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通过CT纹理分析评估人表皮生长因子受体2(HER2)阳性晚期胃癌的肿瘤异质性:与曲妥珠单抗治疗后的生存相关性

Tumor Heterogeneity in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Gastric Cancer Assessed by CT Texture Analysis: Association with Survival after Trastuzumab Treatment.

作者信息

Yoon Sung Hyun, Kim Young Hoon, Lee Yoon Jin, Park Jihoon, Kim Jin Won, Lee Hye Seung, Kim Bohyoung

机构信息

Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Institute of Radiation Medicine, Seoul National University Medical Research Center, Seongnam-si, Korea.

Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Korea.

出版信息

PLoS One. 2016 Aug 12;11(8):e0161278. doi: 10.1371/journal.pone.0161278. eCollection 2016.

Abstract

BACKGROUND

Image texture analysis is a noninvasive technique for quantifying intratumoral heterogeneity, with derived texture features reported to be closely related to the treatment outcome of tumors. Gastric cancer is one of the most common tumors and the third leading cause of cancer-related deaths worldwide. Although trastuzumab is associated with a survival gain among patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer, optimal patient selection is challenging. The purpose of this study was to determine whether CT texture features of HER2-positive gastric cancer were related to the survival rate after trastuzumab treatment.

METHODS AND FINDINGS

Patients diagnosed with HER2-positive advanced gastric cancer from February 2007 to August 2014 were retrospectively selected. Using in-house built software, histogram features (kurtosis and skewness) and gray-level co-occurrence matrices (GLCM) features (angular second moment [ASM], contrast, entropy, variance, and correlation) were derived from the CT images of HER2-positive advanced gastric cancer in 26 patients. All the patients were followed up for more than 6 months, with no confirmed deaths. The patients were dichotomized into a good and poor survival group based on cutoff points of overall survival of 12 months. A receiver-operating characteristics (ROC) analysis was performed to test the ability of each texture parameter to identify the good survival group. Kaplan-Meier curves for patients above and below each threshold were constructed. Using a threshold of >265.8480 for contrast, >488.3150 for variance, and ≤0.1319×10-3. for correlation, all of the area under the ROC curves showed fair accuracy (>0.7). Kaplan-Meier analysis showed statistically significant survival difference between two groups according to optimal cutoff values of contrast, variance, correlation and ASM. However, as this study had a small number of patients, a further study with a larger population will be needed to validate the results.

CONCLUSIONS

Heterogeneous texture features on CT images were associated with better survival in patients with HER2-positive advanced gastric cancer who received trastuzumab-based treatment. Therefore, texture analysis shows potential to be a clinically useful imaging biomarker providing additional prognostic information for patient selection.

摘要

背景

图像纹理分析是一种用于量化肿瘤内异质性的非侵入性技术,据报道,所提取的纹理特征与肿瘤的治疗结果密切相关。胃癌是最常见的肿瘤之一,也是全球癌症相关死亡的第三大主要原因。尽管曲妥珠单抗可使人类表皮生长因子受体2(HER2)阳性的晚期胃癌患者的生存期延长,但最佳患者选择仍具有挑战性。本研究的目的是确定HER2阳性胃癌的CT纹理特征是否与曲妥珠单抗治疗后的生存率相关。

方法与结果

回顾性选取2007年2月至2014年8月诊断为HER2阳性晚期胃癌的患者。使用内部构建的软件,从26例HER2阳性晚期胃癌患者的CT图像中提取直方图特征(峰度和偏度)和灰度共生矩阵(GLCM)特征(角二阶矩[ASM]、对比度、熵、方差和相关性)。所有患者均随访6个月以上,无确诊死亡病例。根据总生存期12个月的截断点,将患者分为生存良好组和生存不良组。进行受试者操作特征(ROC)分析,以测试每个纹理参数识别生存良好组的能力。构建高于和低于每个阈值的患者的Kaplan-Meier曲线。使用对比度>265.8480、方差>488.3150和相关性≤0.1319×10-3的阈值时,所有ROC曲线下面积显示出较好的准确性(>0.7)。根据对比度、方差、相关性和ASM的最佳截断值,Kaplan-Meier分析显示两组之间存在统计学上显著的生存差异。然而,由于本研究患者数量较少,需要进一步开展更大规模人群的研究来验证结果。

结论

CT图像上的异质纹理特征与接受曲妥珠单抗治疗的HER2阳性晚期胃癌患者的较好生存相关。因此,纹理分析显示出有可能成为一种临床有用的影像生物标志物,为患者选择提供额外的预后信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba02/4982686/b028289bc5b3/pone.0161278.g001.jpg

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