Abstract

Background

Lower-grade gliomas (LGGs) with isocitrate dehydrogenase 1 and/or 2 (IDH1/2) mutations have long survival times, making evaluation of treatment efficacy difficult. We investigated the volumetric growth rate of IDH mutant gliomas before and after treatment with established glioma therapies to determine whether a significant change in growth rate could be documented and perhaps be used in the future to evaluate treatment response to investigational agents in LGG trials.

Methods

In this multicenter retrospective study, 230 adult patients with IDH1/2 mutated LGGs (World Health Organization grade II or III) undergoing surgery, radiation, or chemotherapy for progressive non-enhancing tumor were identified. Subjects were required to have 3 MRI scans containing T2/fluid attenuated inversion recovery imaging spanning a minimum of 6 months prior to treatment. A mixed-effect model was used to estimate tumor growth prior to treatment. A subset of 95 patients who received chemotherapy, radiotherapy, or chemoradiotherapy and had 2 posttreatment imaging time points available were evaluated for change in pre- and posttreatment volumetric growth rates using a piecewise mixed model.

Results

The pretreatment volumetric growth rate across all 230 patients was 27.37%/180 days (95% CI: [23.36%, 31.51%]). In the 95 patients with both pre- and posttreatment scans available, there was a significant difference in volumetric growth rates before (26.63%/180 days, 95% CI: [19.31%, 34.40%]) and after treatment (−15.24% /180 days, 95% CI: [−21.37%, −8.62%]) (P < 0.0001). The growth rates for patient subgroup with 1p/19q codeletion (N = 118) was significantly slower than the rate of the 1p/19q non-codeleted group (N = 68) (22.84% vs 35.49%, P = 0.0108).

Conclusion

In this study, we evaluated the growth rates of IDH mutant gliomas before and after standard therapy. Further study is needed to establish whether a change in growth rate is associated with patient survival and its use as a surrogate endpoint in clinical trials for IDH mutant LGGs.

中文翻译：

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IDH 突变低级别胶质瘤的体积分析：治疗前后肿瘤生长率的自然历史研究。

摘要

背景

具有异柠檬酸脱氢酶 1 和/或 2 (IDH1/2) 突变的低级别神经胶质瘤 (LGG) 具有较长的存活时间，因此难以评估治疗效果。我们调查了 IDH 突变神经胶质瘤在用已建立的神经胶质瘤疗法治疗前后的体积增长率，以确定是否可以记录增长率的显着变化，并可能在未来用于评估 LGG 试验中对研究药物的治疗反应。

方法

在这项多中心回顾性研究中，确定了 230 名患有 IDH1/2 突变 LGG（世界卫生组织 II 级或 III 级）的成年患者，这些患者正在接受手术、放疗或化疗以治疗进展性非增强型肿瘤。要求受试者在治疗前至少 6 个月进行 3 次包含 T2/流体衰减反转恢复成像的 MRI 扫描。混合效应模型用于估计治疗前的肿瘤生长。95 名接受化疗、放疗或化放疗且有 2 个可用的治疗后成像时间点的患者子集使用分段混合模型评估治疗前和治疗后体积增长率的变化。

结果

所有 230 名患者的治疗前体积增长率为 27.37%/180 天（95% CI：[23.36%，31.51%]）。在治疗前和治疗后扫描均可用的 95 名患者中，治疗前（26.63%/180 天，95% CI：[19.31%，34.40%]）和治疗后（-15.24%/180 天，95% CI：[19.31%，34.40%]）的体积增长率存在显着差异180 天，95% CI：[−21.37%，−8.62%]) ( P < 0.0001)。具有 1p/19q 编码缺失的患者亚组 ( N = 118)的增长率明显慢于 1p/19q 非编码缺失组 ( N = 68)（22.84% 对 35.49%，P = 0.0108）。

结论

在这项研究中，我们评估了标准治疗前后 IDH 突变神经胶质瘤的生长速率。需要进一步研究以确定生长速率的变化是否与患者存活相关，以及它在 IDH 突变体 LGG 的临床试验中用作替代终点。