Ultrasound: A New Cancer Treatment

Sound Waves That Heal: A New Dawn in Cancer Therapy

A revolution in cancer therapy is emerging, replacing the surgeon's knife with the precision of sound. This new frontier, utilising focused high-frequency ultrasound, offers innovative methods for targeting malignant tumours without invasive procedures. These techniques are heralding a modern period of medical possibility, where recovery times are shortened, and the harsh side effects of traditional therapies may become a thing of the past. The approach promises a fundamental shift in how oncology is practised, offering hope for less traumatic and more effective patient care. An expanding collection of research suggests that ultrasound can not only destroy tumours but also manage secondary cancerous growths and enhance the effectiveness of other treatments.

This evolution in medical technology stems from decades of dedicated research and fortuitous discoveries. Scientists are employing the force of sound in ways previously confined to diagnostic imaging, turning a tool for viewing the body's interior into a weapon against disease. The implications are profound, potentially changing the standard of care for several types of cancer and offering new avenues for patients with limited options. As this technology matures, it heralds a future where cancer treatment is less about enduring hardship and more about targeted, gentle healing.

A Serendipitous Discovery in Michigan

The journey towards this new therapy began unexpectedly in a University of Michigan laboratory at the start of the 2000s. Zhen Xu, then a student pursuing her doctorate in biomedical engineering, was exploring methods to eliminate unhealthy tissue without having to perform surgical procedures. Her research centred on harnessing high-frequency acoustic waves to physically disintegrate tissue, a concept she was testing using pig hearts. The powerful amplifier required for her experiments, however, produced a disruptive noise that drew complaints from her colleagues who occupied the same laboratory space.

To accommodate her peers, Xu decided to modify her experiment. She increased the frequency of the ultrasound pulses, a change that would push the sound beyond the audible spectrum for humans. To her immense surprise, this adjustment not only silenced the complaints but also yielded a dramatic and unforeseen result. The higher pulse rate, with each pulse lasting only a microsecond, had a greater impact on the living tissue compared to her previous methods. In less than a minute after application, a cavity materialized within the tissue of the pig heart, a breakthrough moment that felt almost dreamlike to the young researcher.

The Birth of Histotripsy

Decades after that pivotal moment in the lab, Zhen Xu's accidental discovery has evolved into a recognised medical procedure referred to as histotripsy. The name itself, derived from Greek, means "soft tissue breakdown," a fitting description for its mechanical action. This technique stands as a leading example of the way ultrasound is transforming cancer therapy, offering a non-invasive alternative to traditional surgery. The US Food and Drug Administration (FDA), in October 2023, approved histotripsy for addressing liver malignancies, a significant milestone that validated years of research and development.

This approval was followed by promising results from a compact study backed by HistoSonics, the business entity established to bring Xu's technology to the medical community. The study demonstrated a technical success rate of 95% against tumours in the liver. Although potential side effects like abdominal pain or internal bleeding exist, extensive research indicates that complications are infrequent, establishing the method as generally safe for patients. This regulatory and clinical validation has paved the way for its adoption in healthcare systems worldwide, marking a new chapter in the fight against liver cancer.

NHS Adopts Pioneering Treatment

In a landmark decision in June, Britain became the first nation in Europe to give histotripsy the green light. The National Health Service (NHS) has made the treatment available as part of its Innovative Devices Access Pathway, a preliminary program created to accelerate promising technologies for areas of clinical need. This move signals a significant vote of confidence in the potential of ultrasound-based therapies and places the UK at the forefront of adopting cutting-edge cancer treatments. Patients at Addenbrooke's Hospital in Cambridge are among the first in Europe to benefit from this technology as part of their standard clinical care.

The introduction of histotripsy into the NHS offers a less invasive choice available to individuals with liver cancer, a disease with rising incidence rates in the UK. It is frequently possible to complete the procedure in one visit as an outpatient, sometimes in as little as 30 minutes, eliminating the requirement for a hospital stay. This not only improves the patient experience but also has the potential to free up valuable hospital resources. The technology's arrival is seen by many clinicians as a "game-changer" in terms of both safety and patient comfort.

How Ultrasound Targets Cancer

For many, the term "ultrasound" is synonymous with pregnancy sonograms. In medical imaging, a handheld device called a transducer directs high-frequency acoustic energy into the patient's body. These waves bounce off internal tissues, and the returning echoes are converted into an image, providing a window into what is occurring below the skin's surface. In cancer therapy, this same fundamental principle is applied with much greater intensity. The acoustic waves are focused upon a minuscule section of a tumour in order to destroy it.

Histotripsy devices, for example, channel this powerful energy into a concentrated area measuring just a few millimetres, what Zhen Xu likens to the end of a colouring marker. A robotic arm positions the transducer with immense precision over the tumour to target the correct area. Ultrasound is administered in swift, powerful bursts, which generate minuscule microbubbles inside the tumour. These bubbles then grow and implode within microseconds, a process that mechanically breaks apart the cancerous cells. The body's immune system then naturally clears away the resulting debris.

A Fast and Non-Toxic Procedure

The entire histotripsy procedure is remarkably swift and minimally disruptive for the patient. As a non-toxic and non-surgical method, it typically allows individuals to return home the very same day as their treatment. HistoSonics reports that most procedures take between one and three hours, though the exact duration varies depending on the size and number of tumours. Often, a lone session is sufficient to destroy a tumour; however, individuals with numerous or bigger lesions might require more than one round of treatment.

This approach stands in stark contrast to the rigours of conventional cancer therapies, such as therapies involving radiation or chemotherapy and surgical procedures. The absence of incisions reduces the risk of infection and complications, and the lack of toxic chemicals or ionising radiation eliminates many of the debilitating side effects associated with other treatments. The rapid recovery time means patients can resume their normal activities much sooner, significantly improving their quality of life during a challenging period. The elegance of the procedure lies in its ability to harness a physical force to achieve a biological outcome with precision and minimal collateral damage.

Unanswered Questions and Limitations

Despite its promising benefits, histotripsy is still a relatively new technology, and there are areas that require further investigation. One of the primary unknowns is the long-term data regarding the return of cancer following the therapy. While initial results are positive, more time is needed to build a robust evidence base that confirms its lasting efficacy. Researchers have also voiced worries regarding the theoretical risk of the procedure seeding fresh cancerous growths when tumours disintegrate internally. However, this fear has not been substantiated in trials involving animals conducted to date.

Furthermore, histotripsy may not be a universal solution for all cancers. Bone can act as a barrier, blocking the ultrasound waves from reaching their intended target, which rules out its use for tumours in specific sites. Treating tumours in organs containing gas, such as the lungs, might also be hazardous, as the ultrasound energy might cause unintended harm to adjacent healthy tissues. Nevertheless, HistoSonics is actively conducting studies to explore histotripsy as a possible therapy for cancerous growths of the kidney and pancreas, aiming to expand its application.

An Older Sibling: HIFU

Histotripsy is not the first application of ultrasound for therapy within oncology. A more mature technology called High-Intensity Focused Ultrasound (HIFU) has been employed for many years to target tumours. This method operates on a different principle: it applies a concentrated burst of ultrasound to generate intense heat, in essence, "cooking" the malignant tissue. Richard Price, at the Focused Ultrasound Cancer Immunotherapy Center at the University of Virginia where he is a co-director, compares the process to employing a magnifying lens on a bright day to cause a leaf to ignite, but with sound energy instead of light.

Within the field of oncology, HIFU is likely best recognized as a non-surgical treatment for prostate cancer. A 2024 study indicated that its effectiveness is broadly comparable to that of surgery for localised prostate cancer. Individuals might feel some discomfort and experience adverse effects on the urinary system right after the procedure, but the recovery period is generally more rapid than following a major operation. This allows for a quicker return to daily life, a significant advantage for many patients facing a difficult diagnosis. The procedure highlights ultrasound's utility as a therapeutic instrument.

Safety Measures and Constraints of HIFU

To ensure patient safety and the precision of the treatment, typically, both histotripsy and HIFU are administered while the patient is under a general anaesthetic. This prevents any movement that could lead to accidental harm to adjacent organs or healthy tissues. A key distinction between the two is that histotripsy does not create the intense heat generated by HIFU, an effect that carries a risk of thermal damage to surrounding healthy structures. This makes histotripsy a potentially safer option in certain clinical scenarios where preserving adjacent tissue is critical.

However, HIFU shares some of the same limitations as histotripsy. Obstruction can also occur from bone or gas, which may block the ultrasound waves, preventing them from reaching the targeted tumours. Consequently, it is not a suitable treatment for all types of cancer. For individuals with prostate cancer that has disseminated through the body, for instance, HIFU is not generally considered an option. Despite these constraints, researchers across the globe continue to study HIFU, hoping to apply it to a range of other malignancies, which includes some breast cancer varieties, demonstrating the ongoing effort to expand its therapeutic reach.

Supercharging Treatment with Microbubbles

The therapeutic potential of ultrasound can be greatly boosted by integrating it with contemporary approaches to cancer therapy. One of the most exciting areas of research involves the use of microbubbles. Recent studies suggest that introducing these minuscule bubbles into the circulation and then using ultrasound to activate them gives them the ability to create a temporary opening in the blood-brain barrier. This protective layer normally shields the brain from toxins but also prevents many chemotherapy drugs from reaching brain tumours. Purposely and temporarily breaching this barrier could be a game-changer for treating brain cancer.

This technique could allow therapeutic agents to reach tumours they are intended to target in much higher concentrations. Richard Price describes the drug-delivery aspect of this method as "truly one-of-a-kind," highlighting its transformative potential. The ability to deliver drugs directly to the site of a brain tumour could dramatically improve treatment outcomes for a notoriously difficult-to-treat cancer. This innovative combination of technologies showcases how creative thinking is pushing the boundaries of what is possible in oncology.

Enhancing Drug and Radiation Efficacy

The benefits of ultrasound-enhanced microbubbles are not limited to brain cancer. At Canada's Sunnybrook Health Sciences Centre, research scientist Deepa Sharma has studied this combination across various cancer types. Her findings indicate that it has the potential to significantly improve how drugs are delivered to tumours all over the body, making treatments more effective. This could mean that lower doses of chemotherapy are needed, potentially reducing the severe side effects that often accompany this form of treatment.

Furthermore, Sharma's research suggests that ultrasound-stimulated microbubbles can also amplify the results of radiation therapy. Inflicting harm on the blood vessels within tumours, this technique can lead to greater cancer cell death. This finding implies that doctors could use smaller, safer doses of radiation to get the same clinical outcome, again with fewer devastating long-term consequences for the patient. The ability to enhance the efficacy of existing treatments without increasing their toxicity is a significant step forward in the quest for gentler and more effective cancer care.

A Powerful Ally for Immunotherapy

Ultrasound also appears to be an excellent partner for immunotherapy, which is a therapeutic strategy that harnesses the body's own immune response to combat cancer. Immunotherapy works by helping immune cells recognise and attack malignant cells that could otherwise elude the body's inherent defenses. However, it is not effective for all patients or all types of cancer. Focused ultrasound may help to overcome this limitation.

When focused ultrasound applies heat and causes damage to tumours, it appears to render these malignant tissues more conspicuous and susceptible to the immune system. Exploring this synergy is a key focus at Richard Price's research centre. The process can effectively turn "cold" tumours, that the immune system tends to overlook, into "hot" tumours that provoke a strong immune response. This could significantly expand the volume of patients who can benefit from immunotherapy, opening up new fronts in the war against cancer.

The Ultimate Goal: A Body-Wide Response

An important avenue for subsequent investigation is to determine whether the pairing of ultrasound with immunotherapy can be effective against advanced-stage, or metastatic, cancer. Once cancer has disseminated body-wide, the extraction of one tumour ceases to be an effective strategy. The ultimate goal would be to employ ultrasound to break apart one tumour, which would reveal its specific markers to the immune system. In principle, this could set off a body-wide assault on malignant cells, regardless of their location.

This concept, if proven effective in clinical trials, would be a monumental breakthrough in oncology. Richard Price suggests that medical professionals might one day tackle "a multitude of tumours just by addressing a single one." This would transform the treatment of metastatic cancer, which is currently a far greater challenge to manage compared to localized illness. While clinical trials remain in their initial phases, the theoretical potential of this approach offers a profound sense of hope for patients with advanced cancer.

A New Chapter, Not a Panacea

It is important to maintain a balanced perspective. Ultrasound is not a "panacea" for cancer. Similar to all medical procedures, it comes with its own collection of drawbacks and limitations. The ongoing clinical trials will be crucial in determining its precise role in patient care. A great deal of additional research is needed to fully understand when and how these combined approaches can be most effectively deployed. The scientific community remains cautious but optimistic about the future.

Nevertheless, the techniques presently being used are marking a new phase for cancer treatment. These technologies aim to either replace or significantly improve upon the effective-yet-often-devastating therapies such as surgery, radiation, and chemotherapy. The overarching goal is to make cancer treatment less of an ordeal for patients. Zhen Xu, whose serendipitous discovery helped to launch this field, acknowledges that cancer is an awful disease, but she believes that the treatment should not compound the problem.

A Future of Gentler Healing

The journey of ultrasound from a simple imaging tool to a sophisticated therapeutic weapon is a testament to scientific ingenuity and perseverance. From an accidental discovery in a noisy laboratory to its approval for use in the NHS, this technology has come a long way. Researchers like Zhen Xu and Richard Price, along with countless others around the world, are driven by a common goal: to find better, kinder ways to treat cancer.

As these technologies continue to be refined and their applications expanded, they offer the promise of a future where cancer treatment is more precise, less invasive, and more tailored to the individual patient. The ability to destroy tumours, enhance drug delivery, and boost the immune system, all with acoustic energy, represents a paradigm shift in medicine. The ultimate hope is that these innovations will assist in shielding patients from avoidable distress for many years ahead, turning the tide in the long and arduous battle against cancer.