Concurrent chemoradiotherapy (CCRT) is the main treatment model for locally advanced nasopharyngeal carcinoma (LANPC). Previous study found the apparent diffusion coefficient (ADC) value of primary tumor partly correlated to prognosis for NPC patients. Recent studies reported that the changes of ADC value at pre- and post-treatment was a more sensitive predictor for prognosis. The prognosis for LANPC patients who received the same treatment strategy varies greatly. The early predictor was urgently needed to help for adjusting the treatment strategy. Thus, we aimed to observe the dynamic changes of ADC of gross target volume (GTV) and metastatic lymph nodes (LN) for NPC patients during radiotherapy (RT), and explored the potential correlations between ADC changes and treatment response.A total of 50 squamous NPC (II-IVa, the 8th TNM staging system) patients treated with CCRT were enrolled in this study. All patients received a planned total dose of 66 to 70Gy in 33 fractions at 5 fractions per week using Image-guided intensity modulated radiotherapy (IGRT). The regimen was cisplatin-based chemotherapy for 3 cycles. The patients received diffusion weighted MRI (DWI) scan at pre-RT, the 5th and 15th fractions and immediately post-RT on a 3.0T MRI system (b = 0, 500, 800s/mm2) system. The ADC values of GTV and LN were acquired using a commercially available software. RECIST1.1 criteria was used to evaluate the tumor response. Multivariate analyses were calculated using the logistic regression model. Receiver-operating characteristic (ROC) curve was used to determine the cut-off value of ADC.After the completion of CCRT, the ORR for all the patients was 100% (CR 58%, PR 42%). The mean ADC value of GTV and LN gradually increased from pre-RT to post RT. These changes generally occurred in two stages. For the first stage (from pre-RT to the 5th fraction), the mean ADC value of GTV and LN increased significantly by 20.78% and 22.96% respectively, while the volumes of GTV and LN had minimal changes (GTV:18.42cm3 vs 16.72cm3, LN: 4.67cm3 vs 4.12cm3). As for the second stage (from the 5th fraction to post-RT), the mean ADC value of GTV and LN continued to increase by 45.58% and 41.2% respectively, while the volumes decreased by 86.07% (GTV) and 61.6% (LN). Multivariate analysis showed the mean ADC changes of GTV from pre-RT to the 5th fraction (ΔADC5) was the only independent prognostic factor for treatment response of NPC. ROC showed that the cut-off value for ΔADC5 was 158.82mm2/s (sensitivity:87%; specificity:65%).Mean ADC values of GTV and LN increased dramatically during RT for NPC patients treated with radiotherapy. The mean ADC began to increase at the 5th fraction, while the change of volume was minimal. Early ADC changes at the 5th fraction might be a new and sensitive biomarker to predict the prognosis for NPC patients independently of volume change.Copyright © 2021. Published by Elsevier Inc.