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乳腺癌患者接受标准辅助治疗后，20%～30%的患者最终出现晚期或转移性乳腺癌，尤其激素受体阳性HER2阴性乳腺癌。内分泌治疗（例如氟维司群）是这些患者的主要治疗方法，不过并非所有患者都对内分泌治疗有效，故需预测指标区分可能获益或无法获益的患者。既往研究已经证实，肿瘤之间与肿瘤内部的遗传、生物、代谢差异是治疗失败和耐药的预测指标。近来，18F-氟代脱氧葡萄糖（18F-FDG）正电子发射断层成像＋X线计算机断层成像（PET/CT）根据肿瘤纹理信息和葡萄糖摄取可以评估肿瘤的异质性，与活检基因组方法相比，比较简单而且无创。 2018年9月27日，英国《自然》旗下《科学报告》发表复旦大学附属肿瘤医院、复旦大学上海医学院、复旦大学生物医学影像研究中心、上海分子影像探针工程技术研究中心、复旦大学核物理与离子束应用教育部重点实验室的研究报告，探讨了将18F-FDG PET/CT成像结果（包括肿瘤异质性）作为氟维司群500mg治疗转移性乳腺癌效果预测指标的临床意义。 该研究回顾分析了27例接受氟维司群500mg治疗并且治疗前接受18F-FDG PET/CT检查的雌激素受体阳性HER2阴性转移性乳腺癌患者。对PET/CT扫描常规参数（最大和平均标准摄取值、形变肿瘤体积、全身病变糖酵解值）和异质性参数（肿瘤内部异质性指数、肿瘤之间异质性变异系数）进行分析。主要疗效评定指标为无进展生存，通过生存曲线法进行分析。通过单因素、多因素比例风险回归模型对其他影响因素进行校正。 单因素分析表明，氟维司群无进展生存的显著相关因素：
多因素分析表明，氟维司群无进展生存的显著相关因素：
因此，根据该研究结果，通过18F-FDG测出的肿瘤内部异质性，可能成为激素受体阳性HER2阴性转移性乳腺癌患者氟维司群治疗效果的潜在预测指标。 Sci Rep. 2018 Sep 27;8:14458. Prognostic Value of Tumor Heterogeneity on 18F-FDG PET/CT in HR+HER2- Metastatic Breast Cancer Patients receiving 500 mg Fulvestrant: a retrospective study. Yannan Zhao, Cheng Liu, Yingjian Zhang, Chengcheng Gong, Yi Li, Yizhao Xie, Bingrui Wu, Zhongyi Yang, Biyun Wang. Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China; Center for Biomedical Imaging, Fudan University, Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China; Key Laboratory of Nuclear Physics and Ion-beam Application (MOE), Fudan University, Shanghai, China. Heterogeneity has been demonstrated to be a predictor of treatment failure and drug resistance. Our study aimed to investigate imaging parameters, including tumor heterogeneity, as prognostic factors of response to 500mg fulvestrant using 18F-FDG PET/CT. Twenty-seven estrogen receptor (HR)-positive/HER2-negative metastatic breast cancer patients who received 500mg fulvestrant and underwent 18F-FDG PET/CT before treatment were retrospectively included. In PET/CT scans, conventional parameters (maximum and mean standardized uptake value, metabolic tumor volume [MTV], total lesion glycolysis [TLG]) and heterogeneity parameters (intra-tumor heterogeneity index [HI] and inter-tumor heterogeneity coefficient of variation [COV]) were analyzed. Progression-free survival (PFS) was mainly assessed for efficacy. The survival analyses were performed using the Kaplan-Meier method. Univariate and multivariate analysis were performed using the Cox proportional hazard model. Univariate analysis indicated that a high SUVmax and a high tumor HI at baseline were associated with longer PFS of fulvestrant (P=0.036 and P=0.033, respectively). Liver metastasis, SUVmax and HI were statistically significant in multivariate analysis (P values of 0.017, 0.025 and 0.043, respectively). 18F-FDG based intra-tumor heterogeneity appears to be a potential predicator of efficacy of fulvestrant among HR+HER2- metastatic breast cancer patients. DOI: 10.1038/s41598-018-32745-z |
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