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动态对比增强磁共振成像(DCE-MRI)测量的肿瘤血流变化可能预测单药贝伐珠单抗在复发性上皮性卵巢癌(EOC)和原发性腹膜癌(PPC)患者中的活性:一项妇科肿瘤学组 II 期研究的探索性分析。

Changes in tumor blood flow as measured by Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) may predict activity of single agent bevacizumab in recurrent epithelial ovarian (EOC) and primary peritoneal cancer (PPC) patients: an exploratory analysis of a Gynecologic Oncology Group Phase II study.

机构信息

Gynecologic Oncology, Creighton University School of Medicine, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013 USA.

出版信息

Gynecol Oncol. 2012 Sep;126(3):375-80. doi: 10.1016/j.ygyno.2012.06.002. Epub 2012 Jun 7.

Abstract

OBJECTIVE

To explore feasibility of measuring tumor blood flow as marker for antiangiogenic activity using DCE-MRI (Dynamic Contrast-Enhanced Magnetic Resonance Imaging) in women with recurrent EOC/PPC treated with bevacizumab.

METHODS

In a phase II study, 62 patients with recurrent/persistent EOC/PPC were treated with bevacizumab (15 mg/kg IV q21 days) until disease progression. DCE-MRI was performed pre-cycle 1 and 4 of bevacizumab. Images were analyzed retrospectively by a single experienced blinded radiologist. Tumor and muscle contrast enhancement was measured by region of interest signal intensity within the same DCE-MRI images. Flow rates were obtained with concentration of dye as a function of time. Relative blood flow (RBF) was calculated as a ratio of average blood flow into tumor to muscle tissue. Associations between RBF and characteristics/outcomes were explored.

RESULTS

Sixty-two patients were eligible for study. Unfortunately, only 14 (23%) patients had imaging data available for analysis at baseline and 13 of those same patients (21%) had imaging data available for analysis pre-cycle 4. The RBF distribution was similar from pre-cycle 1 to 4. RBF remained stable for the majority of the cases (median change -0.21). Baseline RBF was not significantly associated with being progression-free at 6 months, microvessel density, 17 month overall survival, tumor response, or platinum sensitivity. However, increases in blood flow rates were associated with likelihood to be progression-free at 6 months.

CONCLUSION

Functional imaging of tumor blood flow is a potential research endpoint that may be explored further. Consideration should be given to timing of endpoint and standardizing the technique.

摘要

目的

探索使用动态对比增强磁共振成像(DCE-MRI)测量肿瘤血流作为贝伐单抗治疗复发性卵巢癌/持续性卵巢上皮性癌(EOC/PPC)患者抗血管生成活性标志物的可行性。

方法

在一项 II 期研究中,62 例复发性/持续性 EOC/PPC 患者接受贝伐单抗(15mg/kg IV q21d)治疗,直至疾病进展。在贝伐单抗治疗的第 1 周期和第 4 周期前进行 DCE-MRI 检查。由一位经验丰富的盲法放射科医生对图像进行回顾性分析。通过同一 DCE-MRI 图像中的感兴趣区信号强度测量肿瘤和肌肉的对比增强。通过染料浓度随时间的变化获得流量率。相对血流(RBF)的计算方法为肿瘤平均血流与肌肉组织的比值。探讨 RBF 与特征/结局的相关性。

结果

62 例患者符合研究条件。遗憾的是,基线时仅有 14 例(23%)患者具有可用于分析的影像学数据,其中 13 例(21%)患者具有可用于分析第 4 周期前的影像学数据。RBF 分布在第 1 周期和第 4 周期相似。大多数情况下 RBF 保持稳定(中位数变化-0.21)。基线 RBF 与 6 个月时无进展生存、微血管密度、17 个月总生存、肿瘤反应或铂类敏感性均无显著相关性。然而,血流率的增加与 6 个月时无进展生存的可能性相关。

结论

肿瘤血流功能成像可能是一个有前途的研究终点,值得进一步探索。应考虑终点时间和标准化技术。

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