Clinical and imaging manifestations of intracerebral hemorrhage in brain tumors and metastatic lesions: a comprehensive overview.

PURPOSE: This observational study aims to provide a detailed clinical and imaging characterization/workup of acute intracerebral hemorrhage (ICH) due to either an underlying metastasis (mICH) or brain tumor (tICH) lesion. METHODS: We conducted a retrospective, single-center study, evaluating patients presenting with occult ICH on initial CT imaging, classified as tICH or mICH on follow-up MRI imaging according to the H-Atomic classification. Demographic, clinical and radiological data were reviewed. RESULTS: We included 116 patients (tICH: 20/116, 17.24%; mICH: 96/116, 82.76%). The most common malignancies causing ICH were lung cancer (27.59%), malignant melanoma (18.10%) and glioblastoma (10.34%). The three most common stroke-like symptoms observed were focal deficit (62/116, 53.45%), dizziness (42/116, 36.21%) and cognitive impairment (27/116, 23.28%). Highest mICH prevalence was seen in the occipital lobe (mICH: 28.13%, tICH: 0.00%; p = 0.004) with tICH more in the corpus callosum (tICH: 10.00%, mICH: 0.00%; p = 0.029). Anticoagulation therapy was only frequent in mICH patients (tICH: 0.00%, mICH: 5.21%; p = 0.586). Hemorrhage (tICH: 12682 mm3, mICH: 5708 mm3, p = 0.020) and edema volumes (tICH: 49389 mm3, mICH: 20972 mm3, p = 0.035) were significantly larger within tICH patients. CONCLUSION: More than half of the patients with neoplastic ICH exhibited stroke-like symptoms. Lung cancer was most common in mICH, glioblastoma in tICH. While clinical presentations were similar, significant differences in tumor location and treatments were discernible.

Developing a non-cadaveric brain tumour surgery lab in resource-constrained settings.

OBJECTIVE: To develop the country's first brain tumour surgery lab in resource-constrained settings, for training young neurosurgeons and residents. METHODS: A workshop was developed using mixed-fidelity models for assessing and training a participant's psychomotor skills, hand-eye coordination, and teaching the principles of brain tumour surgery. Affordable noncadaveric models were used to compare and contrast the benefit of each teaching model. Within the existing space for wet labs at our institution, 8 different dissection stations were set up with adequate space for 2 people to work at a time. Each station was equipped with an operating room-Caliber microscope, a lighting system and a camera linked to a screen and high-powered electric drills and basic surgical equipment. RESULTS: Our team was able to develop and use 3D-printed skull models and animal brain models for training in complex approaches and craniotomy. CONCLUSIONS: Surgical simulation training, in a cost-effective manner, provides the benefit of training residents and students in neurosurgical techniques in a safe, controlled environment leading to improvement in skills and technique.

The need for economic evaluations for neuro-oncology in low- and middleincome: the Pakistan perspective.

The incidence and prevalence of brain tumours have steadily increased within low- and middle-income countries, similar to patterns seen in high-income countries. In addition to the epidemiological landscape of brain tumours in Pakistan, it is important to consider the economics of brain tumour diagnosis and management to inform policy on neuro-oncological healthcare service delivery. The challenges associated with conducting economic evaluations in LMICs include the ability to receive funding for country-specific estimates, dearth of existing data and methodological development, and the need for investment in economic evaluations of health. Economic evaluations are most useful when funding support is given to country-specific initiatives to allocate resources. Cost and cost components must also be meticulously collected to enable accurate calculations of economic evidence for the decision-making process. To put neuro-oncological care at the forefront of the national health agenda, it is crucial for vigorous epidemiological and economic evidence to be available for policymakers.

Use of artificial intelligence and radio genomics in neuroradiology and the future of brain tumour imaging and surgical planning in low- and middleincome countries.

Brain tumour diagnosis involves assessing various radiological and histopathological parameters. Imaging modalities are an excellent resource for disease monitoring. However, manual inspection of imaging is laborious, and performance varies depending on expertise. Artificial Intelligence (AI) driven solutions a non-invasive and low-cost technology for diagnostics compared to surgical biopsy and histopathological diagnosis. We analysed various machine learning models reported in the literature and assess its applicability to improve neuro-oncological management. A scoping review of 47 full texts published in the last 3 years pertaining to the use of machine learning for the management of different types of gliomas where radiomics and radio genomic models have proven to be useful. Use of AI in conjunction with other factors can result in improving overall neurooncological management within LMICs. AI algorithms can evaluate medical imaging to aid in the early detection and diagnosis of brain tumours. This is especially useful where AI can deliver reliable and efficient screening methods, allowing for early intervention and treatment.

Serum liquid biopsy for brain tumours: a scoping analysis of practicable approaches in low- and middle-income countries.

Approaches to brain tumour diagnosis and detecting recurrence after treatment are costly and significantly invasive. Developing peripheral-sample liquid biopsy tools is the key to enhancing our ability to prognosticate brain tumour subtypes and molecular heterogeneity. The present scoping review was designed to discuss current updates in liquid biopsy tools for diagnosis and guiding clinical management of brain tumours; we evaluated the literature within the context of low-and-middle-income country challenges. Circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), cell-free DNA (cfDNA), extracellular vesicle-associated biomarkers, protein biomarkers, microRNAs, and serum metabolites are discussed with the collation of current data supporting their utility in liquid biopsy. Further challenges to implanting liquid biopsy tools at a systematic level are highlighted.

A guideline on guidelines: neuro-oncology guideline standards for low- and middle-income countries.

Guidelines for low- and middle-income countries (LMICs) are needed in complex, multidisciplinary areas such as oncology, requiring mobilising considerable resources and specialists for coordinated care. Neuro-oncology guidelines have been primarily established in countries where technological advancements and robust care pathways facilitate broad resource utilisation. In contrast, LMICs require complex and region-specific interventions to provide equitable care. The present opinion paper is a culmination of our own centre's experience collaborating and developing loco-regional guidelines for brain tumour care, keeping in mind LMIC experiences and expertise available. We intend for the process and methodology to apply to a broader audience of other LMIC authors and clinicians collaborating with LMIC institutions to develop guidelines and clinical recommendations.

Consensus guidelines for the management of pediatric medulloblastoma in low and middle-income countries.

The management of medulloblastoma, a pediatric brain tumor, has evolved significantly with the advent of genomic subgrouping, yet morbidity and mortality remain high in LMICs like Pakistan due to inadequate multidisciplinary care infrastructure. This paper aims to establish evidence-based guidelines tailored to the constraints of such countries. An expert panel comprising neuro-oncologists, neurosurgeons, radiologists, radiation oncologists, neuropathologists, and pediatricians collaborated to develop these guidelines, considering the specific challenges of pediatric brain tumor care in Pakistan. The recommendations cover various aspects of medulloblastoma treatment, including pre-surgical workup, neurosurgery, neuropathology, chemotherapy, radiation therapy, and supportive care. They offer both minimum required and additional optional protocols for more advanced centers, ensuring comprehensive patient management with attention to complications and complexities encountered in Pakistan. The paper's consensus guidelines strive for uniformity in healthcare delivery and address significant gaps in diagnosis, treatment, and follow-up of pediatric medulloblastoma patients.

Consensus guidelines for the management of adult low-grade gliomas for low and middle-income countries.

Low-grade gliomas (LGG) are brain tumors of glial cells origin. They are grade 1 and grade 2 tumors according to the WHO classification. Diagnosis of LGG is made through imaging, histopathological analysis, and use of molecular markers. Imaging alone does not establish the grade of the tumor and thus a histopathological examination of tissue is crucial in establishing the definite histopathological diagnosis. Clinical presentation varies according to the location and size of the tumor. Surgical resection is strongly recommended in LGG over observation to improve overall survival as surgery leads to greater benefit due to progression-free survival. Radiation has shown benefits in LGG patients in randomized controlled trials and chemotherapy with temozolomide has also shown good results. This paper covers the principles of low-grade gliomas management and summarizes the recommendations for the LMICs.

Consensus guidelines for the management of intracranial metastases for low- and middle-income countries.

Metastatic tumours are among the most common types of brain tumours. However, in low- and middle-income countries (LMICs), the numbers are considerably lower. This does not necessarily indicate a decreased incidence but rather points to decreased survival rates or limited access to healthcare. The challenge of achieving better outcomes, along with associated costs and resource constraints, often hinders the effective management of brain metastasis. Even in cases where localised disease can potentially be managed to improve survival, these challenges persist. The purpose of these guidelines is to address these challenges and outline a management strategy within the context of LMICs.

Consensus guidelines for the management of intracranial meningioma for low- and middle-income countries.

Intra-cranial meningiomas represent the most common type of extra-axial brain tumour in adults. Characteristically slow-growing and often asymptomatic, these tumours may only require observation in some cases. However, lesions that cause a significant mass effect necessitate intervention, primarily through surgical means. Additionally, in cases of significant unresectable low-grade residual meningioma or high-grade tumours, radiation therapy becomes essential. Notably, current management guidelines predominantly reflect data derived from high-income countries, failing to address constraints prevalent in the developing world, such as limited financial resources and restricted access to advanced surgical facilities. This manuscript introduces guidelines specifically tailored for the management of meningioma in patients from low- and middle-income countries, considering their unique healthcare challenges and resources.

Judicious and evidence-based use of radiosurgery - recommendations for low-middle income countries.

Surgical removal remains the primary treatment for most brain tumours. However, radiosurgery presents an effective, less invasive alternative or additional treatment for certain types. Our goal was to explore radiosurgery's roles in treating various brain tumours, focussing on its application in low- and middle-income countries (LMICs). We reviewed all relevant systematic reviews, metaanalyses, and guidelines to determine the most effective radiosurgical approaches. Additionally, we consulted a panel of experts with over ten years of experience in LMICs, such as Pakistan. For brain tumours, stereotactic radiosurgery should generally follow a confirmed histopathological diagnosis. Exceptions include tumours identified through Magnetic Resonance Imaging (MRI), like Vestibular Schwannoma (VS), pre-diagnosed Neurofibromatosis type 2 (NF2), multiple typical meningiomas, and metastases with a known histology from another site. While radiosurgery is gaining traction as a primary and adjunct treatment in some LMICs, the lack of regional guidelines, trained personnel, and collaboration among specialists hinders its wider adoption. Addressing these gaps is crucial for expanding radiosurgical care in these regions.

Comparative Efficacy and Safety of Immunotherapy on Non-Small Cell Lung Cancer Patients With Brain Metastases: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Growing evidence suggests that immunotherapy has a positive effect on non-small cell lung cancer (NSCLC) patients with brain metastases (BMs). However, it remains unclear which type of immunotherapy is more efficient. The aim of this network meta-analysis (NMA) was to compare the efficacy and safety of different immunotherapy types and determine the optimal option. METHOD: Four databases (PubMed, Cochrane Library databases, Embase, and Web of Science) and ClinicalTrial.gov were searched from inception until January 26, 2023. Randomized controlled trials (RCTs), prospective nonrandomized trials, or observational studies investigating NSCLC patients with BMs treated by immunotherapy were included. The quality of the included studies was evaluated using the Cochrane risk of bias (ROB) tool and the Newcastle-Ottawa Scale (NOS). The efficacy of immunotherapy on NSCLC patients with BMs was evaluated using frequentist random-effects NMA. RESULT: Eleven studies from 1560 citations, encompassing 1437 participants, were included in this NMA. Statistical analysis showed that pembrolizumab (SMD = 4.35, 95% CI [2.21, 6.60]) and nivolumab+ipilimumab (SMD = 3.81, 95% CI [1.21, 6.40]) could improve overall survival (OS). Pembrolizumab (SMD = 3.32, 95% CI [2.75, 3.90]) demonstrated better effects in improving the overall response rate (ORR). No significant difference in adverse event (AE) was observed between immunotherapy and chemotherapy. CONCLUSION: Our findings indicated that pembrolizumab was the most promising immunotherapy for NSCLC patients with BMs. Nivolumab+ipilimumab might be an alternative choice to improve OS. LIMITATION: Inconsistency tests were not performed because of the scarcity of direct comparison. Besides, high heterogeneity was observed in our NMA.

Glioblastoma in a paper industry worker exposed to high concentrations of formaldehyde: a case report.

Background: Formaldehyde was classified as a Group I Carcinogen by the International Agency for Research on Cancer (IARC) in 2006. While the IARC has stated that there is a lack of evidence that formaldehyde causes brain cancer, three meta-analyses have consistently reported a significantly higher risk of brain cancer in workers exposed to high levels of formaldehyde. Therefore, we report a case of a worker who was diagnosed with glioblastoma after being exposed to high concentrations of formaldehyde while working with formaldehyde resin in the paper industry. Case presentation: A 40-year-old male patient joined an impregnated paper manufacturer and performed impregnation work using formaldehyde resin for 10 years and 2 months. In 2017, the patient experienced a severe headache and visited the hospital for brain magnetic resonance imaging, which revealed a mass. In the same year, the patient underwent a craniotomy for brain tumor resection and was diagnosed with glioblastoma of the temporal lobe. In 2019, a craniotomy was performed owing to the recurrence of the brain tumor, but he died in 2020. An exposure assessment of the work environment determined that the patient was exposed to formaldehyde above the exposure threshold of 0.3 ppm continuously for more than 10 years and that he had high respiratory and dermal exposure through performing work without wearing a respirator or protective gloves. Conclusions: This case report represents the first instance where the epidemiological investigation and evaluation committee of the Occupational Safety and Health Research Institute in Korea recognized the scientific evidence of work-related brain tumors due to long-term exposure to high concentrations of formaldehyde during impregnated paperwork. This case highlights the importance of proper workplace management, informing workers that prolonged exposure to formaldehyde in impregnation work can cause brain tumors and minimizing exposure in similar processes.

Supra-tentorial Ependymomas with ZFTA Fusion, YAP1 Fusion, and Astroblastomas, MN1-altered: Characteristic Imaging Features.

PURPOSE: Supratentorial (ST) ependymoma subgroups are defined by two different fusions with different prognoses. Astroblastomas, MN1-altered, have ependymal-like histopathologic features and represent a differential diagnosis in children. We hypothesized that ZFTA-fused ependymoma and YAP1-fused ependymoma on the one hand, and astroblastoma, MN1-altered, on the other hand, show different MRI characteristics. METHODS: We retrospectively analyzed the preoperative imaging of 45 patients with ST ependymoma or astroblastoma between January 2000 and September 2020, blinded to histomolecular grouping. Several characteristics, such as location, tumor volume, calcifications, solid/cystic component, and signal enhancement or diffusion were evaluated. We compared imaging characteristics according to their molecular subtype (ZFTA-fused, YAP1-fused, and astroblastoma, MN1-altered). RESULTS: Thirty-nine patients were classified as having an ependymoma, 35 with a ZFTA fusion and four with a YAP1 fusion, and six as having an astroblastoma, MN1-altered. YAP1-fused ependymomas were more likely to involve at least 3 lobes than ZFTA-fused ependymomas. Astroblastomas were located in the frontal lobe in 100% of the tumors versus 49% of the ependymomas. Cerebral blood flow by arterial spin labeling was higher in astroblastomas than in ependymomas. There were no differences in the other characteristics between the molecular groups. All the tumors showed common features: intra-axial extra-ventricular tumors, very frequent contrast enhancement (39/43, 91%), a cystic/necrotic component (41/45, 91%), restricted diffusion (32/36, 89%), calcifications (15/18, 83%), and peri-tumoral edema (38/44, 86%). CONCLUSION: The distinction between ST ependymoma subtypes and astroblastomas can be guided by several imaging features. These tumors share common imaging features that may help to differentiate ST ependymomas and astroblastomas from other pediatric ST tumors.

Mature congenital intraventricular intracranial teratoma: A case report and literature review.

Background: Intracranial teratomas represent a rare subset of neoplasms characterized by tissues derived from multiple germ layers within the cranial cavity. These tumors, originating from primordial germ cells, exhibit diverse clinical presentations and histopathological features. While predominantly located along the midline axis, including the suprasellar cistern and pineal region, they can also manifest in less common areas such as ventricles and hypothalamic regions. Histopathologically, they are classified as mature, immature, or malignant based on the degree of tissue differentiation. Case Description: Male patient with prenatal care for congenital hydrocephalus born at 38 weeks gestation with a bulging fontanelle. Postnatal imaging revealed an intraventricular lesion, later diagnosed through magnetic resonance imaging as a mature teratoma invading the lateral ventricle and extending to the hypothalamus. Surgical resection achieved total macroscopic removal followed by successful postoperative ventriculoperitoneal shunting due to evolving hydrocephalus. Conclusion: Teratomas are uncommon tumors, and prognosis depends on tumor size and location, especially considering the rarity of mature teratomas. Complete surgical resection is paramount for treatment, leading to a better prognosis and quicker recovery. In cases where complete removal is challenging, adjuvant therapies and cerebrospinal fluid diversion may be required to enhance therapeutic outcomes and ensure successful resection.

Sodium fluorescein-guided resection of brain metastases: A needed approach or an option? A systematic review and meta-analysis.

PURPOSE: Brain metastases (BM) often leave residual tumors despite having visible margins, which increases the risk of local tumor recurrence and can impact overall patient survival rates. Fluorescence-guided surgery (FGS) utilizing sodium fluorescein (FL) has been reported as an effective technique in recent studies. This study aimed to evaluate the efficacy of FL FGS in improving the extent of resection of brain metastases and its impact on overall survival. METHODS: We conducted a systematic search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Our primary focus was on gross total resection (GTR). Additionally, we extracted survival data and evaluated the risk of bias using a modified version of the Joanna Briggs Institute critical appraisal tool. RESULTS: The study comprised 970 patients with brain metastases through eight different studies. The study found that patients who underwent FL-guided resection had a significantly higher rate of GTR (OR: 2.02, 95% CI: 1.14-3.56, p = 0.0156, I2 = 41.5%). Additionally, the study concluded that FL-guided resection is associated with better overall survival rates (HR: 0.61, 95%CI: 0.47 0.80, p = 0.0003, I2 = 41.5%). CONCLUSION: Our research suggests that the use of FL is associated with a higher rate of GTR and improved overall patient survival. None of the studies we reviewed reported significant complications associated with the use of FL in patients.

Multifraction stereotactic radiotherapy utilizing inhomogeneous dose distribution for brainstem metastases: a single-center retrospective analysis.

Brainstem metastases are challenging to manage owing to the critical neurological structures involved. Although stereotactic radiotherapy (SRT) offers targeted high doses while minimizing damage to adjacent normal tissues, the optimal dose fractionation remains undefined. This study evaluated the efficacy and safety of multifraction SRT with an inhomogeneous dose distribution. This retrospective study included 31 patients who underwent 33 treatments for 35 brainstem lesions using linear accelerator-based multifraction SRT (30 Gy in five fractions, 35 Gy in five fractions or 42 Gy in 10 fractions) with an inhomogeneous dose distribution (median isodose, 51.9%). The outcomes of interest were local failure, toxicity and symptomatic failure. The median follow-up time after brainstem SRT for a lesion was 18.6 months (interquartile range, 10.0-24.3 months; range, 1.8-39.0 months). Grade 2 toxicities were observed in two lesions, and local failure occurred in three lesions. No grade 3 or higher toxicities were observed. The 1-year local and symptomatic failure rates were 8.8 and 16.7%, respectively. Toxicity was observed in two of seven treatments with a gross tumor volume (GTV) greater than 1 cc, whereas no toxicity was observed in treatments with a GTV less than 1 cc. No clear association was observed between the biologically effective dose of the maximum brainstem dose and the occurrence of toxicity. Our findings indicate that multifraction SRT with an inhomogeneous dose distribution offers a favorable balance between local control and toxicity in brainstem metastases. Larger multicenter studies are needed to validate these results and determine the optimal dose fractionation.

Alterations of the Glymphatic System in Glioblastomas: A Systematic Review.

BACKGROUND/AIM: The glioblastomas, aggressive brain tumors with a poor prognosis, have drawn interest in their interaction with the glymphatic system-an emerging brain drainage network. This review explores the relationship between glioblastomas and the glymphatic system, aiming to elucidate their impact on disease progression. The aim of the study was to address the alterations in the glymphatic system in the presence of glioblastoma, and their implications for disease pathogenesis and prognosis. MATERIALS AND METHODS: Following PRISMA guidelines, we conducted a systematic literature review, identifying studies on the glymphatic system in glioblastomas. Four high-quality studies were selected based on stringent criteria. Data extraction involved categorizing key findings, and thematic analysis uncovered recurring patterns in glymphatic alterations associated with glioblastomas. RESULTS: Out of 356 studies, four meeting the high-quality criteria were included. These studies revealed modifications in lymphatic outflow, factors contributing to glymphatic dysfunction, impediments to cerebrospinal fluid drainage, and emerging roles in glioma management. The findings allow a comprehensive understanding of alterations within the glymphatic system in the presence of glioblastoma. CONCLUSION: The glymphatic system in glioblastomas exhibits changes, including diminished lymphatic outflow, disruptions and obstacles to fluid drainage, which represent new dimensions in glioma management. These alterations affect drug delivery, immunotherapy, and imaging interpretation. Future research should prioritize elucidating molecular mechanisms, developing therapeutic strategies, optimizing drug delivery, exploring immunotherapy, and translating findings into clinical practice.

Effect of different optimization parameters in single isocenter multiple brain metastases radiosurgery.

PURPOSE: Automated treatment planning for multiple brain metastases differs from traditional planning approaches. It is therefore helpful to understand which parameters for optimization are available and how they affect the plan quality. This study aims to provide a reference for designing multi-metastases treatment plans and to define quality endpoints for benchmarking the technique from a scientific perspective. METHODS: In all, 20 patients with a total of 183 lesions were retrospectively planned according to four optimization scenarios. Plan quality was evaluated using common plan quality parameters such as conformity index, gradient index and dose to normal tissue. Therefore, different scenarios with combinations of optimization parameters were evaluated, while taking into account dependence on the number of treated lesions as well as influence of different beams. RESULTS: Different scenarios resulted in minor differences in plan quality. With increasing number of lesions, the number of monitor units increased, so did the dose to healthy tissue and the number of interlesional dose bridging in adjacent metastases. Highly modulated cases resulted in 4-10% higher V10% compared to less complex cases, while monitor units did not increase. Changing the energy to a flattening filter free (FFF) beam resulted in lower local V12Gy (whole brain-PTV) and even though the number of monitor units increased by 13-15%, on average 46% shorter treatment times were achieved. CONCLUSION: Although no clinically relevant differences in parameters where found, we identified some variation in the dose distributions of the different scenarios. Less complex scenarios generated visually more dose overlap; therefore, a more complex scenario may be preferred although differences in the quality metrics appear minor.

Critical Issues for Patients and Caregivers in Neuro-Oncology during the COVID-19 Pandemic: What We Have Learnt from an Observational Study.

OBJECTIVE: The COVID-19 pandemic affected neuro-oncological patients and their caregivers regarding tumor care and emotional functioning, including Quality of Life (QoL). This study aimed to understand how COVID-19 affected their psychological state and the relations between patients and health personnel in neuro-oncology. METHODS: A cross-sectional study was conducted on neuro-oncological patients and their caregivers. RESULTS: A total of 162 patients and 66 caregivers completed the questionnaire. Altogether, 37.5% of patients perceived a greater risk of contracting COVID-19 compared to the general population. On a 0-10 scale, the patients' tumor-related anxiety score was 5.8, and their COVID-19-related score was 4.6. The caregivers reported 7.7 and 5.5, respectively. QoL was described as at least good in 75% of both patients and caregivers; the caregivers' care burden increased in 22.7% of cases during the pandemic, with no correlation with QoL. Future perception often changed, both in patients and caregivers. In 18% of cases, the cancer treatment schedule was changed, either by patient decision or by medical decision. However, 93.5% of patients were satisfied with their overall care. CONCLUSIONS: A considerable proportion of patients and caregivers still perceived the tumor disease as more burdensome than the pandemic, and their future as more uncertain. Such data suggest the need to build a productive alliance between patients and health professionals.