Radiotherapy-related Tiredness in Patients with Glioblastoma Multiforme (GBM)

Tiredness may be caused by the brain injury due to the tumor or the treatment in patients with glioblastomamultiforme (GBM). Some patients describe a sense of tiredness particularly after radiation or oral chemotherapy.To evaluate tiredness level of patients with GBM during preoperative, postoperative and radiotherapy we hereeamined a sample of 38 patients. Data were collected over six months in a neurosurgery clinic. Patients assignedto Group I were given a booklet and information about radiotherapy, oral temozolomide and tiredness. GroupII received only the booklet. The chi-squared test were used to determine differences in tiredness betweenGroup I and Group II, with Spearman’s correlation for post-radiotherapy results (3 and 6 months postoperative).In conclusion, the level of tiredness was assessed to be significantly better in Group I than in Group II. Levels oftiredness in patients with GBM were greatly affected by the radiotherapy and oral chemotherapy (temozolomide).     

Overexpression of c-Met is Associated with Poor Prognosis in Glioblastoma Multiforme: A Systematic Review and Meta-Analyses

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.     

Understanding the role of cytokines in Glioblastoma Multiforme pathogenesis

Cytokines play a significant role in cancer diagnosis, prognosis and therapy. The immune system’s failure to recognize the malignant tumor cells and mount an effective response may be the result of tumor-associated cytokine deregulation. Glioblastoma Multiforme (GBM) has a characteristic cytokine expression pattern, and abnormalities in cytokine expression have been implicated in gliomagenesis. Within the heterogeneous GBM microenvironment, the tumor cells, normal brain cells, immune cells, and stem cells interact with each other through the complex cytokine network. This review summarizes the current understanding of the functions of key cytokines on GBM, and highlights potential therapeutic applications targeting these cytokines.     

Evaluation of Nestin and EGFR in Patients with Glioblastoma Multiforme in a Public Hospital in Iran

Introduction: Glioblastoma multiforme (GBM) is a grade IV glioma and accounts for 15% of all primary brain tumors. This GBM has a median survival range of less than 2 years after diagnosis and it is highly vascularized by neoformed vessels. Neoangiogenesis is a crucial factor in the malignant tumoral behavior and prognosis of patients and Nestin protein belongs to class VI which is expressed in endothelial cells of neoformed vessels in GBM. Our study shows the correlation between EGFR mutation and Nestin expression in endothelial of neoformed vessels in GBM. Methods: We analyzed 40 GBM samples by immunohistochemistry staining. The immunohistochemical expression of EGFR in tumoral cells and Nestin in endothelial cells in paraffin sections were analyzed. EGFR scoring was the based on staining intensity. Score 0 shows No staining, Score1, mild to moderate staining and score2 sever staining. Microvascular density (MVD) was evaluated with Nestin-immunoreactive. Results: The mean of MVD was 14.6 ±8.25. Nestin-MVD was significantly higher in GBM with sever vascular prolifration (p-value=0.01). EGFR was expressed in 92.5% of samples. The EGFR scoring for tumoral tissue was 7.5%(score:0), 22.5% (score:1) and 70% (score:2). There was a significant relationship between EGFR expression and MVD (p-value=0.017). Conclusion: We suggest that some important mutations as like as EGFR in GBM is responsible for inducing angiogenesis and vascular proliferation. Nestin overexpression as a novel marker might reflect the extent of neoangiogenesis, thus target therapy against EGFR pathway and anti angiogenic may be useful for GBM treatment.     

Glioblastoma Multiforme: A Review of its Epidemiology and Pathogenesis through Clinical Presentation and Treatment

Glioblastoma multiforme (GBM) is one of the most malignant types of central nervous system tumors. Despite advances in treatment modalities it remains largely incurable. The objective of our review is to provide a holistic picture of GBM epidemiology, etiology, pathogenesis, clinical findings and treatment. A literature search was conducted for GBM at PubMed and Google Scholar, with relevant key words like glioblastoma multiforme, pathogenesis, signs and symptoms, treatment etc., and papers published until 2015 were reviewed. It was found that radiation and certain genetic syndromes are the only risk factors identified to date for GBM. Depending on the tumor site patients may present to the clinic with varying symptoms. To confirm the presence and the extent of tumor, various invasive and non-invasive imaging techniques require employment. The literature survey revealed the pathogenesis to involve aberrations of multiple signaling pathways through multiple genetic mutations and altered gene expression. Although several treatment options are available, including surgery, along with adjuvant chemo- and radio-therapy, the disease has a poor prognosis and patients generally succumb within 14 months of diagnosis.     

MRI Manifestions Correlate with Survival of Glioblastoma Multiforme Patients

Objective To identify the correlation between magnetic resonance manifestation and survival of patients with glioblastoma multiforme(GBM). Methods The magnetic resonance imaging(MRI) images of 30 glioblastoma patients were collected.Imaging features including degrees of contrasted area,edema surrounding the tumor,and intensity in T2-weighted imaging were selected to determine their correlation with patient survival.The relationship between imaging and survival time was studied using SPSS 19.0 software.KaplanMeier survival analysis and log-rank test were used to compare the survival curves. Results Patients with <5%contrasted enhancement area of tumor had longer overall survival(OS) than those with >5%contrasted enhancement area of tumor.Patients without edema surrounding the tumor had longer OS than those with edema.Patients with tumor of hyperintensity and/or isointensity in T2-weighted imaging had longer OS than those with hyperintensity and/or isointensity and hypointensity. Conclusions Some MR imaging features including degrees of contrasted area,edema surrounding the tumor,and intensity in T2- weighted imaging are correlated with the survival of patients with GBM.These features can serve as prognostic indicators for GBM patients.     

Stereotactically Guided Fractionated Re-irradiation in Recurrent Glioblastoma Multiforme

Summary Purpose. To assess the feasibility, efficacy and toxicity of fractionated stereotactic radiotherapy in the treatment of recurrent glioblastoma multiforme. Patients and Methods. From January 1995 to July 2003, 53 patients with histologically proven glioblastoma multiforme were treated at recurrence with fractionated stereotactic radiation therapy. A median dose of 36 Gy using a median fractionation of 5 × 2 Gy/week was applied. Results. Median overall survival was 21 months, and median overall survival from the time point of re-irradiation was 8 months. The median time interval between primary and secondary radiation therapy was 10 months. In this patient population, no variables predicting longer overall survival could be determined. However, neurosurgical resection at relapse was associated with increased survival after re-irradiation (p=0.04), but left progression-free survival unaltered. Treatment was well-tolerated and no severe toxicities developed. Conclusion. Stereotactically guided fractionated re-irradiation is a safe and effective treatment modality in selected cases of recurring glioblastoma multiforme. Since this is not a randomized study, further evaluation in larger patient collectives is warranted. Also, based on recent results of radiochemotherapy in the treatment of primary glioblastoma multiforme, concomitant chemotherapy at relapse might be considered in the future.     

放射治疗合并替莫唑胺治疗多形性胶质母细胞瘤的研究

多形性胶质母细胞瘤（glioblastoma multiforme，GBM）是成人脑肿瘤中最常见的一种，恶性度极高。患者手术后容易复发，其中位生存期小于1年，大多数患者在确诊后2年内死亡。目前标准的治疗方法是手术加术后放疗，加或不加辅助化疗。最近的Ⅲ期临床研究结果显示，替莫唑胺与同期放疗加上辅助化疗的疗效要明显优于单纯放疗。中位生存期由单纯放疗组的12．1个月提高到了14．6个月；2年生存率也由单纯放疗的8％提高到26％。从而肯定了替莫唑胺对于新诊断的GBM患者的疗效。     

Five-Year Survival and Median Survival Time of Nasopharyngeal Carcinoma in Hospital Universiti Sains Malaysia

Background: Nasopharyngeal carcinoma (NPC) is the fourth most common cancer in Malaysia. The objective of this study was to determine the five-year survival rate and median survival time of NPC patients in Hospital Universiti Sains Malaysia (USM). Methods: One hundred and thirty four NPC cases confirmed by histopathology in Hospital USM between 1st January 1998 and 31st December 2007 that fulfilled the inclusion and exclusion criteria were retrospectively reviewed. Survival time of NPC patients were estimated by Kaplan-Meier survival analysis. Log-rank tests were performed to compare survival of cases among presenting symptoms, WHO type, TNM classification and treatment modalities. Results: The overall five-year survival rate of NPC patients was 38.0% (95% confidence interval (CI): 29.1, 46.9). The overall median survival time of NPC patients was 31.30months (95%CI: 23.76, 38.84). The significant factors that altered the survival rate and time were age (p=0.041), cranial nerve involvement (p=0.012), stage (p=0.002), metastases (p=0.008) and treatment (p<0.001). Conclusion: The median survival of NPC patients is significantly longer for age ≤50 years, no cranial nerve involvement, and early stage and is dependent on treatment modalities.     

Presurgical Serum Albumin Levels Predict Survival Time from Glioblastoma Multiforme

To determine whether serum albumin levels, before first surgery, predict time until death, 24 glioblastoma multiforme patients newly diagnosed at Ohio State University and Cleveland Clinic Foundation Hospitals between 1993 and 1995 were followed until 1996. Patients with presurgical serum albumin levels below 3.4mg/dL survived an average (median) of 62 days (95% confidence interval (CI): 34, 135 days) after surgery. Those with serum albumin levels of at least 3.4mg/dL survived an average of 494 days (95% CI: 241, 624 days). The association between serum albumin level and time until death persists when adjusted for demographic and treatment variables using Cox proportional hazards regression. Adjusted hazard ratios, by quartile of presurgical serum albumin level, are: 1.0, 1.2, 0.1, 0.1 (P-value for trend test=0.007). In addition to providing a prognostic indicator, presurgical serum albumin levels can be used to evaluate the success of randomization of clinical trials for glioblastoma multiforme therapies. Our findings are consistent with results seen for tumors at other sites. We speculate that our results may be attributable to an association between low serum albumin levels and physiological events associated with angiogenesis.     

Lack of Sunlight Exposure Influence on Primary Glioblastoma Survival

Background: The prognosis of primary glioblastoma (GBM) is poor. Approximately 2/3 of primary braintumor diagnoses are GBM, of which 95% are primary lesions. In this study, we aimed to evaluate whether moresunlight exposure has an effect on survival of patients with primary GBM. Materials and Methods: A total of111 patients with primary GBM were enrolled from Kayseri in inner Anatolia which has a cold climate (n: 40)and Mersin in Mediterranean region with a warm climate and more sunlight exposure (n: 71). The patients withprimary GBM were divided into two groups as Kayseri and Mersin and compared for progression free survival(PFS) and overall survival (OS).Results: The PFS values were 7.0 and 4.7 months for Kayseri and Mersin groups,respectively (p=0.10) and the repsective OS values were 13.3 and 9.4 months (p=0.13). We did not found anysignificant difference regarding age, sex, comorbidity, smoking, surgery, resurgery, adjuvant chemoradiotherapyand palliative chemotherapy between the groups. Conclusions: We found that more sunlight exposure had noimpact on prognosis of patients with primary GBM, adding inconsistency to the literature about the relationshipbetween sunlight and GBM.     

High-Dose Conformal Radiotherapy Influenced the Pattern of Failure But Did Not Improve Survival in Glioblastoma Multiforme

Background and Purpose: Although glioblastoma multiforme is clearly radiation-resistant, there is evidence of a dose–dependent response relationship. The purpose of the study was to evaluate the impact of higher dose by rotational multileaf collimator (MLC) conformal radiation therapy.

Materials and Methods: From 1984 to 1995, 38 consecutive cases with intracranial glioblastoma multiforme were treated using the rotational MLC conformal therapy. There were 25 men and 13 women with a median age of 47 years (12–73 years, mean 46.5 years). Median Karnofsky performance score was 80 (30–100, mean 78.2). Median tumor volume was 64 cc (8–800 cc, mean 110.3 cc). All underwent surgical intervention (only biopsy in 1, partial resection in 13, subtotal resection in 21, and gross total resection in 3). Radiation dose to was 60 to 80 Gy (median 68.5 Gy, mean 68.3 Gy) in 21 patients treated before 1990 and 90 Gy in the 17 patients thereafter. Biweekly i.v. chemotherapy was also administered for both arms.

Results: The 1-year, 2-year, 5-year, and 10-year overall survival rates were 75%, 42%, 20%, and 15%, respectively. Univariate analysis showed the initial tumor volume, residual tumor volume, and Karnofsky performance score were statistically significant factors for survival. Only the residual tumor volume was statistically significant by multivariate analysis. The 5-year survival rate of patients with residual tumors of 5 cc or less in volume was as good as 37%. Survival of the 90-Gy Group appeared inferior to that of the Low-Dose Group, though no statistical difference was seen (the 3-year survival was 40% vs. 22%). Local failure was observed in 16 of the 19 recurrences in the Low-Dose Group, whereas it was observed in only 4 of the 13 recurrences in the 90-Gy Group. The difference in pattern of failure was statistically significant. Two patients of the High-Dose Group developed radiation necrosis and one died of it.

Conclusions: The high-dose conformal radiotherapy did not improve survival in the disease, but did change the pattern of failure.     

Autophagy Inhibition Promotes Gambogic Acid-induced Suppression of Growth and Apoptosis in Glioblastoma Cells

Objective: To investigate the effects of gambogic acid (GA) on the growth of human malignant glioma cells.Methods: U251MG and U87MG human glioma cell lines were treated with GA and growth and proliferationwere investigated by MTT and colony formation assays. Cell apoptosis was analyzed by annexin V FITC/PI flowcytometry, mitochondrial membrane potential assays and DAPI nuclear staining. Monodansylcadaverine (MDC)staining and GFP-LC3 localisation were used to detect autophagy. Western blotting was used to investigate themolecular changes that occurred in the course of GA treatment. Results: GA treatment significantly suppressedcell proliferation and colony formation, induced apoptosis in U251 and U87MG glioblastoma cells in a timeanddose-dependent manner. GA treatment also lead to the accumulation of monodansylcadaverine (MDC)in autophagic vacuoles, upregulated expressions of Atg5, Beclin 1 and LC3-II, and the increase of punctatefluorescent signals in glioblastoma cells pre-transfected with GFP-tagged LC3 plasmid. After the combinationtreatment of autophagy inhitors and GA, GA mediated growth inhibition and apoptotic cell death was furtherpotentiated. Conclusion: Our results suggested that autophagic responses play roles as a self-protective mechanismin GA-treated glioblastoma cells, and autophagy inhibition could be a novel adjunctive strategy for enhancingchemotherapeutic effect of GA as an anti-malignant glioma agent.     

Glioblastoma multiforme with an abscess: case report and literature review

An intratumoral or peritumoral microbial intracranial abscess is an infrequent diagnosis. The development of this complication may not be preceded by apparent local or general infection in all cases. To identify this diagnosis by radiological (MRI) or laboratory investigations is very intricate. Nevertheless, the recommended life-saving strategy is early surgery with resolution of both the tumor and infection. If subsequent oncological treatment is required, it has to be adjusted for prevention of re-inflammation. The described patient suffered from an intracranial abscess superimposed on a Glioblastoma Multiforme. The confirmed etiological agent was Staphylococcus aureus. The suspected route of microbial migration and colonization in this tumor was bacteremia via agents from thrombophlebitis. The patient is in a good condition following surgery, antimicrobial treatment, and radiotherapy.     

KPS值与晚期肺癌病人中位生存期的关系(附154例临床分析)

分析154例晚期肺癌病人，发现KPS值在10分及10以下、20分、30分、40分、50分、60分及以上者的中位生存期分别为0．36月、1．5月、2．8月、5．4月、10．6月和22．3月，经综合治疗后的有效率（CR＋PR）分别为0、4．2／、22．2％、30％、50％、53．8％。分析结果表明，KPS值每提高10分，中位生存期呈成倍增长．P＜0.01，差异非常显著。KPS值越高，经治疗后的有效率越高，P＜0．05，差异显著。     

CD24 and Nanog expression in Stem Cells in Glioblastoma: Correlation with Response to Chemoradiation and Overall Survival

Background and aim: Glioblastoma (GBM) is one of the most common and aggressive brain tumors with a median survival of 12-14 months. The aim of present study was to evaluate the gene expression profile of stem cell markers Nanog and CD24 in GBM and to determine its relationship to outcome in terms of treatment response and overall survival. Material and methods: This was a retrospective as well as retrospective study which included 51 histologically confirmed cases of GBM. Expression of CD24, and Nanog was evaluated by RT-PCR. Control tissue included debrided brain tissue from open head injury cases. All cases of GBM underwent total surgical resection and subsequently chemotherapy. Immediate treatment response was evaluated at 3 months using Response Evaluation Criteria In Solid Tumors (RECIST) guidelines and overall survival was measured at 36 months. Result: As compared to control gene, expression of CD24 and Nanog was seen to be unregulated to 24.5% and 31.7% respectively. However, the difference in mean expression of cases and controls was not statistically significant. Correlation between expressions of these two markers was also not statistically significant. On univariate cox regression analysis, cases with >2 fold expression of CD24 and Nanog had significantly poor survival as compared to those with 2 fold CD24 expression had a statistically significant correlation with poor survival. Conclusion: An overexpression of CD24 by more than two fold was associated with poor overall survival in GBM. Poor survival may be related to increased "stemness" of tumour cells. Targeted therapy inclusive of drugs targeting stem cells directly or indirectly may be a promising therapeutic option.     

胶质母细胞瘤国际诊疗指南比较评价

胶质母细胞瘤是最常见的WHOⅣ级恶性胶质瘤,其特点是基因不稳定,临床特性难预测。尽管手术、放化疗等治疗手段不断进步,其预后仍然很差,中位生存期只有12~14个月。笔者从数据库和网络共检索到7个近年来不同国家发表的胶质母细胞瘤治疗指南或共识,结果显示,手术切除联合放疗和化疗仍然是胶质母细胞瘤的主要治疗手段,但是各国指南仍存在一些细节上的差异,如分子指标检测、化疗方案、复发后治疗方案等。本文通过对多国治疗指南比较,旨在为我国胶质母细胞瘤患者的治疗提供参考。     

ZMYND11在多形型胶质母细胞瘤中的表达及意义

目的 探讨ZMYND11在多形性胶质母细胞瘤（GBM）中的表达及意义。方法 收集河北医科大学第二医院GBM患者术中肿瘤标本20例（肿瘤组）,重度脑外伤患者正常脑组织标本20例（对照组）,对上述标本进行Western blot及qRT-PCR实验,检测并比较两组ZMYND11的表达;利用ZMYND11过表达的慢病毒转染GBM的细胞系U87细胞使其ZMYND11过表达,通过CCK、Transwell及流式细胞分析检测ZMYND11对U87细胞在增殖、侵袭及凋亡方面的作用;将ZMYND11过表达的U87细胞接种至裸鼠内进行体内试验。结果 肿瘤组中ZMYND11的表达量明显低于对照组（P<0.001）; ZMYND11过表达可明显抑制U87细胞的增殖及侵袭并促进其凋亡,体内实验显示ZMYND11可明显抑制肿瘤的生长。结论 ZMYND11可抑制GBM的发生与发展。     

脑多形性胶质母细胞瘤水肿带大小与预后相关性的分析

目的评价肿瘤外周水肿带对脑多形性胶质母细胞瘤(GBM)的预后影响。方法回顾性分析74例接受适形放射治疗(CRT)多形性胶质母细胞瘤患者的资料。所有患者均经病理组织学证实,其中62例患者经手术全切或次全切术,12例仅行立体定向活检术。55例采用了不同方式的化疗,另外19例患者行单纯放疗,放疗剂量均为60Gy。结果中位生存期为13.9个月,1、2及3年总生存率分别为57.0%、18.0%和12.9%。水肿带最大径≤70mm者中位生存期为19.9个月,>70mm者为9.9个月(P<0.0001);水肿带与肿瘤最大径比值(E/T)≤1.8与>1.8者中位生存期分别为16.6个月和9.9个月(P=0.0004)。中位肿瘤进展时间为7.8个月,1、2年的局部控制率分别为22.4%和8.2%。结论肿瘤边缘水肿带大小以及与肿瘤的比值是影响GBM预后的重要因素,提示水肿带应包括在照射野内,同时在不增加并发症的前提下是否应进一步提高水肿带照射剂量?