胶质母细胞瘤MGMT基因启动子甲基化与蛋白表达

Objective To study the correlation of MGMT gene promoter methylation and protein expression and their regional variation in different specimens obtained from different regions within the tumor in patients with newly diagnosed glioblastoma. Methods Two to four samples in the same tumor were collected from different regions in 30 patients with newly diagnosed glioblastoma patients. In five patients among them,mutispecimens were obtained under assistance of neuronavigation system during the operation. In all samples,MGMT promoter profile were analyzed by Methylation - specific polymerase - Chain - reaction analysis, MSP ,while MGMT protein expression was detected in tissue sections by immunohistochemistry,IHC. Results MGMT promoter methylation was detected in 43. 56% (44/101) specimens. MGMT protein expression in tissue sections was assessed and scored:(1 :no or positive tumor cells < 10%, 2: ≥ 10% ≤50% ,3: > 50%) ,The rate of MGMT staining with a score 1,2,3 in all of tumor sections was 32. 67% ,43.56% ,23. 76% respectively. No significant correlation between MGMT protein expression and promoter methylation(x2 =2. 905, P =0.088) was found. The regional heterogeneity of MGMT protein expression within the same tumor was in 57% (17/30) patients ;and the regional heterogeneity of gene promoter methylation was in37%(11/30)patients. Conclusions MGMT promoter methylation is probably not the only modulating element in MGMT protein expression. The heterogeneity of MGMT protein expression and its promoter methylation in the same tumor questions their guiding significance in making therapeutic scheme for individual patients with malignant glioma in clinical practice.     

胶质母细胞瘤MGMT基因启动子甲基化与蛋白表达

目的 研究新发胶质母细胞瘤中肿瘤不同部位MGMT基因启动子甲基化及其蛋白表达关系及区域差异性.方法 在30例新发胶质母细胞瘤肿瘤不同部位采取2～4块标本,其中5例在术中神经导航引导下采取.甲基化特异性PCR(MSP)法检测标本中MGMT基因启动子甲基化状况,免疫组化法(IHC)检测组织切片MGMT蛋白表达情况.结果 43.56%(44/101)检测肿瘤组织中出现MGMT基因启动子甲基化,免疫组化检测(阴性,细胞弱着色＜10%或细胞无着色;弱阳性,10%≤细胞着色≤50%;强阳性,细胞着色＞50%)发现MGMT蛋白表达情况分别为阴性(32.67%),弱阳性(43.56%),强阳性(23.76%).MGMT基因启动子甲基化与其蛋白表达无明显相关性(x2=2.905,P=0.088).在肿瘤不同取材部位组织之间57%的患者(17/30)MGMT蛋白表达水平与37%患者(11/30)启动子甲基化存在不均一性.结论 MGMT基因启动子甲基化可能不是MGMT蛋白表达的惟一调节因素.同一肿瘤不同取材部位组织MGMT蛋白表达与其基因启动子甲基化水平不均一性的结果 质疑了单一取材标本的检测结果 及其对临床治疗方案选择的指导意义.     

胶质母细胞瘤MGMT基因启动子甲基化与蛋白表达

Objective To study the correlation of MGMT gene promoter methylation and protein expression and their regional variation in different specimens obtained from different regions within the tumor in patients with newly diagnosed glioblastoma. Methods Two to four samples in the same tumor were collected from different regions in 30 patients with newly diagnosed glioblastoma patients. In five patients among them,mutispecimens were obtained under assistance of neuronavigation system during the operation. In all samples,MGMT promoter profile were analyzed by Methylation - specific polymerase - Chain - reaction analysis, MSP ,while MGMT protein expression was detected in tissue sections by immunohistochemistry,IHC. Results MGMT promoter methylation was detected in 43. 56% (44/101) specimens. MGMT protein expression in tissue sections was assessed and scored:(1 :no or positive tumor cells < 10%, 2: ≥ 10% ≤50% ,3: > 50%) ,The rate of MGMT staining with a score 1,2,3 in all of tumor sections was 32. 67% ,43.56% ,23. 76% respectively. No significant correlation between MGMT protein expression and promoter methylation(x2 =2. 905, P =0.088) was found. The regional heterogeneity of MGMT protein expression within the same tumor was in 57% (17/30) patients ;and the regional heterogeneity of gene promoter methylation was in37%(11/30)patients. Conclusions MGMT promoter methylation is probably not the only modulating element in MGMT protein expression. The heterogeneity of MGMT protein expression and its promoter methylation in the same tumor questions their guiding significance in making therapeutic scheme for individual patients with malignant glioma in clinical practice.     

替尼泊甙联合司莫司汀治疗脑胶质瘤疗效与MGMT表达关系的研究

目的 通过观察脑胶质瘤中O6-甲基鸟嘌呤DNA甲基转移酶(MGMT)的表达状态,探讨MGMT在脑胶质瘤中的表达与替尼泊甙(VM-26)联合司莫司汀(Me-CCNU)方案化疗疗效之间的关系. 方法 对资料完整的47例经病理证实的脑胶质瘤患者进行回顾性研究,对患者的胶质瘤病理石蜡切片采用免疫组化法检测MGMT的表达,然后分析MGMT的表达与患者生存率之间关系. 结果 本组患者MGMT阳性表达率为40.4%.MGMT阴性表达组3年生存率为66.7%,平均总生存时间为(67.861±10.094)月;MGMT阳性表达组为52.6%,平均总生存时间为(47.263±7.983)月,比较差异均无统计学意义(P>0.05).11例患者出现I度的骨髓抑制现象,6例患者出现胃部不适、呕吐、腹泻、食欲不振等消化系统症状. 结论 VM-26联合Me-CCNU化疗方案可以有效克服脑胶质瘤中MGMT所带来的化疗耐药性问题,且该方案的毒副作用不大,是一个有效的化疗方案.     

Relationship between O6-methylguanine-DNA methyltransferase levels and clinical response induced by chloroethylnitrosourea therapy in glioma patients.

BACKGROUND: Adjuvant nitrosourea chemotherapy fails to prolong survival significantly as many tumors demonstrate resistance to these drugs. It has been documented in cell lines that O6-methylguanine DNA methyltransferase (MGMT) plays an important role in chloroethylnitrosourea (CENU) drug resistance. METHODS: We evaluated MGMT expression in 22 glioma specimens by using an immunofluorescence assay and compared the results with clinical responses of the patients to CENU-based chemotherapy. RESULTS: Eight tumor samples had no detectable MGMT, whereas other samples had from 9,989 to 982,401 molecules/nucleus. In one group (12 patients), the tumor decreased in size or was stable (effective group), whereas in the other group (10 patients), the tumor demonstrated continuous growth during chemotherapy (progressive group). The Mer- patients (MGMT < 60,000 molecules/nucleus) appeared to have more chance of stable disease or response to CENU therapy than the Mer+ patients (MGMT > 60,000 molecules/nucleus) (X2 = 4.791, p = 0.0286). In patients with glioblastomas multiforme (GBMs), the median time to progression (TTP) of Mer+ patient was shorter than that of Mer- patient (t = 2.04, p = 0.049). As a corollary, the MGMT levels were significantly higher in GBM tumors from the progressive group than those from the effective group (t = 2.26, p = 0.029). However, there was no significant correlation between MGMT levels and either the survival time (r = 0.04, p = 0.8595) or TTP (r = 0.107, p = 0.6444). CONCLUSION: This study suggests that being MGMT positive is indicative of a more aggressive disease that progresses more rapidly with CENU therapy. However, MGMT negative tumors are not always sensitive to CENU agents, suggesting that other factors are also important.     

A pilot study of glioblastoma multiforme in elderly patients: Treatments,O-6-methylguanine-DNA methyltransferase (MGMT) methylation status and survival

Objectives

Elderly Glioblastoma multiforme (GBM) patients have a worse prognosis and receive variable treatments. MGMT gene promoter methylation is linked with improved survival in GBM. We examined treatments administered and survival including in relation to MGMT methylation status in elderly GBM patients.

Patients and methods

Patients ≥65 years with diagnosed GBM between 1/01/2007 and 30/04/2009 and undergoing either a biopsy, subtotal (STR) or gross total resection (GTR) were included. The collected information included MGMT status [methylated (ME) vs. unmethylated (UN)] and survival data. p < 0.05 was considered significant.

Results

59 patients were identified with median age at diagnosis being 72.68 years (65.72–85.04). Treatment included surgery (25 GTR, 8 STR, 26 biopsy), chemoradiation (22) and radiotherapy alone (20). Overall median overall survival (MOS) was 219 days. MOS with chemoradiation was 316 days vs. 143 days without it (p = 0.011). 47 patients had definite MGMT status (28 ME, 19 UN). In ME patients, 9/28 received temozolamide compared to 10/19 in UN category. Temozolamide administration in patients with definite MGMT status was based on WHO performance status (p = 0.007). MOS in UN group was 308 days vs. 167 days in ME group (p = 0.068). In a multivariate Cox model including use of temozolamide, WHO score and methylation status, only temozolamide use was significantly associated with a reduced risk for death (HR 0.443, 95% CI 0.200–0.982, p = 0.045).

Conclusions

In this small cohort of patients, chemoradiation in suitable elderly GBM patients seemed to afford a survival benefit. MGMT methylation was not associated with an improved survival with temozolamide being the only factor leading to a better survival. Temozolamide use should be considered irrespective of MGMT status in this population with future large prospective studies needed to elucidate this further.     

胶质母细胞瘤组织RBM8A表达与病人预后及替莫唑胺化疗敏感性的关系

目的 探讨胶质母细胞瘤（GBM）组织RNA结合基序8A（RBM8A）蛋白表达与病人预后及替莫唑胺（TMZ）化疗敏感性的关系。方法 选取2015年6月至2020年6月手术切除的GBM组织130例及颅脑损伤减压术中切取的非肿瘤脑组织20例（对照）,用免疫组化法检测组织RBM8A表达。术随访时间3~50个月,中位随访时间为12个月。结果 GBM组织RBM8A高表达率[86.15%（112/130）]明显高于对照组[20%（4/20）;P<0.05]。随访期间死亡98例,失访2例;多因素Cox回归分析显示,RBM8A高表达是GBM病人生存预后不良的独立危险因素（P<0.05）。生存曲线分析显示,RBM8A高表达GBM病人中位无复发生存时间和总生存时间均明显低于低表达病人（P<0.05）;RBM8A低表达GBM病人中,TMZ化疗病人无复发生存时间和总生存时间均明显高于未化疗病人（P<0.05）;TMZ化疗与RBM8A高表达GBM病人无复发生存时间和总生存时间无明显关系（P>0.05）。结论 GBM组织RBM8A呈高表达,与病人不良生存预后有关。检测RBM8A有助于评估GBM病人对TMZ化疗敏感性。     

AMOTL2与FKBP51表达水平与胶质母细胞瘤病人预后的关系

目的 探讨胶质母细胞瘤（GBM）类血管动蛋白-2（AMOTL2）与FK506结合蛋白51（FKBP51）表达变化及临床意义。方法 收集2016年6月~2019年6月手术切除的GBM标本92例,以取同期颅脑损伤内减压术切除的非肿瘤脑组织48例为对照。采用免疫组化染色法检测AMOTL2、FKBP51表达。GBM病人术后随访2年,记录无进展生存期和总生存期。结果 GBM组织AMOTL2低表达率、FKBP51高表达率均明显高于对照组（P<0.05）。GBM组织AMOTL2表达水平与P53、EGFR呈明显负相关（P<0.05）,FKBP51表达水平与P53、EGFR呈明显正相关（P<0.05）。Cox比例回归风险模型分析显示,AMOTL2低表达、FKBP51高表达是GBM生存预后不良的独立危险因素（P<0.05）。生存曲线分析显示,AMOTL2高表达组病人无进展生存期、总生存期较低表达组均明显延长（P<0.05）,FKBP51高表达组无进展生存期、总生存期较低表达组均明显缩短（P<0.05）。结论 GBM组织AMOTL2呈低表达,而FKBP51呈高表达,二者均与P53、EGFR表达相关,与病人预后密切相关。     

Geminin表达水平与脑胶质瘤病人预后的关系

目的 探讨Geminin表达水平与脑胶质瘤病人预后的关系.方法 收集2014年1月～2017年1月手术切除并经术后病理证实的脑胶质瘤标本90例,以及因颅脑损伤内减压术切除的非肿瘤脑组织50,采用PCR检测Geminin mRNA表达水平.90例脑胶质瘤根据Geminin mRNA表达水平中位数分为高表达组和低表达组.9...     

Immunohistochemical evaluation of O6‐methylguanine DNA methyltransferase (MGMT) expression in 117 cases of glioblastoma

Temozolomide (TMZ) is an oral alkylating agent which is widely used in the treatment of glioblastoma (GBM) and is composed of astrocytic and/or oligodendroglial tumors, and the evaluation of O⁶‐methylguanine DNA methyltransferase (MGMT) expression is important to predict the response to TMZ therapy. In this study, we conducted immunohistochemical analysis of 117 cases of Japanese GBM including 19 cases of GBM with oligodendroglioma component (GBMO), using a scoring system for quantitative evaluation of staining intensity and proportion of MGMT, and performed survival analysis of these patients. Immunohistochemically, 55 cases (47%) were positive for MGMT with various intensities and proportions (total score (TS) ≥ 2), while 62 cases (53%) were negative (TS = 0). The distribution of MGMT expression pattern was not affected by any clinicopathological parameters such as the histological subtype (GBM vs. GBMO), age and gender. The survival analysis of these patients revealed that the minimal expression of MGMT (TS ≥ 2) was a significant unfavorable prognostic factor (P < 0.001) as well as resectability (P = 0.004). Moreover, multivariate analysis showed that minimal MGMT expression in GBM was the most potent independent predictor for progression free survival (P < 0.001) and also overall patient survival (P < 0.001). This is the first report employing the scoring system for both staining intensity and proportion to evaluate immunohistochemical MGMT expression in GBM. In addition, our results emphases the clinicopathological values of the immunohistochemical approach for MGMT expression in glioma patients as a routine laboratory examination.     

Evaluation status and prognostic significance of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in pediatric high grade gliomas

Introduction  

In this study, we investigated the prognostic and predictive value of MGMT promoter methylation and protein expression in 30 pediatric high grade gliomas (pHGG).     

rCBV变化与VEGF表达对胶质母细胞瘤术后放疗病人生存期的预测研究

目的 探讨相对脑血容量(relative cerebral blood volume,rCBV)变化和血管内皮生长因子(vascular endothelial growth factor,VEGF)表达对胶质母细胞瘤全切手术后辅助放射治疗病人的无进展生存期(PFS)和总生存期(OS)的预测作用.方法 回顾性分析16例外科全切术后辅助放射治疗的胶质母细胞瘤病人的临床资料.在放射治疗前和放射治疗中(累计放射剂量为30 Gy)各进行1次灌注成像检查,计算rCBV值.免疫组化检测VEGF表达.采用Kaplan-Meier生存曲线分析PFS和OS.结果 不同年龄、VEGF表达和rCBV变化的病人,其在PFS的差异具有统计学意义(均P＜0.05).仅有VEGF表达不同的病人在OS的差异具有统计学意义(P＜0.05).结论 VEGF表达和rCBV变化可以作为判定胶质母细胞瘤PFS的预测物.同时,VEGF表达可以作为判定胶质母细胞瘤OS的预测物.     

Correlation of tumor p53 and PCNA with response and survival of glioblastoma in patients treated with an ECOG protocol of pre-irradiation chemotherapy

BACKGROUND: The ability to predict treatment responsiveness and survival of patients with glioblastoma multiforme, the most malignant and most common primary brain tumor, would be a valuable asset. Tumor and proliferation markers such as p53 and PCNA have been immunohistochemically defined and have been useful in other tumors in determining prognosis. Therefore, the authors studied the correlation of responsiveness to treatment, time to progression and survival with p53 and PCNA labeling indices in a pre-irradiation chemotherapy study of the glioblastoma multiforme. METHODS: Immunohistopathology for labeling indices for p53 and PCNA using formalin-fixed, paraffin-embedded tissue from the glioblastomas of 23 patients entered into a phase II ECOG trial of pre-irradiation chemotherapy were defined using the streptavidin-peroxidase technique with AEC chromogen. The labeling indices were correlated with response to treatment time to progression and overall survival. Most patients received three cycles of BCNU for three days over three months and cisplatin monthly for three days over three months prior to external beam irradiation. RESULTS: There were no significant differences in treatment response, time to progression or overall survival in glioblastoma, patients with positive p53 labeling index (> 5%) versus a negative p53 labeling index (< or = 5%) or positive PCNA labeling (> 10%) versus a negative labeling index (< or = 10%) or any combination of P53 and PCNA labeling indices. CONCLUSIONS: Using this protocol of pre-irradiation chemotherapy, p53 and PCNA labeling indices in the glioblastoma multiforme did not predict treatment benefit.     

Expression of O6‐methylguanine DNA methyltransferase (MGMT) and immunohistochemical analysis of 12 pineal parenchymal tumors

Pineal parenchymal tumors (PPTs) are rare neoplasms which occupy less than 1% of primary CNS tumors. Because of their rare incidence, previous reports on PPTs are limited in number and the useful molecular markers for deciding histological grading and even selecting chemotherapy are undetermined. In this study, we conducted immunohistochemical analysis of 12 PPT specimens, especially for expression of O⁶‐methylguanine DNA methyltransferase (MGMT) to assess whether temozolomide (TMZ) could serve as a possible alternative therapy for PPTs. We analyzed 12 PPTs, consisting of three pineocytomas, six PPTs of intermediate differentiation (PPTIDs), and three pineoblastomas. Immunohistochemical analysis was performed using antibodies against MGMT, synaptophysin, neurofilament protein (NF), p53, and neuronal nuclear antigen (NeuN). Immunohistochemically, 11 out of 12 cases were positive for MGMT. The mean MIB‐1 labeling index was less than 1% in pineocytoma, 3.5% in PPTID, and 10.5% in pineoblastoma. All 12 cases were positive for synaptophysin and 11 cases, except one PPTID case, showed positive for NF. Nuclear staining of NeuN was negative in all cases although cytoplasmic staining of NeuN was observed in five cases. No case was positive for p53. Eleven out of 12 cases of PPTs demonstrated MGMT expression, suggesting chemoresistancy to TMZ treatment. This is the first report showing MGMT expression in PPTs. In addition, MIB‐1 labeling index correlated with WHO grade, although the immunoreactivity of synaptophysin, NF, NeuN and p53 did not correlate with the histological grade.     

Sphingosine kinase-1 expression correlates with poor survival of patients with glioblastoma multiforme: roles of sphingosine kinase isoforms in growth of glioblastoma cell lines

Sphingosine-1-phosphate is a bioactive lipid that is mitogenic for human glioma cell lines by signaling through its G protein-coupled receptors. We investigated the role of sphingosine-1-phosphate receptors and the enzymes that form sphingosine-1-phosphate, sphingosine kinase (SphK)-1, and -2 in human astrocytomas. Astrocytomas of various histologic grades expressed three types of sphingosine-1-phosphate receptors, S1P1, S1P2, and S1P3; however, no significant correlation with histologic grade or patient survival was detected. Expression of SphK1, but not SphK2, in human astrocytoma grade 4 (glioblastoma multiforme) tissue correlated with short patient survival. Patients whose tumors had low SphK1 expression survived a median 357 days, whereas those with high levels of SphK1 survived a median 102 days. Decreasing SphK1 expression using RNA interference or pharmacologic inhibition of SphK significantly decreased the rate of proliferation of U-1242 MG and U-87 MG glioblastoma cell lines. Surprisingly, RNA interference to knockdown SphK2 expression inhibited glioblastoma cell proliferation more potently than did SphK1 knockdown. SphK knockdown also prevented cells from exiting G1 phase of the cell cycle and marginally increased apoptosis. Thus, SphK isoforms may be major contributors to growth of glioblastoma cells in vitro and to aggressive behavior of glioblastoma multiforme.     

Prognostic significance of the immunohistochemical expression of O6‐methylguanine‐DNA methyltransferase,P‐glycoprotein,and multidrug resistance protein‐1 in glioblastomas

We studied the expression of O⁶‐methylguanine‐DNA methyltransferase (O⁶‐MGMT), P‐glycoprotein (Pgp), and multidrug resistance protein‐1 (MRP‐1) in 23 glioblastomas using RT‐PCR, methylation‐specific PCR, and immunohistochemistry, and analyzed their association with overall patient survival. Univariate analysis of collected data demonstrated that the expressions of O⁶‐MGMT and MRP‐1 detected by immunohistochemistry, in addition to the consistent factors, including preoperative Karnofsky performance scale (KPS), radical surgery, and tumor location and extension, were significant prognostic factors for the overall survival (OS) of patients with glioblastoma, who received nimustine (ACNU)‐based chemotherapy in association with surgery and radiotherapy. Among them, following multivariate analysis, preoperative KPS, radical surgery, tumor location, and the expression of O⁶‐MGMT remained as significant prognostic factors. These findings suggest that immunohistochemical analysis of O⁶‐MGMT in patients with glioblastoma can be a useful method to predict the effects of chemotherapy and identify alternative chemotherapeutic regimens for O⁶‐MGMT‐positive patients.     

Patterns of care and survival of glioblastoma patients: A comparative study between 2004 and 2008 in Lyon,France

Introduction

The treatment of glioblastomas (GBMs) has changed significantly since 2005. However, the extent to which this change has improved overall survival (OS) of patients treated outside clinical trials remains to be determined.

Methods

We compared the patterns of care and OS of all GBM patients diagnosed in 2004 (n = 105) and in 2008 (n = 130) in our center.

Results

Younger patients (aged < 70 years) diagnosed in 2008 received temozolomide radiochemotherapy as the initial treatment and bevacizumab at recurrence more frequently than those diagnosed in 2004 (69% vs 26% P < 10⁻⁴ and 41% vs 3%, P < 10⁻⁴, respectively). Elderly patients (aged ≥ 70 years) diagnosed in 2008 received an oncological treatment (radiotherapy and/or chemotherapy) more frequently than those diagnosed in 2004 (67% vs 38%, P = 0.006). The patients diagnosed in 2008 had longer OS than those diagnosed in 2004 (10.5 months vs 5.3 months, P = 0.001). This finding was true for both younger and elderly patients (15.3 months vs 8.9 months, P = 0.02 and 6.4 months vs 3.2 months, P = 0.0002, respectively) and when considering only IDH1 wild-type patients (8.9 months vs 5.3 months, P = 0.004).

Conclusion

In our center, the change in the patterns of care for GBMs between 2004 and 2008 has been associated with a significant improvement in OS.     

Ddx5 和 Ddx17在人脑胶质瘤中的表达及其与病人生存期的关系

目的 探讨Ddx5 和 Ddx17在人脑胶质瘤组织中的表达及其与病人生存期的关系。方法 收集2013年1月至2016年6月手术切除的胶质瘤组织120例和颅脑损伤内减压术中切取正常脑组织50例（对照组），采用免疫组化法检测Ddx5 和 Ddx17的表达水平，根据染色评分分为高表达和低表达。采用多因素Cox比例风险模型分析胶质瘤病人生存预后的影响因素。结果 胶质瘤组织Ddx5（70.00%，84/120）和Ddx17（65.83%，79/120）高表达率均明显高于正常脑组织[分别为28.00%（14/50）、38.00%（19/50）；P<0.05]。多因素Cox比例风险模型分析结果显示Ddx5和Ddx17高表达是胶质瘤病人无进展生存期（PFS）和总生存期（OS）较短的独立影响因素（P<0.05）。与低表达组比较，Ddx5和Ddx17高表达组病人PFS和OS均明显缩短（P<0.05）。结论 人脑胶质瘤Ddx5和Ddx17呈高表达，二者均与胶质瘤病人的不良预后有关     

Relationship between costs and symptoms in schizophrenia patients treated with antipsychotic medication: a review

BACKGROUND: The purpose of this review is to understand how changes in costs of illness are related to the effects of antipsychotic medications on symptoms in schizophrenia patients. METHOD: A search of the MEDLINE database was performed using the keywords costs, symptoms, and schizophrenia. Studies published between 1965 and 2003 in English, French, German, or Spanish that assessed costs, symptoms, and relationships between costs and symptoms were reviewed. RESULTS: Twenty studies were identified. Most of the reviewed clinical trials of antipsychotic medications reported a decrease in mean costs of illness and an improvement in symptoms. However, many of the studies did not examine the relationship between changes in costs and symptoms. CONCLUSION: There is little evidence that changes in costs of illness are directly related to the effects of antipsychotic medications on symptoms. This review emphasizes the need for standardizing the assessment of costs and clinical outcomes, looking more specifically at the relationship between types of costs and specific aspects of psychopathology and developing new statistical models relating changes in costs and clinical outcomes.     

The survival impact of significant delays between surgery and radiochemotherapy in glioblastoma patients: A retrospective analysis from a large tertiary center

The optimal timing of adjuvant radiochemotherapy (RCT) in glioblastoma (GBM) patients remains unknown and the paradigm of ‘the sooner, the better’ has been challenged by many recent publications. In this study, we present unique data on the outcomes of patients with significant treatment delays. The study group consisted of 346 GBM patients (median age 56.8 years) who received surgical treatment (total or subtotal resection) and then underwent adjuvant concurrent RCT at one institution. The main endpoint was overall survival (OS). The Univariate and multivariate Cox Proportional-Hazard Model, log-rank test, and Kaplan-Meier method were used for the analysis. The median OS was 18.7 months and the 5-year overall survival was 8.5%. The median time interval from surgery to RCT was 9.8 weeks. The Cox regression showed that the time interval had no statistically significant impact on OS both in uni- and multivariate analysis. The explorative analysis suggested a positive trend for improved survival for patients in the 1st quartile of the time interval, especially for patients with residual disease or local recurrence prior to RCT, However, considering the 6.9 weeks median interval in the 1st quartile, this subgroup should still be regarded as 'moderate delay' compared with other literature data. The results indicate that the time interval is not a clear prognostic factor in the treatment of GBM. Prospective trials are highly warranted, as data suggest that moderate delays in the initiation of adjuvant treatment might be associated with survival benefit.