Text | China Science News trainee reporter Ye Manshan
"Director Yang, I can eat and drink normally now, and I have no problem walking on the ground, and I feel very good, thank you. Today, I was finally able to be discharged from the hospital with peace of mind. At the Wuwei Heavy Ion Center in Gansu Province, 69-year-old Uncle Huang was describing his condition to Yang Qianzi, the deputy chief physician.
Uncle Huang has advanced lung cancer, which cannot be removed by surgery because the lung tumor is too large and close to the stomach and intestines. On September 28, 2023, he was successfully treated after minimally invasive surgery to insert an isolator (gauze pad) to separate the tumor from the gastrointestinal tract, and then administered a high-dose heavy ion therapy.
Since the discovery of the Bragg peak, which releases energy when high-velocity ions come to a halt in the movement of high-speed ions through an object, mankind has been exploring the possibility of using protons and heavy ions to treat cancer. From 1946, when American physicist Robert Wilson first proposed the idea of using proton beams to treat tumors, to 1994, when the world's first heavy ion cancer treatment center was built in Chiba, Japan, a series of developments have attracted great attention from the world.
In this field, China is not inferior, and its self-developed heavy ion cancer treatment device has been settled in many cities. This important instrument of the country not only demonstrates the leading strength of the mainland in the field of heavy ion cancer therapy, but also represents a huge leap in cancer treatment technology. With its unique advantages, heavy ions are unique in the field of cancer radiotherapy and are known as one of the most advanced, scientific and effective therapies today.
From scratch, research and development equipment
In 1988, the Institute of Modern Physics of the Chinese Academy of Sciences (hereinafter referred to as the Institute of Modern Physics) built the first large-scale heavy ion research device in the mainland, the Lanzhou Heavy Ion Accelerator (HIRFL), which not only provided important experimental conditions for the basic research of medium-energy heavy ion physics in the mainland, but also marked the entry of the continental cyclotron technology into the international advanced ranks. In 1991, Lanzhou Heavy Ion Accelerator National Laboratory was established. In 1992, the device won the first prize of the National Science and Technology Progress Award.
It is by using the heavy ion beams of different types and energies provided by the device that the researchers have completed many scientific experiments and achieved important results with international advanced level represented by the synthesis and research of new nuclides, which also laid the foundation for the next heavy ion treatment of cancer.
One day in November 1993, the wind was howling, but the atmosphere in the conference room of the Institute of Modern Physics was extremely hot, because a seminar was being held here on how to use the large scientific device of heavy ions in the future. Each participant offered a different perspective on how to harness the big science apparatus and get the most out of it.
At this time, Wei Zengquan, then director of the second heavy ion beam application room, stood on the podium. His presentation, entitled "Life Science Research", elaborated on his vision for conducting research on heavy ion therapy for cancer.
Wei Zengquan's speech was like a spark, which instantly ignited the enthusiasm of the scientific researchers present. With the dream of discovering the great potential of the biological effects of heavy ions, they have come up with the idea of carrying out related basic research.
As a student of Wei Zengquan, Li Qiang, director of the biomedical center at the Institute of Modern Physics, still remembers the initial significance of the research. "The reason why we are determined to develop a heavy ion cancer treatment device is because heavy ions, empowered by the accelerator, are like a precise scalpel, which can directly hit the lesion, release huge energy, and annihilate cancer cells in one fell swoop. ”
The heavy ion cancer treatment device can not only effectively prevent the residual and recurrence of cancer cells, but also have less toxic side effects on normal tissues, which can reduce the pain caused by radiotherapy to patients. Therefore, heavy ion therapy for cancer is known as the international cutting-edge radiotherapy technology.
However, there are challenges and opportunities. Due to the lack of relevant international standards and the weak domestic research foundation, the researchers of the Institute of Modern Physics are faced with the arduous task of starting from scratch, catching up with the pace of international research and realizing localization.
"At that time, although we knew the huge potential of heavy ion therapy for cancer, it was the first time that we developed a large-scale medical device as a scientific research unit. Xiao Guoqing, former director of the Institute of Modern Physics and head of the medical heavy ion accelerator industrialization project, recalled. Even though there are many difficulties, in order to achieve a breakthrough in domestic technology, all scientific researchers are holding back their strength and vowing to gnaw this "hard bone".
In June 1995, the research project "Basic Research on Advanced Technology in Nuclear Medicine and Radiotherapy" was selected into the National Climbing Program B, and received the support and cooperation of the state and local governments. The relevant departments have provided a variety of human tumor specimens for research, so that the Institute of Modern Physics can build a laboratory equipped with cutting-edge instruments and equipment to comprehensively carry out experimental research on radiation biology and medical physics, as well as animal experiments.
In the early stages of exploration, a central question is how to precisely match the amount of energy required according to the depth and size of the tumor. It's like a precision missile strike, both to ensure that the energy penetrates deep into the tumor and to avoid harming healthy tissue.
Wei Zengquan led the scientific research team to first explore the different ion beam energies required for different tumor depths. At the same time, in order to solve the problem that the shape of the ion beam must be equal to the shape of the tumor, they adjusted the light bar and modulated the beam flow to create a three-dimensional dose sphere that conformed to the shape of the tumor. Thus, the method of artificially controlling the energy and beam shape of the heavy ion beam was born.
A stereododosimeter sphere that mimics the shape of a heavy ion-irradiated tumor. Courtesy of the Institute of Modern Physics
Funding constraints have left researchers with the option to build a local shielded chamber for animal experiments to meet basic experimental needs.
"Among the many heavy ions, which experiment has the best effect, carbon ions, nitrogen ions or argon ions?" Wei Zengquan's team selected animal tumor cells as the experimental subjects, and with the support and cooperation of the Department of Biology of Lanzhou University, after many experiments, many summaries, and gradual improvements, it was finally found that carbon ions had the best effect among all heavy ions.
The success at this moment made Wei Zengquan very excited. This meant that the vision he came up with in 1993 had finally become a reality, and it had also boosted the team's confidence.
A series of exciting results have been followed to confirm that heavy ion therapy is equally effective on human tumor cells. These basic studies have accumulated valuable basic data for the clinical research of heavy ion therapy for cancer, and laid a solid foundation for the research and development of follow-up treatment technologies.
Break through bottlenecks and overcome problems
On March 1, 2006, the first heavy ion therapy device for superficial tumors in mainland China passed the appraisal and acceptance of the expert group. This means that the conditions for clinical trials of heavy ion therapy for superficial tumors are met.
In November of the same year, the research team conducted preliminary clinical trials on four cancer patients using heavy ion therapy technology for the first time. The successful development of clinical trials has made the mainland the fourth country in the world to successfully carry out heavy ion clinical treatment.
Over the next year, the research team worked closely with the hospital to treat the second batch of 9 patients and the third batch of 14 patients using carbon ion beams. These 27 patients involved 12 different cancer types, and all of them achieved significant results. In most patients, the tumor disappeared completely, and the rest of the patients had varying degrees of shrinkage.
What's even more gratifying is that all patients did not experience any local or systemic adverse reactions during the entire treatment process. This result fully demonstrates the great potential and safety of carbon ion radiation therapy in the treatment of a variety of cancers. From 2006 to 2009, the Institute of Modern Physics conducted a total of 103 pre-tumor clinical trials.
Medical physicists use a tank to verify the energy of heavy ion rays. Yuan Haibo/photo
On January 24, 2007, in order to promote the research and application of heavy ion therapy for cancer, the Lanzhou Branch of the Chinese Academy of Sciences, the Institute of Modern Physics, relevant government departments, medical units, as well as domestic radiotherapy experts, accelerator technology and nuclear physics experts gathered together to form a coordination group for heavy ion therapy for cancer.
At the same time, the Institute of Modern Physics established the "Gansu Provincial Clinical Research Base for Heavy Ion Beam Therapy for Tumors", opening a new chapter in the research and application of heavy ion therapy technology.
In July 2008, the cooling and storage ring of Lanzhou heavy ion accelerator passed the national acceptance. Thanks to the major projects deployed by the Chinese Academy of Sciences, the Institute of Modern Physics has completed the construction of the deep treatment experimental terminal and achieved a major breakthrough in key technologies.
In 2009, researchers decided to use the high-energy carbon ions provided by the cooling storage ring of the newly built Lanzhou Heavy Ion Accelerator to carry out deep pre-tumor clinical trial research.
"From 2009 to 2013, a total of 110 patients with deep tumors were enrolled and bravely participated in the pre-clinical trial study. At the same time, we are also in full swing to carry out industrialization work, and are committed to the research and development of a real medical heavy ion accelerator large-scale medical device. Xiao Guoqing said.
encountered a setback for the first time and landed in Gansu
In March 2009, in the office of the director of the Institute of Modern Physics, Xiao Guoqing was a little anxious. He stared at a map on the wall, pointed to the circled place on the map, and said: "It has been several years, but the heavy ion cancer treatment center has not yet landed, and all plans are still in the stage of paper talk. ”
How can technical confidence become a treatment center in reality? Xiao Guoqing thought very clearly: "The Institute of Modern Physics is only a research unit, and it is impossible for it to invest in the construction of a cancer treatment center by itself, and this kind of thing still has to be left to the enterprise." ”
As a result, all parts of the country heard the wind and moved. Xiamen, Guangzhou, Fuzhou and other cities continue to contact the Institute of Modern Physics, striving to build the first heavy ion cancer treatment center in China.
"Our R&D base, processing base, and talent base are all in Lanzhou, and emotionally speaking, we hope that this center can be settled in Gansu. Xiao Guoqing understands that the most important thing at the moment is to implement the market transformation of heavy ion cancer treatment devices. However, the cost of a dedicated device has led some cities to retreat.
What's more, there is a gap between scientific research devices and large-scale medical devices for clinical application, which not only requires technological breakthroughs and dual protection of funds and talents, but also requires the full trust of the medical system.
"Large-scale medical equipment not only needs to be approved by the national health authority, but also needs to consider many factors such as hospital qualifications. At the same time, these devices must obtain a medical device registration certificate from the national drug administration before they can be officially put into clinical treatment. In order to gain these recognitions, we can only continue to explore and find our own way. Li Qiang said.
The extremely strict approval requirements for heavy ion therapy equipment, coupled with the fact that there is no precedent for the approval of domestic medical devices of the same size, make every step from prototype commissioning, equipment testing to clinical trials, and approval and registration like walking on thin ice, and a slight carelessness may fall short.
Due to many reasons, no major hospitals in first-tier cities were found to be the "first person to eat crabs". Seeing that the research results that had taken more than ten years of painstaking efforts could not be implemented, the team members were almost suffocating in the sense of loss and confusion. Everyone silently asks themselves in their hearts: is there any point in doing this?
In order to successfully land the first domestic medical heavy ion accelerator, the research team decided to change their thinking.
On May 2, 2012, the heavy ion tumor treatment center with an investment of 1.6 billion yuan finally started construction in Ronghua Biochemical Industrial Park, Wuwei City, Gansu Province. This marks the official settlement of the malignant tumor treatment center in Wuwei, Gansu Province, and the research and development of heavy ion cancer treatment technology has also taken a substantial step from basic research to people's livelihood application.
A difficult start, but it is beginning to take shape
Wuwei is located in the central part of Gansu Province, at the eastern end of the Hexi Corridor. It is an important node city in the Gansu section of the Silk Road Economic Belt and a national historical and cultural city.
However, when the construction of the Wuwei Heavy Ion Center began in 2012, it was still a lonely building standing in the desert. In addition to the yellow sand, there is an endless wilderness all around.
In the barren land east of Wuwei City and on the southern edge of the Tengger Desert, the builders faced many challenges such as harsh environment, tight funds, and weak team strength. However, they were tenacious like nails, digging deep into this desolate land, overcoming one difficulty after another with perseverance and wisdom.
They have created their own technology of "three-stage decay cooling water tower reuse", successfully achieved zero discharge of radioactive sewage, solved the problem of serious excessive grounding resistance in secondary desert areas, and properly solved the problem of large wind and sand and excessive cleanliness.
For Yang Jiancheng, deputy director of the Institute of Modern Physics, those days are unforgettable. "In the beginning, the working environment was extremely tough, and we had to huddle on the foam board and barely rest. ”
There are dozens of scientific researchers in the team that installed and debugged the heavy ion cancer treatment device. At the beginning of commissioning, the progress was not satisfactory, and the precision of the device was very demanding, and every detail tested their patience and wisdom.
Taking magnetic field accuracy as an example, the magnet parameters had to reach a uniformity of 2/10,000, while the research team could only achieve 3/10,000 at that time. The ions travel about 3 million times a second in the accelerator, and if the accuracy is not up to the mark, the ion beam will deviate every turn, and after 3 million revolutions, the ion beam will not hit the bull's-eye.
The researchers repeatedly adjusted the components, and after half a year of hard work, they finally reached the standard. All the fatigue and suffering of the team members disappeared at that moment. Yang Jiancheng, who usually doesn't like to take pictures, immediately recorded this historic breakthrough moment with photos.
The mainland's first medical heavy ion accelerator device with independent intellectual property rights was officially born, and scientific and technological strength took root in this desolate land.
Medical Heavy Ion Accelerator - Synchrotron. Yuan Haibo/photo
Layout the whole country and go to the market
On November 6, 2018, the head of the medical team gently pressed the button, and the first domestic medical heavy ion accelerator device officially began to treat the first patient.
"We have avoided the technical patents of foreign equipment and designed a unique combination of cyclotron and synchrotron. This structure shortens the circumference of the entire accelerator to 56 meters, while the circumference of the European medical accelerator of the same class is 75 meters, and the circumference of the Japanese accelerator is 62 meters. Yang Jiancheng told reporters that details determine success or failure, especially in the construction of large-scale medical devices.
At the end of December 2015, the Wuwei heavy ion medical device was completed. More than 95% of the parts of this device are made in China, which not only has the same performance and quality as the imported equipment, but also the price is only 1/3 of the imported equipment, and the annual high maintenance cost is also eliminated.
On September 29, 2019, the first domestic medical heavy ion accelerator device "Carbon Ion Therapy System" with completely independent intellectual property rights in mainland China was officially approved and put into operation. As of February 24, 2024, the Wuwei heavy ion therapy device has treated 1,133 patients with remarkable results. The data showed that the 3-year local control rate of 46 clinical trial subjects reached 84%.
Compared with imported equipment, domestic heavy ion therapy equipment not only has advanced technology, low maintenance cost and high cost performance, but also provides continuous technical upgrade services. At present, the importance of independent innovation is becoming increasingly prominent. "The team not only wants to make a medical heavy ion accelerator, but also to do better and be at the forefront of the world. Li Qiang said.
R&D and industrialization team of medical heavy ion accelerator. Yuan Haibo/photo
Nowadays, medical heavy ion accelerators are in full swing in many places. The commissioning of the whole plant of the project in Putian, Fujian Province has reached the design target and is preparing for equipment registration and testing, the main equipment of the project plant in Wuhan, Hubei Province has been installed and will start commissioning soon, and the main equipment of the project plant in Hangzhou, Zhejiang Province has also been installed.
Heavy ion therapy has shown significant efficacy in many solid tumors, especially those that are not inoperable, insensitive to conventional radiation, or recurrent after treatment. With the continuous advancement of technology and the deepening of research, the scope of its indications will be further expanded.
The existing number of equipment is far from meeting the needs of the huge cancer patient population in the mainland. Therefore, the future development direction of medical heavy ion accelerators is miniaturization and low cost.
Yang Jiancheng revealed that the second-generation medical heavy ion accelerator they are developing will have a significant reduction in footprint and power consumption, and the price will be cheaper. Their goal is that the second generation of products occupies only 1/3 of the first generation, reduces power consumption to 1/4, and incorporates more than 20 domestic key patented technologies.
"In the next step, we may use superconductivity to shrink the medical heavy ion accelerator into a room of several hundred square meters. Xiao Guoqing expects that in the future, more hospitals will be equipped with heavy ion accelerators to achieve "double low" equipment cost and patient treatment costs.
Li Qiang has a further dream: "I hope that Continental can become the third heavy ion therapy technology research and development center after Japan and Germany, and set more international standards in this field." ”
Looking forward to the future, they hope to continue to tackle the core technology of heavy ion therapy, and lay a solid foundation in the international field of cancer radiotherapy.