Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Department of Neurology, University of Michigan, Ann Arbor, MI, USA.
J Neurooncol. 2019 Jun;143(2):313-319. doi: 10.1007/s11060-019-03166-3. Epub 2019 Apr 11.
We evaluated whether dose-intensified chemoradiation alters patterns of failure and is associated with favorable survival in the temozolomide era.
Between 2003 and 2015, 82 patients with newly diagnosed glioblastoma were treated with 66-81 Gy in 30 fractions using conventional magnetic resonance imaging. Progression-free (PFS) and overall survival (OS) were calculated using Kaplan-Meier methods. Factors associated with improved PFS, OS, and time to progression were assessed using multivariate Cox model and linear regression.
Median follow-up was 23 months (95% CI 4-124 months). Sixty-one percent of patients underwent subtotal resection or biopsy, and 38% (10/26) of patients with available data had MGMT promoter methylation. Median PFS was 8.4 months (95% CI 7.3-11.0) and OS was 18.7 months (95% CI 13.1-25.3). Only 30 patients (44%) experienced central recurrence, 6 (9%) in-field, 16 (23.5%) marginal and 16 (23.5%) distant. On multivariate analysis, younger age (HR 0.95, 95% CI 0.93-0.97, p = 0.0001), higher performance status (HR 0.39, 95% CI 0.16-0.95, p = 0.04), gross total resection (GTR) versus biopsy (HR 0.37, 95% CI 0.16-0.85, p = 0.02) and MGMT methylation (HR 0.25, 95% CI 0.09-0.71, p = 0.009) were associated with improved OS. Only distant versus central recurrence (p = 0.03) and GTR (p = 0.02) were associated with longer time to progression. Late grade 3 neurologic toxicity was rare (6%) in patients experiencing long-term survival.
Dose-escalated chemoRT resulted in lower rates of central recurrence and prolonged time to progression compared to historical controls, although a significant number of central recurrences were still observed. Advanced imaging and correlative molecular studies may enable targeted treatment advances that reduce rates of in- and out-of-field progression.
我们评估了在替莫唑胺时代，剂量强化放化疗是否会改变失败模式并与更好的生存相关。
2003 年至 2015 年间，82 例新诊断的胶质母细胞瘤患者接受了 66-81Gy/30 次的常规磁共振成像治疗。使用 Kaplan-Meier 方法计算无进展生存期（PFS）和总生存期（OS）。使用多变量 Cox 模型和线性回归评估与改善 PFS、OS 和进展时间相关的因素。
中位随访时间为 23 个月（95%CI 4-124 个月）。61%的患者行次全切除或活检，38%（10/26）有 MGMT 启动子甲基化的患者可提供数据。中位 PFS 为 8.4 个月（95%CI 7.3-11.0），OS 为 18.7 个月（95%CI 13.1-25.3）。仅有 30 例（44%）患者出现中央复发，6 例（9%）为场内复发，16 例（23.5%）为边缘复发，16 例（23.5%）为远处复发。多变量分析显示，年龄较小（HR 0.95，95%CI 0.93-0.97，p=0.0001）、功能状态较好（HR 0.39，95%CI 0.16-0.95，p=0.04）、大体全切除（GTR）而非活检（HR 0.37，95%CI 0.16-0.85，p=0.02）和 MGMT 甲基化（HR 0.25，95%CI 0.09-0.71，p=0.009）与 OS 改善相关。只有远处复发与中央复发（p=0.03）和 GTR（p=0.02）与进展时间延长相关。在长期生存的患者中，迟发性 3 级神经毒性罕见（6%）。
与历史对照相比，剂量递增放化疗导致中央复发率降低和进展时间延长，但仍有大量中央复发。先进的影像学和相关的分子研究可能会实现靶向治疗的进步，从而降低场内和场外进展的发生率。
