Jakacki Regina I, Cohen Kenneth J, Buxton Allen, Krailo Mark D, Burger Peter C, Rosenblum Marc K, Brat Daniel J, Hamilton Ronald L, Eckel Sandrah P, Zhou Tianni, Lavey Robert S, Pollack Ian F
Departments of Pediatrics (R.I.J.), Pathology (R.L.H.) and Neurosurgery (I.F.P.), University of Pittsburgh School of Medicine, Pittsburgh, PA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (K.J.C.); Children's Oncology Group, Operations Office, Monrovia, California (A.B., M.D.K.); Department of Preventive Medicine, University of Southern California, Los Angeles, California (M.D.K, S.P.E.); Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland (P.C.B.); Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York (M.K.R.); Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia (D.J.B.); Department of Mathematics and Statistics, California State University, Long Beach, California (T.Z.); Maurer Family Cancer Care Center, Bowling Green, Ohio (R.S.L.).
Departments of Pediatrics (R.I.J.), Pathology (R.L.H.) and Neurosurgery (I.F.P.), University of Pittsburgh School of Medicine, Pittsburgh, PA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (K.J.C.); Children's Oncology Group, Operations Office, Monrovia, California (A.B., M.D.K.); Department of Preventive Medicine, University of Southern California, Los Angeles, California (M.D.K, S.P.E.); Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland (P.C.B.); Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York (M.K.R.); Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia (D.J.B.); Department of Mathematics and Statistics, California State University, Long Beach, California (T.Z.); Maurer Family Cancer Care Center, Bowling Green, Ohio (R.S.L.)
Neuro Oncol. 2016 Oct;18(10):1442-50. doi: 10.1093/neuonc/now038. Epub 2016 Mar 22.
The prognosis for children with malignant glioma is poor. This study was designed to determine whether lomustine and temozolomide following radiotherapy and concurrent temozolomide improves event-free survival (EFS) compared with historical controls with anaplastic astrocytoma (AA) or glioblastoma (GBM) and whether survival is influenced by the expression of O6-methylguanine-DNA-methyltransferase (MGMT).
Following maximal surgical resection, newly diagnosed children with nonmetastatic high-grade glioma underwent involved field radiotherapy with concurrent temozolomide. Adjuvant chemotherapy consisted of up to 6 cycles of lomustine 90 mg/m(2) on day 1 and temozolomide 160 mg/m(2)/day ×5 every 6 weeks.
Among the 108 eligible patients with AA or GBM, 1-year EFS was 0.49 (95% CI, 0.39-0.58), similar to the original CCG-945-based design model. However, EFS and OS were significantly improved in ACNS0423 compared with the 86 AA or GBM participants treated with adjuvant temozolomide alone in the recent ACNS0126 study (1-sided log-rank P = .019 and .019, respectively). For example, 3-year EFS was 0.22 (95% CI, 0.14-0.30) in ACNS0423 compared with 0.11 (95% CI, 0.05-0.18) in ACNS0126. Stratifying the comparison by resection extent, the addition of lomustine resulted in significantly better EFS and OS in participants without gross-total resection (P = .019 and .00085 respectively). The difference in EFS and OS was most pronounced for participants with GBM (P = .059 and 0.051, respectively), and those with MGMT overexpression (P = .00036 and .00038, respectively).
The addition of lomustine to temozolomide as adjuvant therapy in ACNS0423 was associated with significantly improved outcome compared with the preceding COG ACNS0126 HGG study in which participants received temozolomide alone.
恶性胶质瘤患儿的预后较差。本研究旨在确定与间变性星形细胞瘤（AA）或胶质母细胞瘤（GBM）的历史对照相比，放疗后使用洛莫司汀和替莫唑胺以及同步使用替莫唑胺是否能改善无事件生存期（EFS），以及生存期是否受O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）表达的影响。
在进行最大程度的手术切除后，新诊断的非转移性高级别胶质瘤患儿接受累及野放疗并同步使用替莫唑胺。辅助化疗包括最多6个周期的洛莫司汀90mg/m²，于第1天给药，以及替莫唑胺160mg/m²/天×5天，每6周重复一次。
在108例符合条件的AA或GBM患者中，1年EFS为0.49（95%CI，0.39 - 0.58），与基于最初CCG - 945的设计模型相似。然而，与近期ACNS0126研究中仅接受辅助替莫唑胺治疗的86例AA或GBM参与者相比，ACNS0423中的EFS和总生存期（OS）有显著改善（单侧对数秩检验P值分别为0.019和0.019）。例如，ACNS0423中的3年EFS为0.22（95%CI，0.14 - 0.30），而ACNS0126中的为0.11（95%CI，0.05 - 0.18）。按切除范围分层进行比较，对于未进行全切的参与者，添加洛莫司汀可显著改善EFS和OS（P值分别为0.019和0.00085）。EFS和OS的差异在GBM参与者（P值分别为0.059和0.051）以及MGMT过表达的参与者中最为明显（P值分别为0.00036和0.00038）。
与之前COG ACNS0126 HGG研究（参与者仅接受替莫唑胺治疗）相比，ACNS0423中添加洛莫司汀作为替莫唑胺的辅助治疗与显著改善的结局相关。
