New Technology in Radiotherapy: Heavy Ion Radiotherapy

New Technology in Radiotherapy: Heavy Ion Radiotherapy  

Yan Xiaole¹, Wang Hongwei¹, Li Xuefeng², Hu Tingchao²  

(1. Affiliated Hospital of Inner Mongolia Medical University, 010030; 2. Gansu Wuwei Cancer Hospital, 733099)  

Malignant tumors are the second leading cause of death globally. According to the latest data from the National Cancer Center of China, approximately 4.06 million new cases of malignant tumors are diagnosed annually in China, with about 2.41 million deaths. This means that over 10,000 people are diagnosed with malignant tumors every day in China. Malignant tumors, along with cardiovascular and respiratory diseases, have long been among the top three causes of death in China. The three primary treatments for cancer are surgery, chemotherapy, and radiotherapy. Surgery aims to remove tumors for a cure but is mostly suitable for localized early-stage diseases. Chemotherapy uses chemical drugs to target tumor cells, while radiotherapy employs high-energy rays to damage the DNA of tumor cells, either single or double strands, thereby inhibiting their replication and killing them.  

1. What is Heavy Ion Therapy?  

The goal of radiotherapy is to maximize the release of radiation energy to the tumor area to kill tumor cells while minimizing damage to surrounding normal tissues. Traditional radiotherapy uses photon beams (including X-rays and γ-rays). Over time, traditional radiotherapy has evolved into various forms, such as Gamma Knife, TOMO Therapy, and CyberKnife, all of which fall under photon radiotherapy. Particle radiotherapy, on the other hand, uses particle beams to kill tumor cells, including π mesons, proton beams, and heavy ion beams. Heavy ions are defined as ions heavier than helium (atomic number Z > 2) in the periodic table. Heavy ion therapy typically refers to carbon ion (C6+, a fully ionized carbon atom) therapy. Due to the superior physical dose distribution and biological effects of carbon ions compared to other particles, they stand out among various particle therapies. These charged particles, when accelerated, form proton or heavy ion beams. The energy of high-energy carbon ion beams generally ranges from 100 to 400 MeV/u. When accelerated to about 0.7 times the speed of light, they penetrate the human body and produce the "Bragg Peak Effect," where low energy is deposited in tissues near the tumor target, while most energy is released within the tumor target, inducing DNA double-strand breaks and causing a devastating effect on tumor tissue. Meanwhile, tissues behind the tumor receive minimal damage, thus reducing side effects on surrounding normal tissues.^[2] Additionally, compared to proton beams, carbon ions exhibit higher linear energy transfer (LET), resulting in higher relative biological effectiveness (RBE) and less dependence on oxygen when killing tumor cells.^[1] In simple terms, due to the unique Bragg Peak Effect and higher RBE, heavy ions can deliver precise and powerful strikes to tumor cells, akin to a missile that accurately and efficiently kills tumor cells with high lethality, minimal side effects, and excellent efficacy. Because of their high biological effectiveness and uniform dose distribution, heavy ions are considered the most ideal radiation beams, suitable for reducing the burden of early-stage cancer treatment.  

2. What Diseases Are Suitable for Heavy Ion Therapy?  

With increasing understanding of heavy ion radiotherapy technology and its characteristics, heavy ion radiotherapy has become an important part of tumor radiotherapy. Currently, the focus of research includes dose assessment, reducing toxic side effects, improving cosmetic outcomes for certain diseases, and enhancing local control of diseases. Before selecting heavy ion therapy, it is necessary to assess whether the patient’s irradiation site has inflammation, whether their performance status (PS) score is between 0 and 3, and whether they can maintain a supine or prone position for an extended period. The indications for heavy ion therapy are relatively broad, mainly suitable for the treatment of solid tumors. Generally, diseases suitable for conventional photon radiotherapy are also indications for heavy ion therapy. However, due to the unique radiobiological and physical properties of heavy ion beams, the indications for heavy ion therapy are even broader. Because of its minimal side effects on normal tissues, it is particularly suitable for treating pediatric tumors. Additionally, it has advantages in treating tumors resistant to photon radiotherapy, hypoxic tumors, recurrent tumors requiring re-irradiation, and tumors in special locations. To date, carbon ion radiotherapy has been studied for treating intracranial malignant tumors, head and neck malignant tumors, primary and metastatic lung cancers, gastrointestinal tumors, prostate and urogenital cancers, sarcomas, skin malignancies, breast cancer, gynecological malignancies, and pediatric malignancies.^[3]  

3. The Development of Contemporary Heavy Ion Therapy Technology  

In 1954, the Lawrence Berkeley Laboratory (LBL) in the United States performed the world’s first proton therapy and later focused on heavy ion therapy, finding that the local control rate of tumors was 2-3 times higher than that of conventional photon radiotherapy. Building on this, Japan established heavy ion therapy facilities in Chiba (1994), Hyogo (2002), Gunma (2010), Tosu (2013), Yokohama (2015), Osaka (2018), and Yamagata (2021). Germany also established facilities in Heidelberg (2009) and Marburg (2015), while Italy and Austria built their facilities in 2012 and 2019, respectively.  

China’s research on heavy ion therapy started relatively late. Currently, there are two operational medical carbon ion accelerators in China, located in Shanghai and Wuwei. In 2015, the Shanghai Proton and Heavy Ion Hospital officially began operations. In September 2017, the hospital was certified by the Joint Commission International (JCI), becoming the world’s first JCI-certified proton and heavy ion center. The hospital’s treatment equipment was imported from Germany. By May 6, 2022, the hospital had treated a cumulative total of 4,655 patients. The types of tumors treated cover major categories in China, including nasopharyngeal cancer, intracranial and skull base tumors, early-stage lung cancer, liver cancer, and prostate cancer. The hospital has also developed advanced treatment technologies and facilities, such as rotating treatment beds, rotating treatment chairs, and pencil beam scanning.^[4] The Shanghai Proton and Heavy Ion Accelerator equipment is based on the IONTRIS system from Siemens, Germany, and consists of an ion source, linear accelerator, synchrotron, beam transport system, and treatment system. The entire system is 190 meters long and includes four treatment rooms, three with horizontal beams and one with a 45° beam. Its core component is a 21-meter-diameter synchrotron that can accelerate protons and heavy ions, with proton energies ranging from 50 to 221 MeV and heavy ion energies from 85 to 430 MeV/u, which are adjustable.^[5] Additionally, the IONTRIS system’s unique advantage is the first application of respiratory gating in treatment, enabling dynamic treatment of tumors that move with respiration. During treatment, the beam can be controlled according to the patient’s breathing pattern, adjusting the beam to follow the tumor’s shape, thereby improving the precision of treatment for moving organ targets. ^[6]  

In 2006, the Heavy Ion Research Facility Laboratory (HIRFL) at the Institute of Modern Physics, Chinese Academy of Sciences, established a research team for proton and heavy ion tumor therapy. Using the heavy ion accelerator, the team conducted preliminary clinical trials for heavy ion tumor therapy. After more than a decade of research, in 2019, China’s first medical heavy ion accelerator was built at the Wuwei Heavy Ion Center and received a registration certificate from the National Medical Products Administration. On March 26, 2020, the Wuwei Heavy Ion Cancer Center officially began clinical operations, marking the first domestically developed carbon ion therapy system in China. This carbon ion therapy system uses a third-order resonance slow extraction technique, with key performance indicators reaching international advanced levels. The beam extraction rate exceeds 90%, the duty cycle of the extracted beam reaches 95%, and the beam shutdown time is less than 500 μs.^[7] Additionally, the system can scan beams from multiple angles using treatment heads positioned vertically, horizontally, at 45°, and in a "horizontal + vertical" configuration, significantly improving the efficacy of the carbon ion therapy system.  

4. Heavy Ion Diagnosis and Treatment Process  

1. Outpatient Consultation: Based on the patient’s medical history, the condition is clarified, and an initial assessment is made to determine if heavy ion therapy is indicated. The potential benefits of heavy ion therapy are evaluated based on the type and stage of the tumor.  

2. Multidisciplinary Team (MDT) Discussion: A team of experts, including clinical doctors, radiation physicists, radiation therapists, radiologists, and nuclear medicine physicians, analyzes the tumor’s specific condition and surrounding tissues to further determine if the patient is suitable for heavy ion therapy.  

3. Radiotherapy Planning: The attending physician informs the patient of the detailed treatment methods, steps, and timeline, and obtains informed consent. After creating a mold to fix the patient’s position, CT simulation is used to obtain imaging data of the tumor, and the target area is delineated. The physicist calculates the radiation dose based on the target area, discusses and optimizes the plan with the clinical doctor, and performs dose verification before treatment.  

4. Treatment: Depending on the patient’s condition, the number of treatments and doses vary. Treatment is administered once daily from Monday to Friday, with each session lasting about 10-15 minutes.  

5. Follow-up and Review: After completing the treatment, the attending physician conducts post-treatment examinations and informs the patient of follow-up and review arrangements, including the frequency and methods of follow-up based on the specific situation.  

References  

[1] Malouff TD, Mahajan A, Krishnan S, et al. Carbon Ion Therapy: A Modern Review of an Emerging Technology. Front Oncol. 2020;10:82.  

[2]Ruan H, Okamoto M, Ohno T, et al. Particle radiotherapy for breast cancer[J]. Frontiers in Oncology, 2023, 13: 1107703.  

[3] Malouff TD, Mahajan A, Krishnan S, et al. Carbon Ion Therapy: A Modern Review of an Emerging Technology. Front Oncol. 2020;10:82.  

[4] Introduction to Shanghai Proton and Heavy Ion Hospital[N]. [https://www.sphic.org.cn/yyjs/index_3.aspx](https://www.sphic.org.cn/yyjs/index_3.aspx) (Retrieved on June 1, 2022).  

[5]Liu P, Zhu J. Preliminary Exploration of the Operation of Shanghai Proton and Heavy Ion Accelerator Equipment[J]. Chinese Journal of Radiological Medicine and Protection, 2016, 36(8): 639-640.  

[6]Pang C, Su Y, Xu J, et al. Study on Radiation Field Caused by Proton Beam Loss in High Intensity Heavy-Ion Accelerator[J]. Atomic Energy Science and Technology, 2015, 49: 573-577. DOI:10.7538/yzk.2015.49.S1.0573  

[7]Du X, Liu Y, Liu Y, et al. Progress in Clinical Application of Heavy Ion Therapy System in China[J]. China Medical Device Information, 2022, 28(17): 54-57. DOI:10.15971/j.cnki.cmdi.2022.17.028