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

Mizuki Nishino, Adrian G. Sacher, Leena Gandhi, Zhao Chen, Esra Akbay, Andriy Fedorov, Carl F. Westin, Hiroto Hatabu, Bruce E. Johnson, Peter Hammerman, Kwok kin Wong

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)15-20
Number of pages6
JournalEuropean Journal of Radiology
Volume88
DOIs
StatePublished - Mar 1 2017

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Tumor Burden
Non-Small Cell Lung Carcinoma
Therapeutics
Spiders
crizotinib
Adenocarcinoma
Clinical Trials

Keywords

  • Anaplastic lymphoma kinase inhibitor
  • Co-clinical trial
  • Computed tomography
  • Non-small-cell lung cancer
  • Targeted therapy
  • Tumor volume

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

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

In: European Journal of Radiology, Vol. 88, 01.03.2017, p. 15-20.

Research output: Contribution to journalArticle

Nishino, M, Sacher, AG, Gandhi, L, Chen, Z, Akbay, E, Fedorov, A, Westin, CF, Hatabu, H, Johnson, BE, Hammerman, P & Wong, KK 2017, 'Co-clinical quantitative tumor volume imaging in ALK-rearranged NSCLC treated with crizotinib', European Journal of Radiology, vol. 88, pp. 15-20. https://doi.org/10.1016/j.ejrad.2016.12.028
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. / Co-clinical quantitative tumor volume imaging in ALK-rearranged NSCLC treated with crizotinib. In: European Journal of Radiology. 2017 ; Vol. 88. pp. 15-20.
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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.",
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AU - Nishino, Mizuki

AU - Sacher, Adrian G.

AU - Gandhi, Leena

AU - Chen, Zhao

AU - Akbay, Esra

AU - Fedorov, Andriy

AU - Westin, Carl F.

AU - Hatabu, Hiroto

AU - Johnson, Bruce E.

AU - Hammerman, Peter

AU - Wong, Kwok kin

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N2 - 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.

AB - 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.

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KW - Co-clinical trial

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KW - Tumor volume

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