Lee Kuei C, Moffat Bradford A, Schott Anne F, Layman Rachel, Ellingworth Steven, Juliar Rebecca, Khan Amjad P, Helvie Mark, Meyer Charles R, Chenevert Thomas L, Rehemtulla Alnawaz, Ross Brian D
Department of Radiology, Center for Molecular Imaging, University of Michigan Medical School, Biomedical Sciences Research Building, 109 Zina Pitcher Place, Ann Arbor, MI 48109, USA.
Clin Cancer Res. 2007 Jan 15;13(2 Pt 1):443-50. doi: 10.1158/1078-0432.CCR-06-1888.
The American Cancer Society estimates that in 2006, 212,920 women will be diagnosed with breast cancer and that 40,970 women will die from the disease. The development of more efficacious chemotherapies has improved outcomes, but the rapid assessment of clinical benefit from these agents remains challenging. In breast cancer patients receiving neoadjuvant chemotherapy, treatment response is traditionally assessed by physical examination and volumetric-based measurements, which are subjective and require macroscopic changes in tumor morphology. In this study, we evaluate the feasibility of using diffusion magnetic resonance imaging (MRI) as a reliable and quantitative measure for the early assessment of response in a breast cancer model.
Mice implanted with human breast cancer (MX-1) were treated with cyclophosphamide and evaluated using diffusion MRI and growth kinetics. Histologic analyses using terminal nucleotidyl transferase-mediated nick end labeling and H&E were done on tumor samples for correlation with imaging results.
Cyclophosphamide treatment resulted in a significant reduction in tumor volumes compared with controls. The mean apparent diffusion change for treated tumors at days 4 and 7 posttreatment was 44 +/- 5% and 94 +/- 7%, respectively, which was statistically greater (P < 0.05) than the control tumors at the same time intervals. The median time-to-progression for control and treated groups was 11 and 32 days, respectively (P < 0.05).
Diffusion MRI was shown to detect early changes in the tumor microenvironment, which correlated with standard measures of tumor response as well as overall outcome. Moreover, these findings show the feasibility of using diffusion MRI for assessing treatment response of a breast tumor model in a neoadjuvant setting.
美国癌症协会估计，2006年将有212,920名女性被诊断患有乳腺癌，其中40,970名女性将死于该疾病。更有效的化疗方法的发展改善了治疗效果，但快速评估这些药物的临床益处仍然具有挑战性。在接受新辅助化疗的乳腺癌患者中，传统上通过体格检查和基于体积的测量来评估治疗反应，这些方法主观性强，且需要肿瘤形态发生宏观变化。在本研究中，我们评估了使用扩散磁共振成像（MRI）作为一种可靠的定量方法来早期评估乳腺癌模型中反应的可行性。
将植入人乳腺癌（MX-1）的小鼠用环磷酰胺治疗，并使用扩散MRI和生长动力学进行评估。对肿瘤样本进行末端脱氧核苷酸转移酶介导的缺口末端标记和苏木精-伊红染色的组织学分析，以与成像结果进行相关性分析。
与对照组相比，环磷酰胺治疗导致肿瘤体积显著减小。治疗后第4天和第7天，治疗组肿瘤的平均表观扩散变化分别为44±5%和94±7%，在相同时间间隔内，这一变化在统计学上显著大于（P<0.05）对照组肿瘤。对照组和治疗组的中位进展时间分别为11天和32天（P<0.05）。
扩散MRI显示能够检测肿瘤微环境的早期变化，这与肿瘤反应的标准测量以及总体结果相关。此外，这些发现表明了在新辅助治疗环境中使用扩散MRI评估乳腺肿瘤模型治疗反应的可行性。
