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Frontiers in Oncology 2021Intraorbital tumor could be approached by numerous surgical methods. The neuroendoscopic endonasal approach could provide a feasible corridor for indicated tumors....
Intraorbital tumor could be approached by numerous surgical methods. The neuroendoscopic endonasal approach could provide a feasible corridor for indicated tumors. Herein we present a series of 6 consecutive intraorbital tumors from April 2018 to October 2020, which received endonasal endoscopic resection. Cadaveric dissection was performed for the intraconal approach, and the literature was also reviewed. Five tumors were located intraconally, while one extraconally. The pathology revealed 1 angioleiomyoma, 1 cavernous hemangioma, 1 pilocytic astrocytoma, 1 meningioma, and 2 schwannomas. Five of the six achieved gross total resection, including 3 tumors with lateral extension beyond the optic nerve. Preoperative visual deterioration was observed in 4 of the 6 patients, and all got improvement postoperatively. Transient oculomotor nerve palsy was presented in one patient postoperatively. No cerebrospinal fluid leakage, enophthalmos, or strabismus was observed. The median follow-up time is 27 months (11~41 months). At the 6-month follow-up, the visual acuity remained unchanged compared with that at discharge. Proptosis was resolved in 2 of the 3 patients; diplopia was improved in one patient. In conclusion, endoscopic endonasal intraconal approach could be suitable for selected pathological conditions, and for both medial or beyond medial extraconal and intraconal orbital tumors.
PubMed: 35047399
DOI: 10.3389/fonc.2021.780551 -
Bioengineered Dec 2021Excellent prognostic value of programmed death ligand 1 (PD-L1) is observed in patients with other cancers; however, the prognostic value of PD-L1 in glioblastoma (GBM)... (Meta-Analysis)
Meta-Analysis
Excellent prognostic value of programmed death ligand 1 (PD-L1) is observed in patients with other cancers; however, the prognostic value of PD-L1 in glioblastoma (GBM) remains unclear. Therefore, this meta-analysis evaluated the prognostic value of PD-L1 in GBM. We performed a systematic search in databases to screen eligible articles. The hazard ratio (HR) and 95% confidence interval (95% CI) were extracted from included articles. This meta-analysis included 15 studies, and the forest plot indicated that increased PD-L1 expression was associated with poorer overall survival (OS) of GBM (HR, 1.16; 95% CI, 1.05-1.27; = 0.002). Furthermore, stratified analysis confirmed that PD-L1 expression was associated with unfavorable OS at the protein level (HR, 1.30; 95% CI, 1.13-1.48; < 0.001) and messenger ribonucleic acid (mRNA) level (HR, 1.05; 95% CI, 1.00-1.09; = 0.041). The analysis of a dataset verified the prognostic value of PD-L1 and revealed an association between PD-L1 mRNA expression and the status of isocitrate dehydrogenase (IDH). In conclusion, increased PD-L1 expression predicts unfavorable OS in GBM and may be a promising prognostic biomarker of GBM.
Topics: Adolescent; Adult; Aged; B7-H1 Antigen; Child; Databases as Topic; Female; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; Male; Middle Aged; Prognosis; Publication Bias; RNA, Messenger; Reproducibility of Results; Survival Analysis; Young Adult
PubMed: 34903133
DOI: 10.1080/21655979.2021.1996515 -
European Review For Medical and... Nov 2021The phenomenon is that few randomized control trials (RCTs) directly compared the effects of bevacizumab with other types of standard treatments for recurrent... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The phenomenon is that few randomized control trials (RCTs) directly compared the effects of bevacizumab with other types of standard treatments for recurrent glioblastoma (GBM). We conducted a systematic review and meta-analysis to assess the efficacy of bevacizumab in recurrent GBM patients.
MATERIALS AND METHODS
We searched electronic databases (Medline, Embase, and Web of Science) contrasting the bevacizumab with standard treatments up to May 2021. For the continuous outcomes of median progression-free survival (PFS) and median overall survival (OS), we summarized the mean difference (MD) as the effective index. We used relative risk (RR) to estimate the data with a random-effects model to get the outcomes of objective response rate (ORR), 12-month OS, 6-month PFS, and any mentioned adverse events.
RESULTS
A total of 807 patients in 5 RCTs included into our systematic review and meta-analysis. The results showed bevacizumab could provide benefits of the ORR (RR, 2.67; 95% CI: 1.14-6.26, p = 0.02), median PFS (MD, 1.12 months; 95% CI: 0.35-1.90 months, p = 0.005), but not the median OS (MD, -0.19 months; 95% CI: -1.37-0.99 months, p = 0.75). Whereas the rates of the secondary outcomes of interest were similar between the bevacizumab group and control group, including 6 month-PFS (RR, 1.23; 95% CI, 0.82-1.84, p = 0.32) and 12 month-OS (RR, 0.93; 95% CI, 0.79-1.09, p = 0.36). As for adverse events, patients with bevacizumab showed higher rates of grade 3/4 and any grade hypertension compared with those with standard treatments (RR, 3.71; 95% CI: 1.17-11.76, p = 0.03; RR, 2.68; 95% CI: 1.26-5.76, p = 0.01, respectively).
CONCLUSIONS
This study provides clear proof of the beneficial effects of bevacizumab treatment in recurrent GBM patients. The only observed adverse event was grade 3/4 or any grade hypertension.
Topics: Angiogenesis Inhibitors; Bevacizumab; Brain Neoplasms; Glioblastoma; Humans; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 34787852
DOI: 10.26355/eurrev_202111_27092 -
Annals of Palliative Medicine Nov 2021Gliomas are the most common primary tumors of the central nervous system (CNS). The most common subtype of glioma in adults is grade IV astrocytoma, known as...
BACKGROUND
Gliomas are the most common primary tumors of the central nervous system (CNS). The most common subtype of glioma in adults is grade IV astrocytoma, known as glioblastoma (GB) multiforme. Despite advances in treatment, GB remains a lethal tumor with a poor prognosis, and patients face serious quality of life (QoL) issues. Its poor prognosis is a real public health problem. The present study aimed to determine the exact neurocognitive status and QoL in patients with GB in the Mediterranean region and the different predictive factors responsible for their deterioration.
METHODS
This systematic review was conducted in accordance with PRISMA guidelines. The protocol was registered in the PROSPERO (Identifier: CRD42020188936). The following databases have been independently searched by 2 authors: PubMed, Science Direct, Scopus and Google Scholar.
RESULTS
Thirteen studies were selected (n=13). Four studies (n=4) focused solely on cognitive assessment, five studies (n=5) focused on quality-of-life assessment, and four (n=4) were simultaneously assessed QoL and neurocognitive status. The majority of studies in this review use (Mini-Mental State Examination, MMSE) for an overall cognitive assessment (n=5), other studies use specific batteries for an in-depth assessment of cognitive functions (n=3). The study revealed several affected functions: short and long-term memory, executive functions (EFs), and visuo-constructive abilities. Scale of European Organization for Research and Treatment of Cancer and the Functional Assessment of Cancer Therapy are among the most widely used instruments for assessing QoL. For factors influencing neurocognitive status and QoL, the present review found that: The Karnofsky Performance Scale (KPS), tumor location, age, sex and type of treatment are the most identified. Other studies have reported other factors, such as tumor progression, development of emotional distress, and coping strategies adopted.
DISCUSSION
We conclude that there were many changes in patients with GB during the course of the disease and that most of them were related to age and disease progression. The use of coping strategies based on social support has a positive impact on the QoL.
Topics: Adult; Brain Neoplasms; Cognition; Glioblastoma; Humans; Karnofsky Performance Status; Quality of Life
PubMed: 34775771
DOI: 10.21037/apm-21-1900 -
Biomedicine & Pharmacotherapy =... Jan 2022Glioblastoma (GBM) remains incurable despite the overwhelming discovery of 2-dimensional (2D) cell-based potential therapeutics since the majority of them have met...
Glioblastoma (GBM) remains incurable despite the overwhelming discovery of 2-dimensional (2D) cell-based potential therapeutics since the majority of them have met unsatisfactory results in animal and clinical settings. Incremental empirical evidence has laid the widespread need of transitioning 2D to 3-dimensional (3D) cultures that better mimic GBM's complex and heterogenic nature to allow better translation of pre-clinical results. This systematic scoping review analyses the transcriptomic data involving 3D models of GBM against 2D models from 22 studies identified from four databases (PubMed, ScienceDirect, Medline, and Embase). From a total of 499 genes reported in these studies, 313 (63%) genes were upregulated across 3D models cultured using different scaffolds. Our analysis showed that 4 of the replicable upregulated genes are associated with GBM stemness, epithelial to mesenchymal transition (EMT), hypoxia, and migration-related genes regardless of the type of scaffolds, displaying close resemblances to primitive undifferentiated tumour phenotypes that are associated with decreased overall survival and increased hazard ratio in GBM patients. The upregulation of drug response and drug efflux genes (e.g. cytochrome P450s and ABC transporters) mirrors the GBM genetic landscape that contributes to in vivo and clinical treatment resistance. These upregulated genes displayed strong protein-protein interactions when analysed using an online bioinformatics software (STRING). These findings reinforce the need for widespread transition to 3D GBM models as a relatively inexpensive humanised pre-clinical tool with suitable genetic biomarkers to bridge clinical gaps in potential therapeutic evaluations.
Topics: Animals; Biomarkers; Brain Neoplasms; Cell Culture Techniques; Epithelial-Mesenchymal Transition; Glioblastoma; Humans; Models, Biological; Tissue Scaffolds; Transcriptome
PubMed: 34775238
DOI: 10.1016/j.biopha.2021.112396 -
PloS One 2021To evaluate different hypofractionated radiotherapy (HRT) regimens for newly diagnosed elderly glioblastoma (GBM) patients. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate different hypofractionated radiotherapy (HRT) regimens for newly diagnosed elderly glioblastoma (GBM) patients.
METHODS
We performed a systematic review with network meta-analysis (NMA), including searches on CENTRAL, Medline, EMBASE, CINAHL, clinical trial databases and manual search. Only randomized clinical trials (RCTs) were included. Primary outcomes: overall survival (OS) and adverse events (AE). Secondary outcomes: progression-free-survival (PFS) and quality of life (QoL). We used the Cochrane Risk of Bias (RoB) table for assessing individual studies and CINeMA for evaluating the certainty of the final body of evidence.
RESULTS
Four RCTs (499 patients) were included. For OS, the estimates from NMA did not provide strong evidence of a difference between the HRTs: 40 Gray (Gy) versus 45 Gy (HR: 0.89; CI 95%: 0.42, 1.91); 34 Gy versus 45 Gy (HR: 0.85; CI 95% 0.43, 1.70); 25 Gy versus 45 Gy (HR: 0.81; CI 95% 0.32, 2.02); 34 Gy versus 40 Gy (HR: 0.95; CI 95% 0.57, 1.61); and 25 Gy versus 34 Gy (HR: 0.95; CI 95% 0.46, 1.97). We performed qualitative synthesis for AE and QoL due to data scarcity and clinical heterogeneity among studies. The four studies reported a similar QoL (assessed by different methods) between arms. One RCT reported grade ≥ 3 AE, with no evidence of a difference between arms. PFS was reported in one study (25 Gy versus 40 Gy), with no evidence of a difference between arms.
CONCLUSION
This review found no evidence of a difference between the evaluated HRTs for efficacy and safety.
Topics: Aged; Glioblastoma; Humans; Network Meta-Analysis; Progression-Free Survival; Quality of Life; Radiation Dose Hypofractionation; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 34735442
DOI: 10.1371/journal.pone.0257384 -
Neuro-oncology Apr 2022Detailed prevalence estimates of BRAFV600 mutations and BRAF inhibitor (BRAFi) treatment responses in V600-mutant glioma will inform trial development.
BACKGROUND
Detailed prevalence estimates of BRAFV600 mutations and BRAF inhibitor (BRAFi) treatment responses in V600-mutant glioma will inform trial development.
METHODS
Our systematic review analyzed overall prevalence of BRAFV600 mutations in glioma and BRAFi treatment response.
RESULTS
Based on 13 682 patients in 182 publications, the prevalence of BRAFV600 in epithelioid glioblastoma (eGBM) was 69% [95% CI: 45-89%]; pleomorphic xanthoastrocytoma (PXA): 56% [48-64%] anaplastic pleomorphic xanthoastrocytoma (aPXA): 38% [23-54%], ganglioglioma (GG): 40% [33-46%], and anaplastic ganglioglioma (aGG): 46% [18-76%]. Prevalence in astroblastoma was 24% [8-43%], desmoplastic infantile astrocytoma (DIA): 16% [0-57%], subependymal giant cell astrocytoma (SEGA): 8% [0-37%], dysembryoplastic neuroepithelial tumor (DNET): 3% [0-11%], diffuse astrocytoma (DA): 3% [0-9%], and pilocytic astrocytoma (PA): 3% [2-5%]. We reviewed 394 V600-mutant gliomas treated with BRAFi from 130 publications. One hundred and twenty-nine pediatric low-grade gliomas showed 4 (3.1%) complete response (CR); 53 (41.1%) partial response (PR); 64 (49.6%) stable disease (SD) and 8 (6.2%) progressive disease (PD). 25 pediatric high-grade gliomas showed CR; PR; SD; PD in 4 (16.0%); 10 (40.0%), 4 (16.0%); and 7 (28.0%) respectively. Thirty-nine adult low-grade gliomas showed CR; PR; SD; PD of 4 (10.3%); 17 (43.6%); 16 (41.0%) and 2 (5.1%) respectively. Ninety-seven adult high-grade gliomas showed CR; PR; SD; PD of 6 (6.2%); 31 (32.0%); 27 (27.8%); and 33 (34.0%) respectively.
CONCLUSIONS
BRAFV600 prevalence is highest in eGBM, PXA, aPXA, GG, aGG, and lower in astroblastoma, DIA, SEGA, DNET, DA, and PA. Our data provide the rationale for adjuvant clinical trials of BRAFi in V600-mutant glioma.
Topics: Adult; Astrocytoma; Brain Neoplasms; Child; Glioma; Humans; Mutation; Prevalence; Proto-Oncogene Proteins B-raf
PubMed: 34718782
DOI: 10.1093/neuonc/noab247 -
Asian Pacific Journal of Cancer... Oct 2021The aim of this study is to evaluate the association of c-Met overexpression with survival of glioblastoma multiforme (GBM) patients. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of this study is to evaluate the association of c-Met overexpression with survival of glioblastoma multiforme (GBM) patients.
METHODS
A systematic review with meta-analyses was conducted on related articles from PubMed, EBSCOhost, Scopus, and Cochrane databases with last updated search on October 31, 2020. A total of 7 studies regarding c-Met overexpression and overall survival (OS) and/or progression free survival (PFS) are included in this study.
RESULTS
All studies used immunohistochemistry to examine the expression of c-Met protein. The results showed that the positive rate of c-Met overexpression was detected in approximately 33,9% - 60,5% of GBM patients. c-Met overexpression was related to worse OS (HR: 1,74; 95% CI: 1,482-2,043; Z=6,756; p<0,001) and PFS (HR: 1,66; 95% CI: 1,327-2,066; Z=4,464; p<0,001) in GBM patients. Low heterogeneity of subjects was found in both OS and PFS analyses, I2 values were 7,8% and 0,0%, respectively.
CONCLUSION
In conclusion, c-Met overexpression is significantly related to shorter OS and PFS in GBM patients, so c-Met can be considered as a potential prognostic indicator in GBM.
Topics: Brain Neoplasms; Glioblastoma; Humans; Kaplan-Meier Estimate; Prognosis; Progression-Free Survival; Proto-Oncogene Proteins c-met
PubMed: 34710981
DOI: 10.31557/APJCP.2021.22.10.3075 -
Journal of Neuro-oncology Jun 2022The following questions and recommendations are pertinent to the following: TARGET POPULATION: These recommendations apply to adults with progressive GBM who have...
Congress of Neurological Surgeons systematic review and evidence-based guidelines update on the role of targeted therapies and immunotherapies in the management of progressive glioblastoma.
UNLABELLED
The following questions and recommendations are pertinent to the following: TARGET POPULATION: These recommendations apply to adults with progressive GBM who have undergone standard primary treatment with surgery and/or chemoradiation. QUESTION 1: In adults with progressive glioblastoma is the use of bevacizumab as monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?
RECOMMENDATION
Level III: Treatment with bevacizumab is suggested in the treatment of progressive GBM, as it provides improved disease control compared to historical controls as measured by best imaging response and progression free survival at 6 months, while not providing evidence for improvement in overall survival. QUESTION 2: In adults with progressive glioblastoma is the use of bevacizumab as combination therapy with cytotoxic agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?
RECOMMENDATION
Level III: There is insufficient evidence to show benefit or harm of bevacizumab in combination with cytotoxic therapies in progressive glioblastoma due to a lack of evidence supporting a clearly defined benefit without significant toxicity. QUESTION 3: In adults with progressive glioblastoma is the use of bevacizumab as a combination therapy with targeted agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?
RECOMMENDATION
There is insufficient evidence to support a recommendation regarding this question. QUESTION 4: In adults with progressive glioblastoma is the use of targeted agents as monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?
RECOMMENDATION
There is insufficient evidence to support a recommendation regarding this question. QUESTION 5: In adults with progressive glioblastoma is the use of targeted agents in combination with cytotoxic therapies superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?
RECOMMENDATION
There is insufficient evidence to support a recommendation regarding this question. QUESTION 6: In adults with progressive glioblastoma is the use of immunotherapy monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?
RECOMMENDATION
There is insufficient evidence to support a recommendation regarding this question. QUESTION 7: In adults with progressive glioblastoma is the use of immunotherapy in combination with targeted agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?
RECOMMENDATION
There is insufficient evidence to support a recommendation regarding this question. QUESTION 8: In adults with progressive glioblastoma is the use of immunotherapy in combination with bevacizumab superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?
RECOMMENDATION
There is insufficient evidence to support a recommendation regarding this question.
Topics: Adult; Antineoplastic Agents; Bevacizumab; Brain Neoplasms; Glioblastoma; Humans; Immunotherapy; Neurosurgeons; Practice Guidelines as Topic
PubMed: 34694567
DOI: 10.1007/s11060-021-03876-7 -
Journal of Neuro-oncology Nov 2021Desmoplastic infantile astrocytoma (DIA) and desmoplastic infantile ganglioglioma (DIG) are classified together as grade I neuronal and mixed neuronal-glial tumor of the... (Meta-Analysis)
Meta-Analysis
PURPOSE
Desmoplastic infantile astrocytoma (DIA) and desmoplastic infantile ganglioglioma (DIG) are classified together as grade I neuronal and mixed neuronal-glial tumor of the central nervous system by the World Health Organization (WHO). These tumors are rare and have not been well characterized in terms of clinical outcomes. We aimed to identify clinical predictors of mortality and tumor recurrence/progression by performing an individual patient data meta-analysis (IPDMA) of the literature.
METHODS
A systematic literature review from 1970 to 2020 was performed, and individualized clinical data for patients diagnosed with DIA/DIG were extracted. Aggregated data were excluded from collection. Outcome measures of interest were mortality and tumor recurrence/progression, as well as time-to-event (TTE) for each of these. Participants without information on these outcome measures were excluded. Cox regression survival analyses were performed to determine predictors of mortality and tumor recurrence / progression.
RESULTS
We identified 98 articles and extracted individual patient data from 188 patients. The cohort consisted of 58.9% males with a median age of 7 months. The majority (68.1%) were DIGs, while 24.5% were DIAs and 7.5% were non-specific desmoplastic infantile tumors; DIAs presented more commonly in deep locations (p = 0.001), with leptomeningeal metastasis (p = 0.001), and was associated with decreased probability of gross total resection (GTR; p = 0.001). Gender, age, and tumor pathology were not statistically significant predictors of either mortality or tumor recurrence/progression. On multivariate survival analysis, GTR was a predictor of survival (HR = 0.058; p = 0.007) while leptomeningeal metastasis at presentation was a predictor of mortality (HR = 3.27; p = 0.025). Deep tumor location (HR = 2.93; p = 0.001) and chemotherapy administration (HR = 2.02; p = 0.017) were associated with tumor recurrence/progression.
CONCLUSION
Our IPDMA of DIA/DIG cases reported in the literature revealed that GTR was a predictor of survival while leptomeningeal metastasis at presentation was associated with mortality. Deep tumor location and chemotherapy were associated with tumor recurrence / progression.
Topics: Astrocytoma; Brain Neoplasms; Female; Ganglioglioma; Humans; Infant; Male; Meningeal Carcinomatosis; Neoplasm Recurrence, Local
PubMed: 34613581
DOI: 10.1007/s11060-021-03860-1