Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California, United States of America.
Carl E. Ravin Advanced Imaging Laboratories, Duke University, Durham, North Carolina, United States of America.
PLoS One. 2023 Feb 17;18(2):e0279812. doi: 10.1371/journal.pone.0279812. eCollection 2023.
Bevacizumab-related imaging abnormality (BRIA), appearing as areas of restricted diffusion on magnetic resonance imaging (MRI) and representing atypical coagulative necrosis pathologically, has been observed in patients with brain tumors receiving radiotherapy and bevacizumab. We investigated the role of cumulative radiation dose in BRIA development in a voxel-wise analysis.
Patients (n = 18) with BRIA were identified. All had high-grade gliomas or brain metastases treated with radiotherapy and bevacizumab. Areas of BRIA were segmented semi-automatically on diffusion-weighted MRI with apparent diffusion coefficient (ADC) images. To avoid confounding by possible tumor, hypoperfusion was confirmed with perfusion imaging. ADC images and radiation dose maps were co-registered to a high-resolution T1-weighted MRI and registration accuracy was verified. Voxel-wise normal tissue complication probability analyses were performed using a logistic model analyzing the relationship between cumulative voxel equivalent total dose in 2 Gy fractions (EQD2) and BRIA development at each voxel. Confidence intervals for regression model predictions were estimated with bootstrapping.
Among 18 patients, 39 brain tumors were treated. Patients received a median of 4.5 cycles of bevacizumab and 1-4 radiation courses prior to BRIA appearance. Most (64%) treated tumors overlapped with areas of BRIA. The median proportion of each BRIA region of interest volume overlapping with tumor was 98%. We found a dose-dependent association between cumulative voxel EQD2 and the relative probability of BRIA (β0 = -5.1, β1 = 0.03 Gy-1, γ = 1.3).
BRIA is likely a radiation dose-dependent phenomenon in patients with brain tumors receiving bevacizumab and radiotherapy. The combination of radiation effects and tumor microenvironmental factors in potentiating BRIA in this population should be further investigated.
贝伐珠单抗相关的影像学异常（BRIA）在接受放疗和贝伐珠单抗治疗的脑肿瘤患者中表现为磁共振成像（MRI）上的弥散受限区域，代表病理上非典型凝固性坏死。我们通过体素分析研究了累积辐射剂量在 BRIA 发展中的作用。
确定了 18 例 BRIA 患者。所有患者均为高级别胶质瘤或脑转移瘤，接受放疗和贝伐珠单抗治疗。在弥散加权 MRI 上，用表观弥散系数（ADC）图像半自动分割 BRIA 区域。为避免可能的肿瘤混杂，通过灌注成像确认低灌注。将 ADC 图像和辐射剂量图与高分辨率 T1 加权 MRI 配准，并验证配准精度。使用逻辑模型分析每个体素的累积 2Gy 等效总剂量（EQD2）与 BRIA 发展之间的关系，进行体素正常组织并发症概率分析。使用自举法估计回归模型预测的置信区间。
在 18 例患者中，共治疗 39 个脑肿瘤。患者在出现 BRIA 前接受了中位数为 4.5 个周期的贝伐珠单抗和 1-4 个放疗疗程。大多数（64%）治疗肿瘤与 BRIA 区域重叠。每个 BRIA 感兴趣区体积与肿瘤重叠的中位数比例为 98%。我们发现累积体素 EQD2 与 BRIA 的相对概率之间存在剂量依赖性关联（β0 = -5.1，β1 = 0.03 Gy-1，γ = 1.3）。
BRIA 可能是接受贝伐珠单抗和放疗的脑肿瘤患者中一种与辐射剂量相关的现象。在该人群中，进一步研究辐射效应与肿瘤微环境因素在增强 BRIA 中的联合作用是必要的。
