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Eur J Radiol. 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.

Author information

1
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. Electronic address: Mizuki_Nishino@DFCI.HARVARD.EDU.
2
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.
3
Department of Radiology, Brigham and Women's Hospital, 450 Brookline Ave., Boston MA, 02215, USA.

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

PMID:
28189201
PMCID:
PMC5560072
DOI:
10.1016/j.ejrad.2016.12.028
[Indexed for MEDLINE]
Free PMC Article

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