High-amplitude ultrasound pulses have been used to partially destroy liver tumors in rats, triggering the rodents’ immune systems to clear the remaining cancerous cells and prevent the disease from spreading or returning. Presenting their findings in the journal Cancers, the researchers behind this breakthrough say their technique could lead to effective, non-invasive treatments for some of the most intractable cancers in human patients.
Liver cancer certainly falls into that category, and is associated with a five-year survival rate of just 18 percent in the US. Though many treatment options are available, liver tumors have a tendency to metastasize or recur after these interventions.
In their study, the authors explain that conventional cancer treatments like chemotherapy, radiotherapy, and thermal ablation are effective at destroying tumors, yet also trigger a somewhat unpredictable immune reaction which can be anti-tumor or pro-tumor. Furthermore, they note that the size, location, and stage of a tumor can sometimes make it impossible to target the entire tissue mass with existing treatments.
To replicate these clinical complexities, the researchers decided to destroy only part of each tumor, leaving behind a viable portion in the animals’ livers.
They began by inoculating 22 rats with liver cancer cells and allowing these tumors to develop for up to nine days, reaching a size of 5 to 10 millimeters (0.2 to 0.4 inches). At this point, half of the rats were treated using a technique called histotripsy, which involves blasting the tumors with millisecond-long pulses of high-amplitude ultrasound waves.
This generates an effect known as ultrasound cavitation, whereby tiny bubbles develop and burst within the targeted tissue, causing the destruction of cancerous cells. Traditional ultrasound imaging devices, meanwhile, use lower amplitude pulses in order to avoid causing any damage.
Despite only blasting 50 to 75 percent of each tumor mass with histotripsy, the researchers noted that nine of the 11 treated rats showed complete local tumor regression, with no signs of recurrence of metastasis for the remainder of the 12-week study period. In the days following treatment, the team detected an increase in anti-cancer immune cells such as T-cells and natural killer cells within the tumor microenvironment, indicating that histotripsy may stimulate the animals’ immune systems to destroy the remaining cancer and prevent its spread or return.
“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 study author Zhen Xu in a statement.
In contrast, all 11 of the untreated control rats experienced tumor progression and had to be euthanized within three weeks of initiating the study.
“Histotripsy is a promising option that can overcome the limitations of currently available ablation modalities and provide safe and effective noninvasive liver tumor ablation,” said study author Tejaswi Worlikar. “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.”
A clinical trial involving human subjects with liver cancer is currently underway, and is expected to be completed by the middle of next year. Any replication of these preclinical results would represent a major advancement in the battle against cancer.