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: NeuroNavigation (NN) is a widely used intraoperative imaging guidance technique in neurosurgical operations; however, its value in brainstem glioma (BSG) surgery is inadequately reported and lacks objective proof. This study aims to investigate the applicational value of NN in BSG surgery.Method: A retrospective analysis was performed on 155 patients with brainstem gliomas who received craniotomy from May 2019 to January 2022 at Beijing Tiantan Hospital. Eighty-four (54.2%) patients received surgery with NN. Preoperative and postoperative cranial nerve dysfunctions, muscle strength, and Karnofsky (KPS) were evaluated. Patients’ radiological features, tumor volume, and extent of resection (EOR) were obtained from conventional MRI data. Patients’ follow-up data were also collected. Comparative analyses on these variables were made between the NN group and the non-NN group.Result: The usage of NN is independently related to a higher EOR in diffuse intrinsic pontine glioma (DIPG) (p=0.005) and non-DIPG group (p<0.001). It was observed that fewer patients in the NN group suffered from deterioration of KPS (p=0.032) and cranial nerve function (p=0.017) in non-DIPG group, and deterioration of muscle strength (p=0.040) and cranial nerve function (p=0.038) in DIPG group. Moreover, the usage of NN is an independent protective factor for the deterioration of KPS (p=0.04) and cranial nerve function (p=0.026) in non-DIPG patients and the deterioration of muscle strength (p=0.009) in DIPG patients. Furthermore, higher EOR subgroups were found to be independently related to better prognoses in DIPG patients (p=0.008).Conclusion: NN has significant value in BSG surgery. With the assistance of NN, BSG surgery achieved higher EOR without deteriorating patients’ functions. In addition, DIPG patients may benefit from the appropriate increase of EOR.

Purpose: It remains unclear as to whether patients with brainstem tumor experience complex neuropsychiatric problems. In this cohort study, we specifically investigated behavioral, emotional and cognitive symptoms in pediatric patients with brainstem glioma and healthy individuals. Methods: A total of 146 patients with pediatric brainstem tumors (aged 4–18 years old) and 46 age-matched healthy children were recruited to assess their behaviors and emotions examined by the Child Behavior Checklist. A variety of clinical factors were also analyzed. Results: There were significant differences in most behavioral and emotional symptoms between pediatric patients and healthy subjects. Moreover, patients with pons tumors exhibited significantly higher scores than patients with medulla oblongata tumors (p = 0.012), particularly in concerning the syndrome categories of Withdrawn (p = 0.043), Anxious/depressed symptoms (p = 0.046), Thought Problems (p = 0.004), Attention deficits (p = 0.008), Externalizing problems (p = 0.013), and Aggressive behavior (p = 0.004). A tumor body located in the pontine (p = 0.01, OR = 4.5, 95% CI = 1.4–14.059) or DIPG in the midbrain (p = 0.002, OR = 3.818, 95% CI = 1.629–8.948) appears to act as a risk factor that is associated with more problems in patients with neuropsychiatric symptoms. Conclusions: Pediatric patients with brainstem tumors exhibit severe behavioral and emotional problems. Tumor invades the pontine and midbrain act a risk factor with more problems. It suggests that structural and functional abnormalities in the brainstem will cause prolonged behavioral problems and emotional-cognitive dysfunctions in young children.