O-6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)启动子甲基化状态可预测新诊断的胶质母细胞瘤患者同步放化疗后假性进展的发生率及预后。
MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients.
作者信息
Brandes Alba A, Franceschi Enrico, Tosoni Alicia, Blatt Valeria, Pession Annalisa, Tallini Giovanni, Bertorelle Roberta, Bartolini Stefania, Calbucci Fabio, Andreoli Alvaro, Frezza Giampiero, Leonardi Marco, Spagnolli Federica, Ermani Mario
机构信息
Department of Medical Oncology, Bellaria-Maggiore Hospital, Azienda Unità Sanitaria Locale of Bologna, Bologna, Italy.
出版信息
J Clin Oncol. 2008 May 1;26(13):2192-7. doi: 10.1200/JCO.2007.14.8163.
PURPOSE
Standard therapy for glioblastoma (GBM) is temozolomide (TMZ) administration, initially concurrent with radiotherapy (RT), and subsequently as maintenance therapy. The radiologic images obtained in this setting can be difficult to interpret since they may show radiation-induced pseudoprogression (psPD) rather than disease progression.
METHODS
Patients with histologically confirmed GBM underwent radiotherapy plus continuous daily temozolomide (75 mg/m(2)/d), followed by 12 maintenance temozolomide cycles (150 to 200 mg/m(2) for 5 days every 28 days) if magnetic resonance imaging (MRI) showed no enhancement suggesting a tumor; otherwise, chemotherapy was delivered until complete response or unequivocal progression. The first MRI scan was performed 1 month after completing combined chemoradiotherapy.
RESULTS
In 103 patients (mean age, 52 years [range 20 to 73 years]), total resection, subtotal resection, and biopsy were obtained in 51, 51, and 1 cases, respectively. MGMT promoter was methylated in 36 patients (35%) and unmethylated in 67 patients (65%). Lesion enlargement, evidenced at the first MRI scan in 50 of 103 patients, was subsequently classified as psPD in 32 patients and early disease progression in 18 patients. PsPD was recorded in 21 (91%) of 23 methylated MGMT promoter and 11 (41%) of 27 unmethylated MGMT promoter (P = .0002) patients. MGMT status (P = .001) and psPD detection (P = .045) significantly influenced survival.
CONCLUSION
PsPD has a clinical impact on chemotherapy-treated GBM, as it may express the glioma killing effects of treatment and is significantly correlated with MGMT status. Improvement in the early recognition of psPD patterns and knowledge of mechanisms underlying this phenomenon are crucial to eliminating biases in evaluating the results of clinical trials and guaranteeing effective treatment.
目的
胶质母细胞瘤(GBM)的标准治疗方法是给予替莫唑胺(TMZ),最初与放疗(RT)同步进行,随后作为维持治疗。在此情况下获得的放射影像可能难以解读,因为它们可能显示为放射性假性进展(psPD)而非疾病进展。
方法
组织学确诊为GBM的患者接受放疗加每日持续给予替莫唑胺(75mg/m²/d),如果磁共振成像(MRI)显示无提示肿瘤的强化,则随后进行12个周期的替莫唑胺维持治疗(每28天150至200mg/m²,共5天);否则,进行化疗直至完全缓解或明确进展。在完成联合放化疗后1个月进行首次MRI扫描。
结果
103例患者(平均年龄52岁[范围20至73岁])中,分别有51例、51例和1例实现了全切除、次全切除和活检。36例患者(35%)的MGMT启动子甲基化,67例患者(65%)未甲基化。103例患者中有50例在首次MRI扫描时出现病灶增大,随后32例被归类为psPD,18例为早期疾病进展。MGMT启动子甲基化的23例患者中有21例(91%)记录有psPD,MGMT启动子未甲基化的27例患者中有11例(41%)记录有psPD(P = 0.0002)。MGMT状态(P = 0.001)和psPD检测(P = 0.045)对生存有显著影响。
结论
psPD对接受化疗的GBM有临床影响,因为它可能体现治疗对胶质瘤的杀伤作用,且与MGMT状态显著相关。改善psPD模式的早期识别以及了解该现象的潜在机制对于消除评估临床试验结果时的偏差和保证有效治疗至关重要。