Abstract
Antivascular therapy is a promising approach to the treatment of non-small cell lung cancer (NSCLC), where an imaging modality capable of longitudinally monitoring treatment response could provide early prediction of the outcome. In this study, we sought to investigate the feasibility of using intravoxel incoherent motion (IVIM) diffusion MRI to quantitatively assess the efficacy of the treatments of a vascular-disrupting agent CA4P or its combination with bevacizumab on experimental NSCLC tumors. CA4P caused a strong but reversible effect on tumor vasculature; all perfusion-related parameters-D*, f, fD*, and Ktrans-initially showed a decrease of 30% to 60% at 2 hours and then fully recovered to baseline on day 2 for CA4P treatment or on days 4 to 8 for CA4P + bevacizumab treatment; the diffusion coefficient in tumors decreased initially at 2 hours and then increased from day 2 to day 8. We observed a good correlation between IVIM parameters and dynamic contrast-enhanced MRI (DCE-MRI; Ktrans). We also found that the relative change in f and fD* at 2 hours correlated well with changes in tumor volume on day 8. In conclusion, our results suggest that IVIM is a promising alternative to DCE-MRI for the assessment of the change in tumor perfusion as a result of antivascular agents and can be used to predict the efficacy of antivascular therapies without the need for contrast media injection. Cancer Res; 77(13); 3491-501. ©2017 AACR.
Highlights
Despite recent advances in treatment, advanced non–small cell lung cancer (NSCLC) remains one of the most lethal cancers
We aimed to investigate whether intravoxel incoherent motion (IVIM) DWI can be used as to characterize early changes in tumor perfusion and diffusion as a result of antivascular therapies, including a combretastatin A4 phosphate (CA4P)-based vascular-disrupting therapy and retreatment using a combination of CA4P and bevacizumab
Even orthotopic models such as Lewis lung adenocarcinoma (3LL) can be used, xenografts of human tumor cells such as A549 and H460 have been used more commonly to investigate vascular disruption in NSCLC xenografts in preclinical studies [35, 36], which have led to a number of clinical trials
Summary
Despite recent advances in treatment, advanced non–small cell lung cancer (NSCLC) remains one of the most lethal cancers. The efficacy of currently available chemotherapy for advanced NSCLC, including platinum-based doublet, crizotinib, gefitinib, erlotinib, afatinib, bevacizumab, and pemetrexed, is still limited [1], suggesting an urgent need to develop effective treatments that can significantly improve the overall survival rates. Vascular-disrupting agents (VDA) are a class of anticancer agents that can selectively attack the tumor vasculature and cause catastrophic vascular shutdown, tumor ischemia, and necrosis [2, 3]. 4), are being investigated in phase II/III clinical trials for advanced. Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).
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