Experimental study on the feasibility of optimizing chemotherapy regimen for mouse model of 5-FU resistant gastric cancer by the early changes of apparent diffusion coefficient after chemotherapy / 中华放射学杂志

ABSTRACT

Objective:To prospectively guide the change of chemotherapy regimen in mouse 5-fluorouracil (5-FU) resistance subcutaneous xenograft tumor model derived from gastric cancer patients by the early changes of MRI apparent diffusion coefficient (ADC), and to compare the difference of tumor load between ADC guided dressing change group and volume guided dressing change group.Methods:From January to June 2020, thirty patient-derived xenografts mouse models were established using 5-FU resistant gastric cancer cells coming from patients, and were randomly divided into experimental group and control group by AdaBoost algorithm, with 15 mice in each group. On the 26th day after transplantation, all mice began chemotherapy with 5-FU as the first-line chemotherapy drug, and underwent MR examination once every two days, including T 2WI and diffusion weighted imaging (DWI). Volumes of tumors were measured using an open-source software ITK-SNAP and values of ADC were measured on ADC maps. According to the change rate of tumor ADC value in the experimental group and the tumor volume growth rate in the control group, the replacement time of chemotherapy drugs was determined, and 5-FU was replaced by paclitaxel. The end point of the experiment was the day that the mice entered the cachexia state. Independent-sample t test was used to compare the difference of tumor load between the two groups. Results:After 5-FU treatment, the ADC value of the two groups both increased. The ADC value began to decline on the 4th day after chemotherapy, and the experimental group continued chemotherapy with paclitaxel instead of 5-FU at this time point. The tumor volume growth rate of the control group increased significantly on the 6th day after chemotherapy (from 8.6% to 16.1%), and the control group used paclitaxel instead of 5-FU chemotherapy at this time point. The observed end point was on the 18th day after chemotherapy. The tumor load of the experimental group [(1.82±0.09) cm 3] was lower than that of the control group [(2.01±0.09) cm 3], and the difference was statistically significant ( t=2.25, P=0.033). On the 16th day after chemotherapy in the experimental group and the 18th day after chemotherapy in the control group, the time of paclitaxel administration in both groups was 12 days. The tumor load in the experimental group [(1.61±0.12) cm 3] was also lower than that in the control group [(2.01±0.09) cm 3], and the difference was statistically significant ( t=2.03, P=0.040). Conclusions:For the subcutaneous transplantation model of 5-FU resistant gastric cancer mice, according to the early changes of tumor ADC value after chemotherapy, the replacement of chemotherapy drugs can obtain a lower tumor load, suggesting that it is a feasible method to optimize the chemotherapy regimen.