Infratentorial Tumors Research Articles

ATRT-11. Anatomico-biological correlations define a new layer for ATRT molecular subgroups pointing to potential lineages of origin

Atypical teratoid rhabdoid tumors (ATRT) are divided in three molecular subgroups, the so-called MYC, TYR and SHH subgroups. This heterogeneity suggests some diversity in the cells of origin, which remain hypothetical thus far. A careful radiological review of 55 MRI at diagnosis was performed in parallel with a careful analysis of mouse tumor origin in the Rosa26-CreERT2::Smarcbflox/flox model. Methylation, bulk RNAseq and scRNAseq analyses were integrated to these anatomic information to highlight potential origin for each molecularly and anatomically defined subgroups. We demonstrated that mouse Myc-ATRTs derive from extra-parenchymal meningeal areas, a finding consistant with many human MYC ATRT being clearly of intra-cranial extra-axial origin. Although this finding could point to a neural crest origin, transcriptomic features fail to unravel any lineage-specific signature. We also defined a distinct supra-tentorial SHH ATRT subgroup, characterized both in mouse and Humans by neural features pointing to the ganglionic eminence progenitors as the candidate origin. Finally we identified a distinct infra-tentorial SHH ATRT subgroup, not observed in mice, with hindbrain/midbrain boundary progenitor signature. scRNAseq from human SHH infra-tentorial tumors consistently suggest a dedifferentiation process involving the Notch pathway in the oncogenic transformation of hindbrain/midbrain neural progenitors.

LINC-19. Epidemiological Profile And Management Trends in Pediatric Brain Tumour Patients – 15 Year Experience From a Tertiary Neuro-Oncology Centre In South Asia

INTRODUCTION: Brain tumour in pediatric age group are the most common solid tumour. Commonly occurring tumours include astrocytomas, medulloblastoma and ependymoma. Astrocytoma and medulloblastoma are common in Europe as compared to the Asian countries. AIM: To study the epidemiological profile and trends in management of pediatric brain tumor patients treated at a tertiary Neuro-oncology center. MATERIALS AND METHODS: This a retrospective audit of a prospectively maintained neurosurgical database from January 2007 to December 2021. All pediatric cases (< 18 years) operated by the neurosurgical oncology unit during the study period were included for analysis. CSF diversions and non oncologic surgical procedures were excluded. Demography, referral pattern, surgical and pathological variables of these patients was analyzed from the database and electronic medical records. Patients with missing data were excluded from analysis. RESULTS: 668 patients underwent oncologic surgical procedures. There was a male preponderance (60%) and 35% of children were in the age group of 5-11 years. Hospital received maximum referral from the parent city and state (46%) followed by north india (21%). Supratentorial tumours (52 %) were seen more commonly as compared to infratentorial tumours (39 %). Astrocytoma (31 %) and embryonal tumours( 25 %) were the common histological types. On subset analysis, both astrocytic (70%) and embryonal tumours (57%) were more common in children more than five years. Intraoperative neuromonitoring, intraoperative ultrasound and navigation were used during the surgical procedures as necessary. CONCLUSION: This study is one of the largest single institution analysis of pediatric brain tumours demonstrating trends in the demographic, surgical and pathological variables over 15 years and the observed pattern is similar to published literature from Indian subcontinent.

SURG-11. Evaluation of surgical results and predictive factors of hydrocephalus in pediatric patients with posterior fossa tumors

Abstract INTRODUCTION: Infratentorial tumors represent 45 to 60% of all brain tumors in children and are associated with hydrocephalus in 70 to 90% of cases. The aim of this study is to describe and analyze the surgical results and correlate them with the incidence of hydrocephalus, as well as identify predictive factors of hydrocephalus in patients underwent to a surgical treatment of posterior fossa tumors. METHODS: This is a retrospective observational study, based on demographic, clinical and radiological information of pediatric patients underwent to surgical resection of posterior fossa tumors by a single group between 2011 and 2019. RESULTS: We included 135 patients with a mean age of 7.56 years, mean follow-up of 35.7 months and overall survival of 18.8 months. Considering the histology, most tumors were pilocytic astrocytomas (34.1%), followed by medulloblastomas (27.4%) Total resection was achieved in 77.8% and tumor recurrence was observed in 16.2%. The rate of hydrocephalus was 36.3%, with most shunt procedures performed preoperatively. There was a high rate of complications associated with shunting (42.9%), mostly represented by infection (71.5%). Patients with hydrocephalus were younger (p = 0.001), showing a faster evolution between the onset of symptoms and diagnosis (p = 0.008). Tumor volume (p = 0.1) and location (p = 0.32) were not statistically significant for hydrocephalus, however, the presence of leptomeningeal disease (p = 0.001) was. The resection rate was also significant, with lesions totally resected showing the best results (p = 0.009). Regarding tumor histology, 33.3% of patients with medulloblastoma and 62.5% of patients with ependymoma were shunted. CONCLUSION: One third of children with posterior fossa tumors will require a shunt procedure. Some factors should guide the neurosurgeon during patient counseling and surgical planning to minimize the use of permanent shunts and avoid related complications.

Summary of virtual tumor board platforms and implementation in neuro-oncology.

e13604 Background: Virtual tumor board [VTB] platforms are an important aspect of cancer management. They enable easier access to a multidisciplinary team of experts. VTBs are an emerging resource across various cancer care networks in the United States. Methods: We performed a systematic search of all VTBs incorporating a platform designed for this specific role. We reviewed Xcures, Genomet, Oncolens, Navify Tumor Board, Medical University of South Carolina [MUSC] Virtual Tumor Board, Virtual Tumor Board Tahoe Forest Cancer Center, UC Davis Health Care Center VTB and MassiveBio. Summary data examined include year of launch, demographics, characteristics of cases, average response time, advantages, and how they handle protected health information. Results: 30% of all VTBs examined launched in 2017. All had a HIPAA compliant online environment. Xcures records were reviewed where the median age of female patients was 57yrs and the median age of male patients was 55 years. The data showed that 44% (4.4 out of every 10 patients) with a confirmed treatment chose VTB integrated option. 76% of patients in Xcures registry consist primary CNS tumors. With at least 556 patients in tumor registry which included 46% Glioblastoma cases [96% primary;, 4% secondary], 13% Diffuse midline glioma with H3K27M-mutant cases, 5% Diffuse intrinsic pontine glioma cases, 3% Astrocytoma and Diffuse Astrocytoma cases, 3% Anaplastic astrocytoma cases; Glioma and Diffuse Glioma, 1% Anaplastic Oligodendroglioma cases and &lt; 1% Gliosarcoma, Oligodendroglioma, Pilocytic astrocytoma, Anaplastic pleomorphic Xanthoastrocytoma, Fibrillary astrocytoma, Oligoastrocytoma and Pleomorphic Xanthoastrocytoma cases. In the MUSC VTB, 9 neuro-oncology cases were reviewed. They meet weekly, and average response time was within 24hrs of case review.Patient demographics were not recorded. Genomet Virtual Board de-identifies all patient information; this is a virtual platform primarily focused on neuro-oncology cases. Cases involved a median of 5 specialist most commonly neuro-oncologists, neurosurgeons, radiation oncologists, molecular pathologists and neuroradiologists. Participants had an average of 23 cases reviewed. Case review revealed an age range from 6 months to 84 years [mean age 44.5 years] with 69.6% males and 30.4% females, 43.5% glioblastoma, 8.7% adenocarcinoma, 8.7% infra-tentorial tumor, &lt; 5% each: pineoblastoma, melanoma, hemangioblastoma and pilocytic astrocytoma. Average response time observed in all cases was ≤24 hours. Detailed metrics for number/percentages of brain tumor cases were not available for most other platforms at time of submission. This will be updated at presentation. Conclusions: VTBs have allowed for quicker expert analysis of cases. This has resulted in an accelerated number of cases reviewed with a shortened communication time. More studies are needed to gain additional insight into user engagement

Preoperative and postoperative high angular resolution diffusion imaging tractography of cerebellar pathways in posterior fossa tumors.

This study aimed to utilize high angular resolution diffusion magnetic resonance imaging (HARDI) tractography in the mapping of the pathways of the cerebellum associated with posterior fossa tumors (infratentorial neoplasms) and to determine whether it is useful for preoperative and postoperative evaluation. Retrospective data from 30 patients (age 2-16 yr) with posterior fossa tumor (17 low grade, 13 high grade) and 30 age-sex-matched healthy controls were used. Structural and diffusion-weighted images were collected at a 3-tesla scanner. Tractography was performed using Diffusion Toolkit software, Q-ball model, FACT algorithm, and angle threshold of 45 degrees. Manually assessed regions of interest were placed to identify reconstructed fiber pathways passing through the superior, medial, and inferior cerebellar peduncles for the preoperative, postoperative, and healthy control groups. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), and track volume measures were obtained and analyzed. Statistically significant differences were found between the preop/postop, preop/control, and postop/control comparisons for the volume of the tracts in both groups. Displacement and disruption of the pathways seemed to differ in relation to the severity of the tumor. The loss of pathways after the operation was associated with selective resection during surgery due to tumor infiltration. There were no FA differences but significantly higher ADC in low-grade tumors, and no difference in both FA and ADC in high-grade tumors. The effects of posterior fossa tumors on cerebellar peduncles and reconstructed pathways were successfully evaluated by HARDI tractography. The technique appears to be useful not only for preoperative but also for postoperative evaluation.

Clinical significance of NF2 alteration in grade I meningiomas revisited; prognostic impact integrated with extent of resection, tumour location, and Ki-67 index

NF2 alteration is the most commonly–found genetic abnormality in meningiomas and is known to initiate events for aggressive-type meningiomas. Whereas the prognosis of meningiomas differs depending on their epigenomic/transcriptomic profile, the effect of NF2 alteration on the prognosis of benign meningiomas is not fully elucidated. This study aimed to probe the importance of NF2 alteration in prognosis of WHO grade I meningiomas. A long-term retrospective follow-up (5.3 ± 4.5 years) study involving 281 consecutive WHO grade I meningioma patients was performed. We assessed tumour recurrence in correlation with extent of resection (EOR), histopathological findings, tumour location, and NF2 alteration. “NF2 meningioma” was defined as meningiomas with presence of NF2 mutation and/or 22q loss. Overall, NF2 meningioma per se was not a predictor of prognosis in the whole cohort; however, it was a predictor of recurrence in supratentorial meningiomas, together with EOR and Ki-67. In a striking contrast, NF2 meningioma showed a better prognosis than non-NF2 meningioma in infratentorial lesion. Supratentorial NF2 meningiomas had higher Ki-67 and forkhead box protein M1 expression than those of others, possibly explaining the worse prognosis in this subtype. The combination of NF2 alteration, high Ki-67 and supratentorial location defines subgroup with the worst prognosis among WHO grade I meningiomas. Clinical connotation of NF2 alteration in terms of prognosis of WHO grade I meningioma differs in an opposite way between supratentorial and infratentorial tumors. Integrated anatomical, histopathological, and genomic classifications will provide the best follow-up schedule and proactive measures.

Infra-tentorial brain tumor subtypes in children and adults\u2014surgical outcome in an ethnic population with a single regional tertiary center

BackgroundTo analyze clinically and radiologically the surgical outcome like residual disease, progression of disease, recurrence, disabilities, event-free survival (EFS), and mortality of different infra-tentorial tumor subtypes in children and adults of a strictly non-migratory and ethnic population.MethodsThe 410 histologically proved, out of 589, infra-tentorial brain tumor patients were analyzed clinically and by the imaging post-surgically in a single tertiary center for an ethnic region. In this analytico-observational study, retrospectively postoperative records of 589 infra-tentorial brain tumors from November 1998 to December 2018 (20 years) were retrieved, scrutinized, and compiled. The post-operative clinic-radiological records of 410 patients with proved histopathological examination results were included. Statistical law of variance was applied where-ever necessary.ResultsThe 63.2% of the all 410 operated infra-tentorial brain tumors were males while females predominated in meningiomas and pineoblastomas. About 31.7% infra-tentorial tumors were children (below 18 years). About 54.1% cases were histologically malignant. The residual tumors comprised 40.2% and symptoms of disease-progression occurred in 10.9%. The tumor recurrence occurred in 14.3% while 6.0% patients developed severe disability. The overall mortality was 11.4% but 18.9% in malignant tumors. The event-free survival (EFS) for all the patients was 66.0%, patients with malignancies had 47.7% and benign group had 87.7%.ConclusionThe study, surgical outcome of infra-tentorial brain tumor subtypes in children and adults (approx. 1/3rd of patients being children), conducted in a tertiary center at a remote land-locked location with non-migratory ethnic population as its catchment area, has a significant epidemiological value for the community and the region.

Updates in the classification of ependymal neoplasms: The 2021 WHO Classification and beyond.

Ependymal neoplasms occur at all ages and encompass multiple tumor types and subtypes that develop in the supratentorial compartment, the posterior fossa, or the spinal cord. Clinically, ependymomas represent a very heterogeneous group of tumors from rather benign subependymomas to very aggressive and often deadly childhood ependymomas of the posterior fossa. Newly identified biological markers and classification schemes, e. g. based on global DNA methylation profiling, have led to the definition of 10 types of ependymal tumors and an improved prediction of patients’ outcome by applying the new classification system. While the exact genetic basis for several ependymoma types still remains unclear, the knowledge about ependymoma driving events has significantly increased within the last decade and contributed to a classification based on molecular characteristics and localization rather than histological features alone. Convincing evidence is now pointing towards gene fusions involving ZFTA or YAP1 causing the development of supratentorial ependymomas. Also, H3, EZHIP, or TERT mutations have been detected in a fraction of infratentorial ependymal tumors. Finally, MYCN amplifications have recently been identified in spinal ependymomas, in addition to the previously known mutations in NF2. This review summarizes how recent findings regarding biology, molecular tumor typing, and clinical outcome have impacted the classification of ependymomas as suggested by the updated 2021 WHO CNS tumor classification system. We focus on changes compared to the previous classification of 2016 and discuss how a formal grading could evolve in the future and guide clinicians to treat ependymoma patients.

Profile of Cognitive Impairement in Patients with Brain Tumors in Dr. Moewardi Hospital, Surakarta

Background: Brain tumor is a disease that is difficult to treat and causes high morbidity and morta¬lity. One of the clinical manifestations of brain tumors is cognitive impairment which is the most common neurological problem. The aim of this study is to determine the profile of cognitive impairment in patients with brain tumors. Subjects and Method: The design of this study was a retrospective cross-sectional using secondary data from the Neurology Polyclinic of RSUD Dr. Moewardi in January 2021-March 2022. The subject was diagnosed with a brain tumor based on anamnesis, physical examination, and neuroimaging. Cognitive impairment was inferred through the MoCA-Ina test. The analysis used was univariate descriptive analysis, independent T test, Mann-Whitney test, and Pearson correlation test. Results: There were 29 subjects with a mean MoCA-Ina score (17.97). Primary brain tumors (79.3%), more than metastatic tumors. The majority of patients were diagnosed with meningioma (55.2%). This study showed that there were differences in abstraction scores (p=0.015) and total MoCA-Ina scores (p=0.042) between patients with tumors located in the temporal lobe and non- temporal lobe; differences in abstraction scores (p=0.034) and orientation scores (p=0.042) between patients with supratentorial and infratentorial tumors; and differences in memory scores (p=0.028) between patients with and without radiation history. In addition, this study also found an association between the number of lobes affected by brain tumors with attention score (p=0.027; r=-0.409), abstraction score (p=0.004; r=-0.524), orientation score (p=0.021; r=-0.426), and the total score of MoCA-Ina (p=0.018, r=-0.435). Conclusion: There is an association between brain tumors and cognitive impairment which is concluded through the MoCA-Ina test. The clinical manifestations of cognitive impairment in the patient are in accordance with the neuroanatomical function of the brain affected by the lesion. Keywords: Cognitive, Tumor, MoCA-Ina Correspondence: Maria Yosita Ayu Hapsari. Department of Neurology, Faculty of Medicine, Universitas Sebelas Maret/ Moewardi Hospital, Indonesia. Email: ayositahapsari@gmail.com. Phone: 0813 3155 5412. Indonesian Journal of Medicine (2022), 07(02): 242-250 https://doi.org/10.26911/theijmed.2022.07.02.12

Complications of glioma surgery

Background. Nowadays extensive resection remains the best treatment for gliomas. However, postoperative complications can disturb the benefits of surgery. The risk of surgical complications must be assessed against the benefits of obtaining a total resection, especially for tumors of eloquent brain. Object. The goal of this study was to review present evidence of glioma resection concerning the frequency of complications,their causes, predictive risk factors and current methods of reducing the occurrence of these events. This review strives to consolidate information about complications and preventive measures as well as to establish the utility of tools to improve neurosurgical outcome. Methods. A review of the literature concerning the main postoperative complications in patients with glial tumors was done. We performed a search using key words "cerebral neoplasm", "cerebral tumor", "glioma" and "complications". Papers that namely discussed complications rates were included. Anatomic, physiologic, clinical features were taken into consideration in patients with postoperative complications as well as current methods of investigations. Results. Documented overall complication rates ranged from 10% to 35%, with overall mortality rates of 1.0%-15%. Studies of series undergoing surgery for malignant gliomas found at least one surgical complication in 3.4% of patients with a 4.5% risk in patients for hospital-associated complications such as surgical site infection. There was a wide range of types of complications. The presence of new or worsened neurological deficit was up to 20% as the highest reported rate for treatment of eloquent arias glioma. Relatively common complications were postoperative peritumoral edema (2%-10%), CSF fistula (1%-15%), wound infection (0%-4%), surgery-related hematoma (1%-5%) and early postoperative seizure (1%-12%). The risk for cardiac complications was 0.7%, for respiratory complications - 0.5%, for deep wound infection - 0.8%,for deep venous thromboses - 0.6%, for pulmonary embolus - 3.1%, for acute renal failure -1.3%. Infratentorial tumour location, reoperations and previous radiotherapy were factors related to the incidence of regional complications. Age over 60 and severe comorbidities were risk factors for systemic complications. Conclusion. Postoperative morbidity in glial tumor surgery may be reduced by: encouraging use of standardized protocols for regional and systemic complications, intraoperative navigation that allows surgeon to maximize resection while preserving neurological function, clinical vigilance and attention to details.

Epidemiology of brain tumors among adolescents and young adults in Nigeria

Adolescents and Young Adults (AYA), have distinct endocrine and psychosocial peculiarities. Brain tumors occur less among AYAs, compared to other age groups and with better prognosis. There is however a paucity of literature about brain tumors in AYA in sub-Saharan Africa. We aim to describe the clinical characteristics of brain tumors in AYA across five neurosurgical centers in Nigeria and the associated factors. We report results for older children (10–14 years), adolescents (15–19 years) and young adults (20–24 years). This was a retrospective review of AYA with brain tumors over a 10-year period (2010–2019). Data analysis was by descriptive statistics, Chi square test and multinomial regression at α0.05. There were 104 AYAand the male to female ratio was 1.2:1. Headache (79.8%) and visual symptoms (65.4%) were the most common presenting symptoms. Focal limb weakness (44.1%) occurred less frequently. Median duration of symptoms prior to presentation was 9 months. Glioma was the most common tumor (31, 29.8%) while pituitary adenoma and craniopharyngioma constituted 30.8% of the tumors. Patients with symptom duration of ≤one year were more likely to have infratentorial tumors. There was no significant association between the KPS following intervention and the AYA characteristics. Age group was not significantly associated with any of the presenting symptoms except ataxia, which was significantly higher among the 10 to 14 years group.We have described the epidemiology of brain tumors within AYA in Nigeria and highlighted a need to maximize their care and meet their special needs.

Computational simulations establish a novel transducer array placement arrangement that extends delivery of therapeutic TTFields to the infratentorium of patients with brainstem gliomas.

Background and PurposeTumor treating fields (TTFields) are a non-invasive, efficacious treatment modality currently approved for supratentorial glioblastomas. Despite their ability to improve overall survival in supratentorial tumors, the current placement of arrays is limited to the supratentorial head, precluding its use in infratentorial tumors. Infratentorial malignancies are in need of new therapy modalities given their poor prognoses in both children and adults. The aim of this research is to determine whether rearrangement of TTFields may allow for management of infratentorial tumors.Materials and methodsDelivery of TTFields using Novocure’s prototype Optune™ device human male head model was simulated based on brain MRIs from patients with brainstem gliomas to develop a novel array layout designed to extend adequate infratentorial coverage.ResultsArray placement on the vertex, bilateral posterolateral occiput, and superior-posterior neck achieved intensities above 1.1 V/cm (average 1.7 V/cm; maximum 2.3 V/cm) in the vertical field direction and above 1 V/cm (average 2 V/cm; maximum 2.8 V/cm) in the horizontal field direction of the infratentorium. The calculated field intensity within the simulated tumors were in the therapeutic range and demonstrated the effective delivery of TTFields to the infratentorial brain.ConclusionsOur findings suggest that rearrangement of the TTFields standard array with placement of electrodes on the vertex, bilateral posterolateral occiput, and superior-posterior neck allows for adequate electric field distribution in the infratentorium that is within the therapeutic range.

Supratentorial and spine metastatic medulloblastoma in adults

Medulloblastoma is an infratentorial primitive neuroectodermal tumor that is predominantly found in children. The incidence of medulloblastoma fluctuates between 20-35% in kids and is extraordinarily uncommon to be found in adults. A twenty-four-year-old man presented with a chief complaint of weakness of the lower extremity. Physical examination revealed myelopathy sign at the 12th thoracic level. Past medical history revealed that he had undergone total resection of a medulloblastoma of the cerebellum three years prior to the weakness. A thoracolumbar MRI with gadolinium contrast injection was performed which revealed a solid mass at thoracic vertebra 12 – lumbar 1. Four months after the total resection of the spinal mass, the patient presented again with a chief complaint of vomiting and a severe headache. A head CT scan was done followed by a head MRI with gadolinium contrast injection. A mass was found at the right temporoparietal region and craniotomy for tumor removal was immediately done to resolve the intracranial pressure problem. Pathological anatomy revealed the spinal and intracranial mass as medulloblastoma. This case report presents an adult with primary medulloblastoma of the cerebellum who presented with metastases of the spine and supratentorial regions. However, the incidence of medulloblastoma is very rare in adults and the 5-year survival rate is between 60% - 80% for all adult medulloblastoma patients. Surgeons must be careful in choosing the first management for better prognosis such as surgical management only, surgical management followed by adjuvant therapy, or just a chemotherapeutic-only approach.

Pediatric and Adult Low-Grade Gliomas: Where Do the Differences Lie?

Two thirds of pediatric gliomas are classified as low-grade (LGG), while in adults only around 20% of gliomas are low-grade. However, these tumors do not only differ in their incidence but also in their location, behavior and, subsequently, treatment. Pediatric LGG constitute 65% of pilocytic astrocytomas, while in adults the most commonly found histology is diffuse low-grade glioma (WHO II), which mostly occurs in eloquent regions of the brain, while its pediatric counterpart is frequently found in the infratentorial compartment. The different tumor locations require different skillsets from neurosurgeons. In adult LGG, a common practice is awake surgery, which is rarely performed on children. On the other hand, pediatric neurosurgeons are more commonly confronted with infratentorial tumors causing hydrocephalus, which more often require endoscopic or shunt procedures to restore the cerebrospinal fluid flow. In adult and pediatric LGG surgery, gross total excision is the primary treatment strategy. Only tumor recurrences or progression warrant adjuvant therapy with either chemo- or radiotherapy. In pediatric LGG, MEK inhibitors have shown promising initial results in treating recurrent LGG and several ongoing trials are investigating their role and safety. Moreover, predisposition syndromes, such as neurofibromatosis or tuberous sclerosis complex, can increase the risk of developing LGG in children, while in adults, usually no tumor growth in these syndromes is observed. In this review, we discuss and compare the differences between pediatric and adult LGG, emphasizing that pediatric LGG should not be approached and managed in the same way as adult LCG.

Ophthalmological Evaluation in Children Presenting With a Primary Brain Tumor.

Background:Children with a brain tumor are prone to develop visual impairment, which to date is often underestimated and unrecognized. Our aim was to assess the prevalence of ophthalmological evaluation and abnormal ophthalmological findings, and investigate whether demographic and tumor-related characteristics are associated with abnormal ophthalmological findings in children presenting with a primary brain tumor.Methods:Medical records of all 90 children diagnosed with a primary brain tumor between June 2018 and May 2019 and treated at the Princess Máxima Center for Pediatric Oncology, a tertiary referral center in the Netherlands, were retrospectively reviewed. Univariate regression analysis was used to investigate associations between demographic, tumor-related and clinical characteristics, and abnormal ophthalmological findings.Results:Sixty children (34 male [56.7%]; median [range] age, 9.3 [0–16.9] years) underwent ophthalmological evaluation within 6 weeks before or after diagnosis, 11 children (5 male [45.5%]; median [range] age, 5.7 [0.1–17.2] years) were seen more than 6 weeks before or after diagnosis, and 19 children (7 male [36.8%]; median [range] age, 7.2 [1.9–16.6] years) did not receive ophthalmological evaluation within at least 6 months from diagnosis. A total of 19 children (21.1%) presented with visual symptoms as first sign leading to the diagnosis of a brain tumor. Children who presented with visual symptoms (odds ratio [OR], 22.52; 95% confidence interval [CI], 4.90–103.60) and/or hydrocephalus (OR, 3.60; 95% CI, 1.38–9.36) at diagnosis were more often seen for ophthalmological evaluation. The most common abnormal ophthalmological findings were eye movement disorders (66.0%), papilledema (44.1%), and visual field defects (58.1%). Eye movement disorders occurred more frequently in patients with an infratentorial tumor (OR, 4.71; 95% CI, 1.03–21.65). The risk of papilledema was associated with older age (OR, 1.19; 95% CI, 1.05–1.34), hydrocephalus (OR, 9.63; 95% CI, 2.68–34.61), and infratentorial (OR, 9.11; 95% CI, 1.77–46.78) and supratentorial (OR, 13.13; 95% CI, 1.92–89.52) tumors.Conclusions:In this study, most children with a primary brain tumor underwent ophthalmological evaluation around diagnosis, 21% of the children were not evaluated. The high prevalence of abnormal ophthalmological findings stresses the importance of early standardized ophthalmological evaluation to detect visual impairment and provide timely treatment to potentially prevent permanent visual loss.

Clinical profile, treatment and outcome of pediatric brain tumors in Serbia in a 10-year period: A national referral institution experience.

ObjectiveThis study aimed to evaluate the characteristics of children with primary brain tumors, the effectiveness of treatment modalities, and to detect factors related to the outcome.MethodsA detailed analysis was performed on a series of 173 pediatric patients treated in a Serbian referral oncology institution between 2007 and 2016, based on their clinical, histological, treatment, and follow-up data.ResultsMean survival time of all children was 94.5months. 2-, 5- and 10-year overall survival probabilities were 68.8%, 59.4%, and 52.8%, respectively. Patients with supratentorial tumors had longer survival than patients with infratentorial tumors and patients with tumors in both compartments (p = 0.011). Children with the unknown histopathology (brainstem glioma) and high-grade glioma had a shorter life than embryonal tumors, ependymoma, and low-grade glioma (p<0.001). Survival of the children who underwent gross total resection was longer than the children in whom lesser degrees of resection were achieved (p = 0.015). The extent of the disease is a very important parameter found to be associated with survival. Patients with no evidence of disease after surgery had a mean survival of 123 months, compared with 82 months in patients with local residual disease and 55 months in patients with disseminated disease (p<0.001). By the univariate analysis, factors predicting poor outcome in our series were the presentation of disease with hormonal abnormalities, tumor location, and the extent of the disease, while the factors predicting a better outcome were age at the time of diagnosis, presentation of the disease with neurological deficit, and type of resection. By the multivariate analysis, the extent of the disease remained as the only strong adverse risk factor for survival (HR 2.06; 95% CI = 1.38–3.07; p<0.001).ConclusionsWith an organized and dedicated multidisciplinary team, the adequate outcomes can be achieved in a middle-income country setting. The presence of local residual disease after surgery and disseminated disease has a strong negative effect on survival.

Re-Evaluating Surgery and Re-Irradiation for Locally Recurrent Pediatric Ependymoma — a Multi-Institutional Study

The goal of this study was to evaluate extent of surgical resection, and timing and volume of re-irradiation, on survival for children with locally recurrent ependymoma.Children with locally recurrent ependymoma treated with a second course of fractionated radiotherapy (RT2) from six North American cancer centers were reviewed. The index time was from the start of RT2 unless otherwise stated.35 patients were included in the study. The median doses for first radiation (RT1) and RT2 were 55.8 and 54 Gy, respectively. Median follow-up time was 5.6 years. Median overall survival (OS) for all patients from RT2 was 65 months. Gross total resection (GTR) was performed in 46% and 66% of patients prior to RT1 and RT2, respectively. GTR prior to RT2 was independently associated with improved PFS for all patients (HR 0.41, P = 0.04), with an OS benefit (HR 0.26, P = 0.03) for infratentorial tumors. Median PFS was superior with craniospinal irradiation (CSI) RT2 (not reached) compared to focal RT2 (56.9 months; log-rank P = 0.03). All distant failures (except one) occurred after focal RT2. Local failures after focal RT2 were predominantly in patients with less than GTR pre-RT2.Patients with locally recurrent pediatric ependymoma should be considered for re-treatment with repeat maximal safe resection (ideally GTR) and CSI re-irradiation.

Peritumoral Brain Edema in Metastases May Be Related to Glymphatic Dysfunction.

ObjectivesThe proliferation of microvessels with increased permeability is thought to be the cause of peritumoral brain edema (PTBE) in metastases. The contribution of the glymphatic system to the formation of PTBE in brain metastases remains unexplored. We aimed to investigate if the PTBE volume of brain metastases is related to glymphatic dysfunction.Materials and MethodsA total of 56 patients with brain metastases who had preoperative dynamic susceptibility contrast-enhanced perfusion-weighted imaging for calculation of tumor cerebral blood volume (CBV) and diffusion tensor imaging for calculations of tumor apparent diffusion coefficient (ADC), tumor fractional anisotropy (FA), and analysis along perivascular space (ALPS) index were analyzed. The volumes of PTBE, whole tumor, enhancing tumor, and necrotic and hemorrhagic portions were manually measured. Additional information collected for each patient included age, sex, primary cancer, metastasis location and number, and the presence of concurrent infratentorial tumors. Linear regression analyses were performed to identify factors associated with PTBE volume.ResultsAmong 56 patients, 45 had solitary metastasis, 24 had right cerebral metastasis, 21 had left cerebral metastasis, 11 had bilateral cerebral metastases, and 11 had concurrent infratentorial metastases. On univariable linear regression analysis, PTBE volume correlated with whole tumor volume (β = -0.348, P = 0.009), hemorrhagic portion volume (β = -0.327, P = 0.014), tumor ADC (β = 0.530, P <.001), and ALPS index (β = -0.750, P <.001). The associations of PTBE volume with age, sex, tumor location, number of tumors, concurrent infratentorial tumor, enhancing tumor volume, necrotic portion volume, tumor FA, and tumor CBV were not significant. On multivariable linear regression analysis, tumor ADC (β = 0.303; P = 0.004) and ALPS index (β = -0.624; P < 0.001) were the two independent factors associated with PTBE volume.ConclusionMetastases with higher tumor ADC and lower ALPS index were associated with larger peritumoral brain edema volumes. The higher tumor ADC may be related to increased periarterial water influx into the tumor interstitium, while the lower ALPS index may indicate insufficient fluid clearance. The changes in both tumor ADC and ALPS index may imply glymphatic dysfunction, which is, at least, partially responsible for peritumoral brain edema formation.

EPIDEMIOLOGICAL PATTERNS OF PAEDIATRIC BRAIN TUMORS IN COIMBATORE

Background: Tumors of the nervous system are the second most common childhood tumors after leukemia,constituting approximately 35% of all childhood malignancies and remain the leading cause of cancer related deaths in children. In India,in the absence of a comprehensive population based national cancer registry,we depend on local hospital based registries for assessing the incidence of pediatric brain tumor.Hence,more and more institutional data are required to assess the actual disease load in India. Objective: The main objective of the present study is to assess the epidemiological patterns of brain tumors in children presenting in CMCH. Materials and Methods: Data regarding age,gender,topography and histopathology of 22 pediatric patients (0-18years)with brain tumors operated inCMCH over a period of 5 years(January 2015 to December 2019)was collected retrospectively and analysed. The results obtained were compared with available Indiandata and western literature. Results: Of 22 cases, males(63.6%) outnumbered females. In the present study, the most common anatomical site for brain tumors was cerebellum(45.5%) followed by cerebral hemispheres(36.2%), ventricles(13.6%) and sellar region(4.5%). The present study showed that Infratentorial tumors were more common (54.5%) as compared to Supratentorial tumors (45.5%).Thepresent study revealed that astrocytoma(36.4%) is the most common brain tumor in childhood. other common tumors include medulloblastoma(27.2%), followed by ependymoma(13.6%), oligodendroglioma(9%),pineal gland tumor(4.5%),craniopharyngioma(4.5%) and meningeal tumor(4.5%). Conclusion: From the present series, we conclude that, the frequencies of major histologic types of brain tumors found in the study do not differ substantially from that found in other developed and developing countries. Medulloblastomas and astrocytomas, which form the major histologic types in pediatric patients need special attention.

Neuroimaging of Pediatric Brain Tumors − A Review

Brain tumors are the second most common malignancy and the most common solid tumors in the pediatric population. Most brain tumors in the pediatric population are primary in origin contrary to the adult population. The various factors useful for establishing the diagnosis include the age of the patient, imaging characteristics, and location of the tumor. Infratentorial tumors are more common between 4 and 10 years of age, whereas supratentorial tumors are common in neonates and infants up to 3 years. Conventional computed tomography and magnetic resonance imaging are of paramount importance in the diagnostic evaluation of these tumors which help in their characterization and allow accurate assessment of their extent. The updated World Health Organization classification of brain tumors has incorporated various genetic and molecular parameters. It is essential for the radiologists to be familiar with the imaging features of genetic tumor subtypes as it plays a role in patient management and prognostication. Advanced neuroimaging provides additional information regarding the metabolism and physiology of these lesions, thereby aiding in their diagnosis and follow-up.