Prognosis of patients with multifocal glioblastoma: a case-control study Clinical article
Prognosis of patients with multifocal glioblastoma: a case-control study Clinical article
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DOI：
10.3171/2012.7.jns12147
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发表时间：
2012-10-01
影响因子：
4.1
通讯作者：
Nuno, Miriam
中科院分区：
文献类型：
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作者：
Patil, Chirag G.;Yi, Anthony;Nuno, Miriam
Object.胶质母细胞瘤多灶性病变患者的预后没有很好的记录。本研究的目的是确定多灶性疾病的初始表现是否与较差的生存率。作者回顾性分析了368例新诊断的胶质母细胞瘤患者的记录，并确定了47例多灶性肿瘤患者。然后，使用倾向评分匹配方法，根据年龄、Karnofsky表现量表（KPS）评分和切除程度，将每例多灶性肿瘤患者与1例孤立性胶质母细胞瘤患者进行匹配。放疗和替莫唑胺治疗在2个队列之间也匹配良好。使用Kaplan-Meier估计和对数秩检验来比较患者生存率。结果。多灶性肿瘤的发生率为12.8%（47/368）。多灶性肿瘤患者的中位年龄为61岁，76.6%的KPS评分≥ 70，87.2%的患者接受了活检或肿瘤部分切除。与47例单发胶质母细胞瘤患者相比，47例多灶性肿瘤患者在年龄（p = 0.97）、切除范围（p = 1.0）和KPS评分（p = 0.80）方面几乎完全匹配。年龄（> 65岁）、部分切除或活检、低KPS评分（< 70）与多病灶组中位生存率较差相关。在多病灶组中，19名患者在放射治疗后MRI上出现肿瘤进展，而单病灶组中有11名患者（26.8%）出现肿瘤进展（p = 0.08）。与匹配的孤立性胶质母细胞瘤组的11个月中位生存期（95%CI 10-19个月）相比，多灶性肿瘤患者的6个月中位总生存期（95%CI 4-10个月）显著缩短（p = 0.02，对数秩检验）。多灶性肿瘤患者的2年生存率为4.3%，单灶性队列为29.0%。与孤立性胶质母细胞瘤患者相比，新诊断的多灶性肿瘤患者的死亡风险增加近2倍（风险比1.8，95% CI 1.1-3.1; p = 0.02）。分析肿瘤样本中磷酸化丝裂原活化蛋白激酶、磷酸酶和张力蛋白同源物、O-6-甲基鸟嘌呤-DNA甲基转移酶、层粘连蛋白（31和132）以及表皮生长因子受体扩增的表达，发现多灶性和孤立性胶质母细胞瘤组之间的表达谱无显著差异。新诊断的多灶性胶质母细胞瘤患者的生存率明显低于孤立性胶质母细胞瘤患者。多灶性肿瘤患者在替莫唑胺时代继续构成治疗挑战，并放大了治疗恶性胶质瘤患者时所面临的挑战。(http：//thejns.org/doi/abs/10.3171/2012.7.JNS12147）
Object. The prognosis of patients with glioblastoma who present with multifocal disease is not well documented. The objective of this study was to determine whether multifocal disease on initial presentation is associated with worse survival.Methods. The authors retrospectively reviewed records of 368 patients with newly diagnosed glioblastoma and identified 47 patients with multifocal tumors. Each patient with a multifocal tumor was then matched with a patient with a solitary glioblastoma on the basis of age, Karnofsky Performance Scale (KPS) score, and extent of resection, using a propensity score matching methodology. Radiation and temozolomide treatments were also well matched between the 2 cohorts. Kaplan-Meier estimates and log-rank tests were used to compare patient survival.Results. The incidence of multifocal tumors was 12.8% (47/368). The median age of patients with multifocal tumors was 61 years, 76.6% had KPS scores >= 70, and 87.2% underwent either a biopsy or partial resection of their tumors. The 47 patients with multifocal tumors were almost perfectly matched on the basis of age (p = 0.97), extent of resection (p = 1.0), and KPS score (p = 0.80) compared with 47 patients with a solitary glioblastoma. Age (> 65 years), partial resection or biopsy, and low KPS score (< 70) were associated with worse median survival within the multifocal group. In the multifocal group, 19 patients experienced tumor progression on postradiation therapy MRI, compared with 11 patients (26.8%) with tumor progression in the unifocal group (p = 0.08). Patients with multifocal tumors experienced a significantly shorter median overall survival of 6 months (95% CI 4-10 months), compared with the 11-month median survival (95% Cl 10-19 months) of the matched solitary glioblastoma group (p = 0.02, log-rank test). Two-year survival rates were 4.3% for patients with multifocal tumors and 29.0% for the unifocal cohort. Patients with newly diagnosed multifocal tumors were found to have an almost 2-fold increase in the hazard of death compared with patients with solitary glioblastoma (hazard ratio 1.8, 95% Cl 1.1-3.1; p = 0.02). Tumor samples were analyzed for expression of phosphorylated mitogen-activated protein kinase, phosphatase and tensin homolog, O-6-methylguanine-DNA methyltransferase, laminin (31 and 132, as well as epidermal growth factor receptor amplification, and no significant differences in expression profile between the multifocal and solitary glioblastoma groups was found.Conclusions. Patients with newly diagnosed multifocal glioblastoma on presentation experience significantly worse survival than patients with solitary glioblastoma. Patients with multifocal tumors continue to pose a therapeutic challenge in the temozolomide era and magnify the challenges faced while treating patients with malignant gliomas. (http://thejns.org/doi/abs/10.3171/2012.7.JNS12147)