Wick Wolfgang, Hartmann Christian, Engel Corinna, Stoffels Mandy, Felsberg Jörg, Stockhammer Florian, Sabel Michael C, Koeppen Susanne, Ketter Ralf, Meyermann Richard, Rapp Marion, Meisner Christof, Kortmann Rolf D, Pietsch Torsten, Wiestler Otmar D, Ernemann Ulrike, Bamberg Michael, Reifenberger Guido, von Deimling Andreas, Weller Michael
Department of Neurology and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
J Clin Oncol. 2009 Dec 10;27(35):5874-80. doi: 10.1200/JCO.2009.23.6497. Epub 2009 Nov 9.
The standard of care for anaplastic gliomas is surgery followed by radiotherapy. The NOA-04 phase III trial compared efficacy and safety of radiotherapy followed by chemotherapy at progression with the reverse sequence in patients with newly diagnosed anaplastic gliomas.
Patients (N = 318) were randomly assigned 2:1:1 (A:B1:B2) to receive conventional radiotherapy (arm A); procarbazine, lomustine (CCNU), and vincristine (PCV; arm B1); or temozolomide (arm B2) at diagnosis. At occurrence of unacceptable toxicity or disease progression, patients in arm A were treated with PCV or temozolomide (1:1 random assignment), whereas patients in arms B1 or B2 received radiotherapy. The primary end point was time to treatment failure (TTF), defined as progression after radiotherapy and one chemotherapy in either sequence.
Patient characteristics in the intention-to-treat population (n = 274) were balanced between arms. All histologic diagnoses were centrally confirmed. Median TTF (hazard ratio [HR] = 1.2; 95% CI, 0.8 to 1.8), progression-free survival (PFS; HR = 1.0; 95% CI, 0.7 to 1.3, and overall survival (HR = 1.2; 95% CI, 0.8 to 1.9) were similar for arms A and B1/B2. Extent of resection was an important prognosticator. Anaplastic oligodendrogliomas and oligoastrocytomas share the same, better prognosis than anaplastic astrocytomas. Hypermethylation of the O(6)-methylguanine DNA-methyltransferase (MGMT) promoter (HR = 0.59; 95% CI, 0.36 to 1.0), mutations of the isocitrate dehydrogenase (IDH1) gene (HR = 0.48; 95% CI, 0.29 to 0.77), and oligodendroglial histology (HR = 0.33; 95% CI, 0.2 to 0.55) reduced the risk of progression. Hypermethylation of the MGMT promoter was associated with prolonged PFS in the chemotherapy and radiotherapy arm.
Initial radiotherapy or chemotherapy achieved comparable results in patients with anaplastic gliomas. IDH1 mutations are a novel positive prognostic factor in anaplastic gliomas, with a favorable impact stronger than that of 1p/19q codeletion or MGMT promoter methylation.
间变性胶质瘤的标准治疗方案是手术，随后进行放疗。NOA - 04 III期试验比较了新诊断的间变性胶质瘤患者中，放疗后进展时进行化疗与化疗后进展时进行放疗的疗效和安全性。
患者（N = 318）按2:1:1（A:B1:B2）随机分组，在诊断时分别接受常规放疗（A组）；丙卡巴肼、洛莫司汀（CCNU）和长春新碱（PCV；B1组）；或替莫唑胺（B2组）。出现不可接受的毒性或疾病进展时，A组患者接受PCV或替莫唑胺治疗（1:1随机分配），而B1组或B2组患者接受放疗。主要终点是治疗失败时间（TTF），定义为放疗后及两种化疗顺序中任一种化疗后的进展。
意向性治疗人群（n = 274）中各治疗组的患者特征均衡。所有组织学诊断均经中心确认。A组与B1/B2组的中位TTF（风险比[HR] = 1.2；95%置信区间，0.8至1.8）、无进展生存期（PFS；HR = 1.0；95%置信区间，0.7至1.3）和总生存期（HR = 1.2；95%置信区间，0.8至1.9）相似。切除范围是一个重要的预后因素。间变性少突胶质细胞瘤和少突星形细胞瘤的预后相同，优于间变性星形细胞瘤。O(6)-甲基鸟嘌呤DNA甲基转移酶（MGMT）启动子的高甲基化（HR = 0.59；95%置信区间，0.36至1.0）、异柠檬酸脱氢酶（IDH1）基因突变（HR = 0.48；95%置信区间，0.29至0.77）和少突胶质细胞组织学（HR = 0.33；95%置信区间，0.2至0.55）降低了进展风险。MGMT启动子的高甲基化与化疗和放疗组中PFS的延长相关。
间变性胶质瘤患者初始放疗或化疗取得了可比的结果。IDH1基因突变是间变性胶质瘤中一种新的阳性预后因素，其有利影响强于1p/19q共缺失或MGMT启动子甲基化。
