This guideline was developed under the auspices of the Pediatric Neurosurgery Group of the Neurosurgery Branch of the Chinese Medical Association, the Neuro-oncology Expert Committee of the Chinese Society of Clinical Oncology, and the Neuro-oncology Professional Committee of the China Anti-Cancer Association. Craniopharyngioma is the most common tumor in the sellar turcica region among children, with the majority being adamantinomatous craniopharyngioma (ACP) and a smaller proportion being papillary craniopharyngioma (PCP). Management of craniopharyngioma involves not only tumor control but also the treatment of tumor-related hypothalamic dysfunction and pituitary endocrine disorders. To standardize the diagnosis and management of pediatric craniopharyngioma, this guideline incorporates evidence from 398 literature references. It provides recommendations on diagnostic evaluation, surgical strategies, radiotherapy principles, prognostic assessment, follow-up and long-term management, and targeted therapy. This guideline is intended to serve as a reference for healthcare professionals engaged in pediatric neuro-oncology. Recommendations were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, taking into account the quality of evidence, clinical applicability, and expert consensus. Key recommendations are supported by explanatory rationale. The guideline were reviewed and approved by 35 multidisciplinary experts and 6 external reviewers, followed by formal voting on each recommendation. For areas lacking high-quality evidences, future well-designed clinical trials are recommended to validate and update these recommendations.

H3K27M-mutant diffuse midline glioma (H3K27M-DMG) is a lethal brain tumor predominantly affecting children but increasingly recognized in adults. Emerging evidence suggests potential differences in clinical behavior and survival outcomes between pediatric and adult patients. However, comparative studies remain scarce, and the impact of age on disease progression and treatment response is poorly understood. We conducted a retrospective analysis of 105 patients (51 adults, 54 children) diagnosed with H3K27M-DMG at West China Hospital between January 2016 and August 2021. Clinical data, including demographics, tumor characteristics, treatment modalities, and survival outcomes, were collected. Our analysis revealed that pediatric patients exhibited a shorter median overall survival (OS) than adults (pediatric median OS: 3.65 months [95

In recent years, pediatric brain tumors have emerged as one of the most common malignant tumors among children. The site of tumor growth and the selected treatment modalities can potentially have a profound and significant impact on the reproductive function of pediatric patients, which is intimately associated with the physical and psychological health of children during their developmental process. Current research studies have demonstrated that pediatric patients diagnosed with germ cell tumors, craniopharyngiomas, and medulloblastomas commonly present with reproductive dysfunction. Regrettably, in clinical practice, neurosurgeons frequently fail to allocate sufficient attention to this particular aspect. It is of critical and urgent necessity to explore and elucidate the alterations in reproductive function among pediatric patients with brain tumors, and subsequently institute essential protective measures. This article is dedicated to comprehensively reviewing the latest research advancements regarding the relationship between pediatric brain tumors and reproductive function, thereby providing a valuable reference for safeguarding the reproductive function of pediatric patients afflicted with brain tumors.

OBJECTIVES:The study aims were to explore whether perioperative changes in somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) provide a reliable indicator for assessing postoperative airway management complications. METHODS:The study was a retrospective analysis of patients under 18 years old who underwent posterior cranial fossa surgery between December 2019 and November 2023. Patient demographics, imaging data, surgical records, anesthesia records, neurophysiological data, and airway management complications were reviewed. The airway management complications included extubation failure, tracheostomy, and aspiration. The primary outcome of the study was the efficacy of perioperative changes in SEPs and MEPs for postoperative airway management complications. RESULTS:A reduction in postoperative SEP amplitude was associated with postoperative airway management complications (P = 0.018). The combination of feasible preoperative SEP recording followed by a reduction in postoperative SEP amplitude emerged as a risk factor for complications related to postoperative airway management (P = 0.007). Patients with airway management complications had more days of intubation, and longer intensive care unit and hospital stays compared to negative patients. CONCLUSIONS:The combination of feasible preoperative SEP recording followed by a reduction in postoperative SEP amplitude was a significant risk factor for postoperative airway management complications.

Purpose Diffuse intrinsic pontine glioma (DIPG) is a rare and fatal pediatric malignancy of the brainstem with a lack of effective therapeutic options. This study assesses the efficacy and safety of adding nimotuzumab to temozolomide (TMZ) chemoradiation therapy for newly diagnosed pediatric DIPG. Methods and Materials We conducted an open-label, single-arm, prospective, multicenter study involving children aged 3-15 years with histologically or radiographically confirmed DIPG from April 3, 2021 to April 13, 2023. Nimotuzumab (150 mg/m2/wk) was administered concurrently with local radiation therapy (54 Gy/30 f) and TMZ (75 mg/m2/d) for 6 weeks, followed by adjuvant TMZ (150-200 mg/m2 for 5 consecutive days of a 28-day cycle for 6 cycles) and nimotuzumab (150 mg/m2 biweekly until to disease progression). The primary endpoint was objective response rate (ORR). The secondary endpoints were overall survival (OS), progression-free survival (PFS), and safety. Adverse events were summarized using descriptive statistics. Results Of 48 enrolled patients, with a median age of 7 years (4-14), 28 (58.3%) were histologically confirmed, and 25 (89.3%) had H3K27M mutations. With a median follow-up of 26.5 months (95% CI, 14.6-not applicable), the ORR was 37.5%; the median OS and PFS were 10.5 (8.3-11.2) and 7.8 (5.1-8.4) months; and 1-year OS and PFS rates were 33.3% and 26.9%, respectively. Multivariate analysis showed that a partial response and no steroid use were associated with favorable OS. Distant metastasis was observed in 7 patients (14.6%). The most common grade ≥ 3 treatment-related adverse events were leukopenia (27.1%), lymphopenia (27.1%), and neutropenia (25.0%). Conclusions Adding nimotuzumab to chemoradiation therapy is feasible, with ORR and survival rates favorably comparable with previous data in pediatric DIPG, despite not meeting the prespecified statistical significance for improved ORR compared with historical data. The overall safety profile was manageable, with no new safety concerns.

Hydrocephalus is one of the most common brain disorders and a life-long incurable condition. An empirical "one-size-fits-all" approach of cerebrospinal fluid (CSF) shunting remains the mainstay of hydrocephalus treatment and effective pharmacotherapy options are currently lacking. Macrophage-mediated ChP inflammation and CSF hypersecretion have recently been identified as a significant discovery in the pathogenesis of hydrocephalus. In this study, a pioneering DNA nano-drug (TSOs) is developed by modifying S2 ssDNA and S4 ssDNA with SPAK ASO and OSR1 ASO in tetrahedral framework nucleic acids (tFNAs) and synthesis via a one-pot annealing procedure. This construct can significantly knockdown the expression of SPAK and OSR1, along with their downstream ion channel proteins in ChP epithelial cells, thereby leading to a decrease in CSF secretion. Moreover, these findings indicate that TSOs effectively inhibit the M0 to M1 phenotypic switch of ChP macrophages via the MAPK pathways, thus mitigating the cytokine storm. In in vivo post-hemorrhagic hydrocephalus (PHH) models, TSOs significantly reduce CSF secretion rates, alleviate ChP inflammation, and prevent the onset of hydrocephalus. These compelling results highlight the potential of TSOs as a promising therapeutic option for managing hydrocephalus, with significant applications in the future.

Ivermectin (IVM), a semi-synthetic macrolide parasiticide, has demonstrated considerable effectiveness in combating internal and external parasites, particularly nematodes and arthropods. Its remarkable ability to control parasites has earned it significant recognition, culminating in Satoshi Omura and William C. Campbell's receipt of the 2015 Nobel Prize in Physiology or Medicine for their contributions to the development of IVM. In recent years, investigations have revealed that IVM possesses antitumor properties. It can suppress the growth of various cancer cells, including glioma, through a multitude of mechanisms such as selective targeting of tumor-specific proteins, inducing programmed cell death, and modulation of tumor-related signaling pathways. Hence, IVM holds tremendous potential as a novel anticancer drug. This review seeks to provide an overview of the underlying mechanisms that enable IVM's capacity to suppress glioma. Furthermore, it aims to elucidate the challenges and prospects associated with utilizing IVM as a new anticancer agent.

The clinical features of cerebellar high-grade gliomas (cHGGs) in adults have not been thoroughly explored. This large-scale, population-based study aimed to comprehensively outline these traits and construct a predictive model. Patient records diagnosed with gliomas were collected from various cohorts and analyzed to compare the features of cHGGs and supratentorial HGGs (sHGGs). Cox regression analyses were employed to identify prognostic factors for overall survival and to develop a nomogram for predicting survival probabilities in patients with cHGGs. Multiple machine learning methods were applied to evaluate the efficacy of the predictive model. There were significant differences in prognosis, with SEER-cHGGs showing a median survival of 7.5 months and sHGGs 14.9 months (p < 0.001). Multivariate Cox regression analyses revealed that race, WHO grade, surgical procedures, radiotherapy, and chemotherapy were independent prognostic factors for cHGGs. Based on these factors, a nomogram was developed to predict 1-, 3-, and 5-year survival probabilities, with AUC of 0.860, 0.837, and 0.810, respectively. The model’s accuracy was validated by machine learning approaches, demonstrating consistent predictive effectiveness. Adult cHGGs are distinguished by distinctive clinical features different from those of sHGGs and are associated with an inferior prognosis. Based on these risk factors affecting cHGGs prognosis, the nomogram prediction model serves as a crucial tool for clinical decision-making in patient care.

Abstract BACKGROUND Newly diagnosed pediatric DIPG is a fetal disease with a poor prognosis and lacks of effective treatments. Multiple studies have demonstrated that the median survival time for patients is less than one year. A single-armed, prospective, multicenter study was conducted to evaluate the efficacy and safety of adding nimotuzumab to concurrent chemoradiotherapy for the treatment of newly diagnosed pediatric DIPG. METHODS Patients were 3-15 years old, histologically or imaging confirmed newly diagnosed DIPG, Lansky score ≥ 60, and at least one measurable lesion. Totally 48 patients were enrolled. Nimotuzumab (150mg/m2/w) concurrent chemoradiotherapy (Temozolomide: 75mg/m2 per day. Radiotherapy: 54Gy/30f) were administered for 6 weeks following a maintenance treatment (Nimotuzumab: 150mg/m2 biweekly. Temozolomide: 150-200mg/m2 per day for 5 days every 28 day). The primary endpoint was ORR, with secondary endpoints including 1-year OS rate, PFS and safety. RESULTS Between Apr 3, 2021 and Apr 13, 2023, a total of 48 patients were enrolled with a median age of 7 years old, in which 20 patients radiologically diagnosed DIPG, 28 patients histopathologically confirmed DIPG with 25 (89.3%) had H3K27M mutation. The median follow-up was 15.2 months. The ORR was 31.3% (95%CI, 18.66%-46.25%), mOS was 10.35 months, 1-year OS rate was 27.4% (95%CI, 14.73%-41.73%), mPFS was 6.93 months, and 1-year PFS was 9.5% (95%CI, 2.46%-22.56%). Eight patients (16.7%) experienced grade 3 or above ADRs. The most common toxicities were neutropenia (40%), leukopenia (25.0%), thrombocytopenia (25.0%). anemia (5.0%), flank pain (5.0%). CONCLUSIONS Nimotuzumab combined with concurrent chemoradiotherapy showed survival benifit for newly diagnosed pediatric DIPG patients with tolerable toxicity.

H3K27M mutation status significantly affects the prognosis of patients with diffuse midline gliomas (DMGs), but this tumor presents a high risk of pathological acquisition. We aimed to construct a fully automated model for predicting the H3K27M alteration status of DMGs based on deep learning using whole‐brain MRI.

Family with sequence similarity 20 C (FAM20C) is a Golgi protein kinase that phosphorylates the serine residue in the S-x-E/pS motif of target proteins. FAM20C phosphorylates most secreted proteins, which play important roles in multiple biological processes, including cancer progression, biomineralization, and lipid homeostasis. Numerous studies have documented the potential contribution of FAM20C to the growth, invasion, and metastasis of glioma, breast cancer, and other cancers, as well as to the mineralization process of teeth and bone. In addition, FAM20C has been found to be associated with the occurrence and development of certain cardiovascular diseases and endocrine metabolism disorders. It raises hopes that understanding the disease-specific mechanisms of FAM20C may hold the key to developing new strategies for these diseases. This review comprehensively covers the existing literature to provide a summary of the structure and biological functions of FAM20C, with a particular focus on its roles in the disease context.

Diffuse midline glioma-H3K27M mutant (DMG) and glioblastoma (GBM) are the most lethal brain tumors that primarily occur in pediatric and adult patients, respectively. Both tumors exhibit significant heterogeneity, shaped by distinct genetic/epigenetic drivers, transcriptional programs including RNA splicing, and microenvironmental cues in glioma niches. However, the spatial organization of cellular states and niche-specific regulatory programs remain to be investigated. Here, we perform a spatial profiling of DMG and GBM combining short- and long-read spatial transcriptomics, and single-cell transcriptomic datasets. We identify clinically relevant transcriptional programs, RNA isoform diversity, and multi-cellular ecosystems across different glioma niches. We find that while the tumor core enriches for oligodendrocyte precursor-like cells, radial glial stem-like (RG-like) cells are enriched in the neuron-rich invasive niche in both DMG and GBM. Further, we identify niche-specific regulatory programs for RG-like cells, and functionally confirm that FAM20C mediates invasive growth of RG-like cells in a neuron-rich microenvironment in a human neural stem cell derived orthotopic DMG model. Together, our results provide a blueprint for understanding the spatial architecture and niche-specific vulnerabilities of DMG and GBM.

Bromodomain-Containing Protein 4 (BRD4) is a member of the BET family of bromodomains, which participates in gene transcription process and is closely related to tumor progression. We observed the up-regulated expression of BRD4 in colorectal cancer (CRC) after doxorubicin (DOX) treatment, which might be a potential mechanism for DOX resistance. This study constructed the tumor-targeting (cyclo (Arg-Gly-Asp-D-Phe-Lys)-poly(ethylene glycol)-poly(ε-caprolactone)) (cRGD-PEG-PCL) copolymer for co-delivery of DOX and BRD4 PROTAC degrader ARV-825 (ARV-DOX/cRGD-P) for CRC treatment. The ARV-DOX/cRGD-P complexes elicited synergistic anti-tumor effect via cell cycle arrest and the increased cell apoptosis, and mechanism studies implicated the regulation of proliferation- and apoptosis-related pathways in vitro. Moreover, the administration of ARV-DOX/cRGD-P significantly improved anti-tumor activity in subcutaneous colorectal tumors and colorectal intraperitoneal disseminated tumor models in mice by promoting tumor apoptosis, suppressing tumor proliferation and angiogenesis. Taken together, these data reveal that ARV-825 can heighten DOX sensitivity in CRC treatment and BRD4 is a potential therapeutic target for DOX-resistant CRC. The ARV-DOX/cRGD-P preparations have outstanding anti-cancer effects and may be used for clinical treatment of colorectal cancer in the future.

Background: Hemangiopericytoma (HPC) is a tumor originating from pericytes surrounding the capillary walls. Most HPCs grow slowly, but some display aggressive growth. Treatment for HPC is total resection or resection plus adjuvant radiation. Case presentation: A 14-year-old girl presented with a blood vessel-rich tumor with a smooth surface located on the left side of the parietal bone, attached to the inner surface of the skull. The dura was completely intact. The final diagnosis was HPC based on the histopathologic and immunohistochemical findings. The patient underwent total resection of the tumor and cranioplasty. The dura was not incised because of the lack of invasive growth. Within the 2-year follow-up, the patient showed an excellent prognosis without any local recurrence or positive radiologic features. Conclusion: The patient presented with common intracranial hypertension symptoms. A blood vessel-rich tumor with a smooth surface was attached to the inner surface of the skull with the dura completely intact. Simple surgical resection without radiotherapy offered an excellent prognosis during 2 years of follow-up.

Background: The prognosis of diffuse midline glioma (DMG) patients with H3K27M (H3K27M-DMG) alterations is poor; however, a model that encourages accurate prediction of prognosis for such lesions on an individual basis remains elusive. We aimed to construct an H3K27M-DMG survival model based on DeepSurv to predict patient prognosis. Methods: Patients recruited from a single center were used for model training, and patients recruited from another center were used for external validation. Univariate and multivariate Cox regression analyses were used to select features. Four machine learning models were constructed, and the consistency index (C-index) and integrated Brier score (IBS) were calculated. We used the receiver operating characteristic curve (ROC) and area under the receiver operating characteristic (AUC) curve to assess the accuracy of predicting 6-month, 12-month, 18-month and 24-month survival rates. A heatmap of feature importance was used to explain the results of the four models. Results: We recruited 113 patients in the training set and 23 patients in the test set. We included tumor size, tumor location, Karnofsky Performance Scale (KPS) score, enhancement, radiotherapy, and chemotherapy for model training. The accuracy of DeepSurv prediction is highest among the four models, with C-indexes of 0.862 and 0.811 in the training and external test sets, respectively. The DeepSurv model had the highest AUC values at 6 months, 12 months, 18 months and 24 months, which were 0.970 (0.919–1), 0.950 (0.877–1), 0.939 (0.845–1), and 0.875 (0.690–1), respectively. We designed an interactive interface to more intuitively display the survival probability prediction results provided by the DeepSurv model. Conclusion: The DeepSurv model outperforms traditional machine learning models in terms of prediction accuracy and robustness, and it can also provide personalized treatment recommendations for patients. The DeepSurv model may provide decision-making assistance for patients in formulating treatment plans in the future.

Current treatment of glioma is hampered due to the physical blood-brain barrier (BBB) and the resistance to traditional chemotherapeutic agents. Herein, we proposed a combined treatment strategy based on Cyclo (Arg-Gly-Asp-d-Phe-Lys) (cRGDfk) peptides-modified nanoparticle named cRGD-P in a self-assembly method for the co -delivery of doxorubicin (DOX) and BRD4 PROTAC degrader ARV-825 (ARV). Molecular dynamics simulations showed that cRGD-P could change its conformation to provide interaction sites for perfectly co-loading DOX and ARV. The cRGD-P/ARV-DOX exhibited an average size of 39.95 nm and a zeta potential of-0.25 mV. Increased expression of BRD4 in glioma cells was observed after being stimulated by cRGD-P/DOX, confirming one of the possible mechanisms of DOX resistance and the synergistic tumor inhibition effect of BRD4 degrading ARV combined with DOX. In the study, the combination of DOX and ARV in the cRGD-P nanoparticle system exhibited synergistic suppression of tumor growth in glioma cells on account of cell cycle arrest in the G2/M phase and the activation of tumor cells apoptosis-related pathways including triggering caspase cascade and downregulating Bcl-2 as well as upregulating Bax. The cRGD-P/ARV-DOX system could effectively suppress the heterotopic and orthotopic growth of glioma by increasing tumor apoptosis, inhibiting tumor proliferation, and decreasing tumor angiogenesis in vivo. Therefore, the cRGD-modified nanoparticle to co-deliver DOX and ARV provides a potential platform for exploiting a more effective and safer combination therapy for glioma.

Background Intracranial germinomas are uncommon and constitute less than 1% of all intracranial tumors. They usually arise in the midline of the brain, most commonly in the pineal region. Pineal germinomas tend to spread through the cerebrospinal fluid (CSF). However, pineal germinomas with fast-developing diffuse subarachnoid/leptomeningeal dissemination are extremely rare, especially in young children. Methods The case of a 4-year-old boy with a pineal germinoma who died of diffuse subarachnoid/leptomeningeal dissemination 1 month after radiotherapy is reported. A PubMed search with specific key terms was used to review cases of pineal germinomas with metastasis. Results The patient presented with a two-week history of worsening headache, visual disturbances and nonprojectile vomiting. Parinaud's sign was positive on physical examination. Head computed tomography (CT)/magnetic resonance imaging (MRI) revealed a lesion in the pineal region with eccentric calcification and obvious supratentorial hydrocephalus. Pineal germinoma was suspected. A ventriculoperitoneal (VP) shunt followed by focal radiotherapy ameliorated the headaches and visual disturbances. The patient was discharged home without further treatment due to financial difficulties. One month after discharge, he was readmitted due to worsening headache, vomiting and lethargy. MRI showed a decrease in the size of the pineal lesion but revealed a diffuse leptomeningeal enhancement including the sulcus, basal cistern, prepontine cistern, and supravermian cistern. The patient's condition deteriorated rapidly, and he died 26 hours after readmission. The characteristics of pineal germinomas with metastasis are reported based on a review of the literature. Conclusions Metastases in pineal germinomas predominately occur in adolescents or young adults, most commonly as spinal "drop metastases." Dissemination usually develops several years after the initial tumor diagnosis and has a relatively good clinical prognosis. However, fast widespread subarachnoid/leptomeningeal dissemination and sudden death may occur in a young child before salvage treatment, as in the presented case.

Purpose We aimed to explore the influence of preoperative gamma knife treatment on the clinical effect of microsurgical resection of vestibular schwannoma. Methods The data of patients who underwent vestibular schwannoma resection in our hospital between November 2010 and December 2019 were retrospectively collected. According to the data collected retrospectively and the inclusion and exclusion criteria, we selected these patients and divided them into Group A (with preoperative gamma knife treatment) and Group B (without preoperative gamma knife treatment). The pre/postoperative clinical manifestations, neurological function grade, postoperative complications, tumor recurrence and increase were collected and compared between the two groups. Results There were 40 and 823 patients enrolled in Groups A and B, respectively. There were no significant differences in the general condition, tumor size and side, or neurological performance of the patients in those two groups before the operation. At the last follow-up, the number of patients with poor facial nerve function was 15 (39.5%) in Group A and 170 (20.7%) in Group B (P = 0.021 < 0.05). In Group A and Group B, disequilibrium occurred in 14 (36.8%) patients and 124 (15.1%) patients, respectively, after the operation (P = 0.012 < 0.05). Seven (17.5%) patients had pneumonia in Group A, and 21 (2.6%) patients had pneumonia in Group B (P = 0.04 < 0.05) after the operation. Conclusion When a patient with vestibular schwannoma undergoes microsurgical surgery, the preoperative history with gamma knife treatment may make recovery from postoperative facial paralysis difficult for the patients, making them more prone to suffer from postoperative disequilibrium and postoperative pneumonia.