The ideal way to treat malignant tumors is to kill tumor cells while minimizing damage to adjacent normal tissues. In all current tumor treatment techniques, whether it is traditional surgery, radiotherapy, chemotherapy, or targeted immunotherapy that has achieved major breakthroughs in the past two years, in fact, normal tissue cells will be damaged to varying degrees. Taking brain tumors as an example, radiotherapy and chemotherapy should be performed after surgery, and most of the radiotherapy equipment used in my country is X-ray. In the treatment of low-invasive malignant tumors, in order to achieve a better curative effect, it is necessary to irradiate a certain range of surrounding normal brain tissue. , to achieve the purpose of killing cancer cells to a greater extent, but it often produces severe side effects such as intracranial edema and cognitive impairment. Killing tumors to the greatest extent without harming normal tissue cells is currently the goal of research and development all over the world.
BNCT is an epoch-making cancer treatment that selectively destroys cancer cells without causing severe damage to normal cells. This approach is an effective treatment for highly malignant tumors, such as brain tumors, where healthy and tumor cells are often mixed together. This treatment can precisely kill cancer cells without harming normal cells. Why Boron What's so amazing about neutron capture therapy?
Boron neutron capture therapy is the latest radiation therapy. It is injected by dripping boron-containing compounds. This compound has a strong affinity with cancer cells. After entering the human body, it quickly accumulates in cancer cells (equivalent to our PET scan. time imaging agent), and then irradiated with an epithermal neutron beam for about 1 hour. Neutrons can have a strong nuclear reaction with the boron entering the cancer cells, releasing a highly lethal ray, so as to achieve the effect of blasting the cancer cells from the inside of the cancer cells. At the same time, because the neutron beam is characterized by a very short range, only the length of one cancer cell, it will not harm the surrounding tissue when it kills the cancer cell.
What is the treatment principle of boron neutron capture therapy?
Neutron is one of the nucleons that make up the nucleus, with a mass of 1838 times that of an electron. It is an indispensable component of the nucleus. It was discovered by British scientist Chadwick in 1932. Radiobiological studies have shown that cancerous tissues are usually composed of aerobic and hypoxic cells. Aerobic cancer cells are easily killed by radiation, but hypoxic cancer cells are resistant to X-rays and gamma rays used in conventional radiotherapy. In addition, the electron beam is not sensitive, has strong tolerance, and is not easy to kill, which is the main reason why cancer is easy to recur after conventional radiotherapy.
But strangely, this hypoxic cancer cell is particularly sensitive to neutron rays. After being irradiated with neutron rays, the revival rate of hypoxic cells in the tumor site is almost zero, and the recurrence rate of cancer after surgery is extremely low, which is the unique advantage of neutron cancer therapy. Boron neutron capture therapy uses thermal neutron irradiation to target boron accumulated in the tumor site. When the non-radioactive element boron (10B), which exists in nature, is irradiated with thermal neutrons, a nuclear fission reaction occurs, resulting in a high linear energy conversion. The alpha particle itself decays to 7Li. The α-ray and 7Li particles produced by this technology are very different from X-ray or γ-ray, and their flight distance is short (about the length of one cell). The effect is very small; but the biological effect achieved is more than 2 to 3 times that of X-ray or γ-ray, and the physical effect is equivalent to that of X-ray and γ-ray. Therefore, the radiotherapy community expects better results with BNCT treatment.
Clinical data on boron neutron capture therapy
The theory was born in 1936 and has a history of more than 80 years of development. According to a case report published at the 53rd academic meeting of the Japanese Society for Cancer Therapy held on October 29, 2015 by a research team from Kyoto University and Osaka University in Japan, a clinical trial was conducted on 37 patients with advanced head and neck cancer. After that, the cancer cells disappeared in more than half of the patients.
In addition, from June 2005 to September 2011, BNCT was treated 28 times in 20 patients with recurrent meningioma. All patients had previously received intensive treatment, such as multiple surgeries and multiple radiation treatments. Nineteen of these patients received boron neutron capture therapy. The original tumor size of these patients was between 4.3 cm³ and 109 cm³. After two months of treatment, the mean tumor volume was reduced by 64.5%. The median follow-up time was 13 months. Six patients were still alive at the time of study publication; current median survival times in the boron neutron capture therapy group and post-diagnosis are 45.7 months (32.4-70.7 months) and 14.1 months (8.6-40.4 months), respectively; In symptomatic cases, hemiplegia and facial pain were significantly improved after boron neutron capture therapy. Experts speculate that boron neutron capture therapy may be particularly effective for meningiomas.
Recently, high-precision radiotherapy, proton therapy, has been recognized as the most precise radiotherapy technology in the world because of its ability to precisely and selectively target and kill tumors. Damage to normal tissue, as shown in the figure, the Bragg peak still exposes normal tissue to a portion of the radiation before the proton beam reaches the tumor. Although much less damage to normal tissue than conventional radiotherapy, it still produces radiation. Certain injuries and side effects.
By contrast, boron neutron capture therapy, which allows selective irradiation of cells, is quite different from these approaches. Even normal cells present within the tumor tissue are protected. When illustrated by DVH (dose volume histogram) (bottom panel), the difference is clear: it is observed that the curves of normal tissue dose and tumor (cell) dose do not intersect anywhere. With the exception of BNCT, no treatment DVH curves are completely separated from each other. BNCT can selectively apply a certain dose of radiation to the tumor (cells).
Advantages of boron neutron capture therapy
The reason why BNCT has received widespread attention is because of the following advantages:
1. Good targeting and little damage to surrounding cells and tissues. The boron compound is only absorbed by cancer cells, and the alpha beam, which has three times the biological effect of ordinary radiation and lithium particles, precisely destroys cancer cell DNA.
2. No need for oxygenation effect. Not only can kill oxygen-rich cells, but also kill hypoxic cells and cells in the stationary phase.
3. Its damage to cells is irreversible.
4. New treatments for refractory cancers. Boron neutron capture therapy can be tried for invasive, multiple, recurrent, radiation-resistant, inoperable cancers, and cancers that are poorly suited to radiation therapy.
Which patients are best candidates for boron neutron capture therapy
Suitable for the treatment of a variety of cancer types, including advanced and recurrent cancers:
1. Various malignant primary brain tumors;
2. Melanoma;
3. Head and neck tumors (oral cancer, tongue cancer, pharyngeal cancer, laryngeal cancer, thyroid cancer, parotid gland cancer, outer ear cancer, middle ear cancer);
4. Liver tumors (including several lesions);
5. Bladder cancer;
6. Locally recurrent breast cancer;
7. Lung cancer;
8. Colon cancer;
9. Mesothelioma.
The treatment process of boron neutron capture therapy
Course of treatment: For patients with brain tumors, the course of BNCT is of epoch-making significance. Depending on the condition, the shortest course of treatment only requires one irradiation, and the irradiation time is 30 minutes.
Step 1 pre-administers a specific "boron compound" that is only taken up by and accumulates in cancer cells.
Step 2 When the concentration ratio (T/N ratio) of the boron carrier agent in the tumor tissue to the normal tissue reaches a peak, the tumor site is irradiated with a neutron beam.
Step 3 The boron compound collides with neutrons and kills cancer cells from the inside via "alpha rays," a type of particle beam produced by fission.
Excellent clinical effect of boron neutron capture therapy in the treatment of various types of cancer
1. Neck tumor - complete regression
The standard treatment options for head and neck cancer are surgery, X-ray therapy and chemotherapy. Boron neutron capture therapy allows repeated radiation therapy for relapsed patients who were unable to receive X-rays because of prior X-ray therapy.
The world's first head and neck cancer treated with boron neutron capture was a case of recurrent cancer of the parotid gland. After two BNCT treatments, the tumor completely regressed, and the patient's skin reaction did not reach the level of dry desquamation. It is impossible to avoid damage, such as blisters on the skin, with other treatments. The responses observed in this case demonstrate the high tumor cell selectivity and lethality of BNCT.
2. Brain tumor
Boron neutron capture therapy has excellent clinical effects on malignant brain tumors. Because boron neutron capture therapy allows for a large dose of radiation to be administered at one time, there are cases where the tumor undergoes a rapid complete response (regression and disappearance of the lesion in about two days as shown by MRI), which is different from X-ray therapy.
A 32-year-old male patient with brain tumor, who underwent radiotherapy and chemotherapy after surgery, recurred one year later. After reoperation and chemotherapy, the disease progressed, and he developed paralysis and aphasia. As a symptomatic treatment, the patient received BNCT with the hope of improving symptoms and recuperating at home. Intravenous therapy was terminated within three weeks after BNCT irradiation, and steroids were continued in small amounts. Although there is still mild aphasia symptoms, but has been able to walk independently at home. MRI showed the progression of tumor shrinkage after one day, two weeks and one month of BNCT treatment.
Conclusion: Non-craniotomy BNCT therapy for recurrent malignant glioma has the effect of shrinking the tumor and maintaining the daily living ability of patients.
Great news! Japan's boron neutron capture therapy is about to recruit patients!
In the past ten years, with the rapid development of high-current proton accelerator technology, boron neutron capture therapy has become possible to widely apply in hospitals. The Japanese government has supported boron neutron capture therapy based on strong current proton accelerators as a strategic industry, and has stepped into the stage of industrialization promotion. The United States, Britain, Russia, South Korea and other countries are also stepping up research and development. According to the Global Oncologist Network, three hospitals in Japan are currently installing and debugging boron neutron equipment. Two of them have been debugged and can stably emit neutron beams. It is expected to start receiving patients in early 2020.