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Purpose: Neuronavigation, explored as an intra-operative adjunct for brain tumor surgery three decades ago, has become globally utilized with a promising upward trajectory. This study aims to chart its success from idea to adoption and evolution within the US and globally. Methods: A three-pronged methodology included a systematic literature search, impact analysis using NIH relative citation ratio (RCR) and Altmetric scores, and assessment of patent holdings. Data was dichotomized for US and international contexts. Results: The first neuronavigation publication stemmed from Finland in 1993, marking its inception. Over three decades, the cumulative number of 323 studies, along with the significantly increasing publication trend (r = 0.74, p < 0.05) and distribution across 34 countries, underscored its progressive and global adoption. Neuronavigation, mostly optical systems (58%), was utilized in over 19,000 cases, predominantly for brain tumor surgery (84%). Literature impact showed a robust cumulative median RCR score surpassing that for NIH-funded studies (1.37 vs. 1.0), with US studies having a significantly higher median RCR than international (1.71 vs. 1.21, p < 0.05). Technological evolution was characterized by adjuncts, including micro/exo/endoscope (21%), MRI (17%), ultrasound (10%), and CT (7%). Patent analysis demonstrated academic and industrial representation with an interdisciplinary convergence of medical and computational sciences. Conclusion: Since its inception thirty years ago, neuronavigation has been adopted worldwide, and it has evolved with adjunct technology integration to enhance its meaningful use. The current neuronavigation innovation pipeline is progressing, with academic and industry partnering to advance its further application in treating brain tumor patients. [ABSTRACT FROM AUTHOR]

Purpose: Our study aims to discover the leading topics within glioblastoma (GB) research, and to examine if these topics have "hot" or "cold" trends. Additionally, we aim to showcase the potential of natural language processing (NLP) in facilitating research syntheses, offering an efficient strategy to dissect the landscape of academic literature in the realm of GB research. Methods: The Scopus database was queried using "glioblastoma" as the search term, in the "TITLE" and "KEY" fields. BERTopic, an NLP-based topic modeling (TM) method, was used for probabilistic TM. We specified a minimum topic size of 300 documents and 5% probability cutoff for outlier detection. We labeled topics based on keywords and representative documents and visualized them with word clouds. Linear regression models were utilized to identify "hot" and "cold" topic trends per decade. Results: Our TM analysis categorized 43,329 articles into 15 distinct topics. The most common topics were Genomics, Survival, Drug Delivery, and Imaging, while the least common topics were Surgical Resection, MGMT Methylation, and Exosomes. The hottest topics over the 2020s were Viruses and Oncolytic Therapy, Anticancer Compounds, and Exosomes, while the cold topics were Surgical Resection, Angiogenesis, and Tumor Metabolism. Conclusion: Our NLP methodology provided an extensive analysis of GB literature, revealing valuable insights about historical and contemporary patterns difficult to discern with traditional techniques. The outcomes offer guidance for research directions, policy, and identifying emerging trends. Our approach could be applied across research disciplines to summarize and examine scholarly literature, guiding future exploration. [ABSTRACT FROM AUTHOR]

Purpose: Our study aims to discover the leading topics within glioblastoma (GB) research, and to examine if these topics have "hot" or "cold" trends. Additionally, we aim to showcase the potential of natural language processing (NLP) in facilitating research syntheses, offering an efficient strategy to dissect the landscape of academic literature in the realm of GB research. Methods: The Scopus database was queried using "glioblastoma" as the search term, in the "TITLE" and "KEY" fields. BERTopic, an NLP-based topic modeling (TM) method, was used for probabilistic TM. We specified a minimum topic size of 300 documents and 5% probability cutoff for outlier detection. We labeled topics based on keywords and representative documents and visualized them with word clouds. Linear regression models were utilized to identify "hot" and "cold" topic trends per decade. Results: Our TM analysis categorized 43,329 articles into 15 distinct topics. The most common topics were Genomics, Survival, Drug Delivery, and Imaging, while the least common topics were Surgical Resection, MGMT Methylation, and Exosomes. The hottest topics over the 2020s were Viruses and Oncolytic Therapy, Anticancer Compounds, and Exosomes, while the cold topics were Surgical Resection, Angiogenesis, and Tumor Metabolism. Conclusion: Our NLP methodology provided an extensive analysis of GB literature, revealing valuable insights about historical and contemporary patterns difficult to discern with traditional techniques. The outcomes offer guidance for research directions, policy, and identifying emerging trends. Our approach could be applied across research disciplines to summarize and examine scholarly literature, guiding future exploration. [ABSTRACT FROM AUTHOR]

Cognitive impairment has a profound deleterious impact on long-term outcomes of glioma surgery. The human insula, a deep cortical structure covered by the operculum, plays a role in a wide range of cognitive functions including interceptive thoughts and salience processing. Both low-grade (LGG) and high-grade gliomas (HGG) involve the insula, representing up to 25% of LGG and 10% of HGG. Surgical series from the past 30 years support the role of primary cytoreductive surgery for insular glioma patients; however, reported cognitive outcomes are often limited to speech and language function. The breath of recent neuroscience literature demonstrates that the insula plays a broader role in cognition including interoceptive thoughts and salience processing. This article summarizes the vast functional role of the healthy human insula highlighting how this knowledge can be leveraged to improve the care of patients with insular gliomas. [ABSTRACT FROM AUTHOR]

WHO grade II and III gliomas demonstrate diverse biological behaviors resulting in variable survival outcomes. In the context of glioma prognosis, machine learning (ML) approaches could facilitate the navigation through the maze of factors influencing survival, aiding clinicians in generating more precise and personalized survival predictions. Here we report the utilization of ML models in predicting survival at 12, 24, 36, and 60 months following grade II and III glioma diagnosis. From the National Cancer Database, we analyze 10,001 WHO grade II and 11,456 grade III cranial gliomas. Using the area under the receiver operating characteristic (AUROC) values, we deploy the top-performing models in a web application for individualized predictions. SHapley Additive exPlanations (SHAP) enhance the interpretability of the models. Top-performing predictive models are the ones built with LightGBM and Random Forest algorithms. For grade II gliomas, the models yield AUROC values ranging from 0.813 to 0.896 for predicting mortality across different timeframes, and for grade III gliomas, the models yield AUROCs ranging from 0.855 to 0.878. ML models provide individualized survival forecasts for grade II and III glioma patients across multiple clinically relevant time points. The user-friendly web application represents a pioneering digital tool to potentially integrate predictive analytics into neuro-oncology clinical practice, to empower prognostication and personalize clinical decision-making. [ABSTRACT FROM AUTHOR]

Brain metastases are the most common intracranial neoplasm and are seen in upwards of 10-30% of patients with cancer. For decades, whole brain radiation therapy (WBRT) was the mainstay of treatment in these patients. While WBRT is associated with excellent rates of intracranial tumor control, studies have demonstrated a lack of survival benefit, and WBRT is associated with higher rates of cognitive deterioration and detrimental effects on quality of life. In recent years, strategies to mitigate this risk, such as the incorporation of memantine and hippocampal avoidance have been employed with improved results. Furthermore, stereotactic radiosurgery (SRS) has emerged as an appealing treatment option over the last decade in the management of brain metastases and is associated with superior cognitive preservation and quality of life when compared to WBRT. This review article evaluates the pathogenesis and impact of cranial irradiation on cognition in patients with brain metastases, as well as current and future risk mitigation techniques. [ABSTRACT FROM AUTHOR]

Target population: These recommendations apply to adult patients diagnosed with progressive glioblastoma (pGBM). Question (Q1): In adult patients with pGBM does the use of temozolomide (TMZ) with alternative dosing or the use of TMZ in combination with other cytotoxic treatments result in increased overall survival compared to other chemotherapy? Recommendation: Level III: Adult patients with pGBM might derive benefit in treatment with TMZ, especially those who progress after more than 5 months of TMZ-treatment free interval. Level III: Combination of TMZ with other cytotoxic agents such as nitrosourea, cisplatin, electrohyperthermia, or tamoxifen is not suggested in adult patients with pGBM as a stand-alone therapy. There is insufficient data to make a recommendation about which alternative TMZ dosing provides the best benefits. Question (Q2): In adult patients with pGBM does the use of systemic or in situ nitrosourea result in increased overall survival compared to other chemotherapy? Recommendation: Level III: In the setting of pGBM, fotemustine is suggested in elderly patients with methylated MGMT promoter status. There is insufficient evidence to compare fotemustine to other nitrosoureas. There is insufficient evidence to make a recommendation about the use of in situ nitrosourea in patients with pGBM who underwent the Stupp regimen. Question (Q3): In adult patients with pGBM does the use of platinum compounds and topoisomerase result in increased survival compared to other chemotherapy? Recommendation: Level III: Other chemotherapy including platinum compounds and topoisomerase inhibitors are not suggested to be used in adult patients with pGBM. Level III: Other cytotoxic therapies like perillyl acohol or ketogenic diet are not suggested for use in adult patients with pGBM as a stand-alone therapy. Question (Q4): In adult patients with pGBM does the use of tumor treating field (TTF) result in increased overall survival compared to chemotherapy? Recommendation: Level III: The use of TTF with other chemotherapy may be considered when treating adult patients with pGBM. There is insufficient evidence to recommend TTF to increase overall survival in adult patients with pGBM. Question (Q5): In adult patients with pGBM does the use of oncolytic virotherapy result in increased survival compared to chemotherapy? Recommendation: Level III: Oncolytic virotherapy is not suggested in patients with pGBM. [ABSTRACT FROM AUTHOR]

This document is an abstract supplement from the Journal of Clinical & Translational Science. It includes three separate studies that explore different aspects of health disparities and diversity in healthcare research. The first study examines the impact of race and social determinants of health on the clinical outcomes of glioblastoma multiforme patients over a decade. The second study analyzes the participation of racial and ethnic minorities in decentralized trials, specifically focusing on the ACTIV-6 trial for the treatment of mild to moderate COVID-19. The third study discusses the Collaborative Undergraduate Biostatistics Experience (CUBE), a program aimed at diversifying and raising awareness of collaborative biostatistics among underrepresented minority undergraduate students in STEM fields. [Extracted from the article]

In the past 2 decades, a deeper understanding of the cancer molecular signature has resulted in longer longevity of cancer patients, hence a greater population, who potentially can develop metastatic disease. Spine metastases (SM) occur in up to 70% of cancer patients. Familiarizing ourselves with the key aspects of initial symptom-directed management is important to provide SM patients with the best patient-specific options. We will review key components of initial symptoms assessment such as pain, neurological symptoms, and spine stability. Radiographic evaluation of SM and its role in management will be reviewed. Nonsurgical treatment options are also presented and discussed, including percutaneous procedures, radiation, radiosurgery, and spine stereotactic body radiotherapy. The efforts of a multidisciplinary team will continue to ensure the best patient care as the landscape of cancer is constantly changing. [ABSTRACT FROM AUTHOR]

Target population: These recommendations apply to adults with newly diagnosed or suspected glioblastoma. Question: What is the effect of extent of surgical resection on patient outcome in the initial management of adult patients with suspected newly diagnosed glioblastoma? Recommendation: Level II: Maximal cytoreductive surgery is recommended in adult patients with suspected newly diagnosed supratentorial glioblastoma with gross total resection defined as removal of contrast enhancing tumor. Level III: Biopsy, subtotal resection, or gross total resection is suggested depending on medical comorbidities, functional status, and location of tumor if maximal resection may cause significant neurologic deficit. Question: What is the role of cytoreductive surgery in adults with newly diagnosed bi-frontal "butterfly" glioblastoma? Recommendation: Level III: Resection of newly diagnosed bi-frontal "butterfly" glioblastoma is suggested to improve overall survival over biopsy alone. Question: What is the goal of cytoreductive surgery in elderly adult patients with newly diagnosed glioblastoma? Recommendation: Level III: Elderly patients (> 65 years) show survival benefit with gross total resection and it is suggested they undergo cytoreductive surgery. Question: What is the role of advanced intraoperative guidance techniques in cytoreductive surgery in adults with newly diagnosed glioblastoma? Recommendation: Level III: The use of intraoperative guidance adjuncts such as intraoperative MRI (iMRI) or 5-aminolevulinic acid (5-ALA) are suggested to maximize extent of resection in newly diagnosed glioblastoma. There is insufficient evidence to make a suggestion on the use of fluorescein, indocyanine green, or intraoperative ultrasound. [ABSTRACT FROM AUTHOR]

The American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) Joint Section on Tumors was formed in December of 1984 as the first professional organization devoted to the study and treatment of brain tumors. One year earlier, the Journal of Neuro-Oncology had been established and went on to be sponsored by the Joint Section on Tumors. To celebrate the 35th anniversary of the founding of the Section, we are thrilled to bring you this special issue of Journal of Neuro-Oncology in which current leaders of the Joint Section on Tumors highlight their work and the work of others that have led to significant recent advances in the management of tumors of the central nervous system. [ABSTRACT FROM AUTHOR]

Background: Growth hormone (GH)-secreting pituitary adenomas represent an uncommon subset of pituitary neoplasms. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) have been used as primary or adjuvant treatment. The purpose of this study is to report the long-term tumor control and toxicity from our institution and to perform a systematic literature review of acromegaly patients treated with FSRT. Methods: We retrospectively reviewed all patients treated with FSRT (median dose 50.4 Gray [Gy], range 50.4-54 Gy) between 2005 and 2012 who had: 1) GH-secreting adenoma with persistently elevated insulin growth factor-1 (IGF-1) despite medical therapy and 2) clinical follow up >3 years after FSRT. Patients were treated with modern FSRT planning techniques. Biochemical control was defined as IGF-1 normalization. Systematic review of the literature was performed for FSRT in acromegaly. Results: With a median follow-up of 80 months, radiographic control was achieved in all 11 patients and overall survival was 100%. Long-term biochemical control was achieved in 10 patients (90.9%) with either FSRT alone (36.4%) or FSRT with continued medical management (45.5%). No patient experienced new hypopituitarism, cranial nerve dysfunctions, or visual deficits. Our systematic review found published rates of biochemical control and hypopituitarism vary, with uniformly good radiographic control and low incidence of visual changes. Conclusions: Adjuvant FSRT offered effective long-term biochemical control and radiographic control, and there was a lower rate of complications in this current series. Review of the literature shows variations in published rates of biochemical control after FSRT for acromegaly, but low incidence of serious toxicities. [ABSTRACT FROM AUTHOR]

Many central nervous system (CNS) diseases including stroke, spinal cord injury (SCI), and brain tumors are a significant cause of worldwide morbidity/mortality and yet do not have satisfying treatments. Cell-based therapy to restore lost function or to carry new therapeutic genes is a promising new therapeutic approach, particularly after human iPSCs became available. However, efficient generation of footprint-free and xeno-free human iPSC is a prerequisite for their clinical use. In this paper, we will first summarize the current methodology to obtain footprint- and xeno-free human iPSC. We will then review the current iPSC applications in therapeutic approaches for CNS regeneration and their use as vectors to carry proapoptotic genes for brain tumors and review their applications for modelling of neurological diseases and formulating new therapeutic approaches. Available results will be summarized and compared. Finally, we will discuss current limitations precluding iPSC from being used on large scale for clinical applications and provide an overview of future areas of improvement. In conclusion, significant progress has occurred in deriving iPSC suitable for clinical use in the field of neurological diseases. Current efforts to overcome technical challenges, including reducing labour and cost, will hopefully expedite the integration of this technology in the clinical setting. [ABSTRACT FROM AUTHOR]

Many central nervous system (CNS) diseases including stroke, spinal cord injury (SCI), and brain tumors are a significant cause of worldwide morbidity/mortality and yet do not have satisfying treatments. Cell-based therapy to restore lost function or to carry new therapeutic genes is a promising new therapeutic approach, particularly after human iPSCs became available. However, efficient generation of footprint-free and xeno-free human iPSC is a prerequisite for their clinical use. In this paper, we will first summarize the current methodology to obtain footprint- and xeno-free human iPSC. We will then review the current iPSC applications in therapeutic approaches for CNS regeneration and their use as vectors to carry proapoptotic genes for brain tumors and review their applications for modelling of neurological diseases and formulating new therapeutic approaches. Available results will be summarized and compared. Finally, we will discuss current limitations precluding iPSC from being used on large scale for clinical applications and provide an overview of future areas of improvement. In conclusion, significant progress has occurred in deriving iPSC suitable for clinical use in the field of neurological diseases. Current efforts to overcome technical challenges, including reducing labour and cost, will hopefully expedite the integration of this technology in the clinical setting. [ABSTRACT FROM AUTHOR]

Background: For patients with newly diagnosed high-grade gliomas (HGG), the current standard-of-care treatment involves surgical resection, followed by concomitant temozolomide (TMZ) and external beam radiation therapy (XRT), and subsequent TMZ chemotherapy. For patients with recurrent HGG, there is no standard of care. Stereotactic radiosurgery (SRS) is used to deliver focused, relatively large doses of radiation to a small, precisely defined target. Treatment is usually delivered in a single fraction, but may be delivered in up to five fractions. The role of SRS in the management of patients with HGG is not well established. Methods: The PubMed database was searched with combinations of relevant MESH headings and limits. Case reports and/or small case series were excluded. Attention was focused on overall median survival as an objective measure, and data were examined separately for newly diagnosed and recurrent HGG. Results: With respect to newly diagnosed HGG, there is strong evidence that addition of an SRS boost prior to standard XRT provides no survival benefit. However, recent retrospective evidence suggests a possible survival benefit when SRS is performed after XRT. With respect to recurrent HGG, there is suggestion that SRS may confer a survival benefit but with potentially higher complication rates. Newer studies are investigating the combination of SRS with targeted molecular agents. Controlled prospective clinical trials using advanced imaging techniques are necessary for a complete assessment. Conclusions: SRS has the potential to provide a survival benefit for patients with HGG. Further research is clearly warranted to define its role in the management of newly diagnosed and recurrent HGG. [ABSTRACT FROM AUTHOR]

The past decade has seen a dramatic increase in stem cell research that focuses on glioma stem cells (GSC) and their mechanisms of action, revealing multiple potential targets for primary malignant brain tumors. Herein, we present a novel framework for considering GSC targets based on direct and indirect strategies. Direct strategies target GSC molecular pathways to overcome their resistance to radiation and chemotherapy, block their function or induce their differentiation. Indirect strategies target the microenvironment of the GSC, namely the perivascular, hypoxic and immune niches. Progress made on GSC targets is reviewed in detail and specific pathways are identified in context of the proposed framework. The potential barriers for translation to the clinical setting are also discussed. Overall, targeting GSC provides an unprecedented opportunity for revolutionary approaches to treat high-grade gliomas that continue to have a poor patient prognosis. ( Cancer Sci 2011; 102: 1958-1966) [ABSTRACT FROM AUTHOR]

Arsenic trioxide (As2O3) has shown considerable efficacy in treating hematological malignancies with induction of programmed cell death (PCD) type I, apoptosis. However, the mechanisms underlying the antitumor effect of As2O3 on solid tumors are poorly defined. Previously, we reported that As2O3 induced autophagic cell death (PCD type II) but not apoptosis in human malignant glioma cell lines. The purpose of this study was to elucidate the molecular pathway leading to autophagic cell death. In this study, we demonstrated that the cell death was accompanied by involvement of autophagy-specific marker, microtubule-associated protein light chain 3 (LC3), and damage of mitochondrial membrane integrity, but not by caspase activation. Analysis by cDNA microarray, RT-PCR, and Western blot showed that cell death members of Bcl-2 family, Bcl-2/adenovirus E1B 19-kDa-interacting protein 3 (BNIP3) and its homologue BNIP3-like (BNIP3L), were upregulated in As2O3-induced autophagic cell death. Exogenous expression of BNIP3, but not BNIP3L, induced autophagic cell death in malignant glioma cells without As2O3 treatment. When upregulation of BNIP3 induced by As2O3 was suppressed by a dominant-negative effect of the transmembrane-deleted BNIP3 (BNIP3?TM), autophagic cell death was inhibited. In contrast, BNIP3 transfection augmented As2O3-induced autophagic cell death. These results suggest that BNIP3 plays a central role in As2O3-induced autophagic cell death in malignant glioma cells. This study adds a new concept to characterize the pathways by which As2O3 acts to induce autophagic cell death in malignant glioma cells.Oncogene (2005) 24, 980-991. doi:10.1038/sj.onc.1208095 Published online 13 December 2004 [ABSTRACT FROM AUTHOR]