Early changes in apparent diffusion coefficient as an indicator of response to sorafenib in hepatocellular carcinoma

Abstract

Objective: The relationship between apparent diffusion coefficient (ADC) and chemotherapy has been established. However, whether ADC could be considered as a measure for monitoring response to sorafenib in hepatocellular carcinoma (HCC) has not been demonstrated. This study was to investigate the ADC changes of advanced HCC under sorafenib treatment. Methods: Athymic mice with HepG2 xenografts were allocated to two groups: control and sorafenib (40 mg/kg, bid). T2 and diffusion images were acquired at each time point (0, 10, 14, and 18 d post-therapy). Tumor volume and changes in ADC were calculated. Results: Tumor volumes on Days 10, 14, and 18 after treatment showed significant decreases in the sorafenib-treated group compared with the control. Pretreatment ADC values were not significantly different between the control and treated groups. A slow increase in ADC in the peripheral zone of tumors appeared in the treated group, which was significantly higher compared with the control group on Days 10, 14, and 18. In the central part of tumors on Day 10 after treatment, an increase in ADC appeared in the treated and control groups, the ADC of the control group being significantly lower compared with the treated tumors. From Day 10 to Day 14, the ADC map showed a progressive decrease in the central region of tumors in the treated and control groups. However, this change is more significant in the treated groups. Conclusions: Early changes in mean ADC correlated with sorafenib treatment in HCC, which are promising indicators for predicting sorafenib response in this carcinoma.

Free-breathing 3D diffusion MRI for high-resolution hepatic metastasis characterization in small animals

“…To our knowledge, this is the first study to obtain ADC of abdominal metastases in small animals at high magnetic field. The ADC values measured in this study are consistent with previous reports performed on primary tumors: gastric tumor ADC = 0.6-1.2x10 -3 mm 2 /s [31], intramuscular liver tumor ADC = 5-10x10 -4 mm 2 /s [37], intradermally melanoma xenograft ADC =0.53-1x10 -3 mm 2 /s [1], subcutaneous hepatocellular carcinoma ADC = 1-1.2x10 -3 mm 2 /s [8]. The hepatic metastases developed in our study had similar ADC values than brain metastases (1.3µm 2 /ms) induced by breast cancer cells [38].…”

“…Diffusion MRI allows obtaining functional information on tumors, including the physiological states (cell proliferation/density [1,2], apoptosis [3], necrosis [4]), the stages/ grades [5,6]) and responses to treatments. Indeed, diffusion MRI has been shown to be an earlier biomarker compared to tumor volume [7,8].…”

Multiparametric MR diffusion-weighted imaging for monitoring the ultra-early treatment effect of sorafenib in human hepatocellular carcinoma xenografts

“…This discrepancy may be due to the use of CKD‐516 as the VDA, which destroys established tumor vessels; however, the agent used in our study is an antiangiogenic drug that inhibits new vessel formation and thus may have required more time to alter tissue perfusion compared to the VDA . Our results are in good agreement with the results of several previous dynamic contrast‐enhanced MRI and basic science studies, which indicated that the tumor perfusion change after antiangiogenic drug administration should be evaluated after days or even weeks . Furthermore, similar to our results, a study monitoring the early therapeutic response to sorafenib in renal cell carcinoma xenografts using DCE‐MR revealed that the perfusion‐related metric of K trans did not exhibit any changes 24 hours after treatment .…”

Progress of MRI Radiomics in Hepatocellular Carcinoma

“…These results strongly indicated that immune checkpoint inhibitor-based strategies will soon be primary method in the treatment of advanced HCC, and immunotherapy will introduce a new era of HCC therapy. Traditional contrast-enhanced CT and MRI, including functional imaging, are the most commonly used biomarkers for evaluating the therapeutic response in clinical practice ( 159 – 172 ). Research based on contrast-enhanced CT and MR images has shown the value of radiomics and DL in predicting systemic treatment efficacy for advanced HCC ( 23 , 173 – 175 ).…”

“…Traditional contrast-enhanced CT and MRI, including functional imaging, are the most commonly used biomarkers for evaluating the therapeutic response in clinical practice(159)(160)(161)(162)(163)(164)(165)(166)(167)(168)(169)(170)(171)(172). Research based on contrastenhanced CT and MR images has shown the value of radiomics and DL in predicting systemic treatment efficacy for advanced HCC(23,(173)(174)(175).…”