Early changes in glioblastoma metabolism measured by MR spectroscopic imaging during combination of anti-angiogenic cediranib and chemoradiation therapy are associated with survival
Early changes in glioblastoma metabolism measured by MR spectroscopic imaging during combination of anti-angiogenic cediranib and chemoradiation therapy are associated with survival
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DOI：
10.1038/s41698-017-0020-3
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发表时间：
2017-06-12
影响因子：
7.9
通讯作者：
Batchelor, Tracy T.
中科院分区：
文献类型：
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作者：
Andronesi, Ovidiu C.;Esmaeili, Morteza;Batchelor, Tracy T.
精确评估胶质母细胞瘤联合抗血管生成和放化疗的治疗反应仍然是一个挑战。特别是，早期检测治疗反应的标准解剖成像是混淆的伪反应或伪进展。代谢变化可能对肿瘤生理更有特异性，与血脑屏障通透性的变化更不容易混淆。我们假设磁共振波谱成像探测的代谢变化可以在联合治疗的早期对患者的反应进行分层。我们对新诊断的胶质母细胞瘤患者进行了一项前瞻性纵向成像研究，这些患者参加了泛血管内皮生长因子受体抑制剂cediranib联合标准分次放疗和替莫唑胺（放化疗）的II期临床试验。40例患者在治疗期间每周进行成像，成像方案包括磁共振光谱成像、灌注磁共振成像和解剖磁共振成像。采用接收算子特征、Cox比例风险模型和Kaplan-Meier生存图对数据进行分析。我们观察到，治疗1个月后总胆碱与健康肌酸的比值与总生存率显著相关，并提供单一参数：(1)受试者操作者特征曲线下面积最大（0.859），(2)Cox比例风险模型风险比最高（HR = 85.85, P = 0.006）， (3) Kaplan-Meier生存图分离最大（P = 0.004）。总胆碱/健康肌酸与脑血流呈负相关，但与肿瘤体积无显著相关性。我们的研究结果表明，通过磁共振光谱成像获得的体内代谢生物标志物可能是新诊断的胶质母细胞瘤对抗血管生成治疗联合标准放化疗反应的早期指标。
Precise assessment of treatment response in glioblastoma during combined anti-angiogenic and chemoradiation remains a challenge. In particular, early detection of treatment response by standard anatomical imaging is confounded by pseudo-response or pseudo-progression. Metabolic changes may be more specific for tumor physiology and less confounded by changes in blood-brain barrier permeability. We hypothesize that metabolic changes probed by magnetic resonance spectroscopic imaging can stratify patient response early during combination therapy. We performed a prospective longitudinal imaging study in newly diagnosed glioblastoma patients enrolled in a phase II clinical trial of the pan-vascular endothelial growth factor receptor inhibitor cediranib in combination with standard fractionated radiation and temozolomide (chemoradiation). Forty patients were imaged weekly during therapy with an imaging protocol that included magnetic resonance spectroscopic imaging, perfusion magnetic resonance imaging, and anatomical magnetic resonance imaging. Data were analyzed using receiver operator characteristics, Cox proportional hazards model, and Kaplan-Meier survival plots. We observed that the ratio of total choline to healthy creatine after 1 month of treatment was significantly associated with overall survival, and provided as single parameter: (1) the largest area under curve (0.859) in receiver operator characteristics, (2) the highest hazard ratio (HR = 85.85, P = 0.006) in Cox proportional hazards model, (3) the largest separation (P = 0.004) in Kaplan-Meier survival plots. An inverse correlation was observed between total choline/healthy creatine and cerebral blood flow, but no significant relation to tumor volumetrics was identified. Our results suggest that in vivo metabolic biomarkers obtained by magnetic resonance spectroscopic imaging may be an early indicator of response to anti-angiogenic therapy combined with standard chemoradiation in newly diagnosed glioblastoma.