Division of Neurosurgery, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
Department of Radiation Oncology, Sunnybrook Hospital, University of Toronto, Toronto, Ontario, Canada.
JAMA Neurol. 2015 May;72(5):589-96. doi: 10.1001/jamaneurol.2014.3739.
Despite improvements in survival with aggressive chemoradiation, outcomes for patients diagnosed as having glioblastoma multiforme (GBM) remain poor. Survival is further limited in elderly patients, who are often unable to tolerate multimodality therapy. The appropriate treatment approach for elderly patients (aged >65 years) with GBM remains unclear. While the literature supports the use of standard radiotherapy (60 Gy), several recent studies have suggested that treatment with temozolomide monotherapy or short-course radiotherapy may be a reasonable alternative.
To review literature reporting survival data related to treatment of elderly patients with GBM using either temozolomide alone or radiotherapy alone.
We performed a systematic review to identify articles from the temozolomide era (2005-present) that reported survival data related to treatment of elderly patients with GBM using either temozolomide alone or radiotherapy alone, with consideration of O6-methylguanine-DNA-methyltransferase gene (MGMT) promoter methylation status. PubMed was searched for articles between January 1, 2005, and August 31, 2013, using the search terms glioblastoma, elderly, temozolomide, radiation, hypofractionated, and survival, and references from relevant articles were searched. Selected articles reported overall survival data associated with either temozolomide alone or radiotherapy alone in elderly patients (aged ≥60 years) with GBM; articles were excluded if they did not report survival data from radiotherapy alone or temozolomide alone, were not restricted to an elderly population, did not report original data, were not restricted to patients with primary GBM, were a subgroup analysis of a prior article, were a case report, or could not be located in entirety. Articles were interrogated as per the criteria designated by the Oxford Centre for Evidence-Based Medicine to determine the level of evidence presented, and data from level 1 and 2 studies were used for analysis. From a review of 185 articles, 23 were selected for inclusion and final analysis. From these, we identified 2 level 1 studies and 1 level 2 study that reported overall survival in elderly patients treated with temozolomide alone, and 4 level 1 studies and 2 level 2 studies that reported overall survival in elderly patients treated with radiotherapy alone.
This review of the literature revealed several limitations. First, there is a paucity of randomized clinical studies comparing temozolomide alone with radiotherapy alone in elderly patients with GBM. Second, there is a lack of coherence in the literature for the definition of elderly. Third, the treatment paradigms used are not consistent from study to study. Regardless, the available data did allow the formulation of a recommendation based on level 1 and 2 data.
The literature supports the use of hypofractionated radiotherapy or temozolomide monotherapy in the treatment of elderly patients with GBM. In patients with MGMT promoter methylation, temozolomide monotherapy may have greater benefit than radiotherapy.
尽管采用积极的放化疗后患者的生存率有所提高，但胶质母细胞瘤（GBM）患者的预后仍然较差。老年患者的生存时间进一步受限，他们通常无法耐受多模式治疗。对于年龄大于 65 岁的老年 GBM 患者，合适的治疗方法仍不明确。尽管文献支持使用标准放疗（60Gy），但最近的几项研究表明，替莫唑胺单药治疗或短程放疗可能是一种合理的替代方法。
回顾文献中关于替莫唑胺单药或放疗治疗老年 GBM 患者的生存数据。
我们进行了一项系统综述，以确定从替莫唑胺时代（2005 年至今）开始的文章，这些文章报告了关于替莫唑胺单药或放疗治疗老年 GBM 患者的生存数据，并考虑了 O6-甲基鸟嘌呤-DNA-甲基转移酶基因（MGMT）启动子甲基化状态。我们使用搜索词“glioblastoma”、“elderly”、“temozolomide”、“radiation”、“hypofractionated”和“survival”，在 PubMed 上搜索了 2005 年 1 月 1 日至 2013 年 8 月 31 日之间的文章，并检索了相关文章的参考文献。选择的文章报告了替莫唑胺单药或放疗治疗老年 GBM 患者（年龄≥60 岁）的总生存数据；如果文章未报告放疗或替莫唑胺单药治疗的生存数据、不局限于老年人群、未报告原始数据、不局限于原发性 GBM 患者、不是先前文章的亚组分析、是病例报告或无法完整获取，则将文章排除在外。根据牛津循证医学中心指定的标准，对文章进行了审查，以确定所呈现的证据水平，并对 1 级和 2 级研究的数据进行了分析。从对 185 篇文章的审查中，选择了 23 篇进行纳入和最终分析。从中，我们确定了 2 项 1 级研究和 1 项 2 级研究，报告了替莫唑胺单药治疗老年患者的总生存率，以及 4 项 1 级研究和 2 项 2 级研究，报告了放疗治疗老年患者的总生存率。
对文献的回顾发现了一些局限性。首先，缺乏比较替莫唑胺单药与放疗治疗老年 GBM 患者的随机临床试验。其次，文献中对于老年的定义缺乏一致性。第三，研究之间的治疗方案不一致。尽管如此，可用的数据确实允许根据 1 级和 2 级数据制定建议。
文献支持使用分割放疗或替莫唑胺单药治疗老年 GBM 患者。在 MGMT 启动子甲基化的患者中，替莫唑胺单药治疗可能比放疗更有优势。
