Histotripsy in tumor therapy: advances in non-thermal mechanical ablation, immune modulation, and clinical translation

Abstract

Histotripsy is an emerging non-invasive focused-ultrasound technology that mechanically disrupts tissue through controlled bubble activity rather than sustained thermal coagulation. This review distinguishes shock-scattering cavitational histotripsy, intrinsic threshold histotripsy, and boiling histotripsy and relates their pulse regimes, bubble dynamics, tissue effects, monitoring strategies, and evidence maturity. Mechanical fractionation can expose tumor antigens and damage-associated molecular patterns, but immune outcomes vary by submodality, dose, tumor model, treated fraction, and sampling time; no standardized head-to-head evidence establishes a superior immunological approach. Early prospective liver studies demonstrate high technical feasibility and encouraging local control, whereas post-market cohorts also reveal targeting limitations and uncommon but clinically important vascular, thrombotic, and renal complications. Pancreatic investigation remains ongoing, while the renal CAIN study is completed with registry results and a peer-reviewed first-patient report. A clinically useful dosimetry framework should connect delivered acoustic parameters with in situ cavitation, tissue disruption, imaging or acoustic surrogates, and delayed oncologic and immune endpoints. Histotripsy should currently be viewed as a complementary local therapy with a distinctive mechanical mechanism rather than as a proven replacement for established ablation. Standardized reporting, independently adjudicated safety data, and prospective comparative trials are needed to define its durable oncologic and immunological value.