Nishino Mizuki, Sacher Adrian G, Gandhi Leena, Chen Zhao, Akbay Esra, Fedorov Andriy, Westin Carl F, Hatabu Hiroto, Johnson Bruce E, Hammerman Peter, Wong Kwok-Kin
Department of Radiology, Brigham and Women's Hospital, 450 Brookline Ave., Boston MA, 02215, USA; Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston MA, 02215, USA.
Department of Medical Oncology and Department of Medicine Dana-Farber Cancer Institute and Brigham and Women's Hospital 450 Brookline Ave., Boston MA, 02215, USA.
Eur J Radiol. 2017 Mar;88:15-20. doi: 10.1016/j.ejrad.2016.12.028. Epub 2016 Dec 26.
To evaluate and compare the volumetric tumor burden changes during crizotinib therapy in mice and human cohorts with ALK-rearranged non-small-cell lung cancer (NSCLC).
Volumetric tumor burden was quantified on serial imaging studies in 8 bitransgenic mice with ALK-rearranged adenocarcinoma treated with crizotinib, and in 33 human subjects with ALK-rearranged NSCLC treated with crizotinib. The volumetric tumor burden changes and the time to maximal response were compared between mice and humans.
The median tumor volume decrease (%) at the maximal response was -40.4% (range: -79.5%-+11.7%) in mice, and -72.9% (range: -100%-+72%) in humans (Wilcoxon p=0.03). The median time from the initiation of therapy to maximal response was 6 weeks in mice, and 15.7 weeks in humans. Overall volumetric response rate was 50% in mice and 97% in humans. Spider plots of tumor volume changes during therapy demonstrated durable responses in the human cohort, with a median time on therapy of 13.1 months.
The present study described an initial attempt to evaluate quantitative tumor burden changes in co-clinical imaging studies of genomically-matched mice and human cohorts with ALK-rearranged NSCLC treated with crizotinib. Differences are noted in the degree of maximal volume response between the two cohorts in this well-established paradigm of targeted therapy, indicating a need for further studies to optimize co-clinical trial design and interpretation.
评估并比较克唑替尼治疗期间，携带ALK重排的非小细胞肺癌（NSCLC）小鼠和人类队列的肿瘤体积负荷变化。
对8只接受克唑替尼治疗的携带ALK重排腺癌的双转基因小鼠以及33名接受克唑替尼治疗的携带ALK重排NSCLC的人类受试者进行系列成像研究，以量化肿瘤体积负荷。比较小鼠和人类之间的肿瘤体积负荷变化以及达到最大反应的时间。
在最大反应时，小鼠肿瘤体积减少的中位数（%）为-40.4%（范围：-79.5%至+11.7%），人类为-72.9%（范围：-100%至+72%）（Wilcoxon检验p=0.03）。从治疗开始到最大反应的中位时间，小鼠为6周，人类为15.7周。总体体积反应率在小鼠中为50%，在人类中为97%。治疗期间肿瘤体积变化的蜘蛛图显示人类队列中有持久反应，中位治疗时间为13.1个月。
本研究描述了在对接受克唑替尼治疗的携带ALK重排NSCLC的基因匹配小鼠和人类队列进行的联合临床成像研究中，评估定量肿瘤负荷变化的初步尝试。在这种成熟的靶向治疗模式中，两个队列之间的最大体积反应程度存在差异，这表明需要进一步研究以优化联合临床试验的设计和解读。
