Jungk Christine, Reinhardt Annekathrin, Warta Rolf, Capper David, Deimling Andreas von, Herold-Mende Christel, Unterberg Andreas
Division of Experimental Neurosurgery, Department of Neurosurgery, University Hospital Heidelberg, D-69120 Heidelberg, Germany.
Department of Neuropathology, German Cancer Consortium (DKTK), CCU Neuropathology, German Cancer Research Center, Institute of Pathology, University of Heidelberg, D-69120 Heidelberg, Germany.
Cancers (Basel). 2019 Jul 29;11(8):1072. doi: 10.3390/cancers11081072.
In adults, pilocytic astrocytomas (PA) account for less than 2% of gliomas, resulting in uncertainty regarding the clinical course and optimal treatment, particularly in cases where gross total resection (GTR) could not be achieved. Moreover, information on molecular markers and their prognostic impact is sparse. In order to improve risk stratification, we analyzed our institutional series of 58 patients aged 17 years and older with histology-proven intracranial PA World Health Organization grade I for clinical and molecular prognosticators. Anaplastic and NF1-associated tumors were excluded. O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was determined by pyrosequencing or 450k/850k DNA methylation array. A univariate log-rank test and multivariate StepAIC were applied to identify prognostic factors. The median age was 30 years (range 17-66). Tumors were located in the cerebral/cerebellar hemispheres, midline structures and cerebello-pontine angle in 53%, 38% and 9%. MGMT promoter methylation was present in eight patients (14%). GTR (39/58 patients) significantly reduced the likelihood of tumor recurrence ( = 0.0001). Tumor relapse occurred in 16 patients (28%) after a median progression-free survival (PFS) of 135 months (range 6-153 months); there was one tumor-related death. PFS at 5 and 10 years was 67% and 53%. In multivariate analysis, PFS was significantly prolonged in patients with GTR (HR 0.1; CI 0.03-0.37; < 0.001), unmethylated MGMT promoter (HR 0.18; CI 0.05-0.64; = 0.009) and midline tumors (HR 0.21; CI 0.06-0.78; = 0.02). In conclusion, MGMT promoter methylation status and tumor location were identified as novel prognostic factors in adult PAs, pointing at distinct molecular subtypes and detecting patients in need of close observance and intensified treatment.
在成人中，毛细胞型星形细胞瘤（PA）占胶质瘤的比例不到2%，这导致临床病程和最佳治疗方案存在不确定性，尤其是在无法实现全切除（GTR）的情况下。此外，关于分子标志物及其预后影响的信息很少。为了改善风险分层，我们分析了我院58例17岁及以上经组织学证实为世界卫生组织I级颅内PA患者的临床和分子预后因素。排除间变性和NF1相关肿瘤。通过焦磷酸测序或450k/850k DNA甲基化阵列测定O-6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）启动子甲基化状态。应用单因素对数秩检验和多因素StepAIC来确定预后因素。中位年龄为30岁（范围17 - 66岁）。肿瘤位于大脑/小脑半球、中线结构和桥小脑角的分别占53%、38%和9%。8例患者（14%）存在MGMT启动子甲基化。GTR（39/58例患者）显著降低了肿瘤复发的可能性（P = 0.0001）。16例患者（28%）出现肿瘤复发，中位无进展生存期（PFS）为135个月（范围6 - 153个月）；有1例与肿瘤相关的死亡。5年和10年的PFS分别为67%和53%。多因素分析显示，GTR患者（HR 0.1；CI 0.03 - 0.37；P < 0.001）、MGMT启动子未甲基化患者（HR 0.18；CI 0.05 - 0.64；P = 0.009）和中线肿瘤患者（HR 0.21；CI 0.06 - 0.78；P = 0.02）的PFS显著延长。总之，MGMT启动子甲基化状态和肿瘤位置被确定为成人PA的新预后因素，这表明存在不同的分子亚型，并有助于识别需要密切观察和强化治疗的患者。
