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. 2017 Mar:88:15-20.
doi: 10.1016/j.ejrad.2016.12.028. Epub 2016 Dec 26.

Co-clinical quantitative tumor volume imaging in ALK-rearranged NSCLC treated with crizotinib

Mizuki Nishino  1 , Adrian G Sacher  2 , Leena Gandhi  2 , Zhao Chen  2 , Esra Akbay  2 , Andriy Fedorov  3 , Carl F Westin  3 , Hiroto Hatabu  3 , Bruce E Johnson  2 , Peter Hammerman  2 , Kwok-Kin Wong  2
Affiliations

Co-clinical quantitative tumor volume imaging in ALK-rearranged NSCLC treated with crizotinib

Mizuki Nishino et al. Eur J Radiol. 2017 Mar.

Abstract

Purpose: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Anaplastic lymphoma kinase inhibitor; Co-clinical trial; Computed tomography; Non-small-cell lung cancer; Targeted therapy; Tumor volume.

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Figures

Fig. 1
Fig. 1
Waterfall plots of the proportional tumor volume changes at the maximal response in mice (A) and human (B) cohorts.
Fig. 1
Fig. 1
Waterfall plots of the proportional tumor volume changes at the maximal response in mice (A) and human (B) cohorts.
Fig. 2
Fig. 2
The distribution of the proportional tumor volume changes at the maximal response in mice (A) and human (B) cohorts.
Fig. 3
Fig. 3
Spider plots of tumor volume changes during therapy in mice (A) and human (B) cohorts.
Fig. 3
Fig. 3
Spider plots of tumor volume changes during therapy in mice (A) and human (B) cohorts.
See this image and copyright information in PMC

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