Basis and prospects of radiotherapy combined with high‑intensity focused ultrasound ablation (Review)

Radiotherapy (RT) and high‑intensity focused ultrasound (HIFU) are important local treatments for solid tumors; however, they have notable limitations. RT can damage the surrounding normal tissues and vascular system, limiting the maximum dose that can be safely delivered to the tumor, and potentially contributing to local recurrence. Furthermore, RT courses are typically protracted and cannot easily be repeated in the same field. The efficacy of RT is also reduced in radioresistant cells, such as those in hypoxic niches or in specific cell cycle phases. By contrast, HIFU achieves non‑invasive tumor ablation through focused thermal energy while sparing adjacent tissues. However, its use is restricted to tumors without air or bone in the ultrasound path, such as those in the liver or prostate. Currently, HIFU is primarily used for palliation and cannot eradicate subclinical diseases. Its optimal integration with other modalities remains unknown. A synergistic combination of RT and HIFU has been proposed to overcome these limitations. Preclinical studies have indicated that HIFU can effectively target radioresistant tumor regions, whereas RT can reduce tumor volume and alter the tumor microenvironment, thereby enhancing subsequent HIFU ablation. Some clinical research on cancer, including hepatocellular carcinoma and pancreatic, prostate and bone metastases, suggests that this combined approach can improve outcomes such as pain relief, local control and survival, with a manageable safety profile. The present review summarizes the fundamental rationale and accumulates clinical evidence supporting the combined use of RT and HIFU, and discusses the current challenges and future directions for this integrated approach.