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Objective: In the past, brain stem was treated with surgery or placement of shunt in Pakistan. Gamma Knife surgery is currently an alternative to surgery for deep brain lesions. In the current study, we show the clinical experience of our Centre treated with Gamma Knife surgery Methods: This is a descriptive study conducted between February 2016 and October 2021. We had total 47 patients presented with focal brainstem gliomas which were selected for Gamma knife radiosurgery at the Neurospinal and Cancer Care Institute Karachi. Results: Clinical Response was observed among them 20 (42.55%) patients improved, 22(46.80%) were stable, while 05 (10.63%) got worse The mean duration of symptoms was 31.9(SD10.5± 3months). Karnofsky Performance Status (KPS) scores during Gamma knife radiosurgery were 90 in 24 patients (51%), 80 in 21 patients (44.6%), and 70 in two patients (4.2%). Four patients (10.6%) had received conventional radiotherapy before Gamma knife radiosurgery. Conclusion: Among the diverse gliomas, their peril varies not just by type but also by their intricate location within the brain. The efficacy of gamma knife radiation is excellent particularly when tackling high-grade tumors, exhibiting its prowess in both adult and pediatric cases. [ABSTRACT FROM AUTHOR]

Anaplastic gliomas compromise about 5.9% of primary CNS tumors. The main goal of the operation is the maximum removal of the tumor, reduction of the tumor mass and reduction of the increased intracranial pressure. Different pathohistological subtypes of anaplastic gliomas show significantly different prognosis depending on the applied oncological therapeutic protocol as well as the modality of the applied radiotherapy. The study was designed as a retrospective, clinical observational study. The study included 34 participants who were diagnosed with anaplastic glioma in the followed time period. Survival rates were calculated based on the localization, modality of therapy and complications. We concluded that 20,4% of anaplastic gliomas were formed by transformation from previously operated lower grade gliomas. The initial sign of the disease is the appearance of epileptic seizures. Anaplastic gliomas most oftenly occur in the frontal region, with a frequency of 47%. The incidence of anaplastic gliomas in the temporal lobe is 23,5%. The length of survival is in relation to the localization of tumor expansion(p<0.05). The overall survival in the group of anaplastic gliomas operated on in the Department of Neurooncology KCS in the follow-up period of five years is 52.9%. The application of different chemotherapy modalities is not significant predictor in the length of survival. The radical nature of the operation has significance in the length of patient survival, which confirms the conclusions of most of the conducted studies cited in oncology textbooks. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to identify if clinical features and survival outcomes of insular glioma patients are associated with our classification based on the tumor spread. Methods: Our study included 283 consecutive patients diagnosed with histological grade 2 and 3 insular gliomas. A new classification was proposed, and tumors restricted to the paralimbic system were defined as type 1. When tumors invaded the limbic system (referred to as the hippocampus and its surrounding structures in this study) simultaneously, they were defined as type 2. Tumors with additional internal capsule involvement were defined as type 3. Results: Tumors defined as type 3 had a higher age at diagnosis (p = 0.002) and a higher preoperative volume (p < 0.001). Furthermore, type 3 was more likely to be diagnosed as IDH wild type (p < 0.001), with a higher rate of Ki‐67 index (p = 0.015) and a lower rate of gross total resection (p < 0.001). Type 1 had a slower tumor growth rate than type 2 (mean 3.3%/month vs. 19.8%/month; p < 0.001). Multivariate Cox regression analysis revealed the extent of resection (HR 0.259, p = 0.004), IDH status (HR 3.694, p = 0.012), and tumor spread type (HR = 1.874, p = 0.012) as independent predictors of overall survival (OS). Tumor grade (HR 2.609, p = 0.008), the extent of resection (HR 0.488, p = 0.038), IDH status (HR 2.225, p = 0.025), and tumor spread type (HR 1.531, p = 0.038) were significant in predicting progression‐free survival (PFS). Conclusion: The current study proposes a classification of the insular glioma according to the tumor spread. It indicates that the tumors defined as type 1 have a relatively better nature and biological characteristics, and those defined as type 3 can be more aggressive and refractory. Besides its predictive value for prognosis, the classification has potential value in formulating surgical strategies for patients with insular gliomas. [ABSTRACT FROM AUTHOR]

Pediatric high-grade gliomas (pHGG) are a rare yet devastating malignancy of the central nervous system's glial support cells, affecting children, adolescents, and young adults. Tumors of the central nervous system account for the leading cause of pediatric mortality of which high-grade gliomas present a significantly grim prognosis. While the past few decades have seen many pediatric cancers experiencing significant improvements in overall survival, the prospect of survival for patients diagnosed with pHGGs has conversely remained unchanged. This can be attributed in part to tumor heterogeneity and the existence of the bloodbrain barrier. Advances in discovery research have substantiated the existence of unique subgroups of pHGGs displaying alternate responses to different therapeutics and varying degrees of overall survival. This highlights a necessity to approach discovery research and clinical management of the disease in an alternative subtype-dependent manner. This review covers traditional approaches to the therapeutic management of pHGGs, limitations of such methods and emerging alternatives. Novel mutations which predominate the pHGG landscape are highlighted and the therapeutic potential of targeting them in a subtype specific manner discussed. Collectively, this provides an insight into issues in need of transformative progress which arise during the management of pHGGs. [ABSTRACT FROM AUTHOR]

Background and purpose: Progression-free survival (PFS) remains to be validated as an outcome measure for diffuse WHO grade 2 gliomas, and knowledge about the relationships between PFS, post-progression survival (PPS), and overall survival (OS) in this subset of tumors is limited. We sought to assess correlations between PFS and OS, and identify factors associated with PFS, PPS, and OS in patients treated for diffuse supratentorial WHO grade 2 gliomas. Material and methods: We included 319 patients from three independent observational cohorts. The correlation between PFS and OS was analyzed using independent exponential distributions for PFS and time from progression to death. Cox proportional hazards models were used to determine the effects of covariates on PFS, PPS, and OS. Results: The overall correlation between PFS and OS was rs0.31. The correlation was rs 0.37 for astrocytomas and rs 0.19 for oligodendrogliomas. Longer PFS did not predict longer PPS. Patients with astrocytomas had shorter PFS, PPS, and OS. Larger preoperative tumor volume was a risk factor for shorter PFS, while older age was a risk factor for shorter PPS and OS. Patients who received early radio- and chemotherapy had longer PFS, but shorter PPS and OS. Interpretation: We found a weak correlation between PFS and OS in WHO grade 2 gliomas, with the weakest correlation observed in oligodendrogliomas. Our analyses did not demonstrate any association between PFS and PPS. Critically, predictors of PFS are not necessarily predictors of OS. There is a need for validation of PFS as an endpoint in diffuse WHO grade 2 gliomas. [ABSTRACT FROM AUTHOR]

Simple Summary: Current auto-segmentation methods for glioblastoma utilize mainly pre-operative 1.5T and 3T MRI. The first commercial MRI-linear accelerator (linac) radiation treatment platform acquires low-field (0.35T) post-operative MRI at the delivery of each treatment. This study presents the first automatic brain lesion segmentation network developed for MRI-linac to track tumor changes during radiotherapy. The tumors and resection cavities are automatically segmented using a deep learning network, allowing for daily monitoring of tumor volume changes, creation of tools necessary for adaptive radiotherapy of glioblastoma, and providing MRI regions of interest for further analyses that may discover prognostic markers. Glioblastoma changes during chemoradiotherapy are inferred from high-field MRI before and after treatment but are rarely investigated during radiotherapy. The purpose of this study was to develop a deep learning network to automatically segment glioblastoma tumors on daily treatment set-up scans from the first glioblastoma patients treated on MRI-linac. Glioblastoma patients were prospectively imaged daily during chemoradiotherapy on 0.35T MRI-linac. Tumor and edema (tumor lesion) and resection cavity kinetics throughout the treatment were manually segmented on these daily MRI. Utilizing a convolutional neural network, an automatic segmentation deep learning network was built. A nine-fold cross-validation schema was used to train the network using 80:10:10 for training, validation, and testing. Thirty-six glioblastoma patients were imaged pre-treatment and 30 times during radiotherapy (n = 31 volumes, total of 930 MRIs). The average tumor lesion and resection cavity volumes were 94.56 ± 64.68 cc and 72.44 ± 35.08 cc, respectively. The average Dice similarity coefficient between manual and auto-segmentation for tumor lesion and resection cavity across all patients was 0.67 and 0.84, respectively. This is the first brain lesion segmentation network developed for MRI-linac. The network performed comparably to the only other published network for auto-segmentation of post-operative glioblastoma lesions. Segmented volumes can be utilized for adaptive radiotherapy and propagated across multiple MRI contrasts to create a prognostic model for glioblastoma based on multiparametric MRI. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioma tumor aggressiveness is expressed as tumor grading which is crucial in guiding treatment decisions and clinical trial participation. Accurate and standardized grading systems are essential to optimize care and improve outcomes. However, integrating molecular and clinical information in the grading process has the potential to expose molecular markers that have gained importance in understanding tumor biology as a means of identifying druggable targets. In this study, a novel approach called GradWise is introduced with the goal of enhancing feature selection performance while employing various machine learning models of glioma grading. GradWise combines a rank-based weighted hybrid filter (mRMR) and an embedded feature selection method (LASSO) to select the most relevant features from clinical and molecular predictors and was evaluated using two commonly employed public biomedical datasets, TCGA and CGGA, utilizing two feature selection methods and five supervised models. The findings support existing evidence and provide pioneering results for glioma-specific biomarkers, highlighting the effectiveness of the approach and future directions for biological mechanisms of glioma progression to higher grades. Glioma grading plays a pivotal role in guiding treatment decisions, predicting patient outcomes, facilitating clinical trial participation and research, and tailoring treatment strategies. Current glioma grading in the clinic is based on tissue acquired at the time of resection, with tumor aggressiveness assessed from tumor morphology and molecular features. The increased emphasis on molecular characteristics as a guide for management and prognosis estimation underscores is driven by the need for accurate and standardized grading systems that integrate molecular and clinical information in the grading process and carry the expectation of the exposure of molecular markers that go beyond prognosis to increase understanding of tumor biology as a means of identifying druggable targets. In this study, we introduce a novel application (GradWise) that combines rank-based weighted hybrid filter (i.e., mRMR) and embedded (i.e., LASSO) feature selection methods to enhance the performance of feature selection and machine learning models for glioma grading using both clinical and molecular predictors. We utilized publicly available TCGA from the UCI ML Repository and CGGA datasets to identify the most effective scheme that allows for the selection of the minimum number of features with their names. Two popular feature selection methods with a rank-based weighting procedure were employed to conduct comprehensive experiments with the five supervised models. The computational results demonstrate that our proposed method achieves an accuracy rate of 87.007% with 13 features and an accuracy rate of 80.412% with five features on the TCGA and CGGA datasets, respectively. We also obtained four shared biomarkers for the glioma grading that emerged in both datasets and can be employed with transferable value to other datasets and data-based outcome analyses. These findings are a significant step toward highlighting the effectiveness of our approach by offering pioneering results with novel markers with prospects for understanding and targeting the biologic mechanisms of glioma progression to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: The COVID-19 pandemic has driven the expansion of remote consultations in medical care. However, their implementation in neuro-oncology comprises unique challenges and opportunities. Evidence for how the complex patient–doctor relationships and neurological examinations required in the treatment of brain tumor patients can be translated to video consultation is scarce. Therefore, we analyzed over 3700 consultations at our institution in order to determine how patients that decided to participate in remote consultations distinguished from patients that did not. Additionally, we queried them about their reasons, encounters, problems/limitations, opportunities, emotional impact and future directions regarding their experiences with telemedicine during their treatment with an anonymized survey. With this, we are able to provide guidance on suitable patient subgroups, occasions and future directives to expand and adapt telemedicine patient care in neuro-oncology in an individualized and evidence-based concept. In order to minimize the risk of infections during the COVID-19 pandemic, remote video consultations (VC) experienced an upswing in most medical fields. However, telemedicine in neuro-oncology comprises unique challenges and opportunities. So far, evidence-based insights to evaluate and potentially customize current concepts are scarce. To fill this gap, we analyzed >3700 neuro-oncological consultations, of which >300 were conducted as VC per patients' preference, in order to detect how both patient collectives distinguished from one another. Additionally, we examined patients' reasons, suitable/less suitable encounters, VC's benefits and disadvantages and future opportunities with an anonymized survey. Patients that participated in VC had a worse clinical condition, higher grade of malignancy, were more often diagnosed with glioblastoma and had a longer travel distance (all p < 0.01). VC were considered a fully adequate alternative to face-to-face consultations for almost all encounters that patients chose to participate in (>70%) except initial consultations. Most participants preferred to alternate between both modalities rather than participate in one alone but preferred VC over telephone consultation. VC made patients feel safer, and participants expressed interest in implementing other telemedicine modalities (e.g., apps) into neuro-oncology. VC are a promising addition to patient care in neuro-oncology. However, patients and encounters should be selected individually. [ABSTRACT FROM AUTHOR]

Objective: Interventions to support patients' engagement in shared decision making (SDM) are lacking within high‐grade glioma (HGG) healthcare. Consultation Planning, Recording and Summarising (CPRS) has shown evidence of increasing patient decision self‐efficacy, reducing uncertainty, and regret of decisions. This is the first study of CPRS within a HGG population and delivered over serial medical consultations. Method: A one‐arm prospective qualitative longitudinal design was used to evaluate the CPRS intervention and evaluated with participants at sequential clinic appointments depending on their care, in Edinburgh, Scotland. We report on serial semi structured interviews of 16 patients and their partners. Results: Consultation planning before the consultation supported patients to feel known by strengthening the patient voice within the consultation. It prepared patients to actively participate in the consultation, despite the distressing nature of the content. Recording and summarising supported patients to understand their situation. The provision of a consultation record enabled accurate recall, a paced uptake of information and supported the family to feel fully informed. Ultimately, patients understood why decisions were being made rather than being part of making decisions. Conclusions: The CPRS intervention helped patients to understand and to feel known by increasing patient capacity for communication in the consultation, with support before, during, and after the consultation. The intervention focused on preparing patients for SDM but patients did not perceive that they had meaningful choices to make. Further research could look at the inclusion of patient decision aids to support this process. [ABSTRACT FROM AUTHOR]

Glioblastoma ranks among the most aggressive and lethal of all human cancers. Self-renewing, highly tumorigenic glioblastoma stem cells (GSCs) contribute to therapeutic resistance and maintain cellular heterogeneity. Here, we interrogated superenhancer landscapes of primary glioblastoma specimens and patient-derived GSCs, revealing a kelch domain-containing gene (KLHDC8A) with a previously unknown function as an epigenetically-driven oncogene. Targeting KLHDC8A decreased GSC proliferation and self-renewal, induced apoptosis, and impaired in vivo tumor growth. Transcription factor control circuitry analyses revealed that the master transcriptional regulator SOX2 stimulated KLHDC8A expression. Mechanistically, KLHDC8A bound Chaperonin-Containing TCP1 (CCT) to promote assembly of primary cilia to activate Hedgehog signaling. KLHDC8A expression correlated with Aurora B/C Kinase inhibitor activity, which induced primary cilia and Hedgehog signaling. Combinatorial targeting of Aurora B/C Kinase and Hedgehog displayed augmented benefit against GSC proliferation. Collectively, superenhancer-based discovery revealed KLHDC8A as a novel molecular target of cancer stem cells that promotes ciliogenesis to activate the Hedgehog pathway, offering insights into therapeutic vulnerabilities for glioblastoma treatment. [ABSTRACT FROM AUTHOR]

Determining the aggressiveness of gliomas, termed grading, is a critical step toward treatment optimization to increase the survival rate and decrease treatment toxicity for patients. Streamlined grading using molecular information has the potential to facilitate decision making in the clinic and aid in treatment planning. In recent years, molecular markers have increasingly gained importance in the classification of tumors. In this study, we propose a novel hierarchical voting-based methodology for improving the performance results of the feature selection stage and machine learning models for glioma grading with clinical and molecular predictors. To identify the best scheme for the given soft-voting-based ensemble learning model selections, we utilized publicly available TCGA and CGGA datasets and employed four dimensionality reduction methods to carry out a voting-based ensemble feature selection and five supervised models, with a total of sixteen combination sets. We also compared our proposed feature selection method with the LASSO feature selection method in isolation. The computational results indicate that the proposed method achieves 87.606% and 79.668% accuracy rates on TCGA and CGGA datasets, respectively, outperforming the LASSO feature selection method. [ABSTRACT FROM AUTHOR]

Pediatric high-grade gliomas (pHGGs) are the leading cause of cancer-related deaths in children in the USA. Sixteen percent of hemispheric pediatric and young adult HGGs encode Gly34Arg/Val substitutions in the histone H3.3 (H3.3-G34R/V). The mechanisms by which H3.3-G34R/V drive malignancy and therapeutic resistance in pHGGs remain unknown. Using a syngeneic, genetically engineered mouse model (GEMM) and human pHGG cells encoding H3.3-G34R, we demonstrate that this mutation led to the downregulation of DNA repair pathways. This resulted in enhanced susceptibility to DNA damage and inhibition of the DNA damage response (DDR). We demonstrate that genetic instability resulting from improper DNA repair in G34R-mutant pHGG led to the accumulation of extrachromosomal DNA, which activated the cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway, inducing the release of immune-stimulatory cytokines. We treated H3.3-G34R pHGG-bearing mice with a combination of radiotherapy (RT) and DNA damage response inhibitors (DDRi) (i.e., the blood-brain barrier-permeable PARP inhibitor pamiparib and the cell-cycle checkpoint CHK1/2 inhibitor AZD7762), and these combinations resulted in long-term survival for approximately 50% of the mice. Moreover, the addition of a STING agonist (diABZl) enhanced the therapeutic efficacy of these treatments. Long-term survivors developed immunological memory, preventing pHGG growth upon rechallenge. These results demonstrate that DDRi and STING agonists in combination with RT induced immune-mediated therapeutic efficacy in G34-mutant pHGG. [ABSTRACT FROM AUTHOR]

Glial‐lineage malignancies (gliomas) recurrently mutate and/or delete the master regulators of apoptosis p53 and/or p16/CDKN2A, undermining apoptosis‐intending (cytotoxic) treatments. By contrast to disrupted p53/p16, glioma cells are live‐wired with the master transcription factor circuits that specify and drive glial lineage fates: these transcription factors activate early‐glial and replication programs as expected, but fail in their other usual function of forcing onward glial lineage‐maturation—late‐glial genes have constitutively "closed" chromatin requiring chromatin‐remodeling for activation—glioma‐genesis disrupts several epigenetic components needed to perform this work, and simultaneously amplifies repressing epigenetic machinery instead. Pharmacologic inhibition of repressing epigenetic enzymes thus allows activation of late‐glial genes and terminates glioma self‐replication (self‐replication = replication without lineage‐maturation), independent of p53/p16/apoptosis. Lineage‐specifying master transcription factors therefore contrast with p53/p16 in being enriched in self‐replicating glioma cells, reveal a cause‐effect relationship between aberrant epigenetic repression of late‐lineage programs and malignant self‐replication, and point to specific epigenetic targets for noncytotoxic glioma‐therapy. [ABSTRACT FROM AUTHOR]

Objective: Cingulate cortex and cingulum both play crucial roles in limbic system. The aim of study is to observe and analyze surgical outcomes of cingulate gyrus glioma through extents of resection (EORs), overall survival (OS), and postsurgical neurological outcome. Method: The authors retrospectively studied 95 consecutive adult cases of primary cingulate gliomas that all underwent craniotomies and tumor resection. The patients were classified into unitary sub-region based on the four-division model. The information of clinical symptoms, pathology, EOR, postoperative neurological outcome and survival were analyzed through group comparison. Result: Low-grade gliomas (LGGs) were more prevalent (69.47%) for cingulate gyrus. Diffuse astrocytoma (40.00%) was most common histopathological diagnosis in total. Regarding sub-regions tumor involved in, midcingulate cortex (MCC) glioma was most prevalent (54.74%) followed by anterior cingulate cortex (ACC) glioma. Among all patients, 83 patients (87.37%) received EOR = 90%. In LGG group, 58 patients (87.88%) received EOR = 90%. The achievement of EOR significantly correlated with survival (P = 0.006). MCC cases were significantly associated with short-term morbidity in either language or motor function (P = 0.02). Majority of ACC cases (80.65%) escaped from any short-term deficits and nearly 90% free for permanent morbidity. Tumors in the dominant hemisphere were significantly associated with language dysfunction or cognition dysfunction, either short-term (P=0.0006) or long-term morbidity (P=0.0111). Age was the only postoperative susceptible predictor for all types of transient (P=0.021) and permanent (P=0.02) neurological deficit. Conclusion: Regarding cingulate gyrus glioma, the management of surgical plans could be carried out into four sub-region level. In spite of short-term neurological dysfunction caused by surgical procedure, majority of transient dysfunction could be relieved or recovered in long-term. The necessary effort to prolong overall survival is still to achieve advisable EOR. [ABSTRACT FROM AUTHOR]

Background: Patients diagnosed with high‐grade glioma and their family caregivers often experience intense disease and treatment trajectories. Fluctuations in patient's symptoms lead to enormous burdens for caregivers and the risk of developing symptoms of stress, anxiety, and depression. Aim: The study aim is to explore patient and caregiver experiences and evaluate the relevance of and satisfaction with a multimodal rehabilitative palliative care programme for patients diagnosed with a high‐grade glioma and their family caregivers. Methods: In a longitudinal multi‐methods study, adult patients with high‐grade glioma (n = 17) and their family caregivers (n = 16) completed a 4‐day residential programme and a 2‐day follow‐up programme 3 months later. Participants completed questionnaires after each programme, scoring relevance and satisfaction on a 5‐point Likert scale. Qualitative data were collected during four evaluation group interviews with patients and caregivers. Results: The mean overall satisfaction score was 4.80 (standard deviation [SD], 0.55) for the initial 4‐day programme and 4.28 (SD, 0.83) for the follow‐up programme. Three themes emerged in the evaluation group interviews: (1) meeting peers strengthens social well‐being, (2) the value of information and focusing on individual needs, and (3) accepting life as an unpredictable passage. Conclusion: Participants found completing the REHPA‐HGG programme feasible and rated all sessions highly for relevance and satisfaction. Qualitative findings confirm the value of individualised information, acceptance, and peer interactions. Implication for practice: A multimodal rehabilitative palliative care programme addressed unmet patient and caregiver needs. Peer‐to‐peer interventions for family caregivers may address individual support needs. Similar programmes may maximise benefit by avoiding planned behaviour changes and enhancing palliative approaches. [ABSTRACT FROM AUTHOR]