To evaluate the utility of non-Gaussian diffusion parameters derived from the continuous-time random walk (CTRW) and fractional order calculus (FROC) models for early treatment response assessment in nasopharyngeal carcinoma (NPC) and to compare their performance with the apparent diffusion coefficient (ADC). Diffusion-weighted imaging (DWI) with 13 b-values was performed before and during early treatment in 61 patients with newly diagnosed NPC. Parameters derived from the CTRW and FROC models (DCTRW, αCTRW, βCTRW, DFROC, βFROC, µFROC) and ADC, along with their percentage changes, were compared between residual and non-residual groups after concurrent chemoradiotherapy (CCRT) with (n = 56) or without (n = 5) induction chemotherapy (IC), and between partial responders and stable disease groups in the IC subgroup. Group comparisons were performed using the Mann–Whitney U test or t-test, and predictive performance was evaluated using receiver operating characteristic (ROC) and logistic regression analyses. For IC response, Pre-βFROC, Pre-µFROC, and Pre-βCTRW significantly differentiated partial responders from stable disease groups, with Pre-βFROC demonstrating the highest discriminatory performance (AUC = 0.798). A combined model incorporating βCTRW and µFROC further improved prediction (AUC = 0.817). For the CCRT outcome, several Pre- and Δ% parameters differed significantly between residual and non-residual groups. ΔβCTRW% achieved the highest diagnostic accuracy (AUC = 0.822), while combining ΔβCTRW% with ΔADC% yielded the best overall performance (AUC = 0.878). Diffusion parameters derived from the CTRW and FROC models provide sensitive markers of microstructural heterogeneity in NPC and outperform conventional ADC in early treatment evaluation. Pre-βFROC, Pre-µFROC, and Pre-βCTRW are valuable for predicting IC response, whereas ΔβCTRW% shows strong potential for identifying residual tumor after CCRT. Combined predictive models further enhance diagnostic accuracy, supporting non-Gaussian diffusion imaging as a promising biomarker for early efficacy assessment and personalized management of NPC. This study demonstrates that CTRW and FROC non-Gaussian diffusion models provide earlier and more sensitive markers of treatment response in NPC compared with conventional ADC. Their combined application significantly improves the detection of induction chemotherapy efficacy and post-CCRT residual disease, offering a promising imaging-based approach for early treatment monitoring and individualized therapeutic strategies. Non-Gaussian diffusion models (CTRW and FROC) outperform ADC in early evaluation of treatment response in nasopharyngeal carcinoma. Pre-βFROC, Pre-μFROC, and Pre-βCTRW effectively predict induction chemotherapy response, while ΔβCTRW% serves as the strongest indicator of post-CCRT residual disease. Combined Gaussian and non-Gaussian parameters significantly improve diagnostic accuracy and support personalized treatment planning.
Liu et al. (Wed,) studied this question.