The role of temozolomide in the management of patients with newly diagnosed anaplastic astrocytoma: a comparison of survival in the era prior to and following the availability of temozolomide.
The role of temozolomide in the management of patients with newly diagnosed anaplastic astrocytoma: a comparison of survival in the era prior to and following the availability of temozolomide.
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DOI：
10.1007/s11060-015-2028-2
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发表时间：
2016-03
影响因子：
3.9
通讯作者：
Grossman SA
中科院分区：
文献类型：
--
作者：
Strowd RE;Abuali I;Ye X;Lu Y;Grossman SA
尽管缺乏前瞻性研究证明替莫唑胺（TMZ）对新诊断间变性星形细胞瘤（AAs）患者的生存优势，但在放疗中添加替莫唑胺（TMZ）是常见的临床实践。两项回顾性研究都有方法学上的局限性，提供了相互矛盾的治疗建议。本单机构回顾性研究旨在确定AA患者的生存趋势。纳入1995年至2012年在约翰霍普金斯大学治疗的所有≥18岁的新诊断AA患者。我们在2004年将TMZ纳入高级别胶质瘤治疗方案，将患者分为2004年前和2004年后两组进行分析。收集临床、影像学和病理资料。中位总生存期（OS）采用Kaplan-Meier估计法计算。共发现196例患者；2004年前74人，2004年后122人；平均年龄47±15岁；57%为男性；87%为白色，69%为手术切除。平均放疗剂量5676 + 746 cGy；同步放化疗时间5.8±0.8周；平均辅助化疗4.3 + 2.8周期。各组间基线预后因素无差异。2004年前化疗患者占12% (TMZ = 1，丙卡嗪、洛莫司汀和长春新碱= 2，卡莫司汀= 6)，2004年后化疗患者占94% （TMZ合计p < 0.001）。中位OS为32个月（95% CI 23-43）。2004年后队列的生存期（37个月，24-64）比2004年前（27个月，19-40;HR 0.75, 0.53-1.06, p = 0.11）更长。控制年龄、Karnofsky表现状态和切除程度的多变量分析显示，2004年后接受治疗的患者死亡风险降低36% （HR 0.64, 0.44-0.91, p = 0.015）。本回顾性研究发现，在标准放疗中加入替莫唑胺可改善新诊断AA患者的生存率。在获得前瞻性随机III期数据之前，这些数据支持将TMZ纳入新诊断AA的治疗实践。
Adding temozolomide (TMZ) to radiation for patients with newly-diagnosed anaplastic astrocytomas (AAs) is common clinical practice despite the lack of prospective studies demonstrating a survival advantage. Two retrospective studies, each with methodologic limitations, provide conflicting advice regarding treatment. This single-institution retrospective study was conducted to determine survival trends in patients with AA. All patients ≥18 years with newly-diagnosed AA treated at Johns Hopkins from 1995 to 2012 were included. As we incorporated TMZ into high-grade glioma treatment regimens in 2004, patients were divided into pre-2004 and post-2004 groups for analysis. Clinical, radiographic, and pathologic data were collected. Median overall survival (OS) was calculated using Kaplan–Meier estimates. A total of 196 patients were identified; 74 pre-2004 and 122 post-2004; mean age 47 ± 15 years; 57 % male; 87 % white, 69 % surgical debulking. Mean RT dose 5676 + 746 cGy; duration of concurrent chemoradiation 5.8 ± 0.8 weeks; and mean adjuvant chemotherapy 4.3 + 2.8 cycles. Baseline prognostic factors did not differ between groups. Chemotherapy was administered to 12 % of patients pre-2004 (TMZ = 1, procarbazine, lomustine and vincristine = 2, carmustine wafer = 6) and 94 % post-2004 (TMZ in all, p < 0.001). Median OS was 32 months (95 % CI 23–43). Survival was longer in the post-2004 cohort (37 mo, 24–64) than pre-2004 (27 mo, 19–40; HR 0.75, 0.53–1.06, p = 0.11). Multivariate analysis controlling for age, Karnofsky performance status, and extent of resection revealed a 36 % reduced risk of death (HR 0.64, 0.44–0.91, p = 0.015) in patients treated post-2004. This retrospective review found survival in newly diagnosed patients with AA improved with the addition of temozolomide to standard radiation. Until prospective randomized phase III data are available, these data support the practice of incorporating TMZ in the management of newly-diagnosed AA.