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World Neurosurgery Dec 2023Due to the increased demand for palliative care (PC) in recent years, a model has been proposed to divide PC into primary PC and specialist PC. This article aimed to...
OBJECTIVE
Due to the increased demand for palliative care (PC) in recent years, a model has been proposed to divide PC into primary PC and specialist PC. This article aimed to delineate the indications for primary and specialist PC within 2 common neurosurgical conditions-glioblastoma (GBM) and stroke.
METHODS
A systematic review and bibliometric analysis was conducted to better appreciate the practice trends in PC utilization for GBM and stroke patients using several databases.
RESULTS
There were 70 studies on PC for GBM, the majority of which related to patient preference (22 [31%]). During 1999-2022, there was significant growth in publications per year on this topic at a rate of approximately 0.3 publications per year (P < 0.01). There were 44 studies on PC for stroke, the majority of which related to communication strategies (14 [32%]). During 1999-2022, there was no significant growth in stroke publications per year (P = 0.22).
CONCLUSIONS
Due to the progressively disabling neurological course of GBM, we suggest that a specialty PC team be used in conjunction with the neurosurgical team early in the disease trajectory while patients are still able to communicate their preferences, goals, and values. In contrast, short-term and long-term stages of management of stroke have differing implications for PC needs, with the short-term stage necessitating adept, time-sensitive communication between the patient, family, and care teams. Thus, we propose that primary PC should be included as a core competency in neurosurgery training, among other stroke specialists.
Topics: Humans; Palliative Care; Glioblastoma; Neurosurgery; Bibliometrics; Stroke
PubMed: 37739173
DOI: 10.1016/j.wneu.2023.09.048 -
World Neurosurgery Jun 2024Classifying brain tumors accurately is crucial for treatment and prognosis. Machine learning (ML) shows great promise in improving tumor classification accuracy. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Classifying brain tumors accurately is crucial for treatment and prognosis. Machine learning (ML) shows great promise in improving tumor classification accuracy. This study evaluates ML algorithms for differentiating various brain tumor types.
METHODS
A systematic review and meta-analysis were conducted, searching PubMed, Embase, and Web of Science up to March 14, 2023. Studies that only investigated image segmentation accuracy or brain tumor detection instead of classification were excluded. We extracted binary diagnostic accuracy data, constructing contingency tables to derive sensitivity and specificity.
RESULTS
Fifty-one studies were included. The pooled area under the curve for glioblastoma versus lymphoma and low-grade versus high-grade gliomas were 0.99 (95% confidence interval [CI]: 0.98-1.00) and 0.89, respectively. The pooled sensitivity and specificity for benign versus malignant tumors were 0.90 (95% CI: 0.85-0.93) and 0.93 (95% CI: 0.90-0.95), respectively. The pooled sensitivity and specificity for low-grade versus high-grade gliomas were 0.99 (95% CI: 0.97-1.00) and 0.94, (95% CI: 0.79-0.99), respectively. Primary versus metastatic tumor identification yields sensitivity and specificity of 0.89, (95% CI: 0.83-0.93) and 0.87 (95% CI: 0.82-0.91), correspondingly. The differentiation of gliomas from pituitary tumors yielded the highest results among primary brain tumor classifications: sensitivity of 0.99 (95% CI: 0.99-1.00) and specificity of 0.99 (95% CI: 0.98-1.00).
CONCLUSIONS
ML demonstrated excellent performance in classifying brain tumor images, with near-maximum area under the curves, sensitivity, and specificity.
Topics: Humans; Brain Neoplasms; Glioblastoma; Glioma; Machine Learning; Sensitivity and Specificity
PubMed: 38580093
DOI: 10.1016/j.wneu.2024.03.152 -
BMC Neurology Mar 2024MGMT (O 6 -methylguanine-DNA methyltransferase) promoter methylation is a commonly assessed prognostic marker in glioblastoma (GBM). Epigenetic silencing of the MGMT...
BACKGROUND
MGMT (O 6 -methylguanine-DNA methyltransferase) promoter methylation is a commonly assessed prognostic marker in glioblastoma (GBM). Epigenetic silencing of the MGMT gene by promoter methylation is associated with greater overall and progression free survival with alkylating agent regimens. To date, there is marked heterogeneity in how MGMT promoter methylation is tested and which CpG sites are interrogated.
METHODS
To further elucidate which MGMT promoter CpG sites are of greatest interest, we performed comprehensive searches in PubMed, Web of Science, and Embase and reviewed 2,925 article abstracts. We followed the GRADE scoring system to assess risk of bias and the quality of the studies we included.
RESULTS
We included articles on adult glioblastoma that examined significant sites or regions within MGMT promoter for the outcomes: overall survival, progression free survival, and/or MGMT expression. We excluded systemic reviews and articles on lower grade glioma. fifteen articles met inclusion criteria with variable overlap in laboratory and statistical methods employed, as well as CpG sites interrogated. Pyrosequencing or BeadChip arrays were the most popular methods utilized, and CpG sites between CpG's 70-90 were most frequently investigated. Overall, there was moderate concordance between the CpG sites that the studies reported to be highly predictive of prognosis. Combinations or means of sites between CpG's 73-89 were associated with improved OS and PFS. Six studies identified CpG sites associated with prognosis that were closer to the transcription start site: CpG's 8, 19, 22, 25, 27, 32,38, and CpG sites 21-37, as well as low methylation level of the enhancer regions.
CONCLUSION
The following systematic review details a comprehensive investigation of the current literature and highlights several potential key CpG sites that demonstrate significant association with OS, PFS, and MGMT expression. However, the relationship between extent of MGMT promoter methylation and survival may be non-linear and could be influenced by potential CpG hotspots, the extent of methylation at each CpG site, and MGMT enhancer methylation status. There were several limitations within the studies such as smaller sample sizes, variance between methylation testing methods, and differences in the various statistical methods to test for association to outcome. Further studies of high impact CpG sites in MGMT methylation is warranted.
Topics: Humans; Brain Neoplasms; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Glioblastoma; Glioma; Prognosis; Tumor Suppressor Proteins
PubMed: 38521933
DOI: 10.1186/s12883-024-03605-3 -
Journal of Immunotherapy (Hagerstown,...Laser interstitial thermal therapy (LITT) is a minimally invasive neurosurgical technique used to ablate intra-axial brain tumors. The impact of LITT on the tumor...
Laser interstitial thermal therapy (LITT) is a minimally invasive neurosurgical technique used to ablate intra-axial brain tumors. The impact of LITT on the tumor microenvironment is scarcely reported. Nonablative LITT-induced hyperthermia (33-43˚C) increases intra-tumoral mutational burden and neoantigen production, promoting immunogenic cell death. To understand the local immune response post-LITT, we performed longitudinal molecular profiling in a newly diagnosed glioblastoma and conducted a systematic review of anti-tumoral immune responses after LITT. A 51-year-old male presented after a fall with progressive dizziness, ataxia, and worsening headaches with a small, frontal ring-enhancing lesion. After clinical and radiographic progression, the patient underwent stereotactic needle biopsy, confirming an IDH-WT World Health Organization Grade IV Glioblastoma, followed by LITT. The patient was subsequently started on adjuvant temozolomide, and 60 Gy fractionated radiotherapy to the post-LITT tumor volume. After 3 months, surgical debulking was conducted due to perilesional vasogenic edema and cognitive decline, with H&E staining demonstrating perivascular lymphocytic infiltration. Postoperative serial imaging over 3 years showed no evidence of tumor recurrence. The patient is currently alive 9 years after diagnosis. Multiplex immunofluorescence imaging of pre-LITT and post-LITT biopsies showed increased CD8 and activated macrophage infiltration and programmed death ligand 1 expression. This is the first depiction of the in-situ immune response to LITT and the first human clinical presentation of increased CD8 infiltration and programmed death ligand 1 expression in post-LITT tissue. Our findings point to LITT as a treatment approach with the potential for long-term delay of recurrence and improving response to immunotherapy.
Topics: Male; Humans; Middle Aged; Glioblastoma; Magnetic Resonance Imaging; Laser Therapy; Neoplasm Recurrence, Local; Brain Neoplasms; Hyperthermia, Induced; Immunity; Lasers; Retrospective Studies; Tumor Microenvironment
PubMed: 37727953
DOI: 10.1097/CJI.0000000000000485 -
Radiotherapy and Oncology : Journal of... Jan 2024To evaluate the clinical efficacy and toxicity of brachytherapy as a salvage therapy for patients with recurrent glioblastoma (rGBM). (Review)
Review
PURPOSE
To evaluate the clinical efficacy and toxicity of brachytherapy as a salvage therapy for patients with recurrent glioblastoma (rGBM).
METHODS AND MATERIALS
We searched the PubMed, Embase, and Cochrane libraries from its inception to June 2023, for eligible studies in which patients underwent brachytherapy for rGBM. Outcomes of interest were mOS, mPFS, OS, PFS, and adverse events (AEs). For individual clinical survival outcomes and common AEs, weighted-mean descriptive statistics were calculated as a summary measure using study sample size as the weight. The calculation formula is as follows: weighted-mean = Σwx/Σw (w is the sample size and x is the outcome).
RESULTS
This review included 29 studies with a total of 1202 rGBM patients, including 22 retrospective and 7 prospective studies. The results showed that from the time of brachytherapy, the mOS and mPFS were 6.8 to 24.4 months and 3.7 to 11.7 months. The OS of 6 months, 1 year, 18 months, 2 years, and 3 years after brachytherapy were 58.3 % to 85.2 % (weighted-mean 76.2 %), 26 % to 66 % (weighted-mean 41.9 %), 20 % to 37 % (weighted-mean 27.6 %), 11 % to 23 % (weighted-mean 14.8 %), and 8 % to 15 % (weighted-mean 12.1 %), respectively. The PFS of 6 months and 1 year after brachytherapy were 26.7 % to 86 % (weighted-mean 53.4 %) and 14 % to 81 % (weighted-mean 24.1 %). Most patients with rGBM will experience treatment failure again during the follow-up period, mainly local (10.7 % to 79.4 %) or marginal(3.6 % to 22.2 %) recurrence, followed by distant failure (6.7 % to 57.7 %). Although therapeutic AEs had not been uniformly reported, the overall toxicity rate was considered to be low. The common AEs reported included progressive neurologic deterioration, seizures, CSF leak, brain necrosis, hemorrhage, and infection/meningitis, with a weighted-mean incidence of 1.9 %, 2.4 %, 4.1 %, 5.4 %, 2.1 %, and 3.8 %, respectively.
CONCLUSIONS
The evidence summarized above, albeit mostly level III, suggests that brachytherapy has acceptable safety and good post-treatment clinical efficacy for selected patients with rGBM. Well-designed, high-quality, large-sample randomized controlled and prospective studies are needed to further validate these findings.
Topics: Humans; Re-Irradiation; Glioblastoma; Brachytherapy; Retrospective Studies; Prospective Studies; Neoplasm Recurrence, Local; Salvage Therapy
PubMed: 37972737
DOI: 10.1016/j.radonc.2023.110012 -
World Neurosurgery Nov 2023Glioblastoma (GBM) is a malignant primary brain cancer, among the most devastating and lethal diseases of the central nervous system. Similarly, malignant melanoma (MM)... (Review)
Review
BACKGROUND
Glioblastoma (GBM) is a malignant primary brain cancer, among the most devastating and lethal diseases of the central nervous system. Similarly, malignant melanoma (MM) is responsible for most skin cancer-related deaths. A link between those 2 aggressive cancers has not yet been established. We present here a systematic review of the literature and an exemplificative case.
METHODS
A systematic review of the literature was conducted to assess possible commonalities between MM and GBM. An exemplificative surgical vignette of a 73-year-old patient with the occurrence of a frontobasal GBM after surgical removal of a metastasis of MM in the same location was then detailed.
RESULTS
Fifteen studies published in the English international literature support a link between MM and GBM, both based on epidemiologic and pathophysiologic/genetic aspects. This theory is reinforced by our surgical vignette of a collision tumor with the occurrence of both tumors in the same location several years apart.
CONCLUSIONS
The evidence reported in the literature, as well as our surgical vignette, support a likely link between the pathogenesis of GBM and MM.
Topics: Humans; Aged; Glioblastoma; Melanoma; Neoplasms, Second Primary; Central Nervous System; Skin; Brain Neoplasms
PubMed: 37625631
DOI: 10.1016/j.wneu.2023.08.073 -
Annales D'endocrinologie Aug 2023
Topics: Humans; Astrocytoma; Brain Neoplasms; Magnetic Resonance Imaging; Pituitary Gland; Multiple Endocrine Neoplasia Type 1; Male; Adolescent
PubMed: 37169283
DOI: 10.1016/j.ando.2023.04.004 -
Journal of Cancer Research and Clinical... Jan 2024Accurate and non-invasive estimation of MGMT promoter methylation status in glioblastoma (GBM) patients is of paramount clinical importance, as it is a predictive... (Review)
Review
BACKGROUND
Accurate and non-invasive estimation of MGMT promoter methylation status in glioblastoma (GBM) patients is of paramount clinical importance, as it is a predictive biomarker associated with improved overall survival (OS). In response to the clinical need, recent studies have focused on the development of non-invasive artificial intelligence (AI)-based methods for MGMT estimation. In this systematic review, we not only delve into the technical aspects of these AI-driven MGMT estimation methods but also emphasize their profound clinical implications. Specifically, we explore the potential impact of accurate non-invasive MGMT estimation on GBM patient care and treatment decisions.
METHODS
Employing a PRISMA search strategy, we identified 33 relevant studies from reputable databases, including PubMed, ScienceDirect, Google Scholar, and IEEE Explore. These studies were comprehensively assessed using 21 diverse attributes, encompassing factors such as types of imaging modalities, machine learning (ML) methods, and cohort sizes, with clear rationales for attribute scoring. Subsequently, we ranked these studies and established a cutoff value to categorize them into low-bias and high-bias groups.
RESULTS
By analyzing the 'cumulative plot of mean score' and the 'frequency plot curve' of the studies, we determined a cutoff value of 6.00. A higher mean score indicated a lower risk of bias, with studies scoring above the cutoff mark categorized as low-bias (73%), while 27% fell into the high-bias category.
CONCLUSION
Our findings underscore the immense potential of AI-based machine learning (ML) and deep learning (DL) methods in non-invasively determining MGMT promoter methylation status. Importantly, the clinical significance of these AI-driven advancements lies in their capacity to transform GBM patient care by providing accurate and timely information for treatment decisions. However, the translation of these technical advancements into clinical practice presents challenges, including the need for large multi-institutional cohorts and the integration of diverse data types. Addressing these challenges will be critical in realizing the full potential of AI in improving the reliability and accessibility of MGMT estimation while lowering the risk of bias in clinical decision-making.
Topics: Humans; Glioblastoma; Artificial Intelligence; Reproducibility of Results; DNA Methylation; Brain Neoplasms; DNA Modification Methylases; DNA Repair Enzymes; DNA; Tumor Suppressor Proteins
PubMed: 38291266
DOI: 10.1007/s00432-023-05566-5 -
Journal of Neurosurgery. Pediatrics Nov 2023Seizures can be a debilitating manifestation of underlying neoplastic intracranial pathology. Existing literature offers a paucity of scientific consensus regarding risk...
OBJECTIVE
Seizures can be a debilitating manifestation of underlying neoplastic intracranial pathology. Existing literature offers a paucity of scientific consensus regarding risk factors, seizure semiology, operative techniques, and tumor characteristics in pediatric patients with a concurrent diagnosis of primary intracranial neoplasm and seizures. To address the limited evidence in current literature, the authors systematically reviewed published literature on current clinical characteristics and management strategies for patients presenting concurrently with seizures and a newly diagnosed brain lesion, while aiming to synthesize a potential management protocol or set of recommendations for these patients.
METHODS
An initial search revealed 792 papers, of which 196 studies were excluded, leaving 596 studies available for abstract review. After further stratification, 546 studies were eliminated, leaving 50 studies for eligibility assessment. Of the 50 studies, 12 met the criteria for outcome extraction.
RESULTS
The results indicate that patients with a mean age of 9 years with a newly diagnosed brain tumor and presenting symptoms of seizure are likely to present with daily seizures of the complex partial subtype, with the most likely primary epileptogenic and neoplastic foci occurring in the temporal lobe. The most common tumor subtypes were low-grade gliomas, ganglioglioma, dysembryoplastic neuroepithelial tumor, or astrocytoma. With the aim of gross-total resection, 77.54% of patients are likely to achieve seizure freedom.
CONCLUSIONS
This study highlights the demographic, clinical, seizure, tumor, and postoperative outcomes for pediatric patients presenting with a primary brain tumor and concurrent seizures. Further prospective multicenter studies are necessary to understand and compare varying treatment approaches and to develop standardized guidelines for these patients, with the goal of optimizing neuro-oncological and seizure-related outcomes.
Topics: Humans; Child; Treatment Outcome; Retrospective Studies; Seizures; Glioma; Epilepsy; Brain; Brain Neoplasms
PubMed: 37728409
DOI: 10.3171/2023.6.PEDS22440 -
Journal of Neurosurgery. Pediatrics Jul 2024More than one-third of pediatric patients who undergo resection of intradural spine lesions develop progressive postoperative deformity, with as many as half of these...
OBJECTIVE
More than one-third of pediatric patients who undergo resection of intradural spine lesions develop progressive postoperative deformity, with as many as half of these patients subsequently requiring surgical fusion. Intradural spinal procedures with simultaneous instrumented fusion in children, however, are infrequently performed. Moreover, the rationale for patient selection, outcomes, and safety of this single-stage surgery in children has not been systematically investigated. In this study, the authors review the practice of simultaneous intradural spinal resection and instrumented fusion in pediatric patients and provide two representative case examples from their institution.
METHODS
The authors searched the PubMed and Embase databases and performed a systematic review following the PRISMA protocol. Original articles of pediatric patients (age ≤ 18 years) who underwent intradural spine surgery, regardless of pathology, with concomitant instrumented fusion and reported outcomes were included. An institutional database of all spinal operations with instrumented fusion performed in patients aged ≤ 18 years over a 3-year period was screened to identify those who underwent intradural spine surgery with concomitant fusion.
RESULTS
Nine patients (median age 12 years) from 6 studies who underwent intradural lesion resection and concomitant fusion met inclusion criteria. Among all 11 patients included, primary rationales for concomitant fusion were extensive bone removal (i.e., corpectomy or total facetectomy, 73%), concerns for deformity in the setting of multilevel laminectomy/laminoplasty (18%), and severe baseline deformity (9%). The most represented pathology was neurenteric cyst (55%) followed by schwannoma (18%). Myxopapillary ependymoma, granular cell tumor, and pilocytic astrocytoma each were seen in 1 case. Seven patients (64%) underwent an anterior-approach corpectomy, tumor resection, and fusion, while the remaining 4 patients (36%) underwent a posterior approach. All patients with at least 1 year of follow-up cases achieved bony fusion. CSF leak and new-onset neurological deficit each occurred in 9% (1/11).
CONCLUSIONS
The rationales for performing single-stage intradural resection and fusion in pediatric patients in studies to date include the presence of severe baseline deformity, large extent of bone resection, and multilevel laminectomy/laminoplasty across cervicothoracic or thoracolumbar junctions. As current literature involving this cohort is limited, more data are needed to determine when concomitant fusion in intradural resections is appropriate in pediatric patients and whether its routine implementation is safe or beneficial.
Topics: Humans; Spinal Fusion; Child; Adolescent; Male; Female; Spinal Cord Neoplasms; Ependymoma; Laminectomy; Treatment Outcome; Neurosurgical Procedures; Postoperative Complications
PubMed: 38579345
DOI: 10.3171/2024.1.PEDS23444