Sadeghi-Naini Ali, Sannachi Lakshmanan, Pritchard Kathleen, Trudeau Maureen, Gandhi Sonal, Wright Frances C, Zubovits Judit, Yaffe Martin J, Kolios Michael C, Czarnota Gregory J
Imaging Research - Physical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Imaging Research - Physical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Department of Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Oncotarget. 2014 Jun 15;5(11):3497-511. doi: 10.18632/oncotarget.1950.
Early alterations in textural characteristics of quantitative ultrasound spectral parametric maps, in conjunction with changes in their mean values, are demonstrated here, for the first time, to be capable of predicting ultimate clinical/pathologic responses of breast cancer patients to chemotherapy. Mechanisms of cell death, induced by chemotherapy within tumor, introduce morphological alterations in cancerous cells, resulting in measurable changes in tissue echogenicity. We have demonstrated that the development of such changes is reflected in early alterations in textural characteristics of quantitative ultrasound spectral parametric maps, followed by consequent changes in their mean values. The spectral/textural biomarkers derived on this basis have been demonstrated as non-invasive surrogates of breast cancer chemotherapy response. Particularly, spectral biomarkers sensitive to the size and concentration of acoustic scatterers could predict treatment response of patients with up to 80% of sensitivity and specificity (p=0.050), after one week within 3-4 months of chemotherapy. However, textural biomarkers characterizing heterogeneities in distribution of acoustic scatterers, could differentiate between treatment responding and non-responding patients with up to 100% sensitivity and 93% specificity (p=0.002). Such early prediction permits offering effective alternatives to standard treatment, or switching to a salvage therapy, for refractory patients.
本文首次证明,定量超声频谱参数图纹理特征的早期改变,连同其平均值的变化,能够预测乳腺癌患者对化疗的最终临床/病理反应。化疗在肿瘤内诱导的细胞死亡机制会使癌细胞出现形态学改变,导致组织回声性发生可测量的变化。我们已经证明,这种变化的发展反映在定量超声频谱参数图纹理特征的早期改变中,随后是其平均值的相应变化。在此基础上得出的频谱/纹理生物标志物已被证明是乳腺癌化疗反应的非侵入性替代指标。特别是,对声学散射体的大小和浓度敏感的频谱生物标志物,在化疗3至4个月内的一周后,能够以高达80%的敏感性和特异性(p=0.050)预测患者的治疗反应。然而,表征声学散射体分布异质性的纹理生物标志物,能够区分治疗有反应和无反应的患者,敏感性高达100%,特异性为93%(p=0.002)。这种早期预测能够为难治性患者提供标准治疗的有效替代方案,或转向挽救治疗。