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Introduction Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare diagnosis first incorporated into the WHO Classification of Tumors of the Central Nervous System in 2016. Though historically considered indolent, emerging evidence suggests that the biological behavior of these tumors may be further classified by molecular features of prognostic significance. Methods A retrospective review was conducted in accordance with IRB approval of patients with the histologic diagnosis of DLGNT. Demographic, clinical, and molecular data where abstracted from the medical record when available. Results 10 patients were identified (M = 8, F = 2). Median age at diagnosis was 6 years (range 0.3–21 years), and the most common symptoms at diagnosis were related to obstructive hydrocephalus, for which 3 patients required CSF diversion. MRI findings included diffuse leptomeningeal thickening, nodularity, or coating of the subarachnoid or ependymal surfaces. Histologically, these tumors expressed variable features of neuronal and/or glial differentiation. Four patients (40%) were treated with radiation therapy (all craniospinal), which was upfront for 2 patients. Chemotherapy regimens used included temozolomide, carboplatin and vincristine and vinblastine. NTRK or BRAF-targeted therapy were used upon progression. At follow-up, 6/10 had stable disease (4/6 of whom were on second line therapy), 1 had partial response, 1 passed away from sepsis and 2 were lost to follow-up. The median progression-free survival for the four patients who developed disease progression was 26 months (range 12–34 months). Next generation sequencing of the tumor tissue performed using a high-multiplex PCR-based NGS panel detected BRAF-KIAA1549 (4 patients) and NTRK (1 patient) fusions. Conclusions DLGNT are rare tumors with scarce data about imaging characteristic and standard of care treatment. Our case series reinforces current literature that although these tumors appear low-grade, they can be clinically aggressive. Further study is needed regarding molecular diagnosis and profiling treatment strategies.

BACKGROUND The is no consensus in best practices for the management of hydrocephalus in patients with Diffuse Intrinsic Pontine Glioma (DIPG). To date, the impact on survival of hydrocephalus and Cerebro-Spinal Fluid (CSF) diversion in this population remains to be elucidated. Herein, we describe our institutional experience. METHODS Patients with a clinical and radiological diagnosis of DIPG were identified at the Hospital for Sick Children between 2000–2019. Images at diagnosis and at disease progression were assessed for hydrocephalus using the frontal-occipital ratio (FOR) method. Proportional hazard analyses were used to identify factors correlated with survival. RESULTS Eighty-nine consecutive patients diagnosed with DIPGs were treated at our institution. At diagnosis, 29% (n=26) of patients presented with hydrocephalus, seven patients underwent CSF diversion. Out of the remaining nineteen patients, n=6 had stable or improved hydrocephalus in follow-up scans, n=6 had persistent hydro and n=2 required CSF diversion at the time of disease progression. Seven did not undergo a follow-up scan. Out of sixty-five patients with imaging at the time of progression, fifty-five percent of patients (n=36) presented with hydrocephalus and ten of them required CSF diversion. On univariate analysis, the presence of hydrocephalus or CSF diversion at diagnosis and/or did not correlate with a survival advantage. CONCLUSIONS CSF diversion for the management of hydrocephalus in patients with DIPG does not impact survival and in some cases resolves spontaneously after the initiation of radiotherapy and steroids. This observation needs to be validated in a prospective cohort.

BACKGROUND Traditionally patients presenting with hydrocephalus in the setting of brain metastases were associated with poor outcomes. However, in the area of improved systemic therapies, the prognosis of brain metastases has improved, warranting investigation into the management of concomitant hydrocephalus. METHODS We conducted a retrospective review of 12 consecutive patients with brain metastases presenting with hydrocephalus treated with either endoscopic third ventriculostomy (ETV) or ventriculoperitoneal shunt (VPS) from June 2013 to December 2018. We then compared our outcomes to 77 historical controls from the literature to test the hypothesis that management of hydrocephalus in patients who respond to systemic therapy is associated with improved outcomes. RESULTS The medial overall survival in our cohort was 182 days compared with 91 days in the reported previous studies, with an odds ratio of 0.5 (95% CI 0.24-1.04). In the 5 patients who underwent ETV, the median survival was 182 days versus 77 days reported in the literature, an odds ratio of 0.42 (95% CI 1.28-1.40). Patients with one brain metastasis did not reach median survival with 4 of 5 patients alive at last follow up, while only 3 of 7 patients with at least two metastases were alive at follow up with a median survival of 182 days. Patients who had immunotherapy were associated with improved survival, while leptomeningeal carcinomatosis still was associated with a negative outcome. CONCLUSIONS Patients with brain metastases and hydrocephalus who underwent neurosurgical CSF diversion had improved survival compared with historical controls, particularly in patients with one metastasis or who received immunotherapy. This study supports initial interdisciplinary evaluation of patients with brain metastases by medical and radiation oncology together with neurosurgery to facilitate immediate systemic therapy after relief of hydrocephalus.

Tectal glioma (TG) is an uncommon pediatric low-grade tumor with limited data on long-term outcome. A retrospective review of TG diagnosed in patients ≤ 21 years at our center between 1986 and 2013 identified 19 patients (males=13; median age at diagnosis=10 years [yrs]; range, 0.01-19.99). All patients were diagnosed based on MRI. Initial CSF diversion was necessary in 16 patients (ventriculoperitoneal [VP] shunt= 10; endoscopic third ventriculostomy=6). Ommaya reservoir was inserted in 5 patients. VP shunt revisions (1-12 times) were required in 7 patients; while 2 patients had subdural hematoma due to over-shunting. Biopsy or resection was performed in 7 patients (upfront=5, at progression=2), with histology showing pilocytic astrocytoma (n=6) or low-grade glioma, NOS (n=1). Duplication of chromosome 7q34, marker of KIAA1549-BRAF fusion, was detected in 2 of 4 patients tested. Adjuvant therapy was delivered in 8 patients mostly upon progression, and included focal radiation (n=4), systemic therapy (n=3), or a combination (n=1). The median duration of follow-up was 9.57 yrs (range, 3.64-16.98): 7 experienced progression at median of 0.68 yrs (range, 0.28-8.98), including 2 with metastases. One patient each died due to suicide, obstructive hydrocephalus, and suspected shunt malfunction. Respective 5- and 10yr overall-survival were 92.9 ± 6.9% and 85.1 ± 9.7%. Long-term morbidities included persistent headache (n=8) and visual symptoms (n=7). Significant impairments were seen on measures of intelligence (n=2/9; 22%), working memory (n=2/7; 29%), and processing speed (n=6/6; 100%). Long-term survival of children with TG is satisfactory. Regular follow-up is recommended due to risks of shunt failure, progression, and long-term morbidities.

Primary diffuse leptomeningeal gliomatosis(PDLG) of high grade glioma(HGG) is a rarely documented phenomenon observed in less than 5% of glioblastoma(GBM). Purposes of this study are to investigate the clinical outcomes of PDLG of HGG and to analyze the results according to the procedures of operations. We retrospectively reviewed the medical records of 469 patients of HGG at our institute between 2004 and 2019 and 9 of who with PDLG were enrolled in our study. These 9 patients satisfying the condition of Karnofsky performance status ≥70 and Eastern Cooperative Oncology Group performance status ≤2 were conducted the primary surgical biopsy with or without intracranial pressure control. All patients finished the surgery within about 11 days after the detection of leptomeningeal seeding(LMS) on preoperative MRI images and completed the concurrent chemoradiotherapy(CCRT) with temozolomide(TMZ). Among 9 patients, 7 patients started adjuvant temozolomide and 3 patients completed the six cycles of it. 7 patients had done ICP control operation such as ommaya reservoir insertion, extraventricular drainage, and ventriculoperitoneal shunt within 23.3 days after defined as PLDG and survived nearly 10 months. Their pathologic findings were turned out to be seven glioblastomas and two anaplastic astrocytomas. Their median overall survival was 14 months and the 1- and 2-year overall survival rates were 50.8±17.7% and 16.9±15%, respectively. Compared to the 10-year study of GBM in the same institute between 2004 and 2011, in which 67 patients finished with CCRT with TMZ, the median overall survival was 19 months and the 1- and 2-year overall survival rates were 78.3% and 41.7%. The results indicate that PLDG has a worse outcome and overall survival rate is lower than GBM without LMS, so the earlier start of standard CCRT right after aggressive control of increased ICP like conducting CSF diversion might be helpful for the elongation of life expectancy.