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Journal of Neuro-oncology Apr 2023The extent of resection (EOR) is an independent prognostic factor for overall survival (OS) in adult patients with Glioma Grade 4 (GG4). The aim of the neuro-oncology... (Meta-Analysis)
Meta-Analysis
PURPOSE
The extent of resection (EOR) is an independent prognostic factor for overall survival (OS) in adult patients with Glioma Grade 4 (GG4). The aim of the neuro-oncology section of the Italian Society of Neurosurgery (SINch®) was to provide a general overview of the current trends and technical tools to reach this goal.
METHODS
A systematic review was performed. The results were divided and ordered, by an expert team of surgeons, to assess the Class of Evidence (CE) and Strength of Recommendation (SR) of perioperative drugs management, imaging, surgery, intraoperative imaging, estimation of EOR, surgery at tumor progression and surgery in elderly patients.
RESULTS
A total of 352 studies were identified, including 299 retrospective studies and 53 reviews/meta-analysis. The use of Dexamethasone and the avoidance of prophylaxis with anti-seizure medications reached a CE I and SR A. A preoperative imaging standard protocol was defined with CE II and SR B and usefulness of an early postoperative MRI, with CE II and SR B. The EOR was defined the strongest independent risk factor for both OS and tumor recurrence with CE II and SR B. For intraoperative imaging only the use of 5-ALA reached a CE II and SR B. The estimation of EOR was established to be fundamental in planning postoperative adjuvant treatments with CE II and SR B and the stereotactic image-guided brain biopsy to be the procedure of choice when an extensive surgical resection is not feasible (CE II and SR B).
CONCLUSIONS
A growing number of evidences evidence support the role of maximal safe resection as primary OS predictor in GG4 patients. The ongoing development of intraoperative techniques for a precise real-time identification of peritumoral functional pathways enables surgeons to maximize EOR minimizing the post-operative morbidity.
Topics: Adult; Aged; Humans; Brain Neoplasms; Glioma; Magnetic Resonance Imaging; Neoplasm Recurrence, Local; Neurosurgery; Retrospective Studies
PubMed: 36961622
DOI: 10.1007/s11060-023-04274-x -
Neurosurgery Aug 2023Awake craniotomy (AC) is a common neurosurgical procedure for the resection of lesions in eloquent brain areas, which has the advantage of avoiding general anesthesia to...
BACKGROUND
Awake craniotomy (AC) is a common neurosurgical procedure for the resection of lesions in eloquent brain areas, which has the advantage of avoiding general anesthesia to reduce associated complications and costs. A significant resource limitation in low- and middle-income countries constrains the usage of AC.
OBJECTIVE
To review the published literature on AC in African countries, identify challenges, and propose pragmatic solutions by practicing neurosurgeons in Africa.
METHODS
We conducted a scoping review under Preferred Reporting Items for Systematic Reviews and Meta-Analysis-Scoping Review guidelines across 3 databases (PubMed, Scopus, and Web of Science). English articles investigating AC in Africa were included.
RESULTS
Nineteen studies consisting of 396 patients were included. Egypt was the most represented country with 8 studies (42.1%), followed by Nigeria with 6 records (31.6%). Glioma was the most common lesion type, corresponding to 120 of 396 patients (30.3%), followed by epilepsy in 71 patients (17.9%). Awake-awake-awake was the most common protocol used in 7 studies (36.8%). Sixteen studies (84.2%) contained adult patients. The youngest reported AC patient was 11 years old, whereas the oldest one was 92. Nine studies (47.4%) reported infrastructure limitations for performing AC, including the lack of funding, intraoperative monitoring equipment, imaging, medications, and limited human resources.
CONCLUSION
Despite many constraints, AC is being safely performed in low-resource settings. International collaborations among centers are a move forward, but adequate resources and management are essential to make AC an accessible procedure in many more African neurosurgical centers.
Topics: Adult; Child; Humans; Africa; Brain Neoplasms; Craniotomy; Glioma; Wakefulness; Aged, 80 and over
PubMed: 36961213
DOI: 10.1227/neu.0000000000002453 -
Scientific Reports Mar 2023Glioblastomas presenting topographically at the cerebellopontine angle (CPA) are exceedingly rare. Given the specific anatomical considerations and their rarity, overall...
Glioblastomas presenting topographically at the cerebellopontine angle (CPA) are exceedingly rare. Given the specific anatomical considerations and their rarity, overall survival (OS) and management are not discussed in detail. The authors performed an integrative survival analysis of CPA glioblastomas. A literature search of PubMed, Scopus, and Web of Science databases was performed per PRISMA guidelines. Patient data including demographics, clinical features, neuroimaging, management, follow-up, and OS were extracted. The mean age was 39 ± 26.2 years. The mean OS was 8.9 months. Kaplan-Meier log-rank test and univariate Cox proportional-hazards model identified hydrocephalus (log-rank, p = 0.034; HR 0.34; 95% CI 0.12-0.94; p = 0.038), chemotherapy (log-rank, p < 0.005; HR 5.66; 95% CI 1.53-20.88; p = 0.009), and radiotherapy (log-rank, p < 0.0001; HR 12.01; 95% CI 3.44-41.89; p < 0.001) as factors influencing OS. Hydrocephalus (HR 3.57; 95% CI 1.07-11.1; p = 0.038) and no adjuvant radiotherapy (HR 0.12; 95% CI 0.02-0.59; p < 0.01) remained prognostic on multivariable analysis with fourfold and twofold higher risk for the time-related onset of death, respectively. This should be considered when assessing the risk-to-benefit ratio for patients undergoing surgery for CPA glioblastoma.
Topics: Humans; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Glioblastoma; Cerebellopontine Angle; Survival Analysis; Prognosis; Proportional Hazards Models; Kaplan-Meier Estimate; Retrospective Studies
PubMed: 36932101
DOI: 10.1038/s41598-023-30677-x -
World Neurosurgery Jul 2023Staged surgery for skull base lesions has been utilized to facilitate maximal safe resection and optimize outcomes while minimizing morbidity and complications....
BACKGROUND
Staged surgery for skull base lesions has been utilized to facilitate maximal safe resection and optimize outcomes while minimizing morbidity and complications. Conversely, staged surgery for primary intraparenchymal neoplasms is less commonly performed and has not been reported as extensively within the literature. As such, we performed a systematic review to examine the unique surgical indications for staging, timing between stages, specific surgical approaches utilized, and postoperative complications of staged surgery for primary intra-axial neoplasms.
METHODS
A literature search was conducted in August 2021 using PubMed, Web of Science, and Cochrane databases using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations. Titles and abstracts were evaluated independently by 2 authors, after which articles were selected for final analysis based on application of strict inclusion criteria during full text screen. Each included article was then qualitatively assessed and relevant variables-including operative approaches, timing, and outcomes-were extracted for synthesis.
RESULTS
Of 115 results, 7 articles were included for final analysis and consisted of 17 pediatric and 4 adult patients. Staged approaches were more commonly utilized in the pediatric patient population for resection of astrocytoma and glioma. Pediatric patients had a timing of surgeries ranging from 5-10 days between operations, compared with 18 days to 4 months in adult patients. Complications in pediatric patients were most commonly hemiparesis, hydrocephalus, cranial nerve VI and VII palsies, truncal ataxia, and cerebellar mutism, while complications in adult patients included language and abstract thinking deficits, respiratory failure, and motor weakness.
CONCLUSIONS
This study reports the first comprehensive review of staged surgical procedures for primary, intra-axial cranial neoplasms. There exists a large degree of heterogeneity in complications resulting from staged surgeries for intra-axial neoplasms, which are similar to complications associated with single-stage surgery for intraparenchymal lesions as well as multi-stage surgeries for skull base lesions.
Topics: Adult; Humans; Child; Skull Base; Glioma; Astrocytoma; Postoperative Complications
PubMed: 36924887
DOI: 10.1016/j.wneu.2023.03.046 -
Current Oncology (Toronto, Ont.) Feb 2023Outcomes for patients with high-grade glioma remain poor. Temozolomide (TMZ) is the only drug approved for first-line treatment of glioblastoma multiforme, the most... (Review)
Review
Outcomes for patients with high-grade glioma remain poor. Temozolomide (TMZ) is the only drug approved for first-line treatment of glioblastoma multiforme, the most aggressive form of glioma. Chronotherapy highlights the potential benefit of timed TMZ administration. This is based on pre-clinical studies of enhanced TMZ-induced glioma cytotoxicity dependent on circadian, oscillating expression of key genes involved in apoptosis, DNA damage repair, and cell-cycle mediated cell death. The current systematic review's primary aim was to evaluate the efficacy and toxicity of TMZ chronotherapy. A systemic review of literature following PRISMA guidelines looking at clinical outcomes on TMZ chronotherapy on gliomas was performed. The search in the English language included three databases (PubMed, EMBASE, and Cochrane) and five conferences from 1946 to April 2022. Two independent reviewers undertook screening, data extraction, and risk-of-bias assessment. A descriptive analysis was conducted due to limited data. Of the 269 articles screened, two unique studies were eligible and underwent abstraction for survival and toxicity findings. Both studies-one a retrospective cohort study (n = 166) and the other a prospective randomized feasibility study (n = 35)-were conducted by the same academic group and suggested a trend for improved overall survival, but possibly increased toxicity when TMZ was administered in the morning (vs. evening). There was limited evidence suggesting possible therapeutic value from administering TMZ in the morning, which may be consistent with the pre-clinical observations of the importance of the timing of TMZ administration in vitro. Larger, pragmatic, prospective randomized controlled trials are needed to ascertain the value of TMZ chronotherapy to provide optimized and equitable care for this population.
Topics: Humans; Temozolomide; Retrospective Studies; Prospective Studies; Brain Neoplasms; Glioma; Chronotherapy; Randomized Controlled Trials as Topic
PubMed: 36826108
DOI: 10.3390/curroncol30020147 -
BMC Cancer Feb 2023Glioblastoma, the most common primary malignant brain tumour in adults, is a highly vascular tumour characterised by abnormal angiogenesis. Additional mechanisms of...
BACKGROUND
Glioblastoma, the most common primary malignant brain tumour in adults, is a highly vascular tumour characterised by abnormal angiogenesis. Additional mechanisms of tumour vascularisation have also been reported in glioblastoma, including the formation of tumour cell-derived vessels by vasculogenic mimicry (VM) or the transdifferentiation of tumour cells to endothelial cells. VM and endothelial transdifferentiation have frequently been reported as distinct processes, however, the use of both terms to describe a single process of vascularisation also occurs. Some overlapping characteristics have also been reported when identifying each process. We therefore aimed to determine the markers consistently attributed to VM and endothelial transdifferentiation in the glioblastoma literature.
METHODS
Ovid MEDLINE and Ovid Embase were searched for studies published between January 1999 and July 2021 that assessed VM or tumour to endothelial transdifferentiation in human glioblastoma. The online systematic review tool Covidence was used for screening and data extraction. Extracted data included type of tumour-derived vasculature reported, methods and techniques used, and markers investigated. Studies were grouped based on type of vasculature reported for further assessment.
RESULTS
One hundred and thirteen of the 419 unique records identified were included for analysis. VM was reported in 64/113 studies, while tumour to endothelial transdifferentiation was reported in 16/113 studies. The remaining studies used both terms to describe a single process, did not define the process that occurred, or concluded that neither VM nor endothelial transdifferentiation occurred. Absence of CD34 and/or CD31 in vascular structures was the most common indicator of VM, while expression of CD34 and/or CD31, in addition to various other endothelial, stem cell or tumour cell markers, indicated tumour to endothelial transdifferentiation.
CONCLUSION
Cells derived from tumour to endothelial transdifferentiation express typical endothelial markers including CD34 and CD31, while tumour cells contributing to VM lack CD34 and CD31 expression. Additional tumour markers are required to identify transdifferentiation in glioblastoma tissue, and this process requires further characterisation.
Topics: Adult; Humans; Glioblastoma; Endothelial Cells; Cell Transdifferentiation; Neovascularization, Pathologic; Cell Differentiation; Biomarkers, Tumor
PubMed: 36823554
DOI: 10.1186/s12885-023-10659-y -
Radiation Oncology (London, England) Feb 2023High-grade gliomas are the most common intracranial malignancies, and their current prognosis remains poor despite standard aggressive therapy. Charged particle beams... (Review)
Review
High-grade gliomas are the most common intracranial malignancies, and their current prognosis remains poor despite standard aggressive therapy. Charged particle beams have unique physical and biological properties, especially high relative biological effectiveness (RBE) of carbon ion beam might improve the clinical treatment outcomes of malignant gliomas. We systematically reviewed the safety, efficacy, and dosimetry of carbon-ion or proton radiotherapy to treat high-grade gliomas. The protocol is detailed in the online PROSPERO database, registration No. CRD42021258495. PubMed, EMBASE, Web of Science, and The Cochrane Library databases were collected for data analysis on charged particle radiotherapy for high-grade gliomas. Until July 2022, two independent reviewers extracted data based on inclusion and exclusion criteria. Eleven articles were eligible for further analysis. Overall survival rates were marginally higher in patients with the current standard of care than those receiving concurrent intensity-modulated radiotherapy plus temozolomide. The most common side effects of carbon-ion-related therapy were grade 1-2 (such as dermatitis, headache, and alopecia). Long-term toxicities (more than three to six months) usually present as radiation necrosis; however, toxicities higher than grade 3 were not observed. Similarly, dermatitis, headache, and alopecia are among the most common acute side effects of proton therapy treatment. Despite improvement in survival rates, the method of dose-escalation using proton boost is associated with severe brain necrosis which should not be clinically underestimated. Regarding dosimetry, two studies compared proton therapy and intensity-modulated radiation therapy plans. Proton therapy plans aimed to minimize dose exposure to non-target tissues while maintaining target coverage. The use of charged-particle radiotherapy seems to be effective with acceptable adverse effects when used either alone or as a boost. The tendency of survival outcome shows that carbon ion boost is seemingly superior to proton boost. The proton beam could provide good target coverage, and it seems to reduce dose exposure to contralateral organs at risk significantly. This can potentially reduce the treatment-related dose- and volume-related side effects in long-term survivors, such as neurocognitive impairment. High-quality randomized control trials should be conducted in the future. Moreover, Systemic therapeutic options that can be paired with charged particles are necessary.
Topics: Humans; Adult; Protons; Glioma; Proton Therapy; Headache; Carbon; Alopecia; Necrosis; Dermatitis
PubMed: 36755321
DOI: 10.1186/s13014-022-02187-z -
Cancer Control : Journal of the Moffitt... 2022Glioblastoma multiforme (GBM) makes 60-70% of gliomas and 15% of primary brain tumors. Despite the availability of standard multimodal therapy, 2 years, 3 years, and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Glioblastoma multiforme (GBM) makes 60-70% of gliomas and 15% of primary brain tumors. Despite the availability of standard multimodal therapy, 2 years, 3 years, and 5 years survival rate of GBM are still low. Active immunotherapy is a relatively new treatment option for GBM that seems promising.
METHODS
An electronic database search on PubMed, Cochrane, Scopus, and clinicaltrials.gov was performed to include all relevant studies. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Reported parameters are OS, PFS, AEs, post treatment KPS, and 2 year mortality.
RESULTS
Active immunotherapy provided better OS (HR = .85; 95% CI = .71-1.01; = .06) and PFS (HS = .83; 95% CI= .66 - 1.03; = .11) side albeit not statistically significant. Active immunotherapy reduces the risk of 2 year mortality as much as 2.5% compared to control group (NNT and RRR was 56.7078 and 0,0258, respectively).
CONCLUSION
Active immunotherapy might be beneficial in terms of survival rate in patients with GBM although not statistically significant. It could be a treatment option for GBM in the future.
Topics: Humans; Glioblastoma; Brain Neoplasms; Glioma; Combined Modality Therapy; Immunotherapy, Active; Immunotherapy
PubMed: 36748348
DOI: 10.1177/10732748221079474 -
Frontiers in Oncology 2023The uncommon -altered primary central nervous system (CNS) tumors were recently added to the World Health Organization 2021 classification under the name Astroblastoma,...
The uncommon -altered primary central nervous system (CNS) tumors were recently added to the World Health Organization 2021 classification under the name Astroblastoma, -altered. Another term used to describe them, "High-grade neuroepithelial tumor with alteration" (HGNET-MN1), makes reference to their distinct epigenetic profile but is currently not a recommended name. Thought to occur most commonly in children and predominantly in females, -altered CNS tumors are associated with typical but not pathognomonic histological patterns and are characterized by a distinct DNA methylation profile and recurrent fusions implicating the (meningioma 1) gene. Diagnosis based on histological features alone is challenging: most cases with morphological features of astroblastoma (but not all) show these molecular features, whereas not all tumors with fusions show astroblastoma morphology. There is large variability in reported outcomes and detailed clinical and therapeutic information is frequently missing. Some patients experience multiple recurrences despite multimodality treatment, whereas others experience no recurrence after surgical resection alone, suggesting large clinical and biological heterogeneity despite unifying epigenetic features and recurrent fusions. In this report, we present the demographics, tumor characteristics, treatment, and outcome (including patient-reported outcomes) of three adults with -altered primary CNS tumors diagnosed genome-wide DNA methylation and RNA sequencing. All three patients were females and two of them were diagnosed as young adults. By reporting our neuropathological and clinical findings and comparing them with previously published cases we provide insight into the clinical heterogeneity of this tumor. Additionally, we propose a model for prospective, comprehensive, and systematic collection of clinical data in addition to neuropathological data, including standardized patient-reported outcomes.
PubMed: 36741001
DOI: 10.3389/fonc.2023.1099618 -
European Journal of Cancer (Oxford,... Mar 2023Although anti-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors (RTKIs) have been tested in patients with neuroendocrine tumours (NETs) over... (Meta-Analysis)
Meta-Analysis
Efficacy and toxicity of anti-vascular endothelial growth receptor tyrosine kinase inhibitors in patients with neuroendocrine tumours - A systematic review and meta-analysis.
AIM
Although anti-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors (RTKIs) have been tested in patients with neuroendocrine tumours (NETs) over the last two decades, no study to date has benchmarked efficacy and toxicity of these drugs in this patient population.
METHODS
All phase II and phase III studies of anti-VEGF RTKIs in patients with NETs, published between January 1, 2000 andJuly 31, 2021, across major trial databases, were searched in August 2021 for relevant studies. The primary objectives of the meta-analysis were to compare objective response rate (ORR) and progression-free survival (PFS) between patients with pancreatic NETs (pNETs) and extra-pancreatic NETs (epNETs), and the incidence rate ratio (IRR) of adverse events between patients receiving anti-VEGF RTKIs and control.
RESULTS
1611 patients were available for the meta-analysis; 1194 received anti-VEGF RTKIs. ORR in pNETs was 18% (95% confidence interval (CI) 13-25%), while ORR in epNETs was 8% (95% CI 5-12%); test for differences between pNETs and epNETs (x12 = 8.38, p < .01). Median PFS in pNETs was 13.9 months (95% CI 11.43-16.38 months), while median PFS in epNETs was 12.71 months (95% CI 9.37-16.05 months); test for differences between pNETs and epNETs (x12 = .35, p = .55). With regards to common grade 3/4 adverse events , patients who received anti-VEGF RTKIs were more likely to experience hypertension (IRR 3.04, 95% CI 1.63-5.65) and proteinuria (IRR 5.79, 95% CI 1.09-30.74) in comparison to those who received control.
CONCLUSIONS
Anti-VEGF RTKIs demonstrate anti-tumour effect in both pNETs and epNETs, supporting their development in both populations. These agents also appear to be safe in patients with NETs.
Topics: Humans; Neuroendocrine Tumors; Tyrosine Kinase Inhibitors; Receptor Protein-Tyrosine Kinases; Neuroectodermal Tumors, Primitive
PubMed: 36738541
DOI: 10.1016/j.ejca.2022.12.031