND2 gene at Xp22.13. Other emerging pediatric CNS tumor entities demonstrating ependymal or astroblastoma-like histological features also harbor gene fusions involving chromosome X, 11q22 and 22q12 breakpoint regions. Conclusions: Genomic DNA profiling has facilitated discovery of several new CNS tumor entities, however, traditional methods, such as immunohistochemistry, DNA or RNA sequencing, and cytogenetic studies, including fluorescence in situ hybridization, remain necessary for their accurate biological classification and diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: IDH-wildtype (IDHwt) diffuse gliomas are treated as glioblastoma, however, some of these may show less aggressive clinical courses. The authors investigated the clinical, histopathological, and molecular characteristics of such IDHwt indolent diffuse gliomas (iDGwt), which have not been well documented in the literature. Methods: Adult patients with IDHwt gliomas admitted between 2011 and 2020 were surveyed. In this particular study, the clinical indolence was defined mainly as having a small enhancing lesion and a stable period for more than 1 month before surgery. The current WHO diagnostic criteria were adapted for the diagnoses. Gene mutations and copy number changes in 43 representative glioma-associated genes, MGMT promoter methylation status, and survival data were compared with those of The Cancer Genome Atlas reference cohort. Results: Nine out of 180 surveyed cases (5.0%) fulfilled the present criteria of the iDGwt. Considering the representative regulatory pathways, 8 (88.9%), 4 (44.4%), and 1 (11.1%) case had genetic alterations in the PI3K/MAPK, TP53, and RB pathways, respectively. The frequency of the RB pathway alteration was significantly lower than that in the reference cohort (281 of 362 cases: 77.6%). Two cases (22.2%) showing EGFR amplification met the diagnostic criteria for glioblastoma, and the frequency was significantly lower than that in the reference cohort (412 of 426 cases: 96.7%). The overall survival (median: 37.5 months) in the present series was significantly longer than that in the reference cohort (n = 426, median: 13.9 months). Conclusions: iDGwt lacked the molecular features of glioblastoma except for the PI3K/MAPK pathway alteration. [ABSTRACT FROM AUTHOR]

Purpose: Artificial Intelligence (AI) involves several and different techniques able to elaborate a large amount of data responding to a specific planned outcome. There are several possible applications of this technology in neuro-oncology. Methods: We reviewed, according to PRISMA guidelines, available studies adopting AI in different fields of neuro-oncology including neuro-radiology, pathology, surgery, radiation therapy, and systemic treatments. Results: Neuro-radiology presented the major number of studies assessing AI. However, this technology is being successfully tested also in other operative settings including surgery and radiation therapy. In this context, AI shows to significantly reduce resources and costs maintaining an elevated qualitative standard. Pathological diagnosis and development of novel systemic treatments are other two fields in which AI showed promising preliminary data. Conclusion: It is likely that AI will be quickly included in some aspects of daily clinical practice. Possible applications of these techniques are impressive and cover all aspects of neuro-oncology. [ABSTRACT FROM AUTHOR]

Purpose: Recurrence incidence for paediatric/adolescent high-grade glioma (HGG) exceeds 80%. Reirradiation (reRT) palliates symptoms and delays further progression. Strategies for reRT are scarce: we retrospectively analysed our series to develop rational future approaches. Methods: We re-evaluated MRI + RT plans of 21 relapsed HGG-patients, accrued 2010–2021, aged under 18 years. All underwent surgery and RT + chemotherapy at diagnosis. Pathologic/molecular re-evaluation allowed classification based on WHO 2021 criteria in 20/21 patients. Survival analyses and association with clinical parameters were performed. Results: Relapse after 1st RT was local in 12 (7 marginal), 4 disseminated, 5 local + disseminated. Re-RT obtained 8 SD, 1 PR, 1PsPD, 1 mixed response, 10 PD; neurological signs/symptoms improved in 8. Local reRT was given to 12, followed again by 6 local (2 marginal) and 4 local + disseminated second relapses in 10/12 re-evaluated. The 4 with dissemination had 1 whole brain, 2 craniospinal irradiation (CSI), 1 spine reRT and further relapsed with dissemination and local + dissemination in 3/four assessed. Five local + disseminated tumours had 3 CSI, 1 spine reRT, further progressing locally (2), disseminated (1), n.a. (1). Three had a third RT; three were alive at 19.4, 29, 50.3 months after diagnosis. Median times to progression/survival after re-RT were 3.7 months (0.6–16.2 months)/6.9 months (0.6–17.9 months), improved for longer interval between 1st RT and re-RT (P = 0.017) and for non-PD after reRT (P < 0.001). First marginal relapse showed potential association with dissemination after re-RT (P = 0.081). Conclusions: This is the biggest series of re-RT in paediatric HGG. Considering the dissemination observed at relapse, our results could prompt the investigation of different first RT fields in a randomized trial. [ABSTRACT FROM AUTHOR]

Introduction: Almost 50% of children with intracranial ependymoma experience disease relapse, and their outcomes are extremely poor. The aim of this study was to investigate optimal salvage treatment for pediatric intracranial ependymoma after the first relapse and to identify prognostic factors affecting survival. Methods: We conducted a retrospective analysis of 159 children who underwent initial treatment for intracranial ependymoma at Beijing Tiantan Hospital from 2013 to 2017. Results: Relapse was observed in 73 patients (73/159; 45.9%), with a median age of 7.2 ± 3.5 years old. Molecular subgrouping analysis identified H3K27me3-negative PF-EPNs in 74% of patients, ST-RELA EPNs in 21% of patients, and H3K27me3-positive PF-EPNs in 5% of patients. The 5-year event-free survival (EFS) and overall survival (OS) rates after first relapse were 21.1% (95% CI 16.0–26.2) and 30.5% (95% CI 19.8–30.8), respectively. Patients with GTR at first relapse had higher 5-year EFS and 5-year OS than those with STR (P = 0.031 and P = 0.003) or no surgery (P = 0.007 and P = 0.001). Radiotherapy or re-radiotherapy at first relapse significantly prolonged 5-year EFS and OS (both P < 0.001). Patients with H3K27me3-negative PF-EPN had worse 5-year EFS and OS than those with ST-RELA EPN (P = 0.001 and P = 0.002). Multivariate analysis showed that both tumor resection and radiotherapy at first relapse had independent prognostic significance for survival (all P < 0.05). Conclusion: Children with recurrent intracranial EPN have poor outcomes, and surgery and radiotherapy at first relapse should be encouraged to improve their prognosis. [ABSTRACT FROM AUTHOR]

Purpose: The challenges of treating central nervous system (CNS) tumors in young children are many. These include age-specific tumor characteristics, limited treatment options, and susceptibility of the developing CNS to cytotoxic therapy. The aim of this study was to analyze the long-term survival, health-related, and educational/occupational outcomes of this vulnerable patient population. Methods: Retrospective study of 128 children diagnosed with a CNS tumor under 5 years of age at a single center in Switzerland between 1990 and 2019. Results: Median age at diagnosis was 1.81 years [IQR, 0.98–3.17]. Median follow-up time of surviving patients was 8.39 years [range, 0.74–23.65]. The main tumor subtypes were pediatric low-grade glioma (36%), pediatric high-grade glioma (11%), ependymoma (16%), medulloblastoma (11%), other embryonal tumors (7%), germ cell tumors (3%), choroid plexus tumors (6%), and others (9%). The 5-year overall survival (OS) was 78.8% (95% CI, 71.8–86.4%) for the whole cohort. Eighty-seven percent of survivors > 5 years had any tumor- or treatment-related sequelae with 61% neurological complications, 30% endocrine sequelae, 17% hearing impairment, and 56% visual impairment at last follow-up. Most patients (72%) attended regular school or worked in a skilled job at last follow-up. Conclusion: Young children diagnosed with a CNS tumor experience a range of complications after treatment, many of which are long-lasting and potentially debilitating. Our findings highlight the vulnerabilities of this population, the need for long-term support and strategies for rehabilitation, specifically tailored for young children. [ABSTRACT FROM AUTHOR]

Introduction: Ventriculo-peritoneal shunt (VPS) related ascites is a rare complication of pediatric low grade gliomas (pLGG). Physiopathology of this complication is not fully understood and there is paucity of data regarding the molecular profile of pLGG gliomas complicating with ascites and the optimal management of this unusual event. Methods: International multi-institutional retrospective analysis of patients diagnosed with BRAF altered pLGG and ascites arising as a complication of VPS. Demographics, tumor characteristics, therapeutic approaches and outcomes were recorded. Results: Nineteen patients were identified. Median age at diagnosis was 14 months (R: 2–144). Most patients (17; 89.4%) presented with lesions involving the optic pathway. Mean tumor standard volume was 34.8 cm2 (R: 12.5–85.4). Pilocytic Astrocytoma was the most frequent histological diagnosis (14;7 3.7%). Eight (42.1%) tumors harbored BRAF V600-E mutation and seven (36.8%) KIAA1549 fusion. The onset of ascites was documented at a median time of 5 months following VPS insertion. Four (21%) patients were managed with paracentesis only, 7(36.8%) required both paracentesis and shunt diversion, 7(36.8%) required only a shunt diversion and 1 (5.2%) patient was managed conservatively. Chemotherapy regimen was changed in 10 patients following ascites. Eight patients received targeted therapy (4 dabrafenib/4 trametinib) and 5 were radiated. There were eleven survivors with a median OS of 69 months (R: 3–144). Conclusions: Ascites is an early feature in the clinical course of young patients with midline BRAF altered pLGG, with high mortality rate observed in our cohort. The hypothesis of ascites as an adverse prognostic factor in pLGG warrants further prospective research. [ABSTRACT FROM AUTHOR]