Cancer is a leading cause of morbidity and mortality in the US. Each year, there is roughly 1 new case of cancer per 2000 people, and the estimated annual expenditure for cancer care nationally is approximately $150 billion [1]. Medical research has led to significant improvements in treatment options, quality of life, and life expectancy for many types of cancer. One tumor treatment approach that is receiving growing attention is tumor ablation with histotripsy, which is when ultrasound is used to mechanically destroy targeted cancer tissue.
There are multiple types of cancer treatment, not all of which are applicable to each type of cancer. Chemotherapy and radiation therapy are among the most common options [3]; both aim to directly kill cancer cells through drugs and radiation respectively. Immunotherapy aims to boost normal immune processes to kill cancer cells. By contrast, surgery and several forms of nonsurgical ablation are useful for removing or destroying individual tumors. All treatment types have limitations and possible side effects [2]. There is a major need for treatments with fewer side effects and more targeting ability [3].
A relatively new option for tumor treatment is high-intensity focused ultrasound (HIFU). Ultrasound waves at much higher intensities than what is used for imaging are focused on the target region to destroy tumor tissue with minimal effects on the surrounding region [3,4]. Because of the way the sound energy is focused, it can pass through healthy tissue to attack deeper cancer tissue, though more energy is needed to reach and affect deeper tumors [3].
HIFU has been used to treat a variety of solid malignant tumors in a well-defined volume, including in the pancreas, liver, prostate, breast, uterine fibroids, and soft-tissue sarcomas [3]. In particular, HIFU thermal ablation has grown remarkably as an option for early prostate cancer. High intensity ultrasound is widely used to quickly raise the temperature of a tumor to destroy it [3,4]. The benefits of this technique include reduced toxicity compared to other ablation techniques, not requiring incisions or surgery, and fewer complications compared to conventional treatments [3]. Even so, thermal ablation destroys tumors and surrounding tissues via necrosis, which can trigger an inflammatory immune response that may be pro- or anti-tumor depending on the situation [5].
Researchers are also now investigating purely mechanical ablation with high intensity ultrasound, also known as histotripsy. A sequence of pulses produces bubbles in the target tissue (“cavitation”) that lead to tissue disintegration [3-5]. Early in vitro studies showed that histotripsy had a number of promising characteristics for tumor treatment – for example, it can produce lesions with a very defined, sharp border, suggesting that damage to healthy tissue can be minimized [4,5]. In addition, the microbubbles can be visualized with ultrasound imaging for real-time feedback [3]. Preclinical studies have shown the technique’s success in fully ablating tumors in a number of tissue types [4,5].
A recent study focused on the outcomes of partial tumor ablation with histotripsy, due to some evidence suggesting that histotripsy may have inherent immunostimulatory effects. Researchers targeted 50-75% of the tumor in a rat model of aggressive liver cancer. In 9 out of 11 rats in the partial ablation group, researchers saw complete local tumor regression with no local recurrence or metastasis up to the 12-week study end point. In contrast, all rats in the control group had tumor progression and intrahepatic metastases. Survival outcomes were significantly different between groups. Furthermore, increased immune infiltration of CD11b+, CD8+ and NK cells was observed in the treatment group, which may have contributed to the eventual regression of the untargeted tumor region [5].
Additional research is needed to clarify the limitations and long-term outcomes of ultrasound histotripsy for tumor treatment. If current data is confirmed and if the technique is successful in clinical trials, it could significantly advance the state of cancer treatment.
References
- “Cancer Statistics.” National Cancer Institute | National Institutes of Health. Updated September 25, 2020. https://www.cancer.gov/about-cancer/understanding/statistics
- “Types of Cancer Treatments.” National Cancer Institute | National Institutes of Health. (n.d.). https://www.cancer.gov/about-cancer/treatment/types
- Zhou, Y. F. High intensity focused ultrasound in clinical tumor ablation. World Journal of Clinical Oncology, 2011; 2(1): 8–27. doi: 10.5306/wjco.v2.i1.8
- “High-Intensity Focused Ultrasound (HIFU) for Prostate Cancer.” Cleveland Clinic. (n.d.). https://my.clevelandclinic.org/health/treatments/16541-high-intensity-focused-ultrasound-hifu-for-prostate-cancer
- Worlikar, T. M., et al. Impact of Histotripsy on Development of Intrahepatic Metastases in a Rodent Liver Tumor Model. Cancers, 2022; 14(7): 1612. doi: 10.3390/cancers14071612
