Yale School of Public Health, Yale School of Medicine, P.O. Box 208034, New Haven, CT 06520-8034, USA.
Cancer. 2012 Apr 15;118(8):2163-72. doi: 10.1002/cncr.26494. Epub 2011 Aug 31.
Survival after a glioblastoma multiforme (GBM) diagnosis remained static during the several decades before 1999. We hypothesized that the progressive increase in temozolomide use for GBM treatment that began in 1999 in the United States would be paralleled by a corresponding improvement in survival.
We included 19,674 GBM cases, ages 20 years or greater, diagnosed 1993 to 2007 in the population-based Surveillance, Epidemiology, and End Results Program database. We used proportional hazards models to calculate calendar period hazard ratios (HR) and 95% confidence intervals (CI), adjusted for demographic covariates. We compared survival across periods using the Kaplan-Meier method.
Starting with cases diagnosed in 1999 to 2001, we observed a progressive decrease in HRs compared with cases diagnosed in 1993 to 1995. The multivariate-adjusted HR for 2005 to 2007 versus 1993 to 1995 was 0.69 (95% CI, 0.65-0.72). Age-stratified analyses revealed that this progressive decrease occurred in all age groups except 80+ years. Two-year survival increased from 7% among cases diagnosed in 1993 to 1995 and 1996 to 1998 to 9% among cases diagnosed in 1999 to 2001, 13% in 2002 to 2004, and 17% in 2005 to 2007. The disparity in survival between young and old patients increased in the temozolomide era, with 2-year survival of 39% among cases diagnosed at ages 20 to 44 years and 1% among cases diagnosed at 80+ years in 2005 to 2007.
We observed a modest, but meaningful, population-based survival improvement for GBM patients in the United States. Widespread adoption of temozolomide represents the most likely explanation, although other treatment advances, such as increased extent of surgical resection, also may have played a role.
在 1999 年之前的几十年中,胶质母细胞瘤(GBM)患者的存活率一直保持稳定。我们假设,1999 年在美国开始逐步增加替莫唑胺用于 GBM 治疗,这将与生存状况的相应改善相平行。
我们纳入了 1993 年至 2007 年期间在基于人群的监测、流行病学和最终结果(SEER)数据库中诊断为 20 岁或以上的 19674 例 GBM 病例。我们使用比例风险模型计算日历期风险比(HR)和 95%置信区间(CI),并调整了人口统计学协变量。我们使用 Kaplan-Meier 方法比较了各时期的生存情况。
从 1999 年至 2001 年诊断的病例开始,我们观察到与 1993 年至 1995 年诊断的病例相比,HR 逐渐降低。2005 年至 2007 年与 1993 年至 1995 年相比,多变量调整后的 HR 为 0.69(95%CI,0.65-0.72)。年龄分层分析显示,这种逐渐下降发生在所有年龄组,80 岁以上年龄组除外。2 年生存率从 1993 年至 1995 年和 1996 年至 1998 年诊断的病例中的 7%增加到 1999 年至 2001 年诊断的病例中的 9%,2002 年至 2004 年增加到 13%,2005 年至 2007 年增加到 17%。在替莫唑胺时代,年轻患者和老年患者之间的生存差距增大,2005 年至 2007 年,20 至 44 岁诊断的病例中 2 年生存率为 39%,80 岁以上诊断的病例中 2 年生存率为 1%。
我们观察到美国 GBM 患者的生存状况有适度但有意义的改善。替莫唑胺的广泛应用是最有可能的解释,尽管其他治疗进展,如手术切除范围的扩大,也可能发挥了作用。