Histotripsy is one such therapy that has the promise of changing cancer care.
It is a completely noninvasive approach akin to radiation oncology without the toxicity due to radiation and to high-intensity focused ultrasound without the problems inherent in thermal deposition in tissue with existing ablative therapies.6 The cellular destruction caused by histotripsy stems from acoustic cavitation of the targeted tissue caused by clusters of microbubbles generated inside the tissue by short, alternating, high-amplitude pulses arising from focused ultrasound. As a result, the tissue destruction consists of a tissue homogenate with limited to no recognizable cellular structure, is extremely precise with a well-defined margin, and can be visualized in real time under ultrasound. In addition, recent software developments have allowed the therapy delivery to a target of virtually any size and shape. Clinical trials have started testing histotripsy as a stand-alone therapy for patients with both primary and secondary liver cancer (Figure 1), but an intriguing prospect about histotripsy is its potential as a combination therapy with immuno-oncology drugs. This is probably the most anticipated aspect of this newest therapy, because histotripsy releases neoantigens that can be recognized by the immune system and therefore exploited in combination with checkpoint inhibitors administered systemically to synergize the primary effect of histotripsy. In this manner, the hope is that unlike the traditional and currently clinically available ablative therapies that are limited to patients with early stage cancers, histotripsy could also be used in combination with systemic drugs either as a primer or adjunct therapy to tackle advanced cancers, which would be a true paradigm shift for locoregional therapies. Such results have been demonstrated in animal models and will need to be replicated in human clinical trials but represent an encouraging development in interventional oncology.6