Nature: Four major problems in proton therapy and the latest developments

When it comes to "proton therapy," most people may first associate with protons in chemical nuclei. It is precisely such tiny particles that can be used in cancer treatment to achieve unexpected results and have become the most advanced. Cancer treatment technology.

Recently, Nature published a review summarizing the current status and recent progress of proton therapy for cancer. In order to enable more cancer patients to obtain proton precision treatment, experts have proposed three proposals: reducing the scale of accelerator infrastructure, More accurate protons, expand coverage of medical insurance, and finally use proton therapy as one of the first choices for anti-cancer, so that more patients benefit.

Proton therapy was first proposed in 1946. In 1954, the research team at Lawrence Berkeley National Laboratory conducted the world's first proton therapy for cancer patients. Since then, the United States, Europe, Japan and other countries have begun research on protons in the medical field, but it was not until 1988 that proton therapy was approved by the US FDA, and proton therapy began to shine in the field of cancer treatment.

Currently, there are more than 20 cancer proton beam treatment centers in the United States, including the MD Anderson Cancer Center, the Mayo Medical Center, the Massachusetts General Hospital Cancer Center, the Cancer Proton Beam Treatment Center affiliated with the University of Pennsylvania, and the Florida Medical Association's proton beam therapy. Center and so on.

On May 8, 2015, China's first proton heavy ion hospital, the Shanghai Proton Heavy Ion Hospital in Shanghai International Medical Park, was officially opened. As of now, the number of patients admitted has exceeded 1,000.

Principle of proton therapy

The so-called proton therapy is to use the cyclotron or synchrotron to accelerate the electron nucleus of electrons to about 70% of the speed of light. At this extremely fast speed, it penetrates into the human body and reaches the specific part where the cancer cells are located. And stop, release the maximum energy, produce "Prague peak", kill cancer cells, while effectively protecting the surrounding normal tissue, and side effects are small. For example, when a tumor is directly adjacent to an important organ or structure such as the spinal cord, optic nerve, heart, etc., proton therapy can still protect the function of these important organs or structures while effectively treating the tumor, which is impossible in conventional radiation therapy.

At the same time, compared with other radiosurgery methods, Proton Knife has strong penetrating performance, the best positioning effect on the lesion, and the highest accuracy of machine operation. It causes less radiation to the outside of the lesion and reduces the induction of secondary cancer. The chance. Compared with proton therapy, X-ray therapy is 12 times more likely to induce a second primary tumor, and patients who receive proton therapy have a better quality of life. Foreign clinical treatment data show that proton therapy has an effective rate of more than 95%, and the five-year survival rate is as high as 80%.

In addition, proton knife can also be used for the treatment of tumor recurrence. The tumor relapses after radiotherapy. It can be treated with proton again. It only needs to control the dose and concentration of proton beam, which is impossible in traditional radiotherapy.

Advantages of proton therapy

Clinically, proton beam therapy can usually treat prostate cancer, head and neck cancer, some children's tumors, pancreatic cancer, and even some early breast cancer and lung cancer.

For example, for patients with early prostate cancer, radiation therapy is a common radical treatment for localized prostate cancer. Clinical trials have shown that high radiation doses can achieve better therapeutic results. However, an increase in the radiation dose to the prostate also increases the risk of damage to adjacent normal tissue. The exposure dose of normal rectum during the treatment of external beam radiotherapy is related to the treatment of complications, and more often manifests as rectal bleeding. Therefore, the maximum dose in the lesion area and the minimum dose of the surrounding rectum are the ideal pursuit of radiation therapy.

The same problem is also present in the radiation therapy of lung cancer. Radiotherapy plays an important role in the treatment of metastatic lung cancer. Radiotherapy alone can cure stage I non-small cell lung cancer (NSCLC). Radiotherapy can also be used as a combination of treatments for the treatment of locally advanced NSCLC. High-dose irradiation is required in radical radiotherapy, and treatment and dosage must balance the expected therapeutic toxicity with the possibility of achieving local tumor control.

In fact, in order to limit the risk of radiation damage adjacent to normal tissue, radiotherapy often does not reach the dose to kill the tumor, but proton therapy can achieve the above purpose.

According to Nature, the benefits of proton therapy for cancer are predictable, and the number of patients benefiting from proton therapy will increase as technology advances such as proton accelerators.

"Nature" article points out four major problems in proton therapy

Although proton therapy has an unparalleled advantage over traditional radiotherapy, it still has several problems.

The above-mentioned "Nature" article points out that proton therapy costs at least 2-3 times higher than conventional X-ray radiotherapy, which is a high medical cost for patients from ordinary families. It is difficult to bear, and not all covered by medical insurance. For example, the current cost of a treatment course at Shanghai Proton Heavy Ion Hospital is 278,000 yuan, and only some commercial insurance channels can be taken.

For example, in the United States, although medical insurance covers part of the cancer proton therapy, insurance companies are very demanding for patients with proton therapy indications. Nearly 30% of patients are excluded, insurance does not bear the cost, mainly because of clinical There are too few clinical data to provide significant curative effect during treatment, which forms a vicious circle: the individual's personal medical insurance is not burdened, and the relevant clinical treatment is difficult to carry out.

For patients, the medical costs of proton therapy are difficult to bear, and for hospitals, proton devices are equally difficult to bear.

Since the 1990s, the weight of the accelerator has dropped from hundreds of tons to 20 tons, and the diameter of the accelerator has also tripled. The smallest proton therapy accelerator to date is less than 2 meters in diameter, comparable to a king-size bed. However, with the rotating frame and other auxiliary equipment, even the most Mini-type proton therapy system takes up several hundred square meters, which is several times larger than the traditional 50 square meter treatment room. At present, most hospitals lack It is a real problem to build funds and space for specialized proton therapy institutions.

At the same time, proton therapy still has a more accurate problem. Some doctors say that the proton beam can be accurate within 0.5 cm, which is similar to X-ray. The precision of the proton beam from centimeter to millimeter will be the next. A necessary technical update in one step. Especially when treating lung and liver tumors, the location of the tumor is a moving part, which will be another difficult technical challenge.

In addition, the shortage of professional technicians who are proficient in the installation and commissioning of proton equipment and those who specialize in proton therapy technology are also a major problem.

Improvement suggestions and latest developments

In terms of treatment costs, the journal Nature pointed out that insurance companies should establish a “reference pricing” model to establish uniform payment standards for different treatments with similar therapeutic effects, which will help to collect proton therapy clinical data in new clinical applications. .

In terms of equipment, the goal is to install the proton therapy device in a room. The hospital can build a treatment room without another, which makes it easier for the hospital to replace the existing X-ray treatment device. At the same time, if the price of a proton accelerator device is reduced. Up to $5 million, the era of universal application of proton therapy is not far off, and the corresponding treatment costs will continue to decrease.

In terms of accuracy, several methods for measuring proton beams have been explored. When protons interact with nucleus, they emit traceable gamma rays, which release sound waves when tissue organs are heated and proliferated by proton pulses. This technique can make the proton beam accurate in the range of a few millimeters in the experimental environment, but it has not been applied in clinical treatment. Overcoming the technical obstacles in clinical treatment requires the joint efforts of medical research institutions, doctors and patients.

For the shortage of professional technicians and doctors, one of the solutions proposed by Nature has made the proton therapy workflow similar to traditional X-ray treatment, and can borrow existing radiotherapy doctors and technicians. The other method is more Relying on artificial intelligence and full automation, an expert system is used to form an AI system to guide the patient's treatment process.

It is worth mentioning that the "Nature" publication also mentions three recent advances in proton therapy: proton pencils can accurately illuminate radiation doses onto solid tumors, reducing the need to illuminate patients from multiple angles; rapid imaging methods It can detect small changes in the patient's position and thus change the precise area of ​​the beam; the "soft robot" made of extensible material uses its robotic arm to quickly and comfortably locate the patient, reducing the chance of doctors entering the treatment room frequently.

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ynephrine (or oxedrine) is a drug commonly used for weight loss. While its effectiveness is widely debated, synephrine has gained si

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There is however no occurrence of diverted synephrine for the manufacture of amphetamines, and the naturally occurring synephrine is, due to its phenolic group, unsuitable for such diversion.

Products containing bitter orange or synephrine are suspected of causing adverse cardiovascular reactions. Synephrine is derived primarily from the immature fruit of Citrus aurantium, a relatively small citrus tree, of which several of its more common names include Bitter Orange, Sour Orange, and Zhi shi. Dietary supplements generally supply single oral doses of 3–30 mg, while as a pharmaceutical agent it is given orally or by parenteral injection in 20–100 mg doses as a vasoconstrictor to hypotensive patients.

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