Lamborn Kathleen R, Chang Susan M, Prados Michael D
Department of Neurological Surgery, University of California San Francisco, San Francisco, CA 94143-0112, USA.
Neuro Oncol. 2004 Jul;6(3):227-35. doi: 10.1215/S1152851703000620.
Survival for patients with glioblastoma multiforme is short, and current treatments provide limited benefit. Therefore, there is interest in conducting phase 2 trials of experimental treatments in newly diagnosed patients. However, this requires historical data with which to compare the experimental therapies. Knowledge of prognostic markers would also allow stratification into risk groups for phase 3 randomized trials. In this retrospective study of 832 glioblastoma multiforme patients enrolled into prospective clinical trials at the time of initial diagnosis, we evaluated several potential prognostic markers for survival to establish risk groups. Analyses were done using both Cox proportional hazards modeling and recursive partitioning analyses. Initially, patients from 8 clinical trials, 6 of which included adjuvant chemotherapy, were included. Subsequent analyses excluded trials with interstitial brachytherapy, and finally included only nonbrachytherapy trials with planned adjuvant chemotherapy. The initial analysis defined 4 risk groups. The 2 lower risk groups included patients under the age of 40, the lowest risk group being young patients with tumor in the frontal lobe only. An intermediate-risk group included patients with Karnofsky performance status (KPS) >70, subtotal or total resection, and age between 40 and 65. The highest risk group included all patients over 65 and patients between 40 and 65 with either KPS<80 or biopsy only. Subgroup analyses indicated that inclusion of adjuvant chemotherapy provides an increase in survival, although that improvement tends to be minimal for patients over age 65, for patients over age 40 with KPS less than 80, and for those treated with brachytherapy.
多形性胶质母细胞瘤患者的生存期较短,目前的治疗方法效果有限。因此,人们对在新诊断患者中开展实验性治疗的2期试验很感兴趣。然而,这需要历史数据来比较实验性疗法。了解预后标志物还能在3期随机试验中进行风险分层。在这项对832例多形性胶质母细胞瘤患者的回顾性研究中,这些患者在初次诊断时被纳入前瞻性临床试验,我们评估了几种潜在的生存预后标志物以建立风险组。分析采用Cox比例风险模型和递归划分分析进行。最初,纳入了来自8项临床试验的患者,其中6项包括辅助化疗。随后的分析排除了采用间质近距离放疗的试验,最终仅纳入了计划进行辅助化疗的非近距离放疗试验。初始分析确定了4个风险组。两个低风险组包括40岁以下的患者,风险最低的组是仅额叶有肿瘤的年轻患者。中风险组包括卡诺夫斯基功能状态(KPS)>70、次全切除或全切除且年龄在40至65岁之间的患者。风险最高的组包括所有65岁以上的患者以及40至65岁之间KPS<80或仅接受活检的患者。亚组分析表明,采用辅助化疗可提高生存率,尽管对于65岁以上的患者、40岁以上KPS小于80的患者以及接受近距离放疗的患者,这种改善往往很小。