Co-clinical quantitative tumor volume imaging in ALK-rearranged NSCLC treated with crizotinib
Mizuki Nishino1, Adrian G Sacher2, Leena Gandhi2
1Department 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.
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.
