Histotripsy is the first image-guided ablation technique that is non-invasive, non-ionizing, and non-thermal. Credit: Marcin Szczepanski/Michigan Engineering
In a prime example of “better something than nothing,” researchers at the University of Michigan have shown that if non-invasive sound waves destroy 50% or more of a liver tumor, the immune system kicks in to clear away the rest.
In pre-clinical models with rats, more than 80% of the animals showed no evidence of recurrence or metastases at a 12-week follow-up.
"Even if we don't target the entire tumor, we can still cause the tumor to regress and also reduce the risk of future metastasis," said Zhen Xu, professor of biomedical engineering at U-M and corresponding author of the study.
Regardless of method, it is typically difficult to target and remove the entirety of a cancerous tumor due to size, location and/or stage. That’s why, for the first time, Xu and her colleagues focused on partial tumor ablation, hoping to generate data on effectiveness under less-than-optimal conditions.
The researchers used a relatively new technique called histotripsy, which uses ultrasound waves to destroy cancerous tissue. Using high-pressure, microsecond-length ultrasound pulses, the method forces gas nuclei in target tissue to expand to over 100 µm. These violent and extremely localized mechanical stresses then strain and disrupt cancer cells, breaking up the tumor's structure.
For the study, published in Cancers, the research team treated rats with tumor growth of 5 to 10 mm by delivering 1 to 2 cycle histotripsy pulses at 100 Hz PRF using a custom-built 1 MHz transducer. They targeted only 50 to 70% of the overall tumor volume.
According to subsequent MRI results, complete local tumor regression was demonstrated in 9 of the 11 (81%) histotripsy-treated rats, with no local recurrence or metastasis up to the 12-week study end point. In comparison, 100% of the untreated control rats showed local tumor progression, developed metastases, and were euthanized at 1 to 3 weeks.
Additionally, in the 9 successfully treated rats, histotripsy caused no harmful side effects—unlike current treatment approaches such as radiation and chemotherapy. In fact, the only sign of histotripsy treatment in the rats was a less than 1 mm residual scar observed on histology.
“Histotripsy has been shown to completely ablate the target tissue into a liquid consistency acellular homogenate, which is resorbed by the body within 2 months, leaving mm-length scar tissue,” the researchers explain in their paper.
Liver cancer ranks among the top 10 causes of cancer-related deaths worldwide and in the U.S. Even with multiple treatment options, the prognosis remains poor with 5-year survival rates less than 18% in the U.S. The high prevalence of tumor recurrence and metastasis after initial treatment highlights the clinical need for alternative treatment options such as histotripsy, which is gaining clinical popularity. In fact, after many successful pre-clinical trials, the technique is now being used in a human liver cancer trial in both the U.S. and Europe.
“We hope that our learnings from this study will motivate future preclinical and clinical histotripsy investigations toward the ultimate goal of clinical adoption of histotripsy treatment for liver cancer patients,” said first author Tejaswi Worlikar, a biomedical engineering doctoral student at the University of Michigan.
It’s not just liver cancer, though. Making minor adjustments, other pre-clinical histotripsy investigations have demonstrated the ablation of kidney and prostate tumors, as well.
“The mechanical strength of different tissue types impacts their resistance to histotripsy-induced damage, which can be exploited by selecting optimal parameters for achieving tumor-selective damage, while simultaneously protecting the structural integrity of large blood vessels, nerves, and bile ducts, within the ablation zone,” the researchers explain.
Xu’s research group, specifically, has produced promising results on histotripsy treatment of brain therapy and immunotherapy.