Can ADC changes help mRECIST or LI-RADS treatment response algorithm better diagnose pathological response of HCC after preoperative radiotherapy? Secondary analysis of a prospective phase 2 trial

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Abstract Objectives To explore the role of apparent diffusion coefficient (ADC) changes in predicting pathological response to preoperative radiotherapy (RT) in hepatocellular carcinoma (HCC) compared to existing evaluation criteria, using histopathology as the reference standard. Materials and methods Building on the prospective clinical trial, we included 35 patients with 38 HCCs who underwent preoperative RT followed by hepatectomy between December 2014 and January 2019. Pre- and post-RT ADC parameters (ADCroi and ADCslice measured from representative areas and histogram parameters derived from whole-tumor volume) were compared, and the percentage change of parameters (Δ-parameters%) was calculated to correlate with major pathological response (MPR). The modified Response Evaluation Criteria in Solid Tumors (mRECIST) and Liver Imaging Reporting and Data System Treatment Response (LR-TR) categories were evaluated. ROC analysis was performed to assess discrimination performance. Results ADC values, interquartile range, range, variance, mean absolute deviation, robust mean absolute deviation, and root mean squared increased; energy and total energy decreased; and skewness developed into negative skewness after RT. Higher Δ-ADCroi%, Δ-ADCslice%, Δ-ADCmean%, and Δ-ADCmedian% and lower Δ-energy% and Δ-total energy% were associated with MPR. LR-ADCslice showed the best performance, with significantly higher AUC than mRECIST/LR-TR, Δ-ADCmean%, and Δ-ADCmedian% (0.917 vs 0.708, 0.732, and 0.705, respectively; p = 0.005, 0.029, and 0.023). Responders had significantly better RFS than non-responders according to Δ-ADCroi% (p = 0.024). Conclusions ADC changes have the potential to predict the pathological response of HCC to preoperative RT, thereby enhancing current evaluation criteria. Integration of Δ-ADCslice% and LR-TR yielded the best results. Critical relevance statement Δ-ADCslice%, with high performance in predicting pathological response, excellent inter-observer agreement, and the potential to supplement existing evaluation criteria, is a promising method for determining therapeutic response to preoperative radiotherapy and may facilitate the early indication for further surgery. Key Points Precise assessment of hepatocellular carcinoma response is required for patients undergoing preoperative radiotherapy. Radiotherapy induced an increase in ADC values and heightened intratumoral heterogeneity. As the delineated region of interest expanded, AUC decreased and inter-observer agreement increased. Δ-ADCslice% exhibited excellent performance in predicting pathological response and the potential to supplement existing evaluation criteria. Graphical Abstract

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