Treatment of Tumors Using Ultrasound? The First Results of the Use of Histotripsy Look Promising

Destruction of Tumor Tissue by Ultrasound

Histotripsy represents a non-invasive, non-ionizing, and non-thermal ablation technique that destroys tumor tissue using the principle of acoustic (ultrasound) cavitation. Essentially, it's not a brand-new concept − the principle of acoustic cavitation has been successfully used for a long time in the therapy of kidney and urinary tract stones. The principle involves creating powerful and short ultrasound pulses that induce a short-term gas expansion in the target tissue cells (up to 100 μm) with subsequent collapse within a few hundred microseconds. The high mechanical stress induced by ultrasound cavitation disrupts cell integrity and causes cell death. Through histotripsy, the target tissue is thus destroyed, resulting in an acellular homogenate of liquid consistency that transforms into small scar tissue within 2 months.

From the results of studies published so far, histotripsy appears to exhibit several beneficial indirect effects, in addition to its direct mechanical impact, in the form of immunostimulatory and systemic effects. By destroying the majority of the tumor tissue, it changes the balance of forces and gives the advantage to the immune system in subsequent battles in immunocompetent individuals.

Study Results

The effectiveness and safety of histotripsy have been tested in laboratory conditions for two decades. Liver malignancies were chosen as the model system, representing one of the top 10 causes of death worldwide, most commonly seen as hepatocellular carcinoma or metastases from other primary tumors. Despite the availability of various non-invasive and invasive treatment modalities, liver malignancies are still associated with poor prognosis and short survival times.

One of the groundbreaking studies on the histotripsy method is the study recently published by Worlikar et al. The aim was to determine the effect of partial tumor ablation using histotripsy (approximately 50–75% of tumor tissue) on the progression of the remaining tumor tissue, survival, risk of metastasis, and immune system infiltration in a model of orthotopic metastatic hepatocellular carcinoma in immunocompetent rats. The results were quite surprising − complete tumor regression was recorded on magnetic resonance imaging in 81% of the rats (9/11), and tumor-free survival was observed for the rest of the study period (the next 12 weeks). In contrast, the control group saw tumor progression in 100% of the animals (n = 11), necessitating euthanasia within 1–3 weeks after the start of the study. The survival results were significantly better in the therapeutic group compared to the controls (p < 0.0001). Histological examination performed on days 2 and 7 after therapy showed increased infiltration of CD11b⁺, CD8⁺, and NK cells in the tumor tissue compared to controls, which might explain the regression of the tumor portion not directly affected by histotripsy.

The first human studies testing the effectiveness and safety of the method in patients with liver malignancies are currently underway. The results of one of these studies are already available. The study published by Vidal-Jove et al. demonstrated the feasibility of planned ablation with histotripsy without identifying serious adverse effects of the treatment. The study involved 8 patients, all of whom achieved local tumor control, and 2 even showed stabilization of lesions not affected by histotripsy.

Conclusion

Histotripsy could become a promising non-invasive modality for treating malignant tumors in the future, not just in liver tissue. However, it is necessary to await the results of studies evaluating the effectiveness and safety of this method in human patients.

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Sources:
1. Worlikar T., Zhang M., Ganguly A. et al. Impact of histotripsy on development of intrahepatic metastases in a rodent liver tumor model. Cancers (Basel) 2022; 14 (7): 1612, doi: 10.3390/cancers14071612.
2. Vidal-Jove J., Serres-Creixams X., Ziemlewicz T. J., Cannata J. M. Liver histotripsy mediated abscopal effect-case report. IEEE Trans Ultrason Ferroelectr Freq Control 2021; 68 (9): 3001–3005, doi: 10.1109/TUFFC.2021.3100267.