Brainstem Glioma Research Articles

Gamma knife radiosurgery clinical efficacy for brain stem glioma: The institutional experience

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. doi: https://doi.org/10.12669/pjms.40.10.9658 How to cite this: Kalhoro A, Ahmed K, Hashim ASM. Gamma knife radiosurgery clinical efficacy for brain stem glioma: The institutional experience. Pak J Med Sci. 2024;40(10):2176-2180. doi: https://doi.org/10.12669/pjms.40.10.9658 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

A phase I clinical trial of sonodynamic therapy combined with radiotherapy for brainstem gliomas.

Brainstem gliomas (BSGs) are a class of clinically refractory malignant tumors for which there is no uniform and effective treatment protocol. Ultrasound and radiation can activate hematoporphyrin and produce sonodynamic and radiodynamic effects to kill cancer cells. Therefore, we conducted the first phase I clinical trial of sonodynamic therapy (SDT) combined with radiotherapy (RT) for the treatment of BSGs to verify its safety and efficacy. We conducted a study of SDT combined with RT in 11 patients with BSGs who received SDT and RT after hematoporphyrin administration. Magnetic resonance imaging was performed during this period to assess the tumor, and adverse events were recorded. All adverse events recorded were grade 1-2; no grade 3 or more serious adverse events were observed. Treatment was well tolerated, and no dose-limiting toxicities were observed. There were no treatment-related deaths during the course of treatment. 8 of 11 patients (72.7%) maintained stable disease, 2 (18.2%) achieved partial response, and the tumors were still shrinking as of the last follow-up date. The median progression-free survival (PFS) for patients was 9.2 (95% confidence interval [CI] 6.2-12.2) months, and the median overall survival (OS) was 11.7 (95% CI 9.6-13.8) months. Therefore, SDT combined with RT has a favorable safety and feasibility and shows a preliminary high therapeutic potential.

Clinical, Histologic, and Therapeutic Pattern of Posterior Fossa Tumors in Children in Cameroon: A Cross-sectional Study.

Posterior fossa tumors are significant in pediatric neurooncological populations due to their frequency and morbimortality. We convey a 10-year experience managing pediatric posterior fossa tumors at two reference centers in Cameroon. We conducted a cross-sectional study with data collected retrospectively in the Neurosurgery Department of the Central and General Hospitals of Yaounde from January 2010 to December 2019. Included in the study were all patients aged 0-15 years who underwent surgery for posterior fossa tumors. We retained 43 pediatric posterior fossa tumor files, representing 47.89% of pediatric brain tumors. The male/female sex ratio was 0.86, with a mean age of 6.93 ± 4.345 years. The predominant clinical presentations were headaches + vomiting (97.7%), visual impairment (67.4%), and altered consciousness (14%). The vermis was the most frequent site affected (46.5%). Hydrocephalus was found to be associated with the tumor in 30 patients (69.8%). Tumor excision was total in 90.7% of cases, with cerebrospinal fluid diversion performed within the surgery in 83% of cases. Pilocytic astrocytomas represented 37.2%, medulloblastomas 30.25%, ependymomas 6.9%, and brainstem gliomas 4.6%. The postoperatory mortality rate was 20.9%. The survival rate at 5 years for medulloblastomas was 43%. Pediatric posterior fossa tumors are frequent. Pilocytic astrocytomas are the most common histologic type, followed by medulloblastomas. Radical surgery is the leading standard of care. Adjuvant treatment remains limited.

Childhood brainstem lesions

Brainstem gliomas are more common in the paediatric age group as compared to adults. They have variable clinical presentations, which can range from mild to severe. Radiographic appearance on MRI, anatomical location, and molecular pathology plays a key role in management and prognostication. A multidisciplinary approach based upon the extent and type of tumour is followed. In our study, we have reported 3 such cases who presented in different ways and were diagnosed as brainstem glioma. We have also discussed various modalities of investigation and management.

Brain Stem Glioma Recurrence: Exploring the Therapeutic Frontiers.

Gliomas of the brainstem represent a small percentage of central nervous system gliomas in adults. Due to the proximity of the tumor to critical structures, radical surgery is highly challenging and limited to selected cases. In addition, postoperative treatments, which become exclusive to non-operable patients, do not guarantee satisfactory disease control, making the progression of the disease inevitable. Currently, there is a lack of therapeutic options to control tumor growth after the diagnosis of recurrence. The rarity of these tumors, their distinct behavioral characteristics, and the limited availability of tumor tissue necessary for the development of prognostic and predictive biomarkers contribute to the absence of a standardized approach for treating recurrent brainstem gliomas. A salvage radiotherapy (RT) retreatment could represent a promising approach for recurrent brainstem gliomas. However, to date, it has been mainly evaluated in pediatric cases, with few experiences available to assess the most appropriate RT dose, safety, and clinical responses in adult patients. This comprehensive review aims to identify instances of adult patients with recurrent brainstem gliomas subjected to a secondary course of RT, with a specific focus on the analysis of treatment-related toxicity and outcomes. Through this investigation, we endeavor to contribute valuable insights into the viability and efficacy of salvage RT retreatment in managing recurrent brainstem gliomas in the adult population.

Immunotherapy for children with malignant brain tumors

The incidence of high-grade malignant gliomas (MG) ranges from 35 to 46% of all central nervous system tumors. Despite combined therapy including surgery, radiation treatment and chemotherapy, overall five-year survival does not exceed 10%. The advent of novel immunotherapeutic strategies has promoted a renewed hopes for the treatment of MG. The aim of the present study was to improve the survival rates of glioma patients. Our study included 5 pediatric patients at the median age of 7.6 years (2-16). Three pts had anaplastic astrocytoma (AA) (1st relapse, 1 pt; 2nd relapse, in 2 pts), One patient was diagnosed with glioblastoma multiforme (GBM) (3rd recurrence), and 1 child had diffuse brainstem glioma (BSG). The median time to the first relapse was 12 months (4 to 16), the second relapse occurred at a median of 5 months (1 to 8). The protocol of immunotherapy included combined administration of autologous dendritic cell-based vaccine (DV) and repeated intrathecal/intraventricular injections of donor allogeneic immunocompetent cells (alloIC) for at least 2 years. Two of 3 pts with AA experienced a progression-free interval of 67 and 71 months. One patient with 3rd GBM relapse is alive without any treatment for 13.3 years after starting the immunotherapy. The median time of follow-up was 67 months, with the 2-year overall survival rate of 58%. Two pts died from the disease progression within 6 and 7 months from the beginning of immunotherapy. Over the period of treatment, the patients received a median of 20 alloIC injections (8 to 60), and 18 DV administrations (8 to 44). No serious side-effects were observed. Immunotherapy could be an promising option for treating patients with high-grade malignant gliomas refractory to conventional therapy and, therefore, deserves further investigations.

AB091. Establishment and application of brainstem glioma organoids.

Traditional preclinical experiments on brainstem gliomas mainly rely on patient-derived primary cell lines, but there are problems such as low success rate in establishment and inability to preserve tumor heterogeneity, which limit the clinical transformation. As a new type of in vitro tumor model, organoids have similar structure and function to the original tumor, requiring less tissue for cultivation, with short cycle and high success rate, which is particularly suitable for brainstem glioma biopsy. There is currently no precedent for the successful construction of brainstem glioma organoid models. This new established organoid provides us a more robust preclinical tool for comprehending the pathogenesis and conducting drug screening for this kind of disease. Cultivate patient-derived brainstem glioma organoids in vitro, verify the genetic fidelity and consistency of the organoids through morphological experiments as well as sequencing technology. Then explore the evolutionary direction of multiple types of brainstem gliomas through pseudo-time series analysis. Complete drug screening, natural killer (NK) cell co-culture, oncolytic virus therapy, and other treatments based on organoids in vitro, and evaluate the efficacy. Complete co-culture of organoids and Institute of Cancer Research (ICR) mouse brain slices in vitro. Establish patient-derived organoid xenograft (PDOX) mouse models derived from organoids in vivo. The establishment of organoids of all types of brainstem gliomas was completed for the first time in the world, with a total of 41/48 organoid models derived from patients, with a success rate of 85.4%, covering all segments and pathological types. The results of morphological experiments and sequencing showed that the genetic characteristics of organoids were highly consistent with those of tumor tissues. Drug screening tests for temozolomide and panobinostat were completed in vitro, and NK cell co-culture and oncolytic virus therapy testing were achieved. Co-culture of brainstem glioma organoids and mouse brain slices was achieved in vitro. Furthermore, a PDOX model of brainstem glioma was established. Brainstem glioma organoids can be established maturely, stably, and reliably, and can be used for preclinical drug testing for patients. Animal models derived from brainstem glioma organoids have broad preclinical experimental value.

Addressing barriers in diffuse intrinsic pontine glioma: the transformative role of lipid nanoparticulate drug delivery.

The brainstem tumour known as diffuse intrinsic pontine glioma (DIPG), also known as pontine glioma, infiltrative brainstem glioma is uncommon and virtually always affects children. A pontine glioma develops in the brainstem's most vulnerable region (the "pons"), which regulates a number of vital processes like respiration and blood pressure. It is particularly challenging to treat due to its location and how it invades healthy brain tissue. The hunt for a solution is continually advancing thanks to advances in modern medicine, but the correct approach is still elusive. With a particular focus on brain tumours that are incurable or recur, research is ongoing to discover fresh, practical approaches to target particular areas of the brain. To successfully complete this task, a thorough literature search was carried out in reputable databases like Google Scholar, PubMed, and ScienceDirect. The present article provides a comprehensive analysis of the notable advantages of lipid nanoparticles compared to alternative nanoparticle formulations. The article delves into the intricate realm of diverse lipid-based nanoparticulate delivery systems, which are used in Diffuse Intrinsic Pontine Glioma (DIPG) which thoroughly examines preclinical and clinical studies, providing a comprehensive analysis of the effectiveness and potential of lipid nanoparticles in driving therapeutic advancements for DIPG. There is strong clinical data to support the promising method of using lipid-based nanoparticulate drug delivery for brain cancer treatment, which shows improved outcomes.

A multi-task generative model for simultaneous post-contrast MR image synthesis and brainstem glioma segmentation

ObjectivesThis study aims to generate post-contrast MR images reducing the exposure of gadolinium-based contrast agents (GBCAs) for brainstem glioma (BSG) detection, simultaneously delineating the BSG lesion, and providing high-resolution contrast information. MethodsA retrospective cohort of 30 patients diagnosed with brainstem glioma was included. Multi-contrast images, including pre-contrast T1 weighted (pre-T1w), T2 weighted (T2w), arterial spin labeling (ASL) and post-contrast T1w images, were collected. A multi-task generative model was developed to synthesize post-contrast T1w images and simultaneously segment BSG masks from the multi-contrast inputs. Performance evaluation was conducted using peak signal-to-noise ratio (PSNR), structural similarity index (SSIM), and mean absolute error (MAE) metrics. A perceptual study was also undertaken to assess diagnostic quality. ResultsThe proposed model achieved SSIM of 0.86 ± 0.04, PSNR of 26.33 ± 0.05 and MAE of 57.20 ± 20.50 for post-contrast T1w image synthesis. Automated delineation of the BSG lesions achieved Dice similarity coefficient (DSC) score of 0.88 ± 0.27. ConclusionsThe proposed model can synthesize high-quality post-contrast T1w images and accurately segment the BSG region, yielding satisfactory DSC scores. Clinical relevance statementThe synthesized post-contrast MR image presented in this study has the potential to reduce the usage of gadolinium-based contrast agents, which may pose risks to patients. Moreover, the automated segmentation method proposed in this paper aids radiologists in accurately identifying the brainstem glioma lesion, facilitating the diagnostic process.

Brain Tumors in Pediatric Patients

Pediatric brain tumors are the most common solid tumors in children, comprising a diverse group of neoplasms that vary in histology, location, and behavior. Common types include astrocytomas, medulloblastomas, ependymomas, and brainstem gliomas. Symptoms often depend on the tumor's location and may include headaches, nausea, vomiting, balance issues, and cognitive or behavioral changes. Advances in imaging, surgical techniques, and therapies, including radiation and chemotherapy, have improved outcomes. However, treatment can have long-term effects on cognitive and physical development, making comprehensive care and follow-up essential for pediatric patients. Early published reviews on pediatric brain tumors may have several lacunae, such as limited data on long-term outcomes, emerging treatment modalities, and the genetic and molecular underpinnings of various tumor types. They might also inadequately address the psychosocial impacts on patients and families. Therefore, a comprehensive review is needed to synthesize the latest research on pediatric brain tumors, encompassing advancements in diagnosis, treatment, and survivorship care. This updated review will provide valuable insights for clinicians, researchers, and policymakers to improve managing and supporting children with brain tumors. The review covers various aspects of pediatric brain tumors, focusing on choroid plexus tumors and spinal cord tumors. It discusses treatment strategies, highlighting surgical, radiotherapy, and chemotherapy options. The review also details presenting signs and symptoms of brain tumors in children, such as headaches, nausea, vomiting, balance issues, and changes in behavior or cognition. These insights aim to enhance early diagnosis and effective management, improving outcomes for affected children. This review addresses gaps in earlier studies on pediatric brain tumors by providing comprehensive insights into choroid plexus and spinal cord tumors, updated treatment strategies, and detailed symptoms. It synthesizes recent research to enhance early diagnosis and management, meeting current needs for effective, tailored treatment and improving patient outcomes.

Pediatric brainstem glioma: a rare childhood cancer - clinical profile, treatment, and challenges of management - a single-center experience from a developing country

Introduction: Brainstem gliomas (BSGs) occur in the brainstem, located at the base of the brain. BSGs account for 10-20% of all primary CNS tumors. In a hospital-based study conducted at NICRH, BSGs constituted 7.69% of all childhood brain tumors. Objective: To determine the clinical profiles of childhood BSGs and assess the outcomes of pediatric BSGs while addressing the challenges of management. Methodology: It was a cross-sectional prospective study with a sample size of 44. We included all children during the study period and analyzed their data.The children were under 18 years of age. The study period was January 2020 and October 2022 at the Department of Pediatric Hematology and Oncology at the National Institute of Cancer Research and Hospital (NICRH), Bangladesh. Results: There were 44 patients, comprising 29 males and 15 females. The mean age of onset was 7 years. The majority (43.2%) of children fell within the 5-9 years age group. The most common symptoms were limb weakness, ataxia, and vision defects. The duration of symptoms varied from 10 days to 2 years. Sixteen of the patients experienced intracranial hypertension, which led to the development of hydrocephalus. The lesions were pontine in 18 cases, involving the entire brainstem in 13 cases, both pons and medulla in 7 cases, and medulla in 3 cases. Six patients underwent surgical intervention with histological evaluation, revealing astrocytoma (9.1%), oligodendroglioma (2.3%), and ependymoma (2.3%). Twenty-four (54.5%) patients received treatment, while others were unable to do so. The follow-up period extended to 12 months from the last enrollment. Only 8 patients completed both chemotherapy and radiotherapy treatments; other children discontinued or abandoned treatment due to financial constraints or the unavailability of 3D radiotherapy. Out of 44 children, a total of 41 patients passed away, with a mean survival period of 3.9 months. This is due to the high treatment cost in the private sector and disorganized government medical services for children with cancer. Conclusion: Most of the tumors in this series were located in the pons and demonstrated aggressive characteristics. The majority of our patients did not have access to radiotherapy due to their poor economic condition and the inadequate management of our government health system.

Pediatric diffuse intrinsic pontine glioma radiotherapy response prediction: MRI morphology and T2 intensity-based quantitative analyses.

An easy-to-implement MRI model for predicting partial response (PR) postradiotherapy for diffuse intrinsic pontine glioma (DIPG) is lacking. Utilizing quantitative T2 signal intensity and introducing a visual evaluation method based on T2 signal intensity heterogeneity, and compared MRI radiomic models for predicting radiotherapy response in pediatric patients with DIPG. We retrospectively included patients with brainstem gliomas aged ≤ 18 years admitted between July 2011 and March 2023. Applying Response Assessment in Pediatric Neuro-Oncology criteria, we categorized patients into PR and non-PR groups. For qualitative analysis, tumor heterogeneity vision was classified into four grades based on T2-weighted images. Quantitative analysis included the relative T2 signal intensity ratio (rT2SR), extra pons volume ratio, and tumor ring-enhancement volume. Radiomic features were extracted from T2-weighted and T1-enhanced images of volumes of interest. Univariate analysis was used to identify independent variables related to PR. Multivariate logistic regression was performed using significant variables (p < 0.05) from univariate analysis. Of 140 patients (training n = 109, and test n = 31), 64 (45.7%) achieved PR. The AUC of the predictive model with extrapontine volume ratio, rT2SRmax-min (rT2SRdif), and grade was 0.89. The AUCs of the T2-weighted and T1WI-enhanced models with radiomic signatures were 0.84 and 0.81, respectively. For the 31 DIPG test sets, the AUCs were 0.91, 0.83, and 0.81, for the models incorporating the quantitative features, radiomic model (T2-weighted images, and T1W1-enhanced images), respectively. Combining T2-weighted quantification with qualitative and extrapontine volume ratios reliably predicted pediatric DIPG radiotherapy response. Combining T2-weighted quantification with qualitative and extrapontine volume ratios can accurately predict diffuse intrinsic pontine glioma (DIPG) radiotherapy response, which may facilitate personalized treatment and prognostic assessment for patients with DIPG. Early identification is crucial for radiotherapy response and risk stratification in diffuse intrinsic pontine glioma. The model using tumor heterogeneity and quantitative T2 signal metrics achieved an AUC of 0.91. Using a combination of parameters can effectively predict radiotherapy response in this population.

DIPG-49. SPATIAL TRANSCRIPTOMIC SEQUENCING OF A DIPG PATIENT TUMOUR RESOURCE

Abstract BACKGROUND Diffuse Intrinsic Pontine Glioma (DIPG), the most common subtype of Diffuse Midline Glioma (DMG), is a brainstem high-grade glioma arising in young children and always proves fatal. Major challenges include the disease’s intratumoural genetic and cellular heterogeneity as well as its diffusely invasive phenotype. Research of the last few years has highlighted that interactions between cancer cells, the nervous system and immune cells crucially contribute to tumour cell invasion and disease malignancy. Hence, a better understanding of cancer-promoting interactions is a key requirement to elucidate novel strategies for the treatment of this devastating disease. METHOD We performed spatial transcriptomic sequencing on 10 sequential tumour-infiltrated DIPG patient brainstem regions, using the 10x Genomics Visium platform. RESULTS Spatially-informed analysis and cell type clustering overall highlighted the molecular intratumoural heterogeneity present in the disease. We assessed cell cluster interactions as well as receptor-ligand (RL) pairing, illustrating communication between neuronal, immune cell and tumour clusters. We further determined respective RL pairs involved in such. To address the question whether invasive edges genetically differ from the tumour core, we evaluated genes that are significantly correlated with distal brainstem regions compared to tumour proximal sites. Results revealed gene signatures that are highly associated with neuronal signalling and communication, validating previous findings emphasising the importance of neuron-to-glioma interactions driving DIPG disease progression. CONCLUSION DIPG is a lethal paediatric brainstem glioma for which more durable therapeutic modalities remain to be found. In-depth analysis of this disease is often hampered due to the lack of patient tissue suitable for laboratory studies. Our patient autopsy specimen, spanning the entire tumour-infiltrated brainstem provided a platform to study this aggressive disease in a spatio-temporal manner. This analysis elucidates how DIPG is driven by the tumour microenvironment, including associated receptor-ligand interactions. This has the potential to ultimately discover new treatment targets.

ETMR-01. BRAIN STEM TUMORS IN CHILDREN LESS THAN THREE MONTHS: CLINICAL AND RADIOLOGIC FINDINGS OF A RARE DISEASE

Abstract BACKGROUND Brainstem gliomas account for 10-20% of all central nervous system pediatric neoplasms. Brain stem tumors in children less than three months old at diagnosis are extremely rare. Our aim is to study a retrospective cohort to improve the understanding of the disease course and guide patient management. METHODS This is a multicenter retrospective analysis across the European Society for Pediatric Oncology SIOP-E HGG/DIPG Working Group linked centers and included patients with a brainstem tumor diagnosed between 2009 and 2020 and aged less than 3 months at diagnosis. Clinical data was collected, and imaging characteristics were analyzed blindly and independently by two experienced neuroradiologists. RESULTS Five cases (female; n=4) were identified of which no patient received any therapy. The epicenter of 2 tumors was in the medulla oblongata alone and in the medulla oblongata and the pons in 3 cases. For patients with tumor in equal parts in the medulla oblongata and the pons (n=3) the extension at diagnosis involved the spinal cord; for the 2 patients with the tumor epicenter in the medulla oblongata alone (n=2) the extension at diagnosis included the pons (n=2) and the spinal cord (n=1). Biopsy was performed in one patient identifying a pilocytic astrocytoma. Two patients died rapidly. In one patient autopsy revealed a high-grade glioma (case 3). Three survivors showed either spontaneous tumor regression (n=2) or stable disease (n=1). The surviving patients were followed-up for 10, 7, and 0.6 years, respectively. One case had the typical imaging characteristics of a dorsal exophytic low-grade glioma. CONCLUSIONS No patient fulfilled the radiologic criteria defining a high-grade glioma. Central neuroradiological review and biopsy (if feasible) may provide useful information with regards to the patient’s management.

Clinical outcome, radiological findings, and genetic features of IDH-mutant brainstem glioma in adults.

With the recent advent of genetic testing, IDH-mutant glioma has been found among adult brainstem gliomas. However, the clinical outcome and prognosis of IDH-mutant brainstem gliomas in adults have not been elucidated. This study aimed to investigate the clinical outcome, radiological findings, and genetic features of adult patients with IDH-mutant diffuse brainstem gliomas. Data from adult patients with brainstem glioma at Hokkaido University Hospital between 2006 and 2022 were retrospectively analyzed. Patient characteristics, treatment methods, genetic features, and prognosis were evaluated. Of 12 patients with brainstem glioma with proven histopathology, 4 were identified with IDH mutation. All patients underwent local radiotherapy with 54 Gray in 27 fractions combined with chemotherapy with temozolomide. Three patients had IDH1 R132H mutation and one had IDH2 R172G mutation. The median progression-free survival and overall survival were 68.4months and 85.2months, respectively, longer than that for IDH-wildtype gliomas (5.6months and 12.0months, respectively). At the time of initial onset, contrast-enhanced lesions were observed in two of the four cases in magnetic resonance imaging. As some adult brainstem gliomas have IDH mutations, and a clearly different prognosis from those with IDH-wildtype, biopsies are proactively considered to confirm the genotype.

High Level Immunoglobulin Gene Expression and Reduced Intra-tumoral Bacteria Associated With the Transition from Initial to Progressive Diffuse Intrinsic Pontine Glioma.

In the past decade, diffuse intrinsic pontine glioma (DIPG), the most common childhood brainstem glioma, has benefitted from an increase in tissue-based research because of improved biopsy collection techniques. However, the adaptive immune receptor (IR) features represented by tumor material and tumor infiltrating lymphocytes have remained poorly understood. Herein, we characterized the adaptive immune parameters of DIPG through the recovery of IR recombination reads from RNAseq files representing initial and progressive DIPG samples. An elevated level of immunoglobulin gene expression in the progressive DIPG sample files and a reduced number of bacterial sequencing read recoveries in comparison to RNAseq files representing the initial form of DIPG, was found. Furthermore, the RNAseq files representing both initial and progressive DIPG samples had significant numbers of reads representing Cutibacterium acnes, a bacterium previously linked to prostate cancer development. Results also indicated an opportunity to distinguish overall survival probabilities based on IGL complementarity determining region-3 amino acid sequence physicochemical parameters. Genomics analyses allow for a better understanding of adaptive IR features and bacterial infections in the DIPG setting.

Rapid tumor DNA analysis of cerebrospinal fluid accelerates treatment of central nervous system lymphoma

AbstractDelays and risks associated with neurosurgical biopsies preclude timely diagnosis and treatment of central nervous system (CNS) lymphoma and other CNS neoplasms. We prospectively integrated targeted rapid genotyping of cerebrospinal fluid (CSF) into the evaluation of 70 patients with CNS lesions of unknown cause. Participants underwent genotyping of CSF-derived DNA using a quantitative polymerase chain reaction–based approach for parallel detection of single-nucleotide variants in the MYD88, TERT promoter, IDH1, IDH2, BRAF, and H3F3A genes within 80 minutes of sample acquisition. Canonical mutations were detected in 42% of patients with neoplasms, including cases of primary and secondary CNS lymphoma, glioblastoma, IDH-mutant brainstem glioma, and H3K27M-mutant diffuse midline glioma. Genotyping results eliminated the need for surgical biopsies in 7 of 33 cases (21.2%) of newly diagnosed neoplasms, resulting in significantly accelerated initiation of disease-directed treatment (median, 3 vs 12 days; P = .027). This assay was then implemented in a Clinical Laboratory Improvement Amendments environment, with 2-day median turnaround for diagnosis of CNS lymphoma from 66 patients across 4 clinical sites. Our study prospectively demonstrates that targeted rapid CSF genotyping influences oncologic management for suspected CNS tumors.

Current immunotherapeutic approaches to diffuse intrinsic pontine glioma.

Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain tumour that occurs in the pons of the brainstem and accounts for over 80% of all brainstem gliomas. The median age at diagnosis is 6-7years old, with less than 10% overall survival 2years after diagnosis and less than 1% after 5years. DIPGs are surgically inaccessible, and radiation therapy provides only transient benefit, with death ensuing from relentless local tumour infiltration. DIPGs are now the leading cause of brain tumour deaths in children, with a societal cancer burden in years of life lost (YLL) of more than 67 per individual, versus approximately 14 and 16 YLL for lung and breast cancer respectively. More than 95 clinical drug trials have been conducted on children with DIPGs, and all have failed to improve survival. No single or combination chemotherapeutic strategy has been successful to date because of our inability to identify targeted drugs for this disease and to deliver these drugs across an intact blood-brain barrier (BBB). Accordingly, there has been an increased focus on immunotherapy research in DIPG, with explorations into treatments such as chimeric antigen receptor T (CAR-T) cells, immune checkpoint blockades, cancer vaccines, and autologous cell transfer therapy. Here, we review the most recent advances in identifying genetic factors influencing the development of immunotherapy for DIPG. Additionally, we explore emerging technologies such as Magnetic Resonance-guided Focused Ultrasound (MRgFUS) in potential combinatorial approaches to treat DIPG.

Surgical Management and Short-Term Outcome of Patients with Posterior Fossa Tumor in All Age Groups: Our Perspective

Background: Different types of brain tumor can occur in the region of posterior fossa. Ependymoma, medulloblastoma and pilocytic astrocytoma occur mostly in children and rarely in adults. Brain metastases in adults are the most common malignancies at this site. Other tumors that occur in the posterior fossa are meningioma, schwannoma, hemangioblastoma, brain stem glioma and epidermoid tumors. Posterior fossa tumor has different treatment approaches and prognosis. So, an accurate diagnosis, surgical approaches, complication analysis and outcome assessment are mandatory. Objective: To evaluate the clinical aspects, surgical approach, role of preoperative shunt, post-operative complications, and short-term outcome of patients with posterior fossa tumor in different age groups. Methods: This cross-sectional observational study included 36 patients with posterior fossa tumors that were admitted and operated in the Neurosurgery Department of Rangpur Medical College Hospital between the period of November 2018 and June 2022. In each patient clinically diagnosis was confirmed by MRI of Brain with contrast followed by histopathology. Results: Out of 36 patients, 23(63.9%) patients were male and 13(36.1%) were female. Mean age was 18.01±13.95 SD years (minimum 6 months and maximum 45 years), more common in pediatric age group (36.1% &lt;10 years and 25% between 11-20 years). Common presentations were headache (91.6%), vomiting (83.3%) and ataxia (72.2%). Medulloblastoma (27.8%) and ependymoma (25%) were common histological types. Surgical outcome was excellent in 17 cases (47.2%), while poor in 5.6% and 19.4% patients died. There was no statistically significant association of surgical outcome with age (p=0.148) and sex (p=0.170). Suboccipital craniotomy was superior to other surgical procedures in terms of patient’s outcome (p=0.031). Ependymomas and Astrocytomas had better outcome (p=0.014). Conclusions: Surgical outcome is related to the operative approach and histology of the tumor in this study, but no significant association of patient’s outcome with age, sex and preoperative procedure. J Rang Med Col. March 2024; Vol. 9, No. 1: 3-9

Clinical characteristics and prognostic factors of adult brainstem gliomas: A retrospective analysis of histologically-proven 40 cases.

To illustrate the clinical characteristics and prognostic factors of adult patients pathologically confirmed with brainstem gliomas (BSGs). Clinical data of 40 adult patients pathologically diagnosed with BSGs admitted to Beijing Shijitan Hospital from 2009 to 2022 were recorded and retrospectively analyzed. The primary parameters included relevant symptoms, duration of symptoms, Karnofsky performance status (KPS), tumor location, type of surgical resection, diagnosis, treatment, and survival. Univariate and multivariate analyses were evaluated by Cox regression models. The gliomas were located in the midbrain of 9 patients, in the pons of 14 cases, in the medulla of 5 cases, in the midbrain and pons of 6 cases and invading the medulla and pons of 6 cases, respectively. The proportion of patients with low-grade BSGs was 42.5%. Relevant symptoms consisted of visual disturbance, facial paralysis, dizziness, extremity weakness, ataxia, paresthesia, headache, bucking, dysphagia, dysacousia, nausea, dysphasia, dysosmia, hypomnesia and nystagmus. 23 (57.5%) patients accepted stereotactic biopsy, 17 (42.5%) patients underwent surgical resection. 39 patients received radiotherapy and 34 cases were treated with temozolomide. The median overall survival (OS) of all patients was 26.2 months and 21.5 months for the median progression-free survival (PFS). Both duration of symptoms (P = .007) and tumor grading (P = .002) were the influencing factors for OS, and tumor grading was significantly associated with PFS (P = .001). Duration of symptoms for more than 2 months and low-grade are favorable prognostic factors for adult patients with BSGs.