Assessment of ultrasound effects in human and animal tumors

Ultrasound can be used in various ways for tumor therapy. In this work, two approaches were investigated. The first approach addressed the question of whether CDUS, with a high mechanical index, that involves the destruction of microbubbles, affects tumor perfusion in breast cancer patients to improve response to chemotherapy. Although no improvement in tumor perfusion and response to therapy could be found in patients, destruction of tumor vessels was observed in mouse breast tumors. Differences in the tumor physiology of human and murine breast tumors could explain this contradictory effect. In contrast, a diagnostic ultrasound protocol without microbubble destruction resulted in higher perfusion and macrophage infiltration in mouse tumors. Understanding how ultrasound can alter tumor pathophysiology is important to improve therapeutic application and avoid unknown tumor interference. Therefore, in the second approach, the suitability of ultrasound to induce immune responses in tumors was investigated by a systematic review and several meta-analyses. A systematic review protocol to answer the research question: Does ultrasound alter the immune reaction of peripheral solid tumors in humans and animals compared to control conditions without ultrasound? was developed, registered, and published. After systematically reviewing the literature, data from 96 articles were extracted and analyzed in meta-analyses. The meta-analyses showed that ultrasound treatment triggered an immune response in tumors and increased inflammatory markers in the blood. Subgroup analyses revealed a potential dependence on various experimental characteristics and a combined influence of multiple factors. In particular, stronger effects were observed in young, immature mice, which leads to an overinterpretation of the study results and possibly complicates clinical translation.