Diffuse intrinsic pontine glioma (DIPG) is a rare and fatal pediatric brain tumor. Mutation of p53-induced protein phosphatase 1 (PPM1D) in DIPG cells promotes tumor cell proliferation, and inhibition of PPM1D expression in DIPG cells with PPM1D mutation effectively reduces the proliferation activity of tumor cells. Panobinostat effectively kills DIPG tumor cells, but its systemic toxicity and low blood-brain barrier (BBB) permeability limits its application.In this paper, a nano drug delivery system based on functionalized macrophage exosomes with panobinostat and PPM1D-siRNA for targeted therapy of DIPG with PPM1D mutation is prepared. The nano drug delivery system has higher drug delivery efficiency and better therapeutic effect than free drugs. In vivo and in vitro experimental results show that the nano drug delivery system can deliver panobinostat and siRNA across the BBB and achieve a targeted killing effect of DIPG tumor cells, resulting in the prolonged survival of orthotopic DIPG mice. This study provides new ideas for the delivery of small molecule drugs and gene drugs for DIPG therapy.

OBJECTIVE Unlike its pediatric counterpart, adult diffuse intrinsic pontine glioma (DIPG) remains largely unelucidated. In this study, the authors examined the clinical, radiological, pathological, molecular, and clinical aspects of 96 adult DIPGs. METHODS The National Brain Tumor Registry of China (April 2013–December 2019) was used to collect data on radiologically diagnosed adult DIPG patients. Survival analysis was conducted using Kaplan-Meier curves and univariate and multivariate Cox regression. The chi-square test/Wilcoxon rank-sum test and multivariable logistic regression were used to examine the clinical and radiological characteristics of patients with long-term survival (LTS). Interaction analyses between clinical factors were also conducted. RESULTS The median age at symptom onset was 33.5 years, and the median duration of symptoms was 4.5 months. The frequencies of H3K27M and IDH1 mutations were 37.2% and 26.5%, respectively. All adult DIPG patients had a median overall survival (OS) of 19.5 months, with 1-, 2-, and 3-year survival rates of 67.0%, 42.8%, and 36.0%, respectively. The median OS of 40 patients who did not undergo treatment was 13.4 months. Patients with H3K27M-mutant tumors had a poorer prognosis than those with IDH-mutant tumors (p < 0.001) and H3K27M(−)/IDH–wild-type tumors (p = 0.002), with a median OS of 11.4 months. The median OSs of patients with H3K27M-mutant tumors who received treatment and those who did not were 13.8 months and 7.5 months, respectively (p = 0.016). Among patients with and without a pathological diagnosis, H3K27M mutation (p < 0.001) and contrast enhancement on MRI (p = 0.003), respectively, imparted a worse prognosis. Treatments were the predictive factor for patients with H3K27M-mutant tumors (p = 0.038), whereas contrast enhancement on MRI was the prognostic factor for the H3K27M(−) group (p = 0.038). In addition, H3K27M mutation and treatment were significant predictors for patients with symptom duration ≤ 4 months (H3K27M, p = 0.020; treatment, p = 0.014) and tumors with no contrast enhancement (H3K27M, p = 0.003; treatment, p = 0.042). Patients with LTS were less likely to have cranial nerve palsy (p = 0.002) and contrast enhancement on MRI at diagnosis (p = 0.022). CONCLUSIONS It is recommended that all adult DIPG patients undergo genomic testing for H3K27M and IDH mutations. Despite the low prevalence, additional study is needed to better characterize the efficacy of various treatment modalities in adults with DIPG.

Objective Cerebellar liponeurocytomas (CLPNs) are very rare. Limited studies described this disease and their treatment protocol remain unclear. To better understand the disease, we review the clinical features and outcomes, and propose a treatment protocol based on previously reported cases and cases from our institute. Methods The clinical data were obtained from 7 patients with pathologically confirmed CLPNs, who accepted surgical treatment in our institute between November 2011 and June 2021. We also reviewed the literature and 75 patients with CLPNs were identified between September 1993 and June 2021. Risk factors for Progression-free survival (PFS) were evaluated in the pooled cohort. Results The authors’ cohort included 4 males and 3 females with a mean age of 43.9±14.5 (range: 29-64 years). 3 cases are located in lateral ventricle and 4 cases are located in cerebellum. All 7 cases achieved gross total resection (GTR) and radiotherapy was administered to 2 cases. After a mean follow-up of 44.9±44.4 months, all patients remained well with no recurrence or death. For the reported 75 patients, there are 35 males and 40 females with a mean age of 46.2±13.6 years (range: 6-77 years). Biopsy, gross total resection (GTR) and non-GTR were achieved in 1 (1.3%), 50 (66.7%), and 24 (32%) patients, respectively. Radiotherapy was administered to 16 cases and chemotherapy was administered to only 1 case. After a mean follow-up of 47.5±51.5 months, 3 patients died and tumor recurrence occurred in 17 patients. Multivariate Cox analysis revealed that non-GTR predicted a poor PFS (p=0.030). Kaplan-Meier analysis showed that GTR was significantly associated with better PFS (p=0.0084). PFS rates at 1, 5, 10 years were 92.7%, 78.0%, 23.8% respectively. Conclusions Cerebellar liponeurocytomas (CLPNs) are very rare brain tumors. Although they have favorable clinical prognosis, the recurrence is relatively high. GTR should be the first choice and close follow-up is necessary. Postoperative radiotherapy could not improve PFS in this study. A larger cohort is needed to verify our findings.