Nahed Brian V, Redjal Navid, Brat Daniel J, Chi Andrew S, Oh Kevin, Batchelor Tracy T, Ryken Timothy C, Kalkanis Steven N, Olson Jeffrey J
Department of Neurosurgery, Massachusetts General Hospital, 15 Parkman Street, Wang 745, Boston, MA, 02114, USA.
Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA.
J Neurooncol. 2015 Dec;125(3):609-30. doi: 10.1007/s11060-015-1910-2. Epub 2015 Nov 3.
These recommendations apply to adult patients with recurrent low-grade glioma (LGG) with initial pathologic diagnosis of a WHO grade II infiltrative glioma (oligodendroglioma, astrocytoma, or oligo-astrocytoma).
Do pathologic and molecular characteristics predict outcome/malignant transformation at recurrence?
IDH STATUS AND RECURRENCE: (Level III) IDH mutation status should be determined as LGGs with IDH mutations have a shortened time to recurrence. It is unclear whether knowledge of IDH mutation status provides benefit in predicting time to progression or overall survival. TP53 STATUS AND RECURRENCE: (Level III) TP53 mutations occur early in LGG pathogenesis, remain stable, and are not recommended as a marker of predisposition to malignant transformation at recurrence or other measures of prognosis. MGMT STATUS AND RECURRENCE: (Level III) Assessment of MGMT status is recommended as an adjunct to assessing prognosis as LGGs with MGMT promoter methylation are associated with shorter PFS (in the absence of TMZ) and longer post-recurrence survival (in the presence of TMZ), ultimately producing similar overall survival to LGGs without MGMT methylation. The available retrospective reports are conflicting and comparisons between reports are limited CDK2NA STATUS AND RECURRENCE: (Level III) Assessment of CDK2NA status is recommended when possible as the loss of expression of the CDK2NA via either methylation or loss of chromosome 9p is associated with malignant progression of LGGs. PROLIFERATIVE INDEX AND RECURRENCE: (Level III) It is recommended that proliferative indices (MIB-1 or BUdR) be measured in LGGs as higher proliferation indices are associated with increased likelihood of recurrence and shorter progression free and overall survival. 1P/19Q STATUS AND RECURRENCE: There is insufficient evidence to make any recommendations.
What role does chemotherapy have in LGG recurrence?
TEMOZOLOMIDE AND RECURRENCE: (Level III) Temozolomide is recommended in the therapy of recurrent LGG as it may improve clinical symptoms. Oligodendrogliomas and tumors with 1p/19q co-deletion may derive the most benefit. PCV AND RECURRENCE: (Level III) PCV is recommended in the therapy of LGG at recurrence as it may improve clinical symptoms with the strongest evidence being for oligodendrogliomas. CARBOPLATIN AND RECURRENCE : (Level III) Carboplatin is not recommended as there is no significant benefit from carboplatin as single agent therapy for recurrent LGGs. OTHER TREATMENTS (NITROSUREAS, HYDROXYUREA/IMANITIB, IRINOTECAN, PACLITAXEL) AND RECURRENCE: There is insufficient evidence to make any recommendations. It is recommended that individuals with recurrent LGGs be enrolled in a properly designed clinical trial to assess these chemotherapeutic agents.
What role does radiation have in LGG recurrence?
RADIATION AT RECURRENCE WITH NO PREVIOUS IRRADIATION: (Level III) Radiation is recommended at recurrence if there was no previous radiation treatment. RE-IRRADIATION AT RECURRENCE: (Level III) It is recommended that re-irradiation be considered in the setting of LGG recurrence as it may provide benefit in disease control.
There is insufficient evidence to make any specific recommendations. It is recommended that individuals with recurrent LGGs be enrolled in a properly designed clinical trial to assess the role of surgery at recurrence.
这些建议适用于复发性低级别胶质瘤（LGG）的成年患者，其初始病理诊断为世界卫生组织II级浸润性胶质瘤（少突胶质细胞瘤、星形细胞瘤或少突星形细胞瘤）。
病理和分子特征能否预测复发时的预后/恶性转化？
异柠檬酸脱氢酶（IDH）状态与复发：（III级）应确定IDH突变状态，因为IDH突变的LGG复发时间缩短。目前尚不清楚IDH突变状态的信息在预测进展时间或总生存期方面是否有益。
TP53状态与复发：（III级）TP53突变在LGG发病机制早期出现，且保持稳定，不建议将其作为复发时恶性转化易感性或其他预后指标的标志物。
O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）状态与复发：（III级）建议评估MGMT状态以辅助评估预后，因为MGMT启动子甲基化的LGG与较短的无进展生存期（在未使用替莫唑胺的情况下）和较长的复发后生存期（在使用替莫唑胺的情况下）相关，最终总体生存期与未发生MGMT甲基化的LGG相似。现有回顾性报告存在矛盾，且报告之间的比较有限。
细胞周期蛋白依赖性激酶2A（CDK2NA）状态与复发：（III级）尽可能建议评估CDK2NA状态，因为通过甲基化或9号染色体短臂缺失导致的CDK2NA表达缺失与LGG的恶性进展相关。
（III级）建议在LGG中测量增殖指数（MIB-1或溴脱氧尿苷），因为较高的增殖指数与复发可能性增加以及较短的无进展生存期和总生存期相关。
1p/19q状态与复发：证据不足，无法给出任何建议。
化疗在LGG复发中起什么作用？
替莫唑胺与复发：（III级）建议在复发性LGG的治疗中使用替莫唑胺，因为它可能改善临床症状。少突胶质细胞瘤和1p/19q共缺失的肿瘤可能获益最大。
丙卡巴肼、洛莫司汀和长春新碱（PCV）与复发：（III级）建议在LGG复发时使用PCV进行治疗，因为它可能改善临床症状，证据最充分的是少突胶质细胞瘤。
（III级）不建议使用卡铂，因为卡铂作为复发性LGG的单药治疗没有显著益处。
其他治疗（亚硝基脲类、羟基脲/伊马替尼、伊立替康、紫杉醇）与复发：证据不足，无法给出任何建议。建议复发性LGG患者参加精心设计的临床试验以评估这些化疗药物。
放疗在LGG复发中起什么作用？
复发时未接受过放疗的放疗：（III级）如果之前未接受过放疗，建议在复发时进行放疗。
（III级）建议在LGG复发时考虑再放疗，因为它可能在疾病控制方面提供益处。
证据不足，无法给出任何具体建议。建议复发性LGG患者参加精心设计的临床试验以评估复发时手术的作用。
