Apr 19 2022

Using Sound To Kill Cancer

Sound can be a powerful form of energy, and is often underappreciated. Remember the weirding modules in Dune, that focused and amplified sound as a weapon? That is not an unrealistic technology. If you are near a powerful explosion, even without being exposed to heat or shrapnel, you can be killed by the pressure wave alone, which can cause significant internal damage.

Sound has also been used for years as a medical tool. You are probably most familiar with ultrasound technology, a non-invasive and safe way to image living tissue in real time. Many parents are familiar with this technology, as it is safe enough to image a growing fetus. But sound can also be used medically to destroy, and this application has many potential advantages.

One such technique is called High-Intensity Focused Ultrasound, or histotripsy. This is the latest approach to using sound to destroy unwanted tissue inside the body. There are older techniques that would use sound wave to heat up tissue and cause thermal damage. Histrotripsy uses a different method, and early research suggests this is a potentially significant step forward. The basics of the technology is the use of two highly focused beams of very short (<50 microseconds) bursts of high intensity sound. Where the beams cross, I am assuming through constructive interference, the intensity is great enough to cause cavitation within the tissue.

Cavitation is negative pressure that will cause a bubble of gases to expand inside the cells. These bubbles then collapse, resulting in significant mechanical stress on the cells that destroy them. Repeated applications of the histotripsy over the same area causes these areas of cavitation to coalesce into one large area filled with “liquified homogenate” – i.e. goo. This process can be targeted by simultaneous ultrasound imaging (the cavities appear bright on ultrasound), which makes the entire setup fairly portable and convenient.

Research so far shows that this process has some advantageous features. First, the cavities of tissue destruction have a smooth edge, and do not damage tissue beyond the zone of destruction. Inside the cavity the liquified tissue is simply absorbed by the body over time, leaving behind a hole where the tumor or whatever used to be. There is limited scar tissue and no thermal damage. For some applications there may be other ways to clear the liquified tissue. For example, when studied on prostate tumors, the liquified tissue is immediately removed through the urethra.

There is also another potential advantage – the process does not denature or destroy proteins. Why is this a good thing? Those intact proteins could be antigens, and those antigens can stimulate an immunological response. A recent study using histotripsy on rat liver cancers found that the technique was very effective in destroying the targeted solid tumor. However, the researchers deliberately left behind intact tumor as a model to see what would happen in cases where it is not possible to destroy an entire cancer. They found that in 80% of cases the rat’s immune system cleaned up the rest of the tumor, and prevented recurrence or metastasis. What is possibly happening is that the liquified tissue, with its intact proteins, is providing a strong stimulus to the immune system to target the remaining cancer cells.

The technology is currently approved by the FDA as a “breakthrough” investigational device. It is not approved yet for clinical applications, which are actively being developed and researched. The “breakthrough” designation means that it has unique advantages over existing technologies (which is important in terms of getting ethical approval for human clinical trials). This approach does not use ionizing radiation, like gamma-knife or other radiation-based technology. Ionizing radiation can cause some damage to surrounding non-target tissue. It also does not use heat, which again can cause some non-target damage. It can be precisely focused, at the millimeter level, and has clean boundaries.

The technology is described as a “platform” because it has multiple applications. The most obvious and perhaps most significant, however, is treating solid tumors. The primary advantage here is that this approach is non-invasive – you don’t have to open the body surgically and physically remove the tumor. You can destroy it through healthy tissue, guided by ultrasound, which is also non-invasive. One concern with removing or debulking solid tumors is that the surgical procedure may increase the risk of metastasis by releasing cancerous cells. It is therefore particularly interesting that this technique may actually decrease the risk of metastasis. First, it does not appear to seed cancer cells because it destroys them in place without cutting into tissue. Second, it stimulates the immune system to target any remaining cells.

I am always careful not to overhype a new technology and to look carefully for potential downsides. However, I can’t think of any. Of course this will not be a panacea, and it will have to be specifically researched for every specific application (tumor type, stage, and location, benign tumors, and any other application where tissue ablation is useful). Otherwise, the research so far is very encouraging and there doesn’t seem to be any major downside. It looks like a pretty solid advance. It would not surprise me if this platform quickly becomes the standard of care for solid tumor removal.

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