Endothelial cell ferroptosis influences IDH wild-type glioblastoma growth in recurrent glioblastoma multiforme patients.

Glioblastomas are known for their poor clinical prognosis, with recurrent tumors often exhibiting greater invasiveness and faster growth rates compared to primary tumors. To understand the intratumoral changes driving this phenomenon, we employed single-cell sequencing to analyze the differences between two pairs of primary and recurrent glioblastomas. Our findings revealed an upregulation of ferroptosis in endothelial cells within recurrent tumors, identified by the significant overexpression of the NOX4 gene. Further analysis indicated that knocking down NOX4 in endothelial cells reduced the activity of the ferroptosis pathway. Utilizing conditioned media from endothelial cells with lower ferroptosis activity, we observed a decrease in the growth rate of glioblastoma cells. These results highlighted the complex role of ferroptosis within tumors and suggested that targeting ferroptosis in the treatment of glioblastomas requires careful consideration of its effects on endothelial cells, as it may otherwise produce counterproductive outcomes.

Diagnostic Value of Combined-Diagnostic Methods of Brain Tuberculoma Tissue Specimens: A Case Series.

Background: The diagnosis of brain tuberculoma (BT) is sometimes challenging. Herein, we presented a case series to evaluate the combined-diagnostic methods, including acid-fast bacilli (AFB) stain, polymerase chain reaction (PCR), Gene Xpert, and histopathology, of tuberculoma tissue specimens (TTSs). Patients and Methods: A total of 16 patients (11 human immunodeficiency virus [HIV]-positive, 5 HIV-negative) with BT confirmed by combined-diagnostic methods of TTS were included in this study. Clinical data, including clinical symptoms, laboratory tests, neuroimaging features, histopathology, treatment, and prognosis, were assessed in all patients. Results: There were 10 male and 6 female patients (range, 18-73 years). Acid-fast bacilli stain and PCR of TTSs were positive in 11 and 10 patients, respectively. The sensitivity of Gene Xpert of TTSs was (80.0%; 8/10). Nine (56.3%; 9/16) patients were diagnosed with BT by histopathology. After receiving antituberculosis treatment, 12 (75.0%; 12/16) patients improved clinically to a considerable extent. Conclusions: The combined-diagnostic methods of TTS may improve the diagnostic efficiency of BT.

Clinical characteristics and prognostic analysis of patients with HIV and glioma: A case series and literature review.

Cerebral glial tumors have become increasingly common in human immunodeficiency virus (HIV)-positive patients. The present study aimed to report a series of such cases, explore their clinical and pathological characteristics and subject all the reported cases to a survival analysis. The characteristics, management and prognosis of 10 HIV-positive patients with brain gliomas enrolled in a single hospital were investigated in detail. Immunohistochemical assessment of CD31, CD68 and CD163 was performed in the 10 HIV-positive patients with glioma and 18 HIV-negative patients with glioma. The relevant literature was also reviewed using relevant search terms. The potential predictive factors were screened by univariate and multivariate logistic regression analyses, and a nomogram was established based on the potential predictive factors. A total of 50 patients, including the 10 primary cases, were included in the survival analysis. The median survival time was 9 months. The gliomas of HIV-negative patients had a lower cell count of CD163+ cells than those of HIV-positive patients. High CD4+ T-cell count and the use of highly active antiretroviral therapy (HAART) tended to increase the median survival duration, although not significantly according to the log-rank analysis. In the univariate analysis, only surgery, radiotherapy (RT) and World Health Organization (WHO) tumor grade had significant associations with overall survival. In the multivariate analysis, only RT and WHO grade were independent predictors. In conclusion, gliomas may occur more frequently in HIV-positive populations than is currently recognized. The survival duration of most HIV-positive patients with glioma is determined by the tumor rather than HIV status. Adjuvant radiotherapy and the WHO grade of the glioma are predicted to be independent prognostic factors. Surgical resection followed by RT plus regular HAART is recommended for patients with glioma who are HIV-positive.

A nonsense mutation in VHL causing Von Hippel-Lindau syndrome in a large Chinese family-a genetic study of familial neoplastic disease.

Von Hippel-Lindau (VHL) syndrome is a multi-organ neoplastic disease characterized by highly vascular and cystic tumors in the central nervous system (CNS), retina, and visceral lesions, which are mainly caused by germline mutations in VHL. We aimed to detect novel mutations in VHL gene in families with VHL. Here, a large consanguineous four-generation family with variant phenotypes of VHL syndrome was recruited, and its molecular genetics were tested via Sanger sequencing. And various tools and databases were used to predict the variant pathogenicity, frequency, and protein function. Genetic investigation detected a c.351G > A nonsense mutation in VHL that altered the downstream reading frame and created a premature TGA stop signal, resulting in severely truncated pVHL (p.Trp117Ter). This mutation is absent from most public databases, and functional prediction bioinformatic tools demonstrated that this residue is conserved and that this variant is highly likely to be deleterious. The c.315G > A nonsense mutation in VHL is the causal mutation of this kindred that may lead to clear familial aggregation of VHL syndrome because of the dysfunction of the truncated pVHL.

Initial experience of the treatment of large glioma with microwave ablation-assisted surgical resection.

Aim: This study aimed to investigate the preliminary clinical outcomes of microwave ablation (MWA)-assisted surgical treatment for large glioma. Materials and Methods: In total, six cases of large glioma (diameter >4 cm) were described. All cases were treated with MWA-assisted surgical resection, which was performed using ultrasound to guide the accurate placement of the antenna in the central region of the tumor. The MWA power was 40-45 W, and 6 min was applied. Changes in the ablation area were observed using intraoperative Doppler ultrasound and contrast-enhanced ultrasound (CEUS). Ten patients treated with surgical resection alone were included in the control group. Data on surgical times (i.e., the time from the incision of the dura to the removal of the tumor), intraoperative blood loss, and complications were recorded. Results: The median patient age was 45 years (range: 36.5-60.3 years). The median lesion diameter was 4.9 cm (range: 4.3-5.8). The microwave power was 40-45 W, and the median ablation time was 240 s (range: 208-297 s). The intra-tumoral vascular flow was significantly reduced after MWA. The median surgical time was shorter (38.5 min [range: 34.3-42.8 min]) and the median intraoperative blood loss was less (400 mL, [range: 400-450 mL]) in the combination treatment group than in the surgery-alone group. During the ablation process, no obvious additional neurological deficits were detected; however, a tube-shaped carbonide was found after the operation. Conclusion: MWA may be a useful complement to conventional techniques for the surgical resection of large glioma.

The comparison of the watertight and non-watertight dural closure in supratentorial craniotomy: A single-institute 10-year experience with 698 patients.

Watertight dural closure (WTDC) is considered crucial by many neurosurgeons in cranial base surgery, infratentorial craniotomy, and spinal intradural procedure. Whether WTDC also reduce complications remains controversial in supratentorial craniotomy. The objective of this study is to investigate the relationship between WTDC and CSF-related complications in supratentorial craniotomy for the resection of space-occupying lesions. A retrospective analysis of patients who suffered from intracranial space-occupying lesions at Beijing Ditan Hospital between January 2011 and December 2021 was conducted. A total of 698 cases were reviewed with attention to the operative approach, subgaleal fluid collection, wound healing impairment, postoperative infection, and post-craniotomy headaches. The study included a total of 423 patients with WTDC and 275 patients without WTDC. Patients without WTDC had a significantly higher rate of infection (10.9% vs 4.5% with WTDC, P = .001). The rate of subgaleal fluid collection was 9.7% in the WTDC group and 11.3% in the non-WTDC group, but this difference was not statistically significant (P = .502). They suffered from a greater incidence of post-craniotomy headaches in the WTDC group (13.5% vs 9.5% in the non-WTDC group), but without statistical significance (P = .109). We also found no difference in wound healing impairment (P = .719). There is less postoperative infection associated with WTDC during intracranial space-occupying lesion removal than without WTDC in supratentorial craniotomy.

[Clinical features and genetic analysis of a patient with type 2 neurofibromatosis manifested as oculomotor nerve palsy].

OBJECTIVE: To report on a rare case of Neurofibromatosis type 2 (NF2) manifesting as oculomotor nerve palsy and explore its genetic basis. METHODS: A patient with NF2 who had presented at Beijing Ditan Hospital Affiliated to Capital Medical University on July 10, 2021 was selected as the study subject. Cranial and spinal cord magnetic resonance imaging (MRI) was carried out on the patient and his parents. Peripheral blood samples were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: MRI revealed bilateral vestibular Schwannomas, bilateral cavernous sinus meningiomas, popliteal neurogenic tumors, and multiple subcutaneous nodules in the patient. DNA sequencing revealed that he has harbored a de novo nonsense variant of the NF2 gene, namely c.757A>T, which has replaced a codon (AAG) encoding lysine (K) at position 253 with a stop codon (TAG). This has resulted in removal of the Merlin protein encoded by the NF2 gene from position 253 onwards. The variant was not found in public databases. Bioinformatic analysis suggested that the corresponding amino acid is highly conserved. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+PS2+PM2_Supporting+PP3+PP4). CONCLUSION: The heterozygous nonsense variant c.757A>T (p.K253*) of the NF2 gene probably underlay the disease in this patient with an early onset, atypical but severe phenotype.

Clinical factors predictive of new-onset seizure in patients with AIDS-related brain parenchymal lesion.

PURPOSE: This study aimed to determine the clinical characteristics and risk factors of new-onset seizure in patients with AIDS-related brain parenchymal lesion. METHODS: A retrospective case-control study from January 2015 to December 2021 was conducted to determine the clinical characteristics and etiology of seizures in patients with AIDS-related brain parenchymal lesion. Univariate and multivariate logistic regression analyses were used to identify risk factors associated with seizures. Receiver operating characteristic (ROC) curve was used to analyze seizure prediction efficiency. RESULTS: Among a total of 343 patients with AIDS-related brain lesions, 222 had brain parenchymal lesions. Of the 222 patients in the series (range: 16-81 y), 69 reported an episode of at least one seizure. A logistic regression analysis showed that tuberculoma, cortex involvement, and lesions in parietal lobe were found to have a strong association with higher incidence of seizures, whereas lesions in the periventricular area was less prone to seizure. The area under the ROC curve of these factors was 0.733, indicating these factors could predict seizure effectively. Amongst the 69 patients with seizures in multivariate analysis using logistic regression, multiple lesions significantly associated with focal to bilateral tonic-clonic seizures, and lesions in temporal lobe independently associated with focal impaired awareness seizure. CONCLUSIONS: Our study identified the underlying predictors between seizures and the clinical characteristics in a large population of patients with AIDS-related brain parenchymal lesions. These findings would provide further insights into developing effective prevention and treatment strategies aimed at improving the quality of life in the HIV population.

Exhaustive drainage versus fixed-time drainage for chronic subdural hematoma after one-burr hole craniostomy (ECHO): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Chronic subdural hematomas (CSDHs) are one of the most common neurosurgical conditions. The standard surgical technique includes burr-hole craniostomy, followed by intraoperative irrigation and placement of subdural closed-system drainage. The drainage is generally removed after 48 h, which can be described as fixed-time drainage strategy. According to literature, the recurrence rate is 5-33% with this strategy. In our retrospective study, postoperative hematoma volume was found to significantly increase the risk of recurrence. Based on these results, an exhaustive drainage strategy is conducted to minimize postoperative hematoma volume and achieve a low recurrence rate and good outcomes. METHODS: This is a prospective, multicenter, open-label, blinded endpoint randomized controlled trial designed to include 304 participants over the age of 18-90 years presenting with a symptomatic CSDH verified on cranial computed tomography or magnetic resonance imaging. Participants will be randomly allocated to perform exhaustive drainage (treatment group) or fixed-time drainage (control group) after a one-burr hole craniostomy. The primary endpoint will be recurrence indicating a reoperation within 6 months. DISCUSSION: This study will validate the effect and safety of exhaustive drainage after one-burr hole craniostomy in reducing recurrence rates and provide critical information to improve CSDH surgical management. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04573387. Registered on October 5, 2020.

Diagnostic value of EBV-DNA in CSF for PCNSL in AIDS patients with focal brain lesions: A meta-analysis of diagnostic test.

BACKGROUND: Epstein-Barr virus (EBV) infection plays a crucial role in the progression of acquired immunodeficiency syndrome related primary central nervous system lymphoma (AR-PCNSL). This study aimed at evaluating the diagnostic value of cerebrospinal spinal fluid (CSF) EBV-deoxyribonucleic acid (DNA) for PCNSL in patients with infection of human immunodeficiency (HIV) virus through a meta-analysis of diagnostic test. METHODS: A systematic search in PubMed, Embase, Web of Science, Wanfang, Chinese Biomedical Database and Chinese National Knowledge Infrastructure was conducted before May 10, 2022. Heterogeneity among the studies was assessed using Q test and I2 statistics. Publication bias was assessed using the Deek's funnel plot asymmetry test. Statistical analyses were performed using Stata 16.0 software. The pooled sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratios (DOR) and 95% confidence intervals (CI) were caculated to evaluate the diagnostic value. A symmetric receiver operating characteristic (SROC) curve and the area under the SROC curve (AUC) were constructed to evaluate the test-performance. RESULTS: Twelve studies were included in the final analyses, with a total of 141 patients with AR-PCNSL and 590 controls. The pooled diagnostic values were sensitivity of 0.83 (95% CI: 0.73-0.90), specificity of 0.95 (95%CI: 0.89-0.98), PLR of 17.8 (95%CI: 6.8-46.1), NLR of 0.17 (95%CI: 0.10-0.30), DOR of 102 (95%CI: 28-379), and AUC of 0.94 (95%CI: 0.91-0.96). CONCLUSION: In summary the overall diagnostic value of CSF EBV-DNA is very high and it can be a reliable diagnostic biomarker for AR-PCNSL.

Prognostic Value and Risk Factors of Treatment-Related Lymphopenia in Malignant Glioma Patients Treated With Chemoradiotherapy: A Systematic Review and Meta-Analysis.

Background: Immunotherapy has shown promising therapeutic efficacy in various cancers but not gliomas. Circulating lymphocytes play critical roles in cancer control and responses to immune checkpoint inhibitors. Treatment-related lymphopenia has been associated with poor survival in patients with various tumors. This meta-analysis evaluated the risk and impact of lymphopenia in patients with glioma. Methods: The PubMed, Embase, Web of Science, and Cochrane Library databases were comprehensively searched. Eligible studies were included if they reported the incidence and risk factors of lymphopenia and the impact of lymphopenia on survival. Stata 16.0 was used for this meta-analysis. Results: A total of 21 studies were included in the final systematic review and 20 were included in the quantitative analysis. The overall incidence of grade III/IV lymphopenia was 31.6% [95% confidence interval (CI), 22.3-40.8%]. Pooled results based on pathology of glioma revealed that the incidence in astrocytoma and astrocytoma oligodendroglioma patients was 20.2% (95% CI:5.9-34.4%), and the incidence in glioblastoma patients was 27.6% (95% CI:16.2-38.9%). Lymphopenia was associated with poor overall survival (hazard ratio, 1.99; 95% CI, 1.74-2.27; P< 0.001) compared to no lymphopenia. Brain receiving radiation dose of 20 or 25 Gy, female sex, older age, lower baseline lymphocyte count, and dexamethasone dose > 2 mg instead of baseline use were risk factors for lymphopenia. Conclusions: Treatment-related lymphopenia was associated with decreased survival in patients with glioma. Optimization of chemoradiation regimens, particularly in patients with concurrent risk factors, can reduce lymphopenia and potentially improve survival in the era of immunotherapy.

Diagnostic value of real-time PCR of brain mass lesion in HIV-associated toxoplasmic encephalitis: a case series.

BACKGROUND: Toxoplasmic encephalitis (TE) is a leading cause of brain mass lesions (BML) in human immunodeficiency viruses (HIV)-infected patients. Yet, so far, no accurate diagnostic approach for TE has been developed. Herein, we presented a case series (9 HIV-infected patients with TG confirmed by RT-PCR of BML) to assess the diagnostic value of reverse transcription-polymerase chain reaction (RT-PCR) on TE. METHODS: A total of 9 HIV-infected patients with TE confirmed by RT-PCR of BML were included in this study. Clinical data, including clinical symptoms, blood and CSF analysis, neuroimaging features, histopathological characteristics, treatment, and prognosis, were assessed in all patients. According to the results of RT-PCR of BML, all the patients received oral administration of trimethoprim-sulfamethoxazole combined with antiretroviral therapy (ART). Patients were followed up by telephone or outpatient service. RESULTS: There were 8 male and 1 female patients; their age ranged from 26 to 56 years-old. The main symptom was intracranial hypertension (6/9). Six patients presented multiple brain lesions, which were mainly located in the supratentorial area (7/9). CD4+ count ranged from 11 to 159 cells/µl (median 92 cells/µl), and serological HIV viral load 0-989190 copies/ml (median 192836 copies/ml). IgG and IgM against serum TG were positive in 7 and 1 patients, respectively. Moreover, regarding CSF, IgG against TG was positive in 3 patients, while all patients were negative for IgM. The neuroimaging features on MRI showed no specificity. Four patients were diagnosed with TE by histopathological findings. After receiving anti-Toxoplasma therapy, 8 (8/9) patients improved clinically to a considerable extent. CONCLUSIONS: The application of RT-PCR of BML, together with conventional methods, may significantly improve the diagnostic efficiency of TE.

DZIP3 is a key factor to stratify IDH1 wild-type lower-grade gliomas.

BACKGROUND: Malignant glioma is the most common form of primary malignant brain cancer. Heterogeneity is the hallmark of glioma. DAZ-interacting zinc finger 3 (DZIP3), acts as an RNA-binding RING-type ubiquitin ligase; however, its function in glioma is yet unclear. RESULTS: The DZIP3 expression was related to the World Health Organization (WHO) grade and isocitrate dehydrogenase 1(IDH1) status, as well as the clinical outcome. Malignant cases exhibit lower DZIP3 expression. DZIP3 was an independent predictive factor of good prognosis in all grade and lower grade gliomas (p < 0.0001). Gene enrichment analysis and immunohistochemistry indicated that DZIP3 affected the biological behavior of glioma through the angiogenesis pathway. Moreover, based on DZIP3 expression, IDH1 wild-type lower-grade gliomas could be divided into two groups with different survival time. CONCLUSION: In conclusion, the loss of DZIP3 may be involved in the mechanism of angiogenesis in the invasive biological process of glioma. These findings laid an understanding of DZIP3-specific clinical features in glioma. METHODS: A total of 325 glioma patients from the Chinese Glioma Genome Atlas (CGGA) RNA-seq cohort comprised the training cohort, while 265 patients from the GSE 16011 array cohort formed the validation cohort. The mRNA expression of DZIP3 and clinical characteristics was assessed. DZIP3 protein expression and microvessel density (MVD) were evaluated by immunohistochemistry (IHC).

Galectin-9: A Predictive Biomarker Negatively Regulating Immune Response in Glioma Patients.

BACKGROUND: Glioma is the most frequent primary brain tumor. Immunotherapy is one of the most promising therapeutic approaches for gliomas. T cell immunoglobulin domain and mucin domain-3 can induce the malignancy of gliomas. The function of galectin-9 (GAL-9), as one of the ligands of T cell immunoglobulin domain and mucin domain-3, in glioma has remained elusive. The aim of this study was to characterize the expression of GAL-9 in patients with glioma. METHODS: This study enrolled 1292 patients with glioma from the GSE 16011 array set, the Chinese Glioma Genome Atlas, and The Cancer Genome Atlas datasets. Kaplan-Meier analysis was undertaken to explore the prognostic value of GAL-9. Graphpad software and R language were used for statistical analysis. RESULTS: Expression of GAL-9 was highly correlated with major clinical and molecular features. Patients with high expression of GAL-9 were more susceptible to development of malignant tumors. Gene Ontology analysis revealed that expression of GAL-9 was closely associated with function of immune response in glioma. Clinically, the results of Kaplan-Meier analysis showed that expression of GAL-9 was negatively associated with overall survival in all grades of glioma including high-grade gliomas. High expression of GAL-9 was an independent indicator of poor prognosis. CONCLUSIONS: Our results highlight the pivotal role of GAL-9 in regulation of immune suppressive features of gliomas and indicate that GAL-9 is a promising target for cancer immunotherapy and may lead to development of further therapies.

Correlation of alteration of HLA-F expression and clinical characterization in 593 brain glioma samples.

BACKGROUND: Human gliomas are highly fatal tumors with a significant feature of immune suppression. The association of the immune system in gliomas is gradually revealed, and immunotherapy is expected to improve the survival of glioma patients. In-depth understanding of the immune microenvironment of gliomas and their associated immunotherapy was increased exponentially in recent years. Gliomas provide clinical targets for immunotherapy during the search of key regulators of immune response. Our study focused on the human leukocyte antigen (HLA) system that is responsible for regulating the immune system, and discovered the relationship between HLA-F expression and clinical prognosis in gliomas. METHODS: A total of 593 patients with gliomas were included in our research. Of these, 325 patients were from the Chinese Glioma Genome Atlas (CGGA) and 268 were from the GSE 16011 set. Kaplan-Meier (KM) analysis was performed to explore the prognostic value of HLA-F. t test analysis was used to find the distribution difference in various groups. R language packages are used for other statistical computations and figure drawing. RESULTS: HLA-F was negatively correlated with overall survival (OS) in all grades of glioma and glioblastoma (GBM). Moreover, HLA-F was enriched in GBM and isocitrate dehydrogenase 1 wild-type (IDH1 wt) group and considered HLA-F as a mesenchymal subtype marker. Pearson correlation test showed that HLA-F was correlated with other HLA-I molecules. CONCLUSION: HLA-F expression was positively correlated with malignant phenotype and negatively correlated with OS, indicating that HLA-F could predict the immune state of gliomas and might be a clinical target of glioma immunotherapy.

HOXC8: a predictive glioma biomarker that induces epithelia-mesenchymal transition.

BACKGROUND: The transcription factor Homeobox C8 (HOXC8) is overexpressed and regulates many important genes involved in the proliferation and invasion of many malignant tumors. However, the function of HOXC8 in gliomas remains unclear. METHOD: Based on the Chinese Glioma Genome Atlas (CGGA) set, HOXC8 expression is negatively correlated with overall survival (OS). Small interfering RNA (si-HOXC8) was used to downregulate the mRNA and protein expression levels of HOXC8 to assess glioma cell proliferation, migration and invasion. RESULTS: Patients with higher HOXC8 levels showed poorer prognosis. DAVID analysis results indicated that HOXC8 was related to cell cycle, cell adhesion and immune response. In U251 and LN229 glioma cells treated with small interfering RNA for HOXC8 (si-HOXC8) for gene knockdown, significantly lower cell capacity of growth, migration and invasion was observed. Moreover, HOXC8 knockdown could reduce the protein expression of classical epithelial mesenchymal transition (EMT) related markers. CONCLUSION: HOXC8 may play an important role in glioma proliferation, migration and invasion. These findings indicated that HOXC8 may constitute a novel target for glioma treatment.

Risk of subsequent cancer among pediatric, adult and elderly patients following a primary diagnosis of glioblastoma multiforme: a population-based study of the SEER database.

Purpose/aim of the study: Our objective was to determine the risk of a subsequent malignancy in patients with glioblastoma multiforme (GBM). MATERIALS AND METHODS: Data of patients with a primary diagnosis of GBM were extracted from the Surveillance, Epidemiology, and End Results database. Patients were divided into three age groups: pediatric, ≤19 years of age; adult, 20-59 years; elderly, ≥60 years. Outcomes were overall survival and incidence of second cancer. RESULTS: A total of 24 348 patients with primary GBM were identified during the period from 2004 to 2013: 349 pediatric, 9841 adults and 14 518 elderly. There were significant differences in terms of sex, race, registry site, tumor histological type, tumor size and extension among the groups. The median survival time for pediatric, adult and elderly patients was 15, 15 and 5 months, respectively. Of the study population, 1.8% developed a second malignancy and the rates of the three groups were statistically different. Secondary tumors of the cranial nerves and other nervous system were the most common occurrence in the adults and elderly. Female, registry site, giant cell glioblastoma, undergoing surgery or radiation therapy were associated with developing a second malignancy. CONCLUSIONS: The risk of a second malignancy in GBM patients is 1.8%, and associated with certain patient and treatment factors.

Temozolomide with or without Radiotherapy in Patients with Newly Diagnosed Glioblastoma Multiforme: A Meta-Analysis.

BACKGROUND/AIM: The current meta-analysis evaluated the survival outcomes of newly diagnosed glioblastoma patients treated with radiotherapy (RT) alone and with RT + temozolomide (TMZ). METHODS: Relevant studies were identified by an extensive literature search in Medline, Current Contents and Cochrane databases by 2 independent reviewers using the terms "glioblastoma multiforme/glioblastoma, TMZ, radiation therapy/RT and survival." RESULTS: Results revealed a median survival of 13.41-19 months in the combined treatment group, as opposed to 7.7-17.1 months in the RT-alone group. Progression-free survival (PFS) was also significantly different between the 2 groups (RT + TMZ, 6.3-13 months; RT-alone, 5-7.6 months). While there was no significant difference in the 6-month survival and 6-month PFS rates between the RT + TMZ and RT groups (pooled OR 0.690; p = 0.057 and OR 0.429, p = 0.052, respectively), the 1-year survival and 1-year PFS rates showed significant difference (OR 0.469; p = 0.030 and OR 0.245, p < 0.001, respectively). CONCLUSIONS: Concomitant RT + TMZ is more effective and improves the overall survival and PFS in patients with newly diagnosed glioblastoma.

Prognostic implications of resection extent for patients with glioblastoma multiforme: a meta-analysis.

INTRODUCTION: Surgery is the primary treatment of glioblastoma multiforme (GBM), and a greater extent of resection (EOR) has been shown to be associated with improved survival. Our objective was to perform a meta-analysis comparing the 1-year overall survival (OS) and 1-year progression-free survival (PFS) of GBM patients who receive total resection, incomplete resection, or biopsy only. EVIDENCE ACQUISITION: PubMed and the Cochrane databases were searched until May 19th, 2015 using the terms "glioblastoma/glioblastoma multiforme," "extent of resection," "surgery prognosis/prognostic," "survival rate." Randomized controlled trials (RCTs), two-arm prospective studies, retrospective studies, and cohort studies reporting OS and/or PFS data were included. One-year OS and 1-year PFS were compared. EVIDENCE SYNTHESIS: Three prospective/RCTs, and 3 retrospective studies were included. The 6 studies included 1618 patients: 523 underwent total resections, 857 underwent incomplete resections, and 238 had biopsies. Total resection was associated with greater 1-year OS than incomplete resection (pooled odds ratio [OR] 1.89, 95% confidence interval [CI]: 1.35-2.64, P<0.001), and greater 1-year PFS than incomplete resection (pooled OR 2.11, 95% CI: 1.44-3.09, P<0.001). Analysis by study type (RCT or retrospective) produced similar results, although only one RCT provided 1-year PFS data and there was no significant difference between total resection and incomplete resection in that study. All analyses showed that total resection was associated with greater survival than biopsy only. CONCLUSIONS: Total resection of GBM is associated with improved OS and PFS as compared to incomplete resection or biopsy.

Safety and efficacy of fractionated stereotactic radiotherapy and stereotactic radiosurgery for treatment of pituitary adenomas: A systematic review and meta-analysis.

Accumulated studies have not provided conclusive evidence in regards to the comparative efficacy and safety of fractionated stereotactic radiotherapy and stereotactic radiosurgery for treatment of pituitary adenomas. To address this issue, we performed a meta-analysis with eight studies identified from Medline, PubMed, Cochrane, Google Scholar, and published up to September 17, 2015. Eligible studies reported the disease control rate, endocrine cure rate (for functional adenomas), the rate of occurrence of new-onset hypopituitarism, and visual disturbance rate in patients treated with either stereotactic radiosurgery or fractionated stereotactic radiotherapy. Eight studies enrolled a total of 634 patients with pituitary adenoma, 273 patients underwent a stereotactic radiosurgery and 361 patients underwent fractionated stereotactic radiotherapy. No significant differences were found in efficacy measures, such as disease control rate and endocrine cure rate, between stereotactic radiosurgery and fractionated stereotactic radiotherapy (OR=1.156, p=0.666; OR=0.659, p=0.153, respectively). Additionally, meta-analysis of safety measures, such as the rate of new-onset hypopituitarism and visual disturbance rate, did not show significant differences between different treatments (OR=1.365, p=0.469; OR=0.872, p=0.845 respectively). In conclusion, both stereotactic radiosurgery and fractionated stereotactic radiotherapy have comparable efficacy and safety in the management of pituitary adenoma patients.