Low-grade Brain Tumors Research Articles

Distinct Slow-Wave Activity Patterns in Resting-State Electroencephalography and Their Relation to Language Functioning in Low-Grade Glioma and Meningioma Patients.

IntroductionBrain tumours frequently cause language impairments and are also likely to co-occur with localised abnormal slow-wave brain activity. However, it is unclear whether this applies specifically to low-grade brain tumours. We investigate slow-wave activity in resting-state electroencephalography (EEG) in low-grade glioma and meningioma patients, and its relation to pre- and postoperative language functioning.MethodPatients with a glioma (N = 15) infiltrating the language-dominant hemisphere and patients with a meningioma (N = 10) with mass effect on this hemisphere underwent extensive language testing before and 1 year after surgery. EEG was registered preoperatively, postoperatively (glioma patients only), and once in healthy individuals. Slow-wave activity in delta- and theta- frequency bands was evaluated visually and quantitatively by spectral power at three levels over the scalp: the whole brain, the affected hemisphere, and the affected region.ResultsGlioma patients had increased delta activity (affected area) and increased theta activity (all levels) before and after surgery. In these patients, increased preoperative theta activity was related to the presence of language impairment, especially to poor word retrieval and grammatical performance. Preoperative slow-wave activity was also related to postoperative language outcomes. Meningioma patients showed no significant increase in EEG slow-wave activity compared to healthy individuals, but they presented with word retrieval, grammatical, and writing problems preoperatively, as well as with writing impairments postoperatively.DiscussionAlthough the brain-tumour pathology in low-grade gliomas and meningiomas has a different effect on resting-state brain activity, patients with low-grade gliomas and meningiomas both suffer from language impairments. Increased theta activity in glioma patients can be considered as a language-impairment marker, with prognostic value for language outcome after surgery.

Psychiatric symptoms in children with low-grade glioma and craniopharyngioma: A systematic review

The presentation of psychiatric symptoms in pediatric low-grade brain tumors is challenging because this can delay proper diagnosis and treatment. We performed a systematic review of psychiatric presenting symptoms of low-grade brain tumors in pediatric patients. We searched the PubMed and Web of Science databases of studies published in English from 1977 until 2019 reporting patients aged ≤21 years at the time of tumor diagnosis who exhibited psychiatric/behavioral symptoms before diagnosis of low-grade glioma (LGG), pilocytic astrocytoma (PA), or craniopharyngioma (CP). Our systematic search strategy coupled each tumor type with patient age and presenting symptoms by using different variations of the search terms “childhood” and “psychiatric symptoms” or “behavioral symptoms.” We identified six unique articles that met our inclusion criteria in the LGG search, 27 in the PA search, and 32 in the CP search. Six patients were included in the LGG articles (age range, 3–16 years), 75 in the PA articles (age range, 0.5–21 years), and 87 in the CP articles (age range, 0.67–21 years). The most common presenting symptoms included eating disorders (n = 64) and behavioral changes (n = 49). Our findings demonstrate the need to establish clear criteria for neuroimaging indications for pediatric patients exhibiting eating disorders.

Neuropathology and epilepsy surgery.

Neurosurgical treatment of patients suffering from drug-resistant focal epilepsy is recognized as a successful, yet underutilized medical treatment option. By searching PubMed for articles published between January 2020 and September 2021 with the broad search terms 'neuropathology' AND 'epilepsy surgery', this review highlights the active field of etiology-based epilepsy research in human tissue. All papers addressing the most common epileptogenic human brain disease entities, i.e. focal cortical dysplasia (FCD), brain tumors or hippocampal sclerosis, and written in English language were eligible for our review. We can conclude from this review that etiology-based studies are of foremost interest for (1) the development of prediction models for postsurgical seizure outcome; (2) decipher genetic and molecular alterations to better define disease entities and underlying molecular pathomechanisms, and (3) the translation of human tissue-derived biomarker into clinically useful diagnostics or novel therapeutic targets in the near future. Highlighting FCD brain somatic gain-of-function variants in mammalian target of Rapamycin are a leading pathway to better classify FCD. An integrated genotype-phenotype analysis enables to classify the broad spectrum of low-grade and epilepsy-associated brain tumors. Further DNA-methylation-based disease classification will increase the mechanistic understanding and diagnostic precision of difficult to classify pathologies in the future.

Frequent FGFR1 hotspot alterations in driver-unknown low-grade glioma and mixed neuronal-glial tumors

PurposeLow-grade gliomas (LGG) and mixed neuronal-glial tumors (MNGT) show frequent MAPK pathway alterations. Oncogenic fibroblast growth factor receptor 1 (FGFR1) tyrosinase kinase domain has been reported in brain tumors of various histologies. We sought to determine the frequency of FGFR1 hotspot mutations N546 and K656 in driver-unknown LGG/MNGT and examined FGFR1 immunohistochemistry as a potential tool to detect those alterations.MethodsWe analyzed 476 LGG/MNGT tumors for KIAA-1549-BRAF fusion, IDH1/2, TERT promotor, NF1, H3F3A and the remaining cases for FGFR1 mutation frequency and correlated FGFR1 immunohistochemistry in 106 cases.Results368 of 476 LGG/MNGT tumors contained non-FGFR1 alterations. We identified 9 FGFR1 p.N546K and 4 FGFR1 p.K656E mutations among the 108 remaining driver-unknown samples. Five tumors were classified as dysembryoplastic neuroepithelial tumor (DNT), 4 as pilocytic astrocytoma (PA) and 3 as rosette-forming glioneuronal tumor (RGNT). FGFR1 mutations were associated with oligodendroglia-like cells, but not with age or tumor location. FGFR1 immunohistochemical expression was observed in 92 cases. FGFR1 immunoreactivity score was higher in PA and DNT compared to diffuse astrocytoma, but no correlation between FGFR1 mutation in tumors and FGFR1 expression level was observed.ConclusionFGFR1 hotspot mutations are the fifth most prevailing alteration in LGG/MNGT. Performing FGFR1 sequencing analysis in driver-unknown low-grade brain tumors could yield up to 12% FGFR1 N546/K656 mutant cases.

Incidence and prevalence of major epilepsy-associated brain lesions.

Epilepsy surgery is an effective treatment option for drug-resistant focal epilepsy patients with associated structural brain lesions. However, little epidemiological data are available regarding the number of patients with these lesions. We reviewed data regarding (1) the prevalence and incidence of epilepsy; (2) the proportion of epilepsy patients with focal epilepsy, drug-resistant epilepsy, and drug-resistant focal epilepsies; and (3) the number of epilepsy presurgical evaluations and surgical resections. We also assessed the relative proportion of brain lesions using post-surgical histopathological findings from 541 surgical patients from the Cleveland Clinic and 9,523 patients from a European multi-center cohort. Data were combined to generate surgical candidate incidence and prevalence estimates and the first lesion-specific estimates for hippocampal sclerosis (HS), low-grade epilepsy-associated brain tumors (LEAT), malformations of cortical development (MCD), glial scars, vascular malformations, and encephalitis. The most frequently diagnosed brain lesions were HS (incidence=2.32±0.26 in 100,000, prevalence=19.40±2.16 in 100,000) for adults and MCD (incidence=1.15±0.34 in 100,000, prevalence=6.52±1.89 in 100,000) for children. Our estimates can guide patient advocacy groups, clinicians, researchers, policymakers in education, development of health care strategy, resource allocation, and reimbursement schedules.

Pleomorphic Xanthoastrocytoma: a single institution retrospective analysis and a review of the literature.

Background Pleomorphic xanthoastrocytoma (PXA) is a rare low-grade brain tumor. To date, limited studies have analyzed factors affecting survival outcomes and defined the therapeutic strategy. The aim of this retrospective analysis was to investigate the clinicopathologic characteristics of PXA and identify factors associated with outcomes.Methods We retrospectively analyzed a cohort of 16 adult and children patients with PXA who underwent primary resection from 1997 to 2019, referred to our Radiation Oncology Unit and to Meyer’s Paediatric Hospital. We also reviewed the relevant literature.Results All patients underwent primary surgical resection; 10 patients received adjuvant radiation treatment course, ranging from DTF 54 to 64 Gy; 8 of them received, in addition, concurrent adjuvant chemotherapy; 6 patients underwent only radiological follow-up. After a median follow up was 60 months: median OS was 34.9 months (95% CI 30–218), 1-year OS 87%, 5-years OS 50%, 10-years OS 50%; median PFS 24.4 months (95% CI 13–156), 1-year PFS 80%, 5-years PFS 33%, 10-years PFS 33%. A chi-square test showed a significant association between OS and recurrent disease (p = 0.002) and with chemotherapy adjuvant treatment (p = 0.049). A borderline statistical significant association was instead recognized with BRAF mutation (p = 0.058).ConclusionsDespite our analysis did not reveal a strong prognostic or predictive factor able to address pleomorphic xanthoastrocytoma management; however, in selected patients could be considered the addition of adjuvant radiation chemotherapy treatment after adequate neurosurgical primary resection. Furthermore, recurrent disease evidenced a detrimental impact on survival.

Subependymal Giant Cell Astrocytoma with Tuberous Sclerosis Complex(TSC-SEGA)

Subependymal giant cell astrocytoma(SEGA)is a low-grade brain tumor occurring specifically in patients with tuberous sclerosis complex(TSC). TSC is an autosomal dominant genetic disease affecting multiple body systems and with wide variability in presentation. SEGA usually arises around the caudothalamic groove near the foramen of Monro, and can therefore cause life-threatening complications due to hydrocephalus. SEGA develops due to complete loss of function of the TSC1/TSC2 complex through a two-hit mechanism of biallelic inactivation of the TSC1 or TSC2 gene, leading to activation of mammalian target of rapamycin(mTOR). Identification of a pathogenic variant in TSC1 or TSC2 is sufficient for the diagnosis of TSC. Individuals with SEGAs presenting with acute deterioration due to obstructive hydrocephalus should undergo urgent surgical treatment. mTOR inhibitors have been shown to prevent SEGA growth in patients with TSC. Treatment with mTOR inhibitors is primarily recommended for individuals with non-acute symptomatic or asymptomatic growing or large SEGAs and those who are not surgical candidates or prefer medical treatment over surgery. Long-term treatment with mTOR inhibitors efficiently reduced SEGAs and prevented hydrocephalus. The surgical risks, potential side effects of mTOR inhibitors, and effect on other TSC manifestations should be considered so that the best treatment option is selected.

OL92 - Radiomics features of 11[C]-MET PET/CT in primary brain tumors: preliminary results on grading discrimination using a machine learning model

1096 Background: Nowadays Artificial Intelligence (AI) algorithms have demonstrated remarkable progress in image-recognition tasks and could be useful for the new concept of precision medicine in order to help physicians in the choice of therapeutic strategies for brain tumors. Previous data suggest that, in primary brain tumor, amino acid PET may demarcate more accurately the active disease than paramagnetic enhanced MRI that is the standard method of the evaluation in brain tumors and help in the evaluation of disease grading, as a fundamental basis for the correct clinical management of these patients. The aim of this study is to propose a radiomics workflow in order to create a predictive model on 11[C]-MET PET/CT scan images capable to discriminate between low-grade and high-grade primary brain tumors. Materials and Methods: in this retrospective study we selected fifty-six patients affected by primary brain tumor who underwent 11[C]-MET PET/CT from January 2016 to December 2019 at the Nuclear Medicine department of the Cannizzaro Hospital of Catania. Histological specimen the analysis was available in all patients in order to confirm the diagnosis and grading disease. PET/CT acquisition was performed after 10 minutes from the administration of 11C-Methionine (401-610 MBq) for a time acquisition of 15 minutes. 11[C]-MET PET/CT images were acquired using two scanners (24 patients on a Siemens scan and 32 patients on a GE scan). Then, LIFEx software was used to perform the segmentation and the extraction of features in order to identify the volume of interest (VOI) and to extract features of first, second, and third-order. LIFEx calculates 44 RF reflecting the VOI shape, the VOI voxel values, the histogram of VOI values, or the VOI textural content. A novel mixed descriptive-inferential sequential approach was used to identify a subset of relevant features that correlate with the outcome. A machine learning model based on discriminant analysis was tested in the evaluation of grading prediction (low vs high-grade) of 11[C]-MET PET/CT. Results: The machine learning model applicated in this study to stratify brain tumors as “low” and “high” grade showed discriminant texture features as follow: two features in fixed ROI respectively NGLDM Busyness (p-value: 0.1615) and GLZLM LZLGE (p-value 0.3207); three features in total volume respectively SHAPE Sphericity (p-value 0.0314), SHAPE Compacity (p-value 0.0215) and HISTO Kurtosis (p-value 0.0232). The results of performances, using a semi-automatic and user-independent segmentation process and an innovative feature extraction process on fixed ROI, showed a good performance in prediction of disease grade with an accuracy of 70.31% (AUC 64.13%) in all patients, of 80.51% (AUC 65.73%) in GE tomograph, of 84.98%(AUC 78.91%) in Siemens Tomograph. Using our model of machine learning with discriminant analysis the results of the performances were suboptimal in all patients group( 24 Siemens plus 32 GE) with an accuracy of 57.25 % and AUC of 58.51%. However in subgroup analysis, despite the low number of patients and different scanner, our model demonstrated good performances in the prediction of disease grade as follow: GE Scanner Accuracy 71.64 and AUC 62.8%; Siemens Scanner Accuracy 72,88% and AUC 78.91%. Conclusions: This preliminary study on radiomics features analysis of 11[C]-MET PET/CT suggests a possible value of Artificial Intelligence to assess primary brain tumors and to predict disease outcome in terms of grading discrimination at diagnosis. Further studies are needed to improve radiomics algorithms to personalize predictive and prognostic models and potentially support the medical decision process.

NCOG-42. SYMPTOM ONSET TO TIME OF DIAGNOSIS IN PRIMARY CENTRAL NERVOUS SYSTEM TUMOR PATIENTS: A REVIEW OF FINDINGS FROM THE NOB-NHS

Abstract Prior reports suggest the low prevalence of primary central nervous system (PCNS) tumors and the healthcare setting where patients seek care can contribute to diagnostic delays, potentially affecting prognosis. This descriptive report highlights findings from patient-reported data at presentation collected from a sample of 623 PCNS tumor patients. Participants were White (88%), males (56%), median age at diagnosis 41 (2-79) with high grade (HG) (66%) brain tumors (BT) (89%). Among BT patients, 30% reported ≥ 3 concurrent symptoms at presentation including headaches (40%), seizures (30%), and memory problems or difficulty with balance/walking (20% each). Over half (57%) had symptoms for < 6 months before diagnosis and 60% presented to the Emergency Room. Sixty-five percent of HG BT patients had symptoms for < 6 months prior to diagnosis compared to low grade (LG) tumors (40%) and had surgery in < 1 month from presentation (68% vs 51%, p < 0.01). More HG BT patients presented with weakness in the arms/legs than LG BT (14% vs 8%). Among spine tumor (ST) patients, 45% reported ≥ 3 concurrent symptoms at presentation including back pain (65%), sensory changes (45%), and weakness (40%). Almost half (46%) were symptomatic for > 1 year before diagnosis, presented in an outpatient clinic (64%) with 41% having surgery < 1 month from presentation. Younger (40% vs 16%) and HG ST patients (56% vs 21%) more often reported symptoms for < 6 months before diagnosis. HG ST patients more often presented to Emergency Rooms (67% vs 25%) and had surgery < 1 month from presentation (60% vs 36%). Further analysis of symptom presentation and clinical course is ongoing. Tumor location, grade, patient age and healthcare setting were associated with the time from clinical presentation to diagnosis. Development of aids providing guidance on diagnostic evaluation/treatment to front-line healthcare providers is warranted.

A prospective behavioral and imaging study exploring the impact on long-term memory of radiotherapy delivered for a brain tumor in childhood and adolescence

BackgroundPosterior fossa tumors represent two thirds of brain tumors in children. Although progress in treatment has improved survival rates over the past few years, long-term memory impairments in survivors are frequent and have an impact on academic achievement. The hippocampi, cerebellum and cerebellar-cortical networks play a role in several memory systems. They are affected not only by the location of the tumor itself and its surgical removal, but also by the supratentorial effects of complementary treatments, particularly radiotherapy. The IMPALA study will investigate the impact of irradiation doses on brain structures involved in memory, especially the hippocampi and cerebellum. Methods/designIn this single-center prospective behavioral and neuro-imaging study, 90 participants will be enrolled in three groups. The first two groups will include patients who underwent surgery for a posterior fossa brain tumor in childhood, who are considered to be cured, and who completed treatment at least 5 years earlier, either with radiotherapy (aggressive brain tumor; Group 1) or without (low-grade brain tumor; Group 2). Group 3 will include control participants matched with Group 1 for age, sex, and handedness. All participants will perform an extensive battery of neuropsychological tests, including an assessment of the main memory systems, and undergo multimodal 3 T MRI. The irradiation dose to the different brain structures involved in memory will be collected from the initial radiotherapy dosimetry. DiscussionThis study will provide long-term neuropsychological data about four different memory systems (working memory, episodic memory, semantic memory, and procedural memory) and the cognitive functions (attention, language, executive functions) that can interfere with them, in order to better characterize memory deficits among the survivors of brain tumors. We will investigate the correlations between neuropsychological and neuroimaging data on the structural (3DT1), microstructural (DTI), functional (rs-fMRI), vascular (ASL) and metabolic (spectroscopy) impact of the tumor and irradiation dose. This study will thus inform the setting of dose constraints to spare regions linked to the development of cognitive and memory functions. Trial registrationClinicalTrials.gov: NCT04324450, registered March 27, 2020, updated January 25th, 2021. Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT04324450.

Distinct DNA Methylation Patterns of Subependymal Giant Cell Astrocytomas in Tuberous Sclerosis Complex

Tuberous sclerosis complex (TSC) is a monogenic disorder caused by mutations in either the TSC1 or TSC2 gene, two key regulators of the mechanistic target of the rapamycin complex pathway. Phenotypically, this leads to growth and formation of hamartomas in several organs, including the brain. Subependymal giant cell astrocytomas (SEGAs) are low-grade brain tumors commonly associated with TSC. Recently, gene expression studies provided evidence that the immune system, the MAPK pathway and extracellular matrix organization play an important role in SEGA development. However, the precise mechanisms behind the gene expression changes in SEGA are still largely unknown, providing a potential role for DNA methylation. We investigated the methylation profile of SEGAs using the Illumina Infinium HumanMethylation450 BeadChip (SEGAs n = 42, periventricular control n = 8). The SEGA methylation profile was enriched for the adaptive immune system, T cell activation, leukocyte mediated immunity, extracellular structure organization and the ERK1 & ERK2 cascade. More interestingly, we identified two subgroups in the SEGA methylation data and show that the differentially expressed genes between the two subgroups are related to the MAPK cascade and adaptive immune response. Overall, this study shows that the immune system, the MAPK pathway and extracellular matrix organization are also affected on DNA methylation level, suggesting that therapeutic intervention on DNA level could be useful for these specific pathways in SEGA. Moreover, we identified two subgroups in SEGA that seem to be driven by changes in the adaptive immune response and MAPK pathway and could potentially hold predictive information on target treatment response.

Classification of Low-Grade and High-Grade Glioma from MR Brain Images Using Multiple-Instance Learning with Combined Feature Set

Fully automatic brain image classification of MR brain images is of great importance for research and clinical studies, since the precise detection may lead to a better treatment. In this work, an efficient method based on Multiple-Instance Learning (MIL) is proposed for the automatic classification of low-grade and high-grade MR brain tumor images. The main advantage of MIL-based approach over other classification methods is that MIL considers an image as a group of instances rather than a single instance, thus facilitating an effective learning process. The mi-Graph-based MIL approach is proposed for this classification. Two different implementations of MIL-based classification, viz. Patch-based MIL (PBMIL) and Superpixel-based MIL (SPBMIL), are made in this study. The combined feature set of LBP, SIFT and FD is used for the classification. The accuracies of low-grade–high-grade tumor image classification algorithm using SPBMIL method performed on [Formula: see text], [Formula: see text] and FLAIR images read 99.2765%, 99.4195% and 99.2265%, respectively. The error rate of the proposed classification system was noted to be insignificant and hence this automated classification system could be used for the classification of images with different pathological conditions, types and disease statuses.

A “polymorphous low-grade neuroepithelial tumor of the young (PLNTY)” diagnosed in an adult. Report of a case and review of the literature

Background: Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a rare neuropathological entity, recently introduced in neuro-oncology. These tumors, histologically similar to oligodendrogliomas, cause epilepsy, occurring in children and young adults. Only few cases of PLNTY have been described in literature and all reported cases invariably focused on the onset of these tumors in children and young adults.Case Description: We report the case of a 50-year-old woman suffering from epilepsy since the 1st year of her life. Computed tomography scan and magnetic resonance imaging of the brain documented the presence of a calcified mass involving left temporal lobe. The tumor was surgically excised and the histological examination showed a hypocellular and massively calcified neoplasm with morphological and immunohistochemical features consistent with the diagnosis of “PLNTY.”Conclusion: A review of the literature revealed that there are 31 cases of PLNTY reported in literature, most of which are children or young adults. The present case represents the second PLNTY diagnosed in a middle-aged adult to the best of our knowledge, suggesting that PLNTY should always be included in the differential diagnosis of low-grade brain tumors, also in adult patients.

Functional Connectivity Networks and Their Recruitment During Working Memory Tasks in Adult Survivors of Childhood Brain Tumors.

Background: Assessments of functional connectivity of default mode network (DMN) and positive task-related networks (TRNs) using independent component analysis (ICA) may help describe long-term effects of childhood brain tumors and adjuvant treatments. Methods: Aiming to identify potential neuronal markers that may aid in prognosis and inform interventions to optimize outcomes, this study used ICA to evaluate the presence of functional connectivity networks and their recruitment during a letter n-back task in 23 adult survivors of childhood posterior fossa tumors (9 low grade, 14 high grade) at least 5 years past diagnosis compared with 40 age- and sex-matched healthy peers. Results: DMN components generally demonstrated increasing disengagement as task difficulty increased, and relationships between effective DMN disengagement and improved performance were observed in healthy controls (HCs). Low-grade brain tumor survivors (LGS) demonstrated unique patterns in DMN recruitment that suggested increased involvement of the medial prefrontal cortex in LGS during tasks. TRN components generally demonstrated increasing engagement, which was related to improved task performance in HCs for one executive control network (ECN) component. High-grade brain tumor survivors (HGS) demonstrated distinct challenges recruiting an ECN component at more difficult task levels and showed a relationship between recruitment of another ECN component and task performance, indicating a potential compensatory mechanism for some HGS. Conclusions: Findings suggest the importance of cognitive intervention in both survivor groups and the necessity to track LGS despite their cognitive abilities often resembling those of their healthy peers. Impact statement Distinct functional connectivity patterns were identified between both adult survivor of childhood brain tumor groups and peers during attention and working memory tasks, reflecting different damage and recovery from treatment. Survivors of low-grade tumors demonstrated unique patterns of recruitment of default mode network components in the context of similar cognitive abilities, whereas survivors of high-grade tumors demonstrated poorer cognitive abilities and may be utilizing compensatory executive control network components in the face of challenging tasks. Long-term clinical follow-up and cognitive remediation is warranted for both groups, including low grade cerebellar tumor patients who have traditionally not been monitored as closely.

Altered lipid metabolism marks glioblastoma stem and non-stem cells in separate tumor niches

Glioblastoma (GBM) displays marked cellular and metabolic heterogeneity that varies among cellular microenvironments within a tumor. Metabolic targeting has long been advocated as a therapy against many tumors including GBM, but how lipid metabolism is altered to suit different microenvironmental conditions and whether cancer stem cells (CSCs) have altered lipid metabolism are outstanding questions in the field. We interrogated gene expression in separate microenvironments of GBM organoid models that mimic the transition between nutrient-rich and nutrient-poor pseudopalisading/perinecrotic tumor zones using spatial-capture RNA-sequencing. We revealed a striking difference in lipid processing gene expression and total lipid content between diverse cell populations from the same patient, with lipid enrichment in hypoxic organoid cores and also in perinecrotic and pseudopalisading regions of primary patient tumors. This was accompanied by regionally restricted upregulation of hypoxia-inducible lipid droplet-associated (HILPDA) gene expression in organoid cores and pseudopalisading regions of clinical GBM specimens, but not lower-grade brain tumors. CSCs have low lipid droplet accumulation compared to non-CSCs in organoid models and xenograft tumors, and prospectively sorted lipid-low GBM cells are functionally enriched for stem cell activity. Targeted lipidomic analysis of multiple patient-derived models revealed a significant shift in lipid metabolism between GBM CSCs and non-CSCs, suggesting that lipid levels may not be simply a product of the microenvironment but also may be a reflection of cellular state. CSCs had decreased levels of major classes of neutral lipids compared to non-CSCs, but had significantly increased polyunsaturated fatty acid production due to high fatty acid desaturase (FADS1/2) expression which was essential to maintain CSC viability and self-renewal. Our data demonstrate spatially and hierarchically distinct lipid metabolism phenotypes occur clinically in the majority of patients, can be recapitulated in laboratory models, and may represent therapeutic targets for GBM.

Fully automated glioma tumour segmentation using anatomical symmetry plane detection in multimodal brain MRI

Automatic brain abnormality detection is a major challenge in medical image processing. Manual lesion delineation techniques are susceptible to subjective errors, and therefore, computer aided preliminary screening of a lesion is necessary. This study introduces an efficient and automated algorithm based on the symmetry of the brain structures in the two hemispheres for brain tumour segmentation using multimodal brain magnetic resonoce imaging. Symmetry is a vital clue for determining intensity-based lesion difference in the two hemispheres of brain. A reliable method is proposed for extracting the cancerous region in order to improve the speed and accuracy of brain tumour segmentation. First, a symmetry plane is detected and then through features extracted from both sides of the brain, a similarity measure for comparing the hemisphere is defined. The cancerous region is extracted using similarity measurement, and the accuracy is improved using postprocessing operation. This algorithm is evaluated against the BRATS datasets including high- and low-grade glioma brain tumours. The performance indices are calculated and comparative analysis is implemented as well. Experimental results demonstrate accuracy close to manual lesion demarcation with performance indices.

Early radiotherapy preserves vision in sporadic optic pathway glioma.

Sporadic optic pathway/hypothalamic gliomas represent a unique entity within pediatric low-grade glioma. Despite favorable survival, location makes treatment difficult and local progression debilitating. This study is a longitudinal assessment of visual acuity (VA) among children treated within the last 2 decades. Clinical characteristics were abstracted for patients treated from 2000 to 2018 at Texas Children's Cancer Center in Houston. Ophthalmologic data taken at 3- to 6-month intervals were examined with age-appropriate VA metrics converted to the LogMAR (logarithm of the minimum angle of resolution) scale. Kaplan-Meier blindness-free survival (BFS) curves, calculated as time-to-bilateral functional blindness (LogMAR ≥0.8 in both eyes), were calculated for patients receiving early radiation therapy (RT; upfront or as first-line salvage treatment) or chemotherapy (CT) and evaluated using the log-rank test. Thirty-eight patients with a median follow-up of 8.5 years (range, 2-17 years) were identified. Median age at diagnosis was 3 years (interquartile range, <1-6 years). Early RT was administered in 11 patients (29%). Twenty-seven patients (71%) were treated primarily with CT, initiated at a median age of 3.5 years (range, <1-11 years). Eight patients in the CT group did eventually require RT secondary to VA loss and following multiple lines of CT. Median age at RT for all patients was 11 years (range, 3-17 years). BFS rates were 81% at 5 years and 60% at 8 years for CT and 100% at 5 and 8 years for early RT (P = .017). In a contemporary cohort, early RT, defined as initial or first-line salvage therapy, was found to have superior BFS for appropriately selected patients with sporadic optic pathway/hypothalamic gliomas. Children with low-grade brain tumors of the optic pathway generally have excellent long-term survival; however, given the location of these tumors, there can commonly be threatened vision if the tumor grows. Although radiation is generally deferred in children on the basis of legitimate concerns regarding the effects on the developing brain, it may represent a vision-preserving therapy for well-selected older patients.

Clinical and Neuroimaging Features of Magnetic Resonance−Guided Stereotactic Laser Ablation for Newly Diagnosed and Recurrent Pediatric Brain Tumors: A Single Institutional Series

We describe our single-institutional experience with magnetic resonance-guided stereotactic laser ablation (SLA) for the treatment of newly diagnosed and recurrent pediatric brain tumors. Eighteen consecutive ablation procedures were performed in 17 patients from March 2016-April 2020. Patient demographics, indications, procedures, neuroimaging features, and outcomes were reviewed retrospectively. Seventeen patients (mean age of 11.4 years, 11 boys, 6 girls) underwent SLA with a mean follow-up of 24 months (range: 3-45 months). Tumor histologies included pilocytic astrocytoma (n= 5), ganglioglioma (n= 3), low-grade glioma not otherwise specified (n= 4), glioblastoma (n= 2), meningioma (n= 1), medulloblastoma (n= 1), andmetastatic malignant peripheral nerve sheath tumor (n= 1). SLA was first-line therapy in 10 patients. Mean procedure duration including anesthesia time was 328 minutes (range: 244-529 minutes), and mean postoperative length of stay was 1.5 days (range 1-5 days). The complication rate was 29%, which included 3 patients who experienced postoperative motor changes, which resolved within several weeks of surgery, 1 patient with self-limited intraoperative bradycardia and hypotension, and 1 patient who died postoperatively due to intracranial hemorrhage from a distant lesion. Twelve of 17 patients had a neuroimaging response after SLA (4 complete responses, 8 partial responses, 1 stable disease). Percentage of tumor shrinkage from baseline ranged from 33%-100% (mean 75%). Patients with low-grade glioma exhibited the best responses to SLA (range 3%-100% decrease; mean 90%; 36% complete response rate). SLA is a minimally invasive modality for the treatment of newly diagnosed and recurrent low-grade pediatric brain tumors. Low-grade glioma exhibited the best responses. Identification of ideal candidates for SLA, mitigation of perioperative complications, and demonstration of long-term outcomes need to be better defined in a clinical trial setting.

Can we use intraoperative high-frequency oscillations to guide tumor-related epilepsy surgery?

ObjectiveIn people with low‐grade intrinsic brain tumors, an epileptic focus is often located close to the lesion. High‐frequency oscillations (HFOs) in electrocorticography (ECoG) might help to delineate this focus. We investigated the relationship between HFOs and low‐grade brain tumors and their potential value for tumor‐related epilepsy surgery.MethodsWe analyzed pre‐ and postresection intraoperative ECoG in 41 patients with refractory epilepsy and a low‐grade lesion. Electrodes were designated as overlying the tumor, adjacent resected tissue (peritumoral), or outside the resection bed using magnetic resonance imaging (MRI) and intraoperative photographs. We then used a semiautomated approach to detect HFOs as either ripples (80–250 Hz) or fast ripples (250–500 Hz).ResultsThe rate of fast ripples was higher in electrodes covering tumor and peritumoral tissue than outside the resection (p = .04). Mesiotemporal tumors showed more ripples (p = .002), but not more fast ripples (p = .07), than superficial tumors. Rates of fast ripples were higher in glioma and extraventricular neurocytoma than in ganglioglioma or dysembryoplastic neuroepithelial tumor (DNET). The rate of ripples and fast ripples in postresection ECoG was not higher in patients with residual tumor tissue on MRI than those without. The rate of ripples in postresection ECoG was higher in patients with good than bad seizure outcome (p = .03). Fast ripples outside the resection and in post‐ECoG seem related to seizure recurrence.SignificanceFast ripples in intraoperative ECoG can be used to help guide resection in tumor‐related epilepsy surgery. Preresection fast ripples occur predominantly in epileptogenic tumor and peritumoral tissue. Fast ripple rates are higher in glioma and extraventricular neurocytoma than in ganglioglioma and DNET.

Proton Radiotherapy Could Reduce the Risk of Fatal Second Cancers for Children with Intracranial Tumors in Low- and Middle-Income Countries.

PurposeTo test our hypothesis that, for young children with intracranial tumors, proton radiotherapy in a high-income country does not reduce the risk of a fatal subsequent malignant neoplasm (SMN) compared with photon radiotherapy in low- and middle-income countries.Materials and MethodsWe retrospectively selected 9 pediatric patients with low-grade brain tumors who were treated with 3-dimensional conformal radiation therapy in low- and middle-income countries. Images and contours were deidentified and transferred to a high-income country proton therapy center. Clinically commissioned treatment planning systems of each academic hospital were used to calculate absorbed dose from the therapeutic fields. After fusing supplemental computational phantoms to the patients' anatomies, models from the literature were applied to calculate stray radiation doses. Equivalent doses were determined in organs and tissues at risk of SMNs, and the lifetime attributable risk of SMN mortality (LAR) was predicted using a dose-effect model. Our hypothesis test was based on the average of the ratios of LARs from proton therapy to that of photon therapy ResultsProton therapy reduced the equivalent dose in organs at risk for SMNs and LARs compared with photon therapy for which the for the cohort was 0.69 ± 0.10, resulting in the rejection of H0 (P < .001, α = 0.05). We observed that the younger children in the cohort (2-4 years old) were at a factor of approximately 2.5 higher LAR compared with the older children (8-12 years old). ConclusionOur findings suggest that proton radiotherapy has the strong potential of reducing the risk of fatal SMNs in pediatric patients with intracranial tumors if it were made available globally.