Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
Cancer J. 2012 Jan-Feb;18(1):40-4. doi: 10.1097/PPO.0b013e318243f6c9.
This review will address the current state of individualized cancer therapy for glioblastoma. Glioblastomas are highly malignant primary brain tumors presumably originating from neuroglial progenitor cells. Median survival is less than 1 year.
Recent developments in the morphologic, clinical, and molecular classification of glioblastoma were reviewed, and their impact on clinical decision making was analyzed.
Glioblastomas can be classified by morphology, clinical characteristics, complex molecular signatures, single biomarkers, or imaging parameters. Some of these characteristics, including age and Karnofsky Performance Scale score, provide important prognostic information. In contrast, few markers help to choose between various treatment options. Promoter methylation of the O-methylguanine methyltransferase gene seems to predict benefit from alkylating agent chemotherapy. Hence, it is used as an entry criterion for alkylator-free experimental combination therapy with radiotherapy. Screening for a specific type of epidermal growth factor receptor mutation is currently being explored as a biomarker for selecting patients for vaccination. Positron emission tomography for the detection of ανβ3/5 integrins could be used to select patients for treatment with anti-integrin antiangiogenic approaches.
Despite extensive efforts at defining biological markers as a basis for selecting therapies, most treatment decisions for glioblastoma patients are still based on age and performance status. However, several ongoing clinical trials may enrich the repertoire of criteria for clinical decision making in the very near future. The concept of individualized or personalized targeted cancer therapy has gained significant attention throughout oncology. Yet, data in support of such an approach to glioblastoma, the most malignant subtype of glioma, are limited, and personalized medicine plays a minor role in current clinical neuro-oncology practice. In essence, this concept proposes that tumors that are currently lumped together based on common morphologic features can be subclassified in a way that the resulting subentities are more homogeneous, for example, in molecular signatures and will therefore be amenable to selective therapeutic interventions. At present, the major "biomarkers" used to allocate treatment in glioblastoma are age and Karnofsky Performance Scale score, and these markers have so far survived all efforts at more sophisticated approaches to the management of this disease. Treatment allocation basically means intensity of treatment, especially the use of the standard-of-care or radiotherapy alone beyond age 65 to 70 years or below a Karnofsky Performance Scale score of 60.
本文综述了胶质母细胞瘤个体化治疗的现状。胶质母细胞瘤是一种高度恶性的原发性脑肿瘤，可能起源于神经胶质前体细胞。中位生存期不足 1 年。
回顾了胶质母细胞瘤的形态学、临床和分子分类的最新进展，并分析了它们对临床决策的影响。
胶质母细胞瘤可通过形态学、临床特征、复杂的分子特征、单一生物标志物或影像学参数进行分类。其中一些特征，包括年龄和卡诺夫斯基表现状态评分，提供了重要的预后信息。相比之下，很少有标志物有助于在各种治疗方案之间做出选择。O-甲基鸟嘌呤甲基转移酶基因启动子甲基化似乎预测烷基化剂化疗获益，因此，它被用作无烷基化剂实验联合放化疗的入组标准。目前正在探索表皮生长因子受体特定突变的筛查，作为选择患者进行疫苗接种的生物标志物。正电子发射断层扫描用于检测 ανβ3/5 整联蛋白，可用于选择接受抗整联蛋白抗血管生成治疗的患者。
尽管在定义生物学标志物作为选择治疗方法的基础方面进行了广泛的努力，但胶质母细胞瘤患者的大多数治疗决策仍基于年龄和表现状态。然而，目前正在进行的几项临床试验可能会在不久的将来丰富临床决策的标准。个体化或个性化靶向癌症治疗的概念在肿瘤学领域引起了广泛关注。然而，支持这种胶质母细胞瘤（最恶性的神经胶质瘤亚型）治疗方法的数据有限，个性化医学在当前的临床神经肿瘤学实践中作用有限。从本质上讲，这个概念提出，目前基于常见形态特征进行分组的肿瘤可以通过一种方式进行分类，使由此产生的亚实体更加同质，例如在分子特征上，并且因此可以接受选择性治疗干预。目前，用于胶质母细胞瘤治疗分配的主要“生物标志物”是年龄和卡诺夫斯基表现状态评分，到目前为止，这些标志物经受住了所有试图对这种疾病进行更复杂管理的方法的考验。治疗分配基本上意味着治疗强度，特别是在 65 至 70 岁以上或卡诺夫斯基表现状态评分低于 60 时，使用标准护理或放疗以外的治疗。
