There are several hypotheses about the possible synergistic effect of EBRT and MR-HIFU. By combining both modalities, a substantial proportion of patients with painful bone metastases are expected to experience early pain relief and improved response durability. Additionally, it is recognised that radiation and heat both induce tumour-specific immune responses. Since the mechanism of action of EBRT and MR-HIFU differ, MR-HIFU provides an alternative means to overcome radio-resistance and is recommended for patients with bone metastasis for whom radiotherapy (RT) is considered to have failed.
Moreover, the two methods may be synergistic in first-line, or when applied nearly simultaneously, due to their different mechanisms of action. Heat-induced coagulative ablation is the main action of MR-HIFU, hence its pain palliation effect is expected to be rapid. However, heat distribution is often spatially heterogeneous in bone metastases because absorption of ultrasound energy depends on many factors including the degree of bone lysis or formation, and incident ultrasound angle. Therefore, it might be that the more long-term, systemic responses of EBRT of the tumour and its micro-environment, reduction of tumour-induced compression and inactivation of osteoclasts, can be augmented by local ablation of periosteal nerve ablation by MR-HIFU.