Functional 4-D clustering for characterizing intratumor heterogeneity in dynamic imaging: evaluation in FDG PET as a prognostic biomarker for breast cancer.
Functional 4-D clustering for characterizing intratumor heterogeneity in dynamic imaging: evaluation in FDG PET as a prognostic biomarker for breast cancer.
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DOI：
10.1007/s00259-021-05265-8
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发表时间：
2021-11
影响因子：
9.1
通讯作者：
Kontos D
中科院分区：
文献类型：
--
作者：
Chitalia R;Viswanath V;Pantel AR;Peterson LM;Gastounioti A;Cohen EA;Muzi M;Karp J;Mankoff DA;Kontos D
基于探头的动态（4-D）成像模式在空间和动力学上捕获乳腺肿瘤内异质性。通过具有不同功能行为的肿瘤亚群表征异质性可以阐明肿瘤生物学，以提高靶向治疗特异性并实现精确的临床决策。我们提出了一种无监督聚类算法的4-D成像，集成马尔可夫随机场（MRF）的图像分割与时间序列分析，以表征动态肿瘤内异质性。我们将其应用于动态FDG PET扫描，通过确定不同的时间-活性曲线（TAC）的空间邻近约束。我们首先使用模拟动态数据评估算法性能。然后，我们将我们的算法应用于50名患有局部晚期乳腺癌的妇女的数据集，这些妇女在治疗前通过动态FDG PET成像，并随后监测疾病复发。然后从每个肿瘤内的功能不同的子区域提取功能性肿瘤异质性（FTH）特征。进行交叉验证的事件发生时间分析，以评估与已建立的组织病理学和动力学预后标志物相比，FTH特征的预后价值。将FTH特征添加到已知疾病复发预测因子的基线模型中，并建立FDG PET摄取和动力学标记物，将一致性统计量（C统计量）从0.59提高到0.74（p = 0.005）。FTH标记的无监督分层聚类鉴定了对应于高和低FTH的肿瘤异质性的两种显著（p < 0.001）表型。FDG通量的分布，或Ki，在两种表型之间有显著差异（p = 0.04）。我们的研究结果表明，在预测乳腺癌无复发生存率方面，FTH的成像标记物在标准PET成像指标之外增加了独立价值，因此值得进一步研究。在线版本包含补充材料，可通过10.1007/s 00259 -021-05265-8获得。
Probe-based dynamic (4-D) imaging modalities capture breast intratumor heterogeneity both spatially and kinetically. Characterizing heterogeneity through tumor sub-populations with distinct functional behavior may elucidate tumor biology to improve targeted therapy specificity and enable precision clinical decision making. We propose an unsupervised clustering algorithm for 4-D imaging that integrates Markov-Random Field (MRF) image segmentation with time-series analysis to characterize kinetic intratumor heterogeneity. We applied this to dynamic FDG PET scans by identifying distinct time-activity curve (TAC) profiles with spatial proximity constraints. We first evaluated algorithm performance using simulated dynamic data. We then applied our algorithm to a dataset of 50 women with locally advanced breast cancer imaged by dynamic FDG PET prior to treatment and followed to monitor for disease recurrence. A functional tumor heterogeneity (FTH) signature was then extracted from functionally distinct sub-regions within each tumor. Cross-validated time-to-event analysis was performed to assess the prognostic value of FTH signatures compared to established histopathological and kinetic prognostic markers. Adding FTH signatures to a baseline model of known predictors of disease recurrence and established FDG PET uptake and kinetic markers improved the concordance statistic (C-statistic) from 0.59 to 0.74 (p = 0.005). Unsupervised hierarchical clustering of the FTH signatures identified two significant (p < 0.001) phenotypes of tumor heterogeneity corresponding to high and low FTH. Distributions of FDG flux, or Ki, were significantly different (p = 0.04) across the two phenotypes. Our findings suggest that imaging markers of FTH add independent value beyond standard PET imaging metrics in predicting recurrence-free survival in breast cancer and thus merit further study. The online version contains supplementary material available at 10.1007/s00259-021-05265-8.
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DOI：
10.1158/1078-0432.ccr-14-0990
发表时间：
2015-01-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
O'Connor JP;Rose CJ;Waterton JC;Carano RA;Parker GJ;Jackson A
通讯作者：
Jackson A
影响因子：
9.3
作者：
Karp, Joel S.;Viswanath, Varsha;Daube-Witherspoon, Margaret E.
通讯作者：
Daube-Witherspoon, Margaret E.
影响因子：
82.9
作者：
Andor N;Graham TA;Jansen M;Xia LC;Aktipis CA;Petritsch C;Ji HP;Maley CC
通讯作者：
Maley CC
影响因子：
19.7
作者：
Li H;Zhu Y;Burnside ES;Drukker K;Hoadley KA;Fan C;Conzen SD;Whitman GJ;Sutton EJ;Net JM;Ganott M;Huang E;Morris EA;Perou CM;Ji Y;Giger ML
通讯作者：
Giger ML
影响因子：
4.8
作者：
DICE, LR
通讯作者：
DICE, LR