Identification of predictive markers based on functional imaging of metastatic spreading at the time of surgery after neoadjuvant radiotherapy

Neoadjuvant radiotherapy (NeoRT) improves tumor local control and tumor resection in many cancers. The timing between the end of the NeoRT and surgery are driven by the occurrence of side effects or the tumor downsizing. Some studies demonstrated that the timing of surgery and the RT schedule could influence tumor dissemination. Our aim is to evaluate with functional MRI the impact of the radiation treatment on the tumor microenvironment and subsequently to determine the best timing to perform surgery.
We used a model of NeoRT, 4T1 cells were implanted in the flank of BalbC mice. Seven days after, tumors were irradiated with 2x5Gy than we surgically removed this lesion 11 days after RT. Diffusion Weighted (DW) and Dynamic Contrast Enhancement (DCE) -MRI was performed every 2 days during 11 days between RT and surgery. We developed a homemade “portacath” specifically dedicated for mice and for repetitive I.V. contrast agent injection. For DW-MRI, we performed sequences with 10 different B-value to achieve IntraVoxel Incoherent Motion analysis. For DCE-MRI, we used FSEMS sequence for keeping the same slices as with DW-MRI. For both images, we performed analysis on the entire tumor volume.
We obtained very promising preliminary results showing good uniformity in the ADC (Attenuation Diffusion Coefficient). We succeeded to follow mice with imaging during the 11 days without major troubles. We observed less variability of the ADC signal during the 11 days in the irradiated tumors compared to the control. The signal to noise ratio was relatively poor for the diffusion sequence and need to be improved.
For the first time, we demonstrate the feasibility of repetitive MRI functional imaging in a mice model of NeoRT. These results open perspectives for studying modifications of the tumor microenvironment induced by neoadjuvant RT. The techniques need to be improved and correlated to the tumor dissemination in function of the RT schedule and timing of surgery.