Consensus guidelines for the management of posterior fossa tumour for low- and middle-income countries.

The posterior fossa is a limited compartment therefore lesions compressing its structures can result in devastating outcomes. It can cause significant neurological deficit due to mass effect on critical structures and hydrocephalus. Due to the nature of the infratentorial region, urgent surgical intervention is often the first-line option. Surgical neuro-oncologists guide patients and caregivers through the course of this disease and to inform them about the various options for management and long-term outcome optimisation. There is currently conflicting data; however, institutional experiences can guide us towards achieving improvements in surgical outcomes and quality of life. Advances in molecular classifications coupled with highdose radiation treatment improve our capacity for improving overall survival in these patients. Common childhood tumours are ependymomas, medulloblastomas, and juvenile pilocytic astrocytomas, while adults often present with metastases, and less commonly, cerebellar haemangioblastomas and gliomas. This paper outlines management strategies with consideration for multidisciplinary care and resourcelimited settings.

Supratentorial and Infratentorial Ependymoma.

Ependymomas are the third most common intracranial tumor in children, presenting in both the supratentorial and infratentorial compartments. They may present in infants, young children, and adolescents with symptoms depending on size, location, and the age of the patient. The ideal imaging for evaluation and treatment is MRI. This is crucial for preoperative evaluation and planning, as well as postoperative assessment and evaluating the efficacy of treatment. Essentially without exception, aggressive surgery aimed at complete resection is the initial and most important factor in the long-term outcome of all these children. Histopathologic diagnosis for intracranial pediatric ependymoma has been narrowed to grade II and grade III, no longer characterized as classic and anaplastic. Subsequent conformal photon or proton beam irradiation is an established post-surgical therapy, with solid evidence that it benefits survival and offers lower toxicity to the normal brain of the young child. Although chemotherapeutic treatment has not been generally impactful, immunotherapeutic interventions may be on the horizon. Updated molecular subgrouping of ependymoma is changing the post-resection approach of these tumors with regard to both treatment and outcome. Excluding spinal ependymoma and subependymoma, there are four subtypes that are defined by genetic characteristics, two found in the supratentorial compartment, ST-EPN-YAP1 and ST-EPN-ZFTA, and two in the posterior fossa, PF-EPN-A and PF-EPN-B. Younger children harboring ZFTA fusion-positive supratentorial and type A posterior fossa tumors, regardless of histology, tend toward the poorest outcomes. On the contrary, older children with supratentorial YAP1 fusion-positive ependymomas and type B posterior fossa tumors may survive with surgery alone. The paradigm shift regarding the behavior of the various childhood ependymoma subtypes will hopefully lead to targeted, individualized therapies and improved outcomes.

Effects of cognitive-motor intervention for pediatric posterior fossa tumor survivors: results of a pilot study.

The purpose of this prospective pilot study was to evaluate the feasibility and effects of cognitive-motor intervention on the cognitive and motor abilities of pediatric survivors of posterior fossa tumors. The study involved patients aged 7 to 18 years with cognitive deficits who had completed primary treatment for posterior fossa tumors. 25 participants (Mage=11.3 ± 2.93, 64% male; 17 medulloblastoma, 1 ependymoma, 1 desmoplastic medulloblastoma, 6 piloid astrocytoma; 22 in remission (Mmonths =45), 3 in stabilization (Mmonths=49)) were recruited from the Research Institute for Brain Development and Peak Performance. The intervention consisted of two phases with a 3-month break for home training, and a total duration of 6 months. Each phase lasted 7 weeks and included two assessment procedures (pre- and post-intervention) and 10 training sessions over a period of 5 weeks (two 3-hour sessions per week). At baseline and pre- and post-intervention, all participants underwent a battery of cognitive and motor tests. Each training session included gross motor training (GMT), graphomotor training (GT), and cognitive-motor training (CMT). Statistical analysis was performed using the Friedman test for repeated measures and post-hoc Durbin-Conover test. The results indicated significant improvements in visuospatial working memory, visual attention, eye-hand coordination, semantic verbal fluency, auditory-motor synchronization, reaction time, and a decrease in the rate of ataxia. These improvements remained stable even in the absence of direct intervention. The findings demonstrate positive effects and feasibility of the intervention and suggest the need for further research in this area including randomized controlled feasibility studies with a larger sample.

Impact of Molecular Subgroups on Prognosis and Survival Outcomes in Posterior Fossa Ependymomas: A Retrospective Study of 412 Cases.

BACKGROUND AND OBJECTIVES: Posterior fossa ependymomas (PFEs) are rare brain tumors classified as PF-EPN-A (PFA) and PF-EPN-B (PFB) subgroups. The study aimed to evaluate the prognosis and survival outcomes in PFEs, with a focus on the impact of molecular subgroups. METHODS: A retrospective study was conducted on 412 patients with PFEs. Kaplan-Meier survival analyses were conducted to evaluate the overall survival (OS) and progression-free survival. Cox regression analyses were conducted to assess the prognostic factors. A nomogram was developed to predict the OS rates of PFEs. RESULTS: The study revealed significant differences between PFA and PFB in patient and tumor characteristics. PFAs were associated with poorer OS (hazard ratios [HR] 3.252, 95% CI 1.777-5.950, P < .001) and progression-free survival (HR 4.144, 95% CI 2.869-5.985, P < .001). World Health Organization grade 3 was associated with poorer OS (HR 2.389, 95% CI 1.236-4.617, P = .010). As for treatment patterns, gross total resection followed by radiotherapy or the combination of radiotherapy and chemotherapy yielded the most favorable OS for PFA ( P = .025 for both), whereas gross total resection followed by radiotherapy rather than observation showed improved OS for PFB ( P = .046). The nomogram demonstrated a high degree of accuracy and discrimination capacity for the prediction of OS rates for up to 10 years. In addition, 6 cases of PFA (3.51%) with H3K27M mutations were identified. CONCLUSION: PFAs demonstrate worse prognosis and survival outcomes compared with PFBs. Both PFAs and PFBs necessitate maximal resection followed by intensive adjuvant therapies in long-term effects.

Development of Chromosome 1q+ Specific Treatment for Highest Risk Pediatric Posterior Fossa Ependymoma.

PURPOSE: There are no effective treatment strategies for children with highest-risk posterior fossa group A ependymoma (PFA). Chromosome 1q gains (1q+) are present in approximately 25% of newly diagnosed PFA tumors, and this number doubles at recurrence. Seventy percent of children with chromosome 1q+ PFA will die because of the tumor, highlighting the urgent need to develop new therapeutic strategies for this population. EXPERIMENTAL DESIGN: In this study, we utilize 1q+ PFA in vitro and in vivo models to test the efficacy of combination radiation and chemotherapy in a preclinical setting. RESULTS: 5-fluorouracil (5FU) enhances radiotherapy in 1q+ PFA cell lines. Specifically, 5FU increases p53 activity mediated by the extra copy of UCK2 located on chromosome 1q in 1q+ PFA. Experimental downregulation of UCK2 resulted in decreased 5FU sensitivity in 1q+ PFA cells. In in vitro studies, a combination of 5FU, retinoid tretinoin (ATRA), and radiation provided the greatest reduction in cellular proliferation and greatest increase in markers of apoptosis in 1q+ PFA cell lines compared with other treatment arms. Similarly, in vivo experiments demonstrated significant enhancement of survival in mice treated with combination radiation and 5FU and ATRA. CONCLUSIONS: These results are the first to identify a chromosome 1q+ specific therapy approach in 1q+ PFA. Existing phase I studies have already established single-agent pediatric safety and dosages of 5FU and ATRA, allowing for expedited clinical application as phase II trials for children with high-risk PFA.

Oculomotor Impairments in Children After Posterior Fossa Tumors Treatment.

Posterior fossa tumors (PFT) are the most common pediatric brain tumors, and the study of the somatic and cognitive status of PFT survivors still remains a critical problem. Since cerebellar damage can affect eye movement centers located in the vermis and hemispheres, such patients suffer from disturbances in visual perception, visual-spatial functions, reading, etc. Our investigation aimed at describing oculomotor impairments in PFT survivors linked to core oculomotor functions assessed through eye tracking method: gaze holding, reflexive saccades, and organization of voluntary saccades and their dependency on age at tumor diagnosis. Also, we investigated the relationship between oculomotor functions and ataxia measured with International Cooperative Ataxia Rating Scale (ICARS). A total of 110 children (patients and age-matched healthy controls, aged 9-17 years old) participated in the study. We found that the earlier the child had a tumor, the more impaired gaze holding (p = 0.0031) and fewer isometric saccades (p = 0.035) were observed at the time of examination. The above-mentioned functions in healthy controls improved with age. Visual scanning was also impaired compared to controls but was not related to age at diagnosis. A positive correlation between ICARS scores and number of hypermetric saccades (r = 0.309, p = 0.039), but no correlation with the number of hypometric saccades (r = - 0.008, p = 0.956). Furthermore, number of hypometric saccades did not differ between patients and controls (p = 0.238). Thus, primarily hypermetric saccades can be considered a prominent oculomotor symptom of cerebellar tumors. Our study provides basis for new methods of PFT diagnosis and rehabilitation procedure evaluation, both playing essential roles in modern pediatric neurooncology.

Posterior fossa tumors in children: current insights.

While in adults most intracranial tumors develop around the cerebral hemispheres, 45 to 60% of pediatric lesions are found in the posterior fossa, although this anatomical region represents only 10% of the intracranial volume. The latest edition of the WHO classification for CNS tumors presented some fundamental paradigm shifts that particularly affected the classification of pediatric tumors, also influencing those that affect posterior fossa. Molecular biomarkers play an important role in the diagnosis, prognosis, and treatment of childhood posterior fossa tumors and can be used to predict patient outcomes and response to treatment and monitor its effectiveness. Although genetic studies have identified several posterior fossa tumor types, differing in terms of their location, cell of origin, genetic mechanisms, and clinical behavior, recent management strategies still depend on uniform approaches, mainly based on the extent of resection. However, significant progress has been made in guiding therapy decisions with biological or molecular stratification criteria and utilizing molecularly targeted treatments that address specific tumor biological characteristics. The primary focus of this review is on the latest advances in the diagnosis and treatment of common subtypes of posterior fossa tumors in children, as well as potential therapeutic approaches in the future.   Conclusion: Molecular biomarkers play a central role, not only in the diagnosis and prognosis of posterior fossa tumors in children but also in customizing treatment plans. They anticipate patient outcomes, measure treatment responses, and assess therapeutic effectiveness. Advances in neuroimaging and treatment have significantly enhanced outcomes for children with these tumors. What is Known: • Central nervous system tumors are the most common solid neoplasms in children and adolescents, with approximately 45 to 60% of them located in the posterior fossa. • Multimodal approaches that include neurosurgery, radiation therapy, and chemotherapy are typically used to manage childhood posterior fossa tumors What is New: • Notable progress has been achieved in the diagnosis, categorization and management of posterior fossa tumors in children, leading to improvement in survival and quality of life.

[Pediatric posterior fossa tumors]. / Infratentorielle Hirntumoren bei Kindern.

CLINICAL ISSUE: Tumors of the posterior fossa account for about 50-55% of brain tumors in childhood. DIAGNOSTIC WORKUP: The most frequent tumor entities are medulloblastomas, pilocytic astrocytomas, ependymomas, diffuse midline gliomas and atypical teratoid-rhabdoid tumors. Neuroradiological differential diagnosis with magnetic resonance imaging (MRI) is of considerable importance for preoperative planning as well as planning of follow-up therapy. PERFORMANCE: Most important findings for differential diagnosis of pediatric posterior fossa tumors are tumor location, patient age and the intratumoral apparent diffusion assessed by diffusion-weighted imaging. ACHIEVEMENTS: Advanced MR techniques like MRI perfusion and MR spectroscopy can be helpful both in the initial differential diagnosis and in tumor surveillance, but exceptional characteristics of certain tumor entities should be kept in mind. PRACTICAL RECOMMENDATIONS: Standard clinical MRI sequences including diffusion-weighted imaging are the main diagnostic tool in evaluating posterior fossa tumors in children. Advanced imaging methods can be helpful, but should never be interpreted separately from conventional MRI sequences.

Impact of physical activity on postural stability and coordination in children with posterior fossa tumor: randomized control phase III trial.

BACKGROUND: Posterior fossa tumor is a type of brain tumor that is located at the borders of both the brain stem and cerebellum. The cerebellum is the brain region in charge of balance and coordination. Pediatric patients diagnosed with posterior fossa tumor have been reported to fall frequently. OBJECTIVES: The aim of this study is to investigate the effectiveness of balance and coordination training in these children. METHODS: This randomized control clinical trial (ClinicalTrials.gov Identifier: NCT04528316) was carried out between September 2020 and April 2021 at Children's Cancer Hospital-57357. The inclusion criteria were patients with posterior fossa tumor in maintenance phase and, age between 5 and 12 years. The exclusion criteria were patients who had a genetic disorder or suffer from mental retardation, a chronic lung disease, severe cardiomyopathy, or a neuromuscular disease that does not relate to tumor. The study participants were randomly assigned into three groups: Group I/Control group: they received Pilates core stability exercises program, Group II/Postural stability group: they received the same program plus HUMAC balance program, and Group III/Coordination group: they received the same program plus coordination exercises of BOT-2. The semi-parametric proportional odds model was used to compare follow-up scores of the Postural stability group vs Control, and Coordination group vs Control, while adjusting for baseline values. All tests were two sided, with alpha set to 0.05. RESULTS: Sixty children including 38 boys and 22 girls were enrolled in this study. In all three groups, postural stability and coordination improved significantly in terms of modified clinical test of sensory integration of balance, center of pressure, limits of stability, bilateral coordination, and upper-limb coordination. CONCLUSION: The current study supports the value of adding postural stability and coordination training to the physiotherapy plan for children with posterior fossa tumor. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: ClinicalTrials.gov Identifier: NCT04528316 on August 27, 2020.

Comparison of neuropsychological functioning in pediatric posterior fossa tumor survivors: Medulloblastoma, low-grade astrocytoma, and healthy controls.

BACKGROUND: Neuropsychological comparison of medulloblastoma (MB) and cerebellar low-grade astrocytoma (LGA) survivors to controls can clarify treatment-related neurocognitive late effects. While both brain tumor groups undergo surgery to the posterior fossa, children with MB additionally receive craniospinal irradiation with boost and chemotherapy. This study provides an updated comparison of neuropsychological functioning in these two groups and examines effects of demographic risk factors upon outcomes. PROCEDURE: Forty-two children (16 MB, nine LGA, and 17 controls) completed measures of intellectual functioning, verbal learning/memory, visual-motor integration, and fine-motor functioning. The effects of age at diagnosis, time since diagnosis, gender, fatigue, and social status on neuropsychological functioning were examined. RESULTS: MB survivors demonstrated the worst neurocognitive late effects, but they were less severe and extensive than in prior studies. LGA survivors' mean scores were below normative expectations in working memory, processing speed, and fine-motor functioning. In this overall sample, processing speed difficulties were independent of fine-motor functioning and fatigue. Higher parental education was associated with better intellectual functioning, working memory, delayed recall, and visual-motor integration. Neuropsychological function was not associated with gender, age at diagnosis, or time since diagnosis. CONCLUSION: The results support that contemporary treatment approaches with craniospinal irradiation plus boost and chemotherapy confer the greatest risk for late effects, while surgical resection is associated with subtle but important neurocognitive difficulties. Ultimately, this study furthers our understanding of factors impacting neuropsychological function in pediatric MB and LGA survivors and contributes to empirical support for close monitoring and targeted interventions into survivorship.