胶质母细胞瘤的复发模式及相关因素分析

目的:探究手术后胶质母细胞瘤(glioblastoma, GBM)的复发模式及预后影响因素。方法:回顾性收集并分析2017年01月至2020年12月期间就诊于我院的105例胶质母细胞瘤患者的资料,基于连续的影像学表现将肿瘤复发模式划分为局部复发及非局部复发。进一步收集患者的临床及病理特征,分析不同复发模式的影响因素。结果:这项单中心回顾性研究包括105例手术切除后的胶质母细胞瘤患者。所有患者的中位无进展生存期(progression-free survival, PFS)为9.8个月;中位总生存期(overall survival, OS)为22.8个月。在49例(67.1%)和24例(32.9%)患者中观察到局部和非局部复发模式。73例复发患者中局部复发患者的中位PFS为4.8个月,非局部复发的患者为9.9个月(P=0.045)。未观察到OS与复发模式之间的相关性(P=0.242)。单因素回归分析示病灶部位(P=0.002)、室管膜下区受侵犯情况(P=0.009)、MGMT启动子甲基化状况(P=0.013)、 TERT启动子突变状况(P=0.031)、化疗与否(P=0.000)与PF...     

贝伐珠单抗治疗复发胶质母细胞瘤疗效和预后分析

  目的   探讨贝伐珠单抗治疗复发胶质母细胞瘤的疗效及预后因素。  方法  回顾性分析2011年12月至2020年7月中山大学肿瘤防治中心接受贝伐珠单抗治疗的81例成人复发胶质母细胞瘤患者的临床资料,评价其疗效和不良反应,以总生存期为预后指标进行单因素和Cox比例风险模型多因素分析。  结果  81例患者的客观有效率为62.9%,疾病控制率为80.2%,90.1%的患者生存质量状况（KPS）评分和神经症状有改善。中位无进展生存期（median progression-free survival,mPFS）和中位总生存期（median overall survival,mOS）分别为4.4个月（95%CI:4.0～4.8）和7.8个月（95%CI:6.8～8.8）。单因素分析显示用药时机（首次或≥2次复发时用药）、剂量（5 mg/kg,6～9 mg/kg,10 mg/kg）和是否联合化疗对mOS无影响,多因素分析显示KPS评分和MGMT启动子甲基化状态是影响mOS的独立预后因素。不良事件主要为1～2级。  结论  贝伐珠单抗可以改善成人复发胶质母细胞瘤患者的生存质量,治疗耐受性好。KPS评分和MGMT启动子甲基化状态是影响mOS的独立预后因素,贝伐珠单抗在复发后的用药时机、剂量、是否联合化疗对mOS无影响。      

肿瘤电场治疗仪治疗复发脑胶质母细胞瘤的前瞻性单中心单臂探索性研究

  目的  评价肿瘤电场治疗仪用于治疗复发胶质母细胞瘤患者的初步安全性和有效性。  方法  选取2020年4月至2020年8月期间中南大学湘雅医院和解放军总医院6例受试者,均为男性,中位年龄53（48～68）岁。入组复发胶质母细胞瘤受试者并收集临床资料,通过观察受试者治疗期间不良事件的发生率、肿瘤进展时间（time to progression,TTP）和总生存时间（overall survival,OS）评估治疗的安全性和有效性。  结果  入组6例受试者中位随访时间10.9（8.4～22.7）个月,所有受试者发生肿瘤进展,5例随访至死亡,截至随访截止1例生存。中位肿瘤进展时间（median time to progression,mTTP）为4.7个月（95%CI:3.62～5.78）,中位无进展生存时间（median progression-free survival,mPFS）为4.7个月（95%CI:3.62～5.78）,中位总生存时间（median overall survival,mOS）为10.9个月（95%CI:8.86～12.94）。客观缓解率（CR+PR）33.3%;疾病控制率（SD+PR+CR）83.3%。治疗相关的不良事件主要为头皮皮疹,发生率为66.7%,经调整电极片黏贴位置、保持创口干燥、涂抹类固醇类软膏或抗生素软膏后均可有效缓解。  结论  肿瘤电场治疗仪用于治疗复发胶质母细胞瘤的受试者在电场治疗过程中呈现良好的初步安全性和有效性。      

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。     

多形性胶质母细胞瘤33例影像学特点及手术治疗评估

 【摘要】　目的　总结分析多形性胶质母细胞瘤（GBM）的临床表现、影像学特点及手术治疗预后,为其临床诊断和治疗提供一定参考依据。方法　回顾性总结分析33例经病理证实的GBM患者的临床资料特点。结果　GBM患者临床症状多以头痛为主诉,磁共振成像（MRI）表现均为不规则形稍长T1、稍长T2混杂信号,水肿与占位效应明显,钆喷酸葡胺（GD-DTPA）增强后病灶不规则形环状强化;行手术切除（其中8例行显微手术）,31例无严重并发症;随访3个月,32例无肿瘤复发,1例死亡。结论　GBM其临床诊治及影像学具有相对特征性,通过这些指标能明显优化术前评估,以提高术后患者生存率与生活质量。     

铁死亡相关复发风险模型预测胶质母细胞瘤患者的临床结局与免疫浸润

目的构建铁死亡相关胶质母细胞瘤(GBM)复发预后风险模型并评价患者预后。方法通过CGGA和FerrDb数据库筛选复发GBM中铁死亡相关差异表达基因,经过Lasso分析构建nomogram模型,并利用TCGA数据验证预测效能。基因本体功能和信号通路富集分析影响患者预后的机制,通过ESTIMATE算法和TIMER数据库研究肿瘤免疫浸润与免疫检测点表达情况。结果WWTR1、PLIN2、BID是GBM复发的重要铁死亡相关基因,结合性别、年龄构建的nomogram校正曲线一致性良好,1、3、5年AUC分别为0.65、0.66、0.63(CGGA)和0.68、0.76、0.79(TCGA)。高风险亚型中上皮间充质转化、KRAS和炎性反应通路活性明显上调(P<0.05),免疫细胞浸润较少(P<0.05),且风险评分与免疫抑制检测点呈正相关(r=0.43~0.57,P<0.05)。结论基于3个铁死亡相关复发风险基因构建预后评分模型,发现浸润性免疫细胞和免疫检测点影响GBM患者预后。     

阿帕替尼治疗耐药的复发胶质母细胞瘤的临床研究

目的:探讨阿帕替尼治疗替莫唑胺(temozolomide,TMZ)耐药的复发胶质母细胞瘤(glioblastoma,GBM)的疗效和不良反应,并观察治疗过程中免疫因子的变化.方法:选取2018年7月至2020年10月郑州大学附属肿瘤医院标准方案治疗失败的GBM患者51例,给予阿帕替尼和TMZ治疗.阿帕替尼500 mg/...     

脑胶质母细胞瘤术后辅助治疗的研究进展

恶性胶质瘤（MG）是颅内常见的原发性肿瘤。其中,多形胶质母细胞瘤（GBM）是恶性程度最高的肿瘤,GBM呈浸润性生长,单纯手术往往难以彻底根除,术后复发率很高,中位生存期（MST）多为9—15个月。近年来GBM的临床治疗取得了一些进展,许多学者越来越重视手术后的其他治疗方法,包括放疗、化疗、分子靶向治疗等。     

上皮样胶质母细胞瘤10例报告并文献复习

背景与目的:上皮样胶质母细胞瘤(epithelioid glioblastoma,EGBM)是一种罕见的胶质母细胞瘤亚型,国内外报道较为少见.探讨EGBM的临床、病理学及影像学特征.方法:回顾性分析2014—2019年在华山医院北院经手术后病理学检查证实的10例EGBM的临床资料,对其临床、病理学及影像学特征进行归纳总...     

间变性少突胶质细胞瘤术后复发转变为胶质母细胞瘤1例并文献复习

胶质瘤是中枢神经系统最常见的原发恶性肿瘤[1].尽管接受了手术、放疗、化疗和靶向治疗等各种治疗,其复发率仍极高.关于低级别胶质瘤复发进展转变为高级别胶质瘤可见相关报道[2-3],然而间变性少突胶质细胞瘤复发转变为胶质母细胞瘤的案例较为少见,现报道如下.     

Salvage Chemotherapy with CPT-11 for Recurrent Glioblastoma Multiforme

Background: A prospective Phase II study of CPT-11 in adult patients with recurrent supratentorial glioblastoma multiforme (GBM). Methods: Forty patients (25 men, 15 women) ages 32–71 years (median 59), with recurrent GBM were treated. All patients had previously been treated with surgery and involved field radiotherapy (median dose 60Gy; range 59–60). Additionally, all patients were treated with adjuvant chemotherapy (BCNU in 20, PCV in 18, Procarbazine in 2). Twenty-five patients (62%) were on anticonvulsants (phenytoin in 15, carbamazepine in 10) and 26 patients (65%) were on dexamethasone. Recurrent disease was defined by neuroradiographic disease progression (>25% increase in tumor dimensions) using gadolinium-enhanced MR imaging. The starting dose of CPT-11 was 400mg/m² followed in three weeks by 500mg/m², operationally defined as one cycle. At week 6, all patients were evaluated with MRI and neurological examination. Results: All patients were evaluable. Two doses (one cycle) of CPT-11 were administered to all patients. CPT-11-related toxicity included: diarrhea (16 patients, 40%); thrombocytopenia (9 patients, 23%); and neutropenia (6 patients, 15%). No patient required transfusion nor was treatment for neutropenic fever required. No treatment-related deaths were observed. All patients demonstrated progressive disease following one cycle of CPT-11. Conclusions: The lack of response to CPT-11 in this patient group with recurrent GBM suggests either CPT-11 has minimal activity or CPT-11 doses/schedule utilized in this study were sub-optimal. The latter is supported by the modest toxicity seen in this study and the previously documented enhanced clearance of CPT-11 in patients on anticonvulsants and dexamethasone.     

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.     

Systemic Temozolomide Combined with Loco-regional Mitoxantrone in Treating Recurrent Glioblastoma

Twenty-two recurrent GBM patients were enrolled for second tumor debulking with local positioning of a Rickam reservoir, in order to locally deliver chemotherapy with the aim of controlling local tumor recurrence. We designed a protocol using systemic temozolomide (150 mg/sqm days 1–5 every 28) in association with mitoxantrone, delivered through the reservoir (4 mg/day 1–5 every 28) positioned into the area of tumor exeresis. After re-operation a residual tumor mass no larger than 2 cm was identified in 18/22 patients. The patients were treated with monthly cycles of chemotherapy until evolution of the tumor, but in no case for more than 10 cycles. Responses were evaluated by MRI scans performed every 2 months and images assessed according to MacDonald’s criteria. Response rate: no complete responses (CR), 5 partial responses (PR), 13 stable disease (SD) and 4 progressive disease (PD) occurred. The median progression-free survival (PFS) and survival time (ST) of the whole group of treated patients was 7 and 11 months, respectively and more than a quarter of the patients survived over 18 months. During the study, the patients’ compliance was complete and no dropouts occurred. Hematological toxicity was mild and after repeated local injections only minor neurological side-effects occurred. Despite some bias in patients’ selection not excluded in this pilot study, results are interesting: the PFS was as long as the survival of recurrent GBM reported in the literature.     

Glioblastoma in the elderly

BACKGROUND:

Glioblastoma (GBM) is the most common malignant primary brain tumor, and approximately 50% of cases occur in patients aged ≥65 years. However, to the authors' knowledge, there is no accepted standard treatment for elderly GBM patients, and specific prognostic factors in the elderly GBM population have not been systematically studied to date.

METHODS:

The Memorial Sloan‐Kettering Cancer Center institutional database was used to identify patients with histologically confirmed GBM who were aged ≥65 years at the time of diagnosis.

RESULTS:

Three hundred ninety‐four GBM patients with a median age of 71.9 years (59% of whom were men) were included. Approximately 18% of patients underwent biopsy, whereas 82% underwent tumor resection; 81% received radiotherapy (RT), and 43% received adjuvant chemotherapy. The median overall survival was 8.6 months; at the time of last follow?up, 90% of patients had died, and the median follow‐up of the 39 surviving patients was 12 months. In a multivariate analysis, younger age, better Karnofsky performance status (KPS), single tumor, and surgical resection were found to be independent predictors of survival. Comparing 103 patients who received adjuvant chemotherapy with 48 who were only followed after RT, there was a 55% decrease in the risk of death (hazards ratio, 0.45; 95% confidence interval, 0.30‐0.66 [P < .0001]) after adjusting for age, KPS, extent of surgical resection, and number of lesions.

CONCLUSIONS:

Similar to studies in younger GBM patients, advancing age, KPS, and extent of tumor resection were found to be independent prognostic factors in the current study. Although survival is inferior in older GBM patients, age alone should not disqualify patients from aggressive therapy with surgical resection, RT, and chemotherapy. Cancer 2009. © 2009 American Cancer Society.     

Phase II Study of Lonidamine and Diazepam in the Treatment of Recurrent Glioblastoma Multiforme

Recurrent glioblastoma multiforme (GBM) is resistant to most therapeutic endeavours, with low response rates and survival rarely exceeding 6 months. There are no standard chemotherapeutic regimens and new therapeutic approaches have to be found. We report an open-label, uncontrolled, multicentre phase II trial of lonidamine (LND) and diazepam in 16 patients with GBM at first relapse and a Karnofsky performance status 70. The treatment regimen consisted of LND 450mg/day and diazepam 15mg/day orally of every 28-day cycle until progression or unacceptable toxicity. Patients received a median of three cycles (range, 1–12). No complete or partial response was observed. Therefore, according to the design of the study, no additional patients were enrolled and the trial was closed. Nevertheless, seven stabilizations (50%) were observed. Median time to progression was 8 weeks (range, 5–19 weeks). Median overall survival from recurrence was 15 weeks (range, 14–61 weeks). No grade 3–4 toxicity, except somnolence, was observed and there were no therapy-related deaths. Dose reduction for diazepam due to somnolence (grade III) was performed in 9 patients. The combination of LND and diazepam is well tolerated. LND and diazepam, acting on two distinct mitochondrial sites involved in cellular energy metabolism, may exert a cytostatic effect on tumour growth as shown by the high percentage of stable patients. The LND–diazepam at the used dosing schedule did not show a complete or partial response. LND plus diazepam may be interesting in the adjuvant setting or associated to chemotherapy to act on different targets and increase the therapeutic index.     

甲状腺癌的再次手术治疗

目的探讨甲状腺癌再次手术的必要性及其手术方式。方法回顾性分析我科于1998年2月-2003年10月231例甲状魄癌再次手术的临床资料。结果首次甲状腺肿块切除术62例，行甲状腺腺叶次全切除128例，行甲状腺腺叶加峡部切除术41例。无一例行Ⅵ区淋巴结清扫。首次手术病理类型：乳头状癌158例，滤泡型癌67例，髓样癌6例。根据外院资料及我院B超及CT检查。均再次行手术治疗，其中行甲状腺残叶加峡部切除术55例。行甲状腺残叶加峡部加Ⅵ区清扫87例，单行Ⅵ区清扫9例，行功能性颈淋巴结清扫包括Ⅵ区32例，行甲状腺癌联合根治术23例，行全甲状腺切除加功能性颈淋巴结清扫25例。再次手术后病理证实腺叶中癌残留的132例（69．5％），Ⅵ区淋巴结有转移81例，其中9例行Ⅵ区清扫者均有转移。颈部淋巴结有转移71例。结论甲状腺癌行局部切除术，残癌率高，再次行手术治疗是必要的。     

Glioblastoma Multiforme in the Elderly: A Therapeutic Challenge

Summary Introduction: Elderly patients with glioblastoma multiforme (GBM) are frequently excluded from cancer therapy trials, treated suboptimally or not treated at all. The average survival in elderly patients is 4–8 months. The goal of the present study was to evaluate the efficacy of different treatment options in terms of survival in an elderly population affected with GBM. Materials and methods: About 34 Patients with primary supratentorial GBM aged 65 or higher were included in this study. All patients underwent craniotomy and tumor mass resection. After surgery they received radiation therapy, chemotherapy and radioimmunotherapy in different combinations. Results: Overall median survival was 10.5 months with one patient still alive at 35 months. Survival was longer for patients who underwent total resection instead of partial (13 months vs 4 months, P = 0.006). If total en-bloc resection was used a further survival advantage was obtained (16months for en-bloc resection, 9months for inside-out resection, P = 0.008). Where a second surgical intervention was performed median survival was 21 months (P = 0.05). Survival according to adjuvant therapy has been 21 months (radiotherapy, chemotherapy, radioimmunotheraphy), 18 months (radiotherapy, chemotherapy) and 7 months (radiotherapy) (P = 0.0001). Conclusions: We think that single prognostic factor such as age should be not a reason for undertreatment.     

胃癌术后复发再次手术治疗分析(附38例)

目的探讨胃癌手术后复发的因素及其再次手术的适应证。方法对胃癌术后复发的38例患者进行再次手术,并对手术方法、术后并发症、死亡率及术后病理的结果进行分析。结果再次手术的术后生存时间超过5年者8例,超过3年者6例,超过2年者6例,超过1年者2例,1年以内死亡者16例。剖腹探查者6例分别于术后的4~8个月内死亡。结论对胃癌手术后复发者,再次手术能否切除病灶主要取决于其复发的方式。吻合口或残胃复发者,即使侵及邻近脏器,只要未出现远处转移,且心肺功能可耐受手术者都应再次手术。     

A Retrospective Review of Re-irradiating Patients' Recurrent High-grade Gliomas

Aims

After radical treatment, most high-grade gliomas (HGG) recur locally. Upon recurrence, no standard treatment exists. Options include re-resection, salvage systemic therapy and re-irradiation. This retrospective study evaluated patients who underwent re-irradiation for recurrent HGGs and assessed prognostic factors and their influence on management.

A Phase I Trial of Continuously Infused Intratumoral Bleomycin for the Treatment of Recurrent Glioblastoma Multiforme

Intratumoral (IT) chemotherapy has theoretical advantages in the treatment of brain tumors. The blood–brain barrier is not a factor in drug delivery, and large concentrations of drug can be instilled in the tumor with little systemic toxicity. Bleomycin has activity against gliomas and is a cell cycle selective agent whose efficacy should be enhanced by continuous infusion. We performed a phase I trial to test the feasibility of IT chemotherapy using a refillable, sustained release device, and to determine the maximum tolerable dose of IT bleomycin. The study was an open-ended dose escalation study. A modified Ommaya reservoir (containing a semipermeable membrane) was implanted with the delivery tube in the center of the tumor. Groups of three patients with recurrent glioblastoma multiforme were entered at progressively higher dose levels of bleomycin. The study closed when all patients at a given starting dose level developed toxicity. Nine patients received doses ranging from 5 to 34U/wk; the median total cumulative dose was 195 U. No dose limiting systemic toxicity was detected. Neurologic toxicity occurred only at doses above 16U/wk. We conclude that continuously infused IT bleomycin is well tolerated; the MTD (and recommended dose for a phase II efficacy trial) of IT bleomycin is 16U/wk.