Tumor Microenvironment Modifications Recorded With IVIM Perfusion Analysis and DCE-MRI After Neoadjuvant Radiotherapy: A Preclinical Study.

Purpose: Neoadjuvant radiotherapy (NeoRT) improves tumor local control and facilitates
tumor resection in many cancers. Some clinical studies demonstrated that both timing of
surgery and RT schedule influence tumor dissemination, and subsequently patient overall
survival. Previously, we developed a pre-clinical model demonstrating the impact of
NeoRT schedule and timing of surgery on metastatic spreading. We report on the impact
of NeoRT on tumor microenvironment by MRI.
Methods: According to our NeoRT model, MDA-MB 231 cells were implanted in the
flank of SCID mice. Tumors were locally irradiated (PXI X-Rad SmART) with 2x5Gy and
then surgically removed at different time points after RT. Diffusion-weighted (DW) and
Dynamic contrast enhancement (DCE) MRI images were acquired before RT and every
2 days between RT and surgery. IntraVoxel Incoherent Motion (IVIM) analysis was used
to obtain information on intravascular diffusion, related to perfusion (F: perfusion factor)
and subsequently tumor vessels perfusion. For DCE-MRI, we performed semiquantitative analyses.
Results: With this experimental model, a significant and transient increase of the
perfusion factor F [50% of the basal value (n=16, p<0.005)] was observed on day 6
after irradiation as well as a significant increase of the WashinSlope with DCE-MRI at day 6
(n=13, p<0.05). Using immunohistochemistry, a significant increase of perfused vessels
was highlighted, corresponding to the increase of perfusion in MRI at this same time point.
Moreover, Tumor surgical resection during this peak of vascularization results in an
increase of metastasis burden (n=10, p<0.05).
Conclusion: Significant differences in perfusion-related parameters (F and WashinSlope)
were observed on day 6 in a neoadjuvant radiotherapy model using SCID mice. These modifications are correlated with an increase of perfused vessels in histological analysis
and also with an increase of metastasis spreading after the surgical procedure. This
experimental observation could potentially result in a way to personalize treatment, by
modulating the time of surgery guided on MRI functional data, especially tumor perfusion.