IntroductionNasopharyngeal carcinoma (NPC) is a common malignant tumor primarily treated by radiotherapy with or without chemotherapy. Chemoradiotherapy frequently contributes to cognitive impairments, which are associated with abnormal brain activity. This study aimed to longitudinally explore the stage-specific changes of regional spontaneous brain activity in NPC patients during different phases of chemoradiation treatment.MethodsTwenty patients diagnosed with stage III-IV NPC were enrolled in this study from January 2022 to December 2023. All patients received two cycles of chemotherapy (1st follow-up) followed by one cycle of chemotherapy plus radiotherapy (2nd follow-up). Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from all patients at baseline, 1st follow-up and 2nd follow-up. Based on rs-fMRI data after preprocessing, the metrics of regional homogeneity (ReHo) and fractional aptitude of low-frequency fluctuation (fALFF) values were calculated and compared to measure the changes of regional spontaneous activity in the brain.ResultsThe NPC patient group showed increased ReHo values in the right middle cingulate gyrus at the 1st follow-up when compared with baseline. In addition, the NPC patient group exhibited increased ReHo values in the left calcarine fissure at the 2nd follow-up when compared with the 1st follow-up. The NPC patient group demonstrated decreased fALFF values in the right inferior temporal gyrus at the 2nd follow-up when compared with baseline.ConclusionThis longitudinal study revealed distinct stage-specific brain activity changes during chemoradiotherapy in NPC patients. Chemotherapy induced transient compensatory increases in ReHo in the middle cingulate gyrus, while subsequent radiotherapy led to increased activity in the calcarine fissure. Combined treatment resulted in decreased spontaneous activity in the inferior temporal gyrus, a key component of the default mode network. These temporal dynamics suggest evolving compensatory mechanisms followed by eventual functional alterations, providing neurobiological insights into the progressive nature of treatment-related cognitive impairments and potential biomarkers for monitoring brain changes during cancer treatment.