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质子放疗联合替莫唑胺治疗低级别胶质瘤患者中假性进展和其他治疗相关效应的增加。

Increase of pseudoprogression and other treatment related effects in low-grade glioma patients treated with proton radiation and temozolomide.

机构信息

Duke University School of Medicine, Durham, NC, USA.

Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.

出版信息

J Neurooncol. 2019 Mar;142(1):69-77. doi: 10.1007/s11060-018-03063-1. Epub 2018 Nov 28.

Abstract

INTRODUCTION

Concurrent radiotherapy and temozolomide (TMZ) is associated with radiographic pseudoprogression (PsP) in glioblastoma. The occurrence of PsP and other treatment effects is less well understood in low-grade gliomas (LGG). The purpose of this study is to evaluate whether the addition of TMZ to radiotherapy increases the incidence of PsP in adults with LGG treated with proton radiotherapy (PRT).

METHODS

Chart review and volumetric MRI-analysis was performed on radiotherapy-naive adults with WHO grade II or IDH mutant WHO grade III gliomas treated with PRT between 2005 and 2015. Progression was defined by histology, new chemotherapy initiation, or progressive increase in lesion volume beyond 40% from baseline. Post treatment related effects (PTRE) were defined as new/increased T2/FLAIR or abnormal enhancement which eventually resolved or stabilized without evidence of progression for a period of 6-12 months. PsP was defined as the subset of PRTE suspicious for progression or volumetrically increased at least 40% from baseline. Pearson's chi-squared test and Cox-proportional hazards models were used for statistical analysis.

RESULTS

There were 119 patients meeting inclusion criteria. There was an increased risk of PsP following PRT + TMZ versus PRT-alone (HR = 2.2, p = 0.006, on Cox univariate analysis). Presence of PsP was associated with improved OS (p = 0.02 with PsP as time-varying covariate).

CONCLUSIONS

TMZ use, when added to PRT, was associated with increased PsP in patients with LGG; however, patients with PsP tended to achieve longer survival.

摘要

简介

在胶质母细胞瘤中,同步放化疗和替莫唑胺(TMZ)与放射性假性进展(PsP)相关。在低级别胶质瘤(LGG)中,PsP 和其他治疗效果的发生情况了解较少。本研究的目的是评估替莫唑胺联合放射治疗是否会增加接受质子放射治疗(PRT)治疗的成人 LGG 患者中 PsP 的发生率。

方法

对 2005 年至 2015 年间接受 PRT 治疗的未经放疗的成人 II 级或 IDH 突变型 III 级弥漫性星形细胞瘤患者进行了病历回顾和容积 MRI 分析。进展通过组织学、新化疗开始或病灶体积从基线增加超过 40%定义。治疗后相关效应(PTRE)定义为新出现/增加的 T2/FLAIR 或异常增强,最终在 6-12 个月内没有进展的证据而得到解决或稳定。PsP 被定义为 PRTE 的亚组,怀疑进展或体积从基线增加至少 40%。使用 Pearson 卡方检验和 Cox 比例风险模型进行统计分析。

结果

符合纳入标准的患者有 119 例。与 PRT 单药治疗相比,PRT+TMZ 后 PsP 的风险增加(HR=2.2,p=0.006,Cox 单变量分析)。存在 PsP 与 OS 改善相关(p=0.02,PsP 作为时变协变量)。

结论

当替莫唑胺联合 PRT 用于治疗 LGG 时,与 PsP 增加相关;然而,存在 PsP 的患者倾向于获得更长的生存时间。

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