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Biomedicines Jan 2024Gliomas are aggressive brain tumors with poor prognosis even after surgical removal and radio-chemotherapy, stressing the urgency to find alternative therapies. Several... (Review)
Review
Gliomas are aggressive brain tumors with poor prognosis even after surgical removal and radio-chemotherapy, stressing the urgency to find alternative therapies. Several preclinical studies evaluating the anticancer effect of curcumin in animal models of glioma are reported, but a systematic review with meta-analysis of these studies, considering the different experimental conditions used, has not been made up to this date. A search in different databases (Pubmed, Web of Science, Scopus, and SciELO) following the PRISMA statement was conducted during November 2023 to systematically identify articles assessing the effect of curcumin in murine xenograft models of glioma and identified 15 articles, which were subdivided into 24 studies. Tumor volume before and after treatment with curcumin or vehicle was extracted and the efficacy of curcumin was evaluated by performing a random effects meta-analysis of the data. Publication bias and the impact of different experimental conditions on curcumin efficacy were assessed. Treatment with curcumin decreased tumor volume. Comparing curcumin with control groups, the overall weighted standardized difference in means was -2.079 (95% CI: -2.816 to -1.341; -value < 0.001). The curcumin effect was observed for different animal models, types of glioma cells, administration routes, and curcumin formulations. Publication bias was identified but does not invalidate curcumin's effectiveness. The findings suggest the potential therapeutic efficacy of curcumin against glioma.
PubMed: 38397870
DOI: 10.3390/biomedicines12020268 -
AJNR. American Journal of Neuroradiology Oct 2023The molecular profile of gliomas is a prognostic indicator for survival, driving clinical decision-making for treatment. Pathology-based molecular diagnosis is...
BACKGROUND
The molecular profile of gliomas is a prognostic indicator for survival, driving clinical decision-making for treatment. Pathology-based molecular diagnosis is challenging because of the invasiveness of the procedure, exclusion from neoadjuvant therapy options, and the heterogeneous nature of the tumor.
PURPOSE
We performed a systematic review of algorithms that predict molecular subtypes of gliomas from MR Imaging.
DATA SOURCES
Data sources were Ovid Embase, Ovid MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science.
STUDY SELECTION
Per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 12,318 abstracts were screened and 1323 underwent full-text review, with 85 articles meeting the inclusion criteria.
DATA ANALYSIS
We compared prediction results from different machine learning approaches for predicting molecular subtypes of gliomas. Bias analysis was conducted for each study, following the Prediction model Risk Of Bias Assessment Tool (PROBAST) guidelines.
DATA SYNTHESIS
Isocitrate dehydrogenase mutation status was reported with an area under the curve and accuracy of 0.88 and 85% in internal validation and 0.86 and 87% in limited external validation data sets, respectively. For the prediction of promoter methylation, the area under the curve and accuracy in internal validation data sets were 0.79 and 77%, and in limited external validation, 0.89 and 83%, respectively. PROBAST scoring demonstrated high bias in all articles.
LIMITATIONS
The low number of external validation and studies with incomplete data resulted in unequal data analysis. Comparing the best prediction pipelines of each study may introduce bias.
CONCLUSIONS
While the high area under the curve and accuracy for the prediction of molecular subtypes of gliomas are reported in internal and external validation data sets, limited use of external validation and the increased risk of bias in all articles may present obstacles for clinical translation of these techniques.
Topics: Humans; Glioma; Machine Learning; Prognosis; Magnetic Resonance Imaging; Mutation
PubMed: 37770204
DOI: 10.3174/ajnr.A8000 -
International Journal of Radiation... Jun 2024Reirradiation is increasingly used in children and adolescents/young adults (AYA) with recurrent primary central nervous system tumors. The Pediatric Normal Tissue... (Review)
Review
PURPOSE
Reirradiation is increasingly used in children and adolescents/young adults (AYA) with recurrent primary central nervous system tumors. The Pediatric Normal Tissue Effects in the Clinic (PENTEC) reirradiation task force aimed to quantify risks of brain and brain stem necrosis after reirradiation.
METHODS AND MATERIALS
A systematic literature search using the PubMed and Cochrane databases for peer-reviewed articles from 1975 to 2021 identified 92 studies on reirradiation for recurrent tumors in children/AYA. Seventeen studies representing 449 patients who reported brain and brain stem necrosis after reirradiation contained sufficient data for analysis. While all 17 studies described techniques and doses used for reirradiation, they lacked essential details on clinically significant dose-volume metrics necessary for dose-response modeling on late effects. We, therefore, estimated incidences of necrosis with an exact 95% CI and qualitatively described data. Results from multiple studies were pooled by taking the weighted average of the reported crude rates from individual studies.
RESULTS
Treated cancers included ependymoma (n = 279 patients; 7 studies), medulloblastoma (n = 98 patients; 6 studies), any CNS tumors (n = 62 patients; 3 studies), and supratentorial high-grade gliomas (n = 10 patients; 1 study). The median interval between initial and reirradiation was 2.3 years (range, 1.2-4.75 years). The median cumulative prescription dose in equivalent dose in 2-Gy fractions (EQD2; assuming α/β value = 2 Gy) was 103.8 Gy (range, 55.8-141.3 Gy). Among 449 reirradiated children/AYA, 22 (4.9%; 95% CI, 3.1%-7.3%) developed brain necrosis and 14 (3.1%; 95% CI, 1.7%-5.2%) developed brain stem necrosis with a weighted median follow-up of 1.6 years (range, 0.5-7.4 years). The median cumulative prescription EQD2 was 111.4 Gy (range, 55.8-141.3 Gy) for development of any necrosis, 107.7 Gy (range, 55.8-141.3 Gy) for brain necrosis, and 112.1 Gy (range, 100.2-117 Gy) for brain stem necrosis. The median latent period between reirradiation and the development of necrosis was 5.7 months (range, 4.3-24 months). Though there were more events among children/AYA undergoing hypofractionated versus conventionally fractionated reirradiation, the differences were not statistically significant (P = .46).
CONCLUSIONS
Existing reports suggest that in children/AYA with recurrent brain tumors, reirradiation with a total EQD2 of about 112 Gy is associated with an approximate 5% to 7% incidence of brain/brain stem necrosis after a median follow-up of 1.6 years (with the initial course of radiation therapy being given with conventional prescription doses of ≤2 Gy per fraction and the second course with variable fractionations). We recommend a uniform approach for reporting dosimetric endpoints to derive robust predictive models of late toxicities following reirradiation.
Topics: Humans; Re-Irradiation; Necrosis; Child; Neoplasm Recurrence, Local; Central Nervous System Neoplasms; Adolescent; Brain; Brain Stem; Ependymoma; Young Adult; Child, Preschool; Medulloblastoma; Radiation Injuries
PubMed: 38300187
DOI: 10.1016/j.ijrobp.2023.12.043 -
Neuro-oncology Advances 2023The distinction between viable tumor and therapy-induced changes is crucial for the clinical management of patients with gliomas. This study aims to quantitatively...
BACKGROUND
The distinction between viable tumor and therapy-induced changes is crucial for the clinical management of patients with gliomas. This study aims to quantitatively assess the efficacy of arterial spin labeling (ASL) biomarkers, including relative cerebral blood flow (rCBF) and absolute cerebral blood flow (CBF), for the discrimination of progressive disease (PD) and treatment-related effects.
METHODS
Eight articles were included in the synthesis after searching the literature systematically. Data have been extracted and a meta-analysis using the random-effect model was subsequently carried out. Diagnostic accuracy assessment was also performed.
RESULTS
This study revealed that there is a significant difference in perfusion measurements between groups with PD and therapy-induced changes. The rCBF yielded a standardized mean difference (SMD) of 1.25 [95% CI 0.75, 1.75] ( < .00001). The maximum perfusion indices (rCBF and CBF) both showed equivalent discriminatory ability, with SMD of 1.35 [95% CI 0.78, 1.91] ( < .00001) and 1.56 [95% CI 0.79, 2.33] ( < .0001), respectively. Similarly, accuracy estimates were comparable among ASL-derived metrices. Pooled sensitivities [95% CI] were 0.85 [0.67, 0.94], 0.88 [0.71, 0.96], and 0.93 [0.73, 0.98], and pooled specificities [95% CI] were 0.83 [0.71, 0.91], 0.83 [0.67, 0.92], 0.84 [0.67, 0.93], for rCBF, rCBF and CBF, respectively. Corresponding HSROC area under curve (AUC) [95% CI] were 0.90 [0.87, 0.92], 0.92 [0.89, 0.94], and 0.93 [0.90, 0.95].
CONCLUSION
These results suggest that ASL quantitative biomarkers, particularly rCBF and CBF, have the potential to discriminate between glioma progression and therapy-induced changes.
PubMed: 37841694
DOI: 10.1093/noajnl/vdad122 -
AJNR. American Journal of Neuroradiology Jun 2024Visually Accessible Rembrandt (Repository for Molecular Brain Neoplasia Data) Images (VASARI) features, a vocabulary to establish reproducible terminology for glioma...
BACKGROUND
Visually Accessible Rembrandt (Repository for Molecular Brain Neoplasia Data) Images (VASARI) features, a vocabulary to establish reproducible terminology for glioma reporting, have been applied for a decade, but a systematic performance evaluation is lacking.
PURPOSE
Our aim was to conduct a systematic review and meta-analysis of the performance of the VASARI features set for glioma assessment.
DATA SOURCES
MEDLINE, Web of Science, EMBASE, and the Cochrane Library were systematically searched until September 26, 2023.
STUDY SELECTION
Original articles predicting diagnosis, progression, and survival in patients with glioma were included.
DATA ANALYSIS
The modified Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was applied to evaluate the risk-of-bias. The meta-analysis used a random effects model and forest plot visualizations, if ≥5 comparable studies with a low or medium risk of bias were provided.
DATA SYNTHESIS
Thirty-five studies (3304 patients) were included. Risk-of-bias scores were medium ( = 33) and low ( = 2). Recurring objectives were overall survival ( = 18) and isocitrate dehydrogenase mutation (; = 12) prediction. Progression-free survival was examined in 7 studies. In 4 studies (glioblastoma = 2, grade 2/3 glioma = 1, grade 3 glioma = 1), a significant association was found between progression-free survival and single VASARI features. The single features predicting overall survival with the highest pooled hazard ratios were multifocality (hazard ratio = 1.80; 95%-CI, 1.21-2.67; I = 53%), ependymal invasion (hazard ratio = 1.73; 95% CI, 1.45-2.05; I = 0%), and enhancing tumor crossing the midline (hazard ratio = 2.08; 95% CI, 1.35-3.18; I = 52%). mutation-predicting models combining VASARI features rendered a pooled area under the receiver operating characteristic curve of 0.82 (95% CI, 0.76-0.88) at considerable heterogeneity (I = 100%). Combined input models using VASARI plus clinical and/or radiomics features outperformed single data-type models in all relevant studies ( = 17).
LIMITATIONS
Studies were heterogeneously designed and often with a small sample size. Several studies used The Cancer Imaging Archive database, with likely overlapping cohorts. The meta-analysis for was limited due to a high study heterogeneity.
CONCLUSIONS
Some VASARI features perform well in predicting overall survival and mutation status, but combined models outperform single features. More studies with less heterogeneity are needed to increase the evidence level.
PubMed: 38937115
DOI: 10.3174/ajnr.A8274 -
World Journal of Stem Cells May 2024Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy. Glioma stem cells (GSCs), a subset within tumors,...
BACKGROUND
Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy. Glioma stem cells (GSCs), a subset within tumors, contribute to resistance, tumor heterogeneity, and plasticity. Recent studies reveal GSCs' role in therapeutic resistance, driven by DNA repair mechanisms and dynamic transitions between cellular states. Resistance mechanisms can involve different cellular pathways, most of which have been recently reported in the literature. Despite progress, targeted therapeutic approaches lack consensus due to GSCs' high plasticity.
AIM
To analyze targeted therapies against GSC-mediated resistance to radio- and chemotherapy in gliomas, focusing on underlying mechanisms.
METHODS
A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to September 30, 2023. The search strategy utilized relevant Medical Subject Heading terms and keywords related to including "glioma stem cells", "radiotherapy", "chemotherapy", "resistance", and "targeted therapies". Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated resistance to radiotherapy resistance (RTR).
RESULTS
In a comprehensive review of 66 studies on stem cell therapies for SCI, 452 papers were initially identified, with 203 chosen for full-text analysis. Among them, 201 were deemed eligible after excluding 168 for various reasons. The temporal breakdown of studies illustrates this trend: 2005-2010 (33.3%), 2011-2015 (36.4%), and 2016-2022 (30.3%). Key GSC models, particularly U87 (33.3%), U251 (15.2%), and T98G (15.2%), emerge as significant in research, reflecting their representativeness of glioma characteristics. Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) (27.3%) and Notch (12.1%) pathways, suggesting their crucial roles in resistance development. Targeted molecules with mTOR (18.2%), CHK1/2 (15.2%), and ATP binding cassette G2 (12.1%) as frequent targets underscore their importance in overcoming GSC-mediated resistance. Various therapeutic agents, notably RNA inhibitor/short hairpin RNA (27.3%), inhibitors ( LY294002, NVP-BEZ235) (24.2%), and monoclonal antibodies ( cetuximab) (9.1%), demonstrate versatility in targeted therapies. among 20 studies (60.6%), the most common effect on the chemotherapy resistance response is a reduction in temozolomide resistance (51.5%), followed by reductions in carmustine resistance (9.1%) and doxorubicin resistance (3.0%), while resistance to RTR is reduced in 42.4% of studies.
CONCLUSION
GSCs play a complex role in mediating radioresistance and chemoresistance, emphasizing the necessity for precision therapies that consider the heterogeneity within the GSC population and the dynamic tumor microenvironment to enhance outcomes for glioblastoma patients.
PubMed: 38817336
DOI: 10.4252/wjsc.v16.i5.604 -
Journal of Clinical Medicine May 2024Primary spinal cord diffuse gliomas (SpDG) are rare tumors that may harbor, like diffuse intrinsic pontine gliomas (DIPG), H3 mutations. According to the WHO (2021),... (Review)
Review
Primary spinal cord diffuse gliomas (SpDG) are rare tumors that may harbor, like diffuse intrinsic pontine gliomas (DIPG), H3 mutations. According to the WHO (2021), SpDGs are included in diffuse midline H3K27-altered gliomas, which occur more frequently in adults and show unusual clinical presentation, neuroradiological features, and clinical behavior, which differ from H3 G34-mutant diffuse hemispheric glioma. Currently, homogeneous adult-only case series of SpDG, with complete data and adequate follow-up, are still lacking. We conducted a qualitative systematic review, focusing exclusively on adult and young adult patients, encompassing all studies reporting cases of primitive, non-metastatic SpDG with H3 mutation. We analyzed the type of treatment administered, survival, follow-up duration, and outcomes. We identified 30 eligible articles published between 1990 and 2023, which collectively reported on 62 adult and young adult patients with primitive SpDG. Postoperative outcomes were assessed based on the duration of follow-up, with outcomes categorized as either survival or mortality. Patients who underwent surgery were followed up for a mean duration of 17.37 months, while those who underwent biopsy had a mean follow-up period of 14.65 months. Among patients who were still alive, the mean follow-up duration was 18.77 months. The radiological presentation of SpDG varies widely, indicating its lack of uniformity. Therefore, we presented a descriptive scenario where SpDG was initially suspected to be a meningioma, but was later revealed to be a malignant SpDG with H3 mutation.
PubMed: 38792513
DOI: 10.3390/jcm13102972 -
European Journal of Clinical... May 2024Central nervous system (CNS) tumors are among the most common malignancies in various age ranges. Low-grade glioma (LGG) can account for nearly 30% of pediatric CNS... (Review)
Review
BACKGROUND
Central nervous system (CNS) tumors are among the most common malignancies in various age ranges. Low-grade glioma (LGG) can account for nearly 30% of pediatric CNS malignancies. Progression or recurrence after the first-line treatments is common among these patients. Therefore, more treatments are required. Bevacizumab as an anti-VEGF antibody has come into the spotlight recently and is especially used in relapse or recurrence settings. This review aims to study the safety and efficacy of bevacizumab for patients with recurrent LGG.
METHODS
This study was conducted according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, Scopus, Web of Science, and Embase were comprehensively searched using the relevant key terms until 24th August 2023 to retrieve the studies that investigated clinical outcomes of bevacizumab in patients with recurrent LGG. All statistical analysis was performed by STATA v.17.
RESULTS
A total of 1306 papers were gathered, out of which 13 were incorporated in the meta-analysis. The pooled incidence rate of treatment according to the RANO scale was 70% (95% CI = 43-98%) for objective response rate, 26% (95% CI = 58-96%) for partial response, 21% (95% CI = 15-28%) for minor response, 14% (95% CI = 3-24%) for complete response, 48% (95% CI = 37-59%) for stable disease, and 8% (95% CI = 4-11%) for progressive disease. Furthermore, according to progressive survival after treatment, it was 4% (95% CI = -1 to 9%) for 6-month PFS, 41% (95% CI = 32-50%) for 2-year PFS, and 29% (95% CI = 22-35%) for 3-year PFS.
CONCLUSION
According to the RANO scale and PFS, clinicians should be aware that Bevacizumab could be a favorable alternative therapy for recurrent LGG. Furthermore, bevacizumab exhibits minimal toxicity and high tolerability in recurrent LGG.
PubMed: 38733390
DOI: 10.1007/s00228-024-03695-5 -
Journal of Medical Imaging and... Jun 2024Gliomas are the most commonly occurring type of primary brain tumors. They account for 32% of all brain tumors and 80% of all malignant intracranial tumors. Gliomas are... (Meta-Analysis)
Meta-Analysis Comparative Study Review
INTRODUCTION
Gliomas are the most commonly occurring type of primary brain tumors. They account for 32% of all brain tumors and 80% of all malignant intracranial tumors. Gliomas are separated into four grades according to the World Health Organization. While low-grade gliomas generally have a favorable outlook, high-grade gliomas cause significant morbidity and mortality Given the lack of clarity about the causes of gliomas and their potential lethality, early diagnosis and identification is crucial.
METHODS
The systematic literature search was based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The electronic databases used were the following: Google Scholar, MEDLINE (PubMed), and EMBASE, and Cochrane Library. Medical subject headings (MeSH) and Boolean operators were used to find any relevant literature. To evaluate the quality of the studies used, a quality assessment was performed using the QUADAS-2.
RESULTS
Four papers concerning the PET/MR modality that included 122 patients while on the other hand we had five papers about the PET/CT modality that included 251 patients. On both sides, the patients were mostly male and the overall mean age 45 ± 10 years. The overall sensitivity and specificity of the PET/MR modality was found to be 89% (95% CI, p = 1.00) and 84% (95% CI, p = 1.00) respectively. In the four included studies revolving around PET/MR, the accuracy was found out to be: 78%, 96.4%, 100%, and N/R.
CONCLUSION
The PET/MR modality was deemed to be slightly diagnostically better than the PET/CT modality. More studies investigating the efficacy of using hybrid FDG PET/MR in gliomas are encouraged to shed light on its potential role in clinical use. Conducting prospective randomized studies that directly compare the sensitivity and specificity of PET/CT and PET/MR for glioma would help establish the role of imaging modalities for diagnosis of glioma.
Topics: Humans; Glioma; Brain Neoplasms; Magnetic Resonance Imaging; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Sensitivity and Specificity; Multimodal Imaging
PubMed: 38490940
DOI: 10.1016/j.jmir.2024.02.008 -
Child's Nervous System : ChNS :... Jul 2024Pediatric optic pathway/hypothalamic gliomas (OPHG) pose challenges in treatment due to their location and proximity to vital structures. Surgical resection plays a key... (Meta-Analysis)
Meta-Analysis Review
Pediatric optic pathway/hypothalamic gliomas (OPHG) pose challenges in treatment due to their location and proximity to vital structures. Surgical resection plays a key role in the management of OPHG especially when the tumor exhibits mass effect and causes symptoms. However, data regarding outcomes and complications of surgical resection for OPHG remains heterogenous. The authors performed a systematic review on pediatric OPHG in four databases: PubMed, EMBASE, Cochrane Library, and Google Scholar. We included studies that reported on the visual outcomes and complications of OPHG resection. A meta-analysis was performed and reported per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 26 retrospective studies were included. Seven hundred ninety-seven pediatric patients with OPHG undergoing surgical resection were examined. A diagnosis of NF1 was confirmed in 9.7%. Gross total resection was achieved in 36.7%. Intraorbital optic pathway gliomas showed a significantly higher gross total resection rate compared to those located in the chiasmatic/hypothalamic region (75.8% vs. 9.6%). Postoperatively, visual acuity improved in 24.6%, remained unchanged in 68.2%, and worsened in 18.2%. Complications included hydrocephalus (35.4%), anterior pituitary dysfunction (19.6%), and transient diabetes insipidus (29%). Tumor progression post-resection occurred in 12.8%, through a mean follow-up of 53.5 months. Surgical resection remains an essential strategy for treating symptomatic and large pediatric OPHG and can result in favorable vision outcomes in most patients. Careful patient selection is critical. Patients should be monitored for hydrocephalus development postoperatively and followed up to assess for tumor progression and adjuvant treatment necessity.
Topics: Humans; Child; Postoperative Complications; Hypothalamic Neoplasms; Glioma; Optic Nerve Glioma; Neurosurgical Procedures; Treatment Outcome; Child, Preschool
PubMed: 38649470
DOI: 10.1007/s00381-024-06407-7