Beyond Immunotherapy: Two Precision Physical Therapies Gaining Traction in Oncology, Highlighted in Recent IPO Filings

At the age of six, Emily had already been battling cancer for two years. Despite exhausting all conventional clinical treatments, physicians were unable to stabilize her condition. Just as traditional therapies reached their limits, immunotherapy brought about a miracle. Twenty-eight days after commencing immunotherapy, the six-year-old girl was successfully cured of cancer.

This is Novartis’s CAR-T therapy. When the FDA held its vote on Novartis’s CAR-T therapy this July, Emily was also present at the site.

Since 2014, cancer therapies related to cell therapy and immunotherapies such as PD-1/PD-L1 inhibitors have sparked successive waves of enthusiasm in the global healthcare sector. With the FDA’s approval of Novartis’ CAR-T therapy, industry excitement around immunotherapy has reached unprecedented heights.

Precision medicine technologies, represented by immunotherapy, are transforming existing medical diagnostic models and will bring about a new wave of revolutionary innovation in medicine.

So, does precision medicine include immunotherapy as the only option? Of course not.

At the 2017 Shenzhen International BT Leaders Summit held on September 21, Chen Yazhu, an academician of the Chinese Academy of Engineering and an expert in tumor physical therapy technologies, shared new insights into the application of physical therapy techniques in cancer treatment, beyond immunotherapy. The following is a curated report by VCBeat.

Chen Yazhu, Academician of the Chinese Academy of Engineering, Chair Professor at Shanghai Jiao Tong University, and Expert in Physical Therapy Technologies for Oncology.

Chen Yazhu is a renowned expert in biomedical engineering in China, one of the pioneers of non-invasive medical technology in China, and a leading figure in Zhonglou ultrasonic therapy.

Biomedicine is an interdisciplinary field that represents a deep integration of medicine and the natural sciences. It can be broadly divided into two major areas: one focuses on diagnosis and treatment, addressing existing diseases; the other emphasizes prevention, aiming to prevent diseases before they occur.

Clinical care primarily focuses on the diagnosis, treatment, and rehabilitation of diseases. However, with advancements in technology and a deeper understanding of disease mechanisms, prevention is assuming an increasingly prominent role in healthcare. The aim of molecular diagnostics in oncology is to enable early detection and timely intervention for tumors.

Physical therapies for tumors are commonly used clinical modalities, including X-rays and gamma rays, as well as radiation therapy, ultrasound, radiofrequency, microwaves, laser, infrared, and thermocoagulation devices.

Radiotherapy is a widely recognized modality for cancer treatment. Clément Ader, Wilhelm Conrad Röntgen, and Pierre and Marie Curie can all be regarded as the pioneers of this technology. Modern medical technology has advanced beyond the early stage of targeting whole organs; it has progressed from the macroscopic to the microscopic level, and even to the molecular and genetic levels. This series of advancements has significantly enhanced contemporary radiotherapy techniques.

For instance, a decade ago, Shandong Cancer Hospital was still administering radiotherapy under the guidance of conventional medical imaging; today, however, we can observe radiotherapy technologies based on precision medicine, particularly those leveraging advanced PET/CT techniques.

Proton and heavy ion therapy is the internationally recognized, most advanced radiotherapy technology. Protons and heavy ions both belong to particle beams; when delivering radiation “strikes” against solid tumors, they can deliver potent irradiation to the tumor lesion while sparing normal tissues, thereby maximizing therapeutic efficacy.

Shanghai has taken the lead in establishing a proton and heavy ion therapy hospital. The facility began operations in 2013 and was officially launched in 2014. To date, it has treated more than 200 patients. In addition, proton and heavy ion therapy hospitals have been successively established in Shandong, Lanzhou, and Taiwan. Beyond these four institutions, other regions are also actively making preparations.

What is the global situation outside of China?

It is understood that there are approximately 60 proton and heavy ion therapy centers worldwide, with 21 located in the United States. Apart from the United States, China, and Japan, most countries have a relatively small number of such facilities.

Whether it is proton beam therapy or heavy ion beam therapy, the capital costs, operational expenses, and patient fees are all extremely high. Furthermore, this technology does not achieve a cure in a single session; treatment typically requires multiple fractions. If each session costs RMB 200,000, how many patients can afford such expenses? In addition, cancer is a highly complex disease. Even if proton or heavy ion beam therapy successfully eliminates the tumor, there is no guarantee against future recurrence.

After all, radiotherapy technology has a history of over 200 years, and when combined with intelligent imaging techniques, it offers advantages in terms of maturity and reliability. With technological advancements, radiotherapy has made significant progress compared to ten years ago and is widely recognized as a reasonable treatment method.

High-Intensity Focused Ultrasound (HIFU) Tumor Therapy System is an emerging international oncology treatment platform that integrates ultrasound focusing, magnetic resonance imaging (MRI), and ultrasonic imaging technologies, enabling precise localization and intelligent control.

Focused ultrasound is a novel, non-invasive, safe, and eco-friendly therapeutic technology with minimal side effects, suitable for treating conditions in the brain, eyes, heart, breasts, and other areas. In 2011, Time magazine named it one of the 50 Best Inventions of the Year, and it is internationally recognized as one of the truly non-invasive treatment modalities.

Focused ultrasound is a therapeutic modality that has rapidly emerged in this century. When ultrasound waves propagate through biological tissues, they generate thermal effects, mechanical effects, cavitation effects, and subsequent biochemical effects. The Haijixing (CZF-type ultrasonic therapeutic device), currently well-recognized in clinical practice, leverages these properties to act on pathological tissues, inducing protein denaturation, promoting tissue remodeling, and improving microcirculation to achieve therapeutic outcomes.

Meanwhile, ultrasound can increase the permeability of tumor cell membranes, thereby enhancing sensitivity to radiotherapy and chemotherapy. More interestingly, ultrasound can stimulate the body's immune system, boost immune function, and inhibit the spread of cancer cells.

Ultrasound exhibits favorable tissue penetration, localization, and energy deposition capabilities, enabling it to penetrate superficial tissues and focus on target tissues at specific depths. Compared with conventional chemotherapy and radiotherapy, ultrasound therapy offers superior advantages.

Ultrasound therapy is primarily used to treat uterine fibroids, prostate cancer, benign prostatic hyperplasia, liver tumors, and breast tumors. It can also be combined with ultrasound-targeted drug delivery, and applied in cosmetic and plastic surgery, among other indications.

Ultrasound therapy has demonstrated remarkable efficacy both domestically and internationally. For instance, in the treatment of uterine fibroids, this non-invasive approach preserves the uterus and does not compromise future fertility. Guided by magnetic resonance imaging (MRI) and B-mode ultrasound, ultrasound therapy can achieve thermal ablation of uterine fibroids. This enables non-invasive treatment that does not adversely affect patients’ future quality of life.

This technology has been certified by Harvard Medical School, and InSigh Tec’s products have received FDA approval for the treatment of uterine fibroids. Countries such as Japan and Italy have long incorporated ultrasound therapy into clinical practice.

China introduced ultrasound therapy several years ago. Shanghai General Hospital and Zhongshan Hospital, Fudan University, have both adopted foreign technologies and equipment, cumulatively treating over 300 patients.

Ultrasound therapy has achieved widespread global adoption and continues to be applied and promoted. However, High-Intensity Focused Ultrasound (HIFU) technology still faces numerous challenges, including focusing methods, real-time temperature monitoring, thermal dose control, efficacy assessment, and safety and reliability concerns.

Based on this, a team from Shanghai Jiao Tong University proposed PHIFU (a novel phased-array focused ultrasound multimodal therapy technology), introducing for the first time a multimodal, personalized treatment concept that combines high-temperature ablation with hyperthermia.

By integrating with medical imaging and magnetic resonance imaging (MRI), PHIFU enables precise localization and calibration, facilitating non-invasive temperature measurement and real-time monitoring. More importantly, it allows for real-time assessment of therapeutic efficacy under MRI guidance.

PHIFU is primarily targeted at localized tumors such as uterine fibroids and breast tumors. Multiple MR-PHIFU treatment products have entered clinical trials, with participating companies including Zhonghui Medical, Shanghai Shende Medical, and Ningbo Xingaoyi.

Chen Yazhu revealed that, in addition to localized tumors, the future focal point for PHIFU applications will be major brain diseases. PHIFU can open the blood-brain barrier, allowing large-molecule drugs to reach brain tumors, thereby addressing the current challenge where many drugs are unable to penetrate into the tumor site.

However, intracranial ultrasound requires extremely high precision and rapid focusing, while also avoiding the risks of intracranial cavitation and standing waves. Although successful clinical trials have already been conducted abroad, this research faces numerous challenges, and China currently lags slightly behind.

Whether it is novel radiotherapy techniques or emerging ultrasound-based therapies, as they gradually overcome the limitations of traditional physical therapies, new physical modalities will, alongside biological therapies, become a new trend in cancer treatment.

Current physical therapy is evolving toward the standards of precision and non-invasiveness. Undoubtedly, precision physical therapy will also become an integral part of precision medicine. Rather than engaging in a zero-sum competition, biological therapy and physical therapy should work synergistically to jointly achieve greater precision and efficacy in tumor treatment.