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利用影像学和分子生物标志物及多元模型预测放疗后正常组织并发症概率(NTCP)。

Prediction of Normal Tissue Complication Probability (NTCP) After Radiation Therapy Using Imaging and Molecular Biomarkers and Multivariate Modelling.

机构信息

Medical Physics Department, Isfahan University of Medical Science, Isfahan, Iran.

Research & Education, Department of Radiation Oncology, Isfahan Milad Hospital, Isfahan, Iran.

出版信息

J Mol Neurosci. 2023 Aug;73(7-8):587-597. doi: 10.1007/s12031-023-02136-9. Epub 2023 Jul 18.

DOI:10.1007/s12031-023-02136-9
PMID:37462853
Abstract

The aim of this study was to design a predictive radiobiological model of normal brain tissue in low-grade glioma following radiotherapy based on imaging and molecular biomarkers. Fifteen patients with primary brain tumors prospectively participated in this study and underwent radiation therapy. Magnetic resonance imaging (MRI) was obtained from the patients, including T1- and T2-weighted imaging and diffusion tensor imaging (DTI), and a generalized equivalent dose (gEUD) was calculated. The radiobiological model of the normal tissue complication probability (NTCP) was performed using the variables gEUD; axial diffusivity (AD) and radial diffusivity (RD) of the corpus callosum; and serum protein S100B by univariate and multivariate logistic regression XLIIIrd Sir Peter Freyer Memorial Lecture and Surgical Symposium (2018). Changes in AD, RD, and S100B from baseline up to the 6 months after treatment had an increasing trend and were significant in some time points (P-value < 0.05). The model resulting from RD changes in the 6 months after treatment was significantly more predictable of necrosis than other univariate models. The bivariate model combining RD changes in Gy40 dose-volume and gEUD, as well as the trivariate model obtained using gEUD, RD, and S100B, had a higher predictive value among multivariate models at the sixth month of the treatment. Changes in RD diffusion indices and in serum protein S100B value were used in the early-delayed stage as reliable biomarkers for predicting late-delayed damage (necrosis) caused by radiation in the corpus callosum. Current findings could pave the way for intervention therapies to delay the severity of damage to white matter structures, minimize cognitive impairment, and improve the quality of life of patients with low-grade glioma.

摘要

本研究旨在设计一种基于影像学和分子生物标志物的低级别胶质瘤放疗后正常脑组织预测性放射生物学模型。15 名原发性脑肿瘤患者前瞻性参与本研究并接受放射治疗。对患者进行磁共振成像(MRI)检查,包括 T1 和 T2 加权成像和弥散张量成像(DTI),并计算广义等效剂量(gEUD)。使用 gEUD;胼胝体的轴向弥散度(AD)和径向弥散度(RD);以及血清蛋白 S100B 等变量,通过单变量和多变量逻辑回归来进行正常组织并发症概率(NTCP)的放射生物学模型分析。XLIIIrd Sir Peter Freyer Memorial Lecture and Surgical Symposium(2018)。治疗后 6 个月内 AD、RD 和 S100B 的变化呈上升趋势,在某些时间点具有统计学意义(P 值<0.05)。治疗后 6 个月 RD 变化的模型比其他单变量模型更能预测坏死。包含 Gy40 剂量-体积和 gEUD 的 RD 变化的双变量模型,以及使用 gEUD、RD 和 S100B 获得的三变量模型,在治疗第 6 个月的多变量模型中具有更高的预测价值。RD 扩散指数和血清蛋白 S100B 值的变化可用于早期迟发性阶段,作为预测胼胝体辐射引起的迟发性损伤(坏死)的可靠生物标志物。目前的研究结果为干预治疗铺平了道路,以延迟白质结构损伤的严重程度,最大限度地减少认知障碍,并提高低级别胶质瘤患者的生活质量。

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本文引用的文献

1
NTCP Modeling of Late Effects for Head and Neck Cancer: A Systematic Review.头颈部癌晚期效应的NTCP模型:一项系统综述。
Int J Part Ther. 2021 Jun 25;8(1):95-107. doi: 10.14338/20-00092. eCollection 2021 Summer.
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Volumetric and actuarial analysis of brain necrosis in proton therapy using a novel mixture cure model.利用新型混合治愈模型对质子治疗中的脑坏死进行容积和保险统计分析。
Radiother Oncol. 2020 Jan;142:154-161. doi: 10.1016/j.radonc.2019.09.008. Epub 2019 Sep 25.
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The S100B story: from biomarker to active factor in neural injury.
S100B 蛋白的故事:从神经损伤的生物标志物到活性因子。
J Neurochem. 2019 Jan;148(2):168-187. doi: 10.1111/jnc.14574. Epub 2018 Nov 12.
4
Understanding the Physiopathology Behind Axial and Radial Diffusivity Changes-What Do We Know?理解轴向和径向扩散率变化背后的生理病理学——我们了解什么?
Front Neurol. 2018 Feb 27;9:92. doi: 10.3389/fneur.2018.00092. eCollection 2018.
5
Evidence of progressive tissue loss in the core of chronic MS lesions: A longitudinal DTI study.慢性多发性硬化症病灶核心组织进行性丢失的证据:一项纵向 DTI 研究。
Neuroimage Clin. 2017 Dec 8;17:1028-1035. doi: 10.1016/j.nicl.2017.12.010. eCollection 2018.
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Regional susceptibility to dose-dependent white matter damage after brain radiotherapy.脑部放疗后白质损伤剂量依赖性的区域易感性。
Radiother Oncol. 2017 May;123(2):209-217. doi: 10.1016/j.radonc.2017.04.006. Epub 2017 May 2.
7
Dose-dependent white matter damage after brain radiotherapy.脑部放疗后剂量依赖性白质损伤。
Radiother Oncol. 2016 Nov;121(2):209-216. doi: 10.1016/j.radonc.2016.10.003. Epub 2016 Oct 21.
8
Diffusion tensor imaging predicts cognitive function change following partial brain radiotherapy for low-grade and benign tumors.扩散张量成像可预测低级别和良性肿瘤患者局部脑放疗后的认知功能变化。
Radiother Oncol. 2016 Aug;120(2):234-40. doi: 10.1016/j.radonc.2016.06.021. Epub 2016 Jul 11.
9
Inflammatory cytokines influence measures of white matter integrity in Bipolar Disorder.炎症细胞因子影响双相情感障碍中白质完整性的指标。
J Affect Disord. 2016 Sep 15;202:1-9. doi: 10.1016/j.jad.2016.05.047. Epub 2016 May 24.
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Radiation oncology in the era of precision medicine.精准医学时代的放射肿瘤学。
Nat Rev Cancer. 2016 Apr;16(4):234-49. doi: 10.1038/nrc.2016.18. Epub 2016 Mar 18.