Heavy particles on tumors
How does radiation therapy work?
Blog of Toshiba, Habr
Peaceful atom is not only Chernobyl and Fukushima. With proper and careful use, it can bring invaluable benefits to humanity, for example, when it comes to breakthrough technologies in the field of energy. But not only: today we will talk about radiation therapy for the treatment of cancer.
According to data from the Global Burden of Disease Cancer Collaboration study, which was published by an international team of scientists from 195 countries in the fall of 2019, from 2007 to 2017, the number of cancer cases in the world increased by a third. In 2017, 24.5 million people fell ill with cancer, 9.6 million died from it. And radiation therapy has become the most dynamically developing method of treating oncological diseases. In terms of effectiveness, it does not lag behind other methods and at the same time treats the patient's body with mercy.
The room where radiation therapy is carried out (here – with the help of the i-ROCK device), today may not look like a hospital ward, but rather like the room of a spaceship from the distant future. Source: Toshiba.
How is cancer treated?
They prevent the division of tumor cells and its proliferation and spread of the disease throughout the body, as well as provoke its death. In general, the tumor can be removed by cutting out of the affected organ or together with it, or poisoned, trying to make sure that the rest of the body is not poisoned at the same time. The latter, fortunately, can be done due to the peculiarities of cancer cells. But chemotherapy, and even more so the removal of an organ or part of it, often affects the body very disastrously. Therefore, scientists are working on alternative methods with scientifically proven effectiveness. One of them is radiation therapy.
Radiation therapy (or radiotherapy) is the use of radiation to fight malignant tumors. With the help of radiation, which is directed directly to the tissues affected by the tumor and affects its cells at the genetic level, they can be completely destroyed or at least their growth and division can be restrained. Despite the fact that these words themselves sound quite scary – purposefully irradiating a living person with radiation! – this method has proven its effectiveness and safety.
The effect of radiation therapy is also based on the characteristics of tumor cells: as scientists have found out, the fact that such a cell divides faster than usual leads to the fact that it is more influenced by radiation. On the one hand, rapid division allows them to spread at a high speed in the body, on the other hand, it makes it possible to introduce a kind of "friend–foe" recognition system and to influence radiation exclusively on them. As a result of irradiation, the division of tumor cells slows down and / or stops, they disintegrate and are gradually eliminated from the body.
When exposed to radiation on a cell, the first task is to damage its DNA. As a result, the cell is inactivated, that is, it will lose the ability to divide, and as a result, this will lead to its death. At the same time, the DNA molecule is completely destroyed in tumor cells and partially, without losing the possibility of recovery, in healthy ones. Modern technologies at the same time allow minimizing the impact of radiation on healthy cells. How this can be achieved, we will tell you a little below.
Compared with surgery and chemotherapy, radiation therapy has a number of advantages. So, if chemotherapy has an effect on the patient's body as a whole, which can significantly weaken it and give unpleasant negative consequences, then radiation therapy is aimed exclusively at the tumor and normally has only a minimal effect on neighboring healthy cells. Of course, in the case of systemic cancer, which has managed to cover several organs, chemotherapy can work more effectively.
If we compare radiation therapy with surgery, then even here the first one has an undoubted advantage: it does not require surgery, which in some cases will be difficult for the patient to tolerate, especially if his body is already significantly weakened by the disease and its subsequent treatment. In addition, it is not so easy to get to some tumors by purely surgical means, and there is a risk of damage to neighboring organs.
Radiation therapy allows you to achieve the same result – the complete disappearance of the tumor – without having to go under the knife. This method of treatment works best when getting rid of neoplasms that have not had time to spread through the body in individual organs, for example, in the brain, lung, stomach, prostate, and so on.
In modern oncology, radiation therapy can be used both separately by itself and in combination with other methods of treatment – surgical and chemotherapy. In particular, a treatment regimen is common when surgical intervention and radiation are used simultaneously.
In this case, there may be such types of radiation therapy: neoadjuvant (before surgery) and adjuvant (after surgery). Neoadjuvant irradiation helps to reduce the size of the tumor in order to bring it to an operable state and reduce the risk of metastases, and adjuvant is used to combat local tumor relapses.
How does radiation enter the body and what harm can it cause?
Irradiation of exceptionally harmful cells is a filigree job. The most important question that arises before a doctor can be formulated as follows: how can particles be delivered to the right place and not accidentally irradiate anything superfluous?
There are three methods of radiation therapy: remote, contact and systemic.
Systemic radiation therapy implies that radioactive drugs are injected into the patient's body (by ingestion or intravenously). They will be distributed through the bloodstream and affect the tumor foci. So, for example, with the help of capsules that contain radioactive iodine, some types of thyroid cancer are treated.
When using contact radiation therapy (also known as brachytherapy), radiation sources are placed either inside the damaged organ or in the cavity next to it. In some cases, the emitters can be placed even on the surface of the skin.
The remote method has become the most common, when an external radiation source is used, and healthy tissues can lie between it and the target. The latter receive minimal damage, since almost the entire radiation dose is released into the tumor at the last millimeters of the particle path. To achieve this, special devices were initially used, which, to put it simply, were a container with a radioactive substance and a mechanism that allows forming a narrow beam of radiation.
One of the pioneers of this method of treatment was the Canadian medical physicist Harold Elford Jones – a group of scientists under his leadership in the early 1950s created the so-called "cobalt cannon", which used radioactive cobalt-60.
And the first special medical particle accelerator was assembled and applied in London (Great Britain) in 1953. What for? To achieve greater penetration and efficiency of radiation and to get deeply located tumors. And it is in the direction of the development of radiotherapy using linear particle accelerators that progress has been moving and is moving in the last half century.
Gordon Isaacs, the first patient cured in 1957 of retinoblastoma (a malignant tumor of the retina in children) using a linear accelerator built and applied by American scientist Henry Kaplan. As a result of treatment, the boy's eyesight was saved, and he himself lived a long life. Source: Wikimedia Commons.
Radiation therapy can be wave or corpuscular. Wave radiation, in which X-rays or gamma rays were directed at tumor cells, began to be used in medicine earlier (in particular, it was the gamma radiation produced by the Jones cobalt cannon), and it generally coped with its tasks, although with wave irradiation it is impossible to direct radiation clearly to damaged cells.
Today, corpuscular irradiation is considered more effective. In this case, beams of elementary particles are directed at the tumor: photons, neutrons or heavy ions. And it is irradiation with heavy ions that is currently considered the most technologically advanced method of radiotherapy, because due to their mass (not for nothing are they called heavy) they form a kind of shock wave and therefore destroy the DNA of cancer cells more effectively – fewer irradiation sessions are required to successfully get rid of the tumor using heavy ions.
X-rays (left) and heavy ion rays (right). Heavy ions are directed clearly at the tumor, minimizing damage to healthy tissues. Source: Toshiba.
As for other particles, they have less ability to penetrate into tissues. Therefore, the lightest of them – electrons – are used only for the treatment of skin diseases. Heavier photons penetrate deeper, but still do not have the same impact force as heavy ions. Photons also treat tumors in internal organs, but with a larger number of irradiation sessions.
Is radiation therapy harmless? No. Despite the obvious advantages, like any intensive treatment, radiation therapy rarely passes for the body completely without a trace. The consequences of its use may be local radiation burns, and the vessels that are in close proximity to the tumor may become more brittle. This leads to the risk of small focal hemorrhages.
There is also a possibility of long-term side effects as a result of the ingress of tumor decay products into the blood. However, they are still not deadly – unlike malignant tumors. According to experts, the effect of radiation therapy can be compared with a sunburn: its effects are not always immediately visible, but may manifest over time. Thus, there is a non-zero probability that after 10-20 years, the patient may begin to change at the DNA level or the cancer will return.
What do the most modern installations for radiation therapy look like, or What can be done to treat more and better?
Three hospitals in Japan have already ordered heavy ion radiation therapy units from Toshiba, and the company has supplied the equipment to customers. And the i-ROCK heavy ion accelerator is successfully operating at the Kanagawa Cancer Center in Kanagawa Prefecture. Using their example, you can see in which directions the evolution of radiation therapy methods is taking place today.
This is what the heavy ion accelerator from Toshiba Energy Systems & Solutions looks like at the Radiation Oncology Center in Kanagawa (i-ROCK). In the near future, a similar system will appear in Russia: A corresponding agreement has already been signed between the Ministry of Health of the Russian Federation and the Japanese corporation. Source: Toshiba.
i-ROCK is an impressive device that occupies several rooms, the total area of which is comparable to the area of a gym. In it, with the help of a linear particle accelerator, a beam of heavy ions accelerates to 70% of the speed of light before starting to attack the tumor. The amount of energy that is transferred to cancer cells in this case significantly exceeds the amount of X-ray energy or proton energy.
Heavy ions come from two directions at once, which increases the effectiveness of treatment, that is, allows you to achieve tumor mortification in fewer sessions. Moreover, the emitters can rotate 360 degrees, thereby achieving high accuracy of exposure.
Modern installations, including i-ROCK, have learned to minimize damage to healthy tissues during irradiation. To do this, it was necessary to make the particle beam thin and the radiation strength sufficient to damage the tumor, but not the tissues around. In i-ROCK, a 3D scanning method of the tumor is used, thanks to which it is possible to attack only the tumor itself, no matter how complex it may be, with high accuracy. This is called High-speed Scanning Beam Irradiation.
We take carbon ions, accelerate them strongly in a linear accelerator and direct them into the patient's body, exactly on target. Source: Toshiba.
When using the 3D scanning method developed by Toshiba during heavy ion therapy, irradiation of the tumor occurs as if it is shaded with a thin pencil. This method allows you to affect tumors of complex shape and act with precision and efficiency. Another consequence of using this method is that it is possible to exclude the stage of long–term equipment setup and the use of collimators and filters, which must be made individually for each patient.
And what to do with organs that normally move, as long as their owner is alive, for example, with the lungs? On inhalation, the tumor in the lung will be in one position, on exhalation, healthy tissues will be in its place under the beam. To avoid this, Toshiba engineers have added to the installation a tool for monitoring the patient's body in real time, allowing you to turn on the radiation when the organ is in the focus of the emitter, and turn it off when it moves. Combining irradiation with respiratory synchronization and observation of the irradiation zone using an oblique X-ray projection in real time with re-scanning technology, Toshiba engineers have learned to perform fast and accurate irradiation of neoplasms in uniform doses not only on stationary, but also on moving organs.
Due to the observation of the patient's insides in real time, damage to healthy tissues during radiotherapy is minimized. Source: Toshiba.
Among other things, such a combination of technologies and methods, on the one hand, reduces the preparation time for treatment and its cost for the patient, and on the other hand, increases the number of patients that the hospital can accept during the reporting period, and therefore speeds up the payback of equipment. Toshiba has helped to reduce the time required for patient placement by creating an effective positioning system, and the total time spent in the therapy room is significantly reduced with the use of high-speed 3D scanning irradiation. The Toshiba positioning system automatically calculates the discrepancy between the computed tomogram of the irradiation zone obtained during therapy planning and the X-ray taken directly in the room where the irradiation is carried out, and adjusts the position of the robotic bed on which the patient is located. If, when using radiation therapy devices of the previous generation, the average duration of the session from the patient's entrance into the room to his exit was 26 minutes, now it has been reduced to 11 minutes.
Finally, another area of work of engineers is to reduce the weight and size of the entire complex of equipment, which in turn ultimately increases the availability of treatment for each patient. Here Toshiba also has something to be proud of: she created the world's most compact (as of October 1, 2017) rotating gantry (the so-called movable device used to hold and target medical equipment to a fixed patient) used in heavy ion therapy. This was achieved through the use of superconducting technologies. If gantry can rotate 360 degrees around the patient, this allows you to accurately aim at the tumor from any direction, reduce or eliminate damage to healthy tissues, place the patient in the right way faster and reduce his discomfort, and at the same time eliminate the deformation of organs as much as possible; moreover, subsequently, during the next irradiation sessions, the patient's position can be quickly reproduced.
Scientists of the National Institutes of Quantum and Radiological Research and Technology (National Institutes for Quantum and Radiological Science and Technology – QST; a Japanese research organization established in 2016 by merging the National Institute of Radiological Research and several divisions of the Japan Atomic Energy Agency), in June 2019 created a compact rotary gantry using a superconducting magnet, which made it possible to reduce the weight of the equipment by about 300 tons. A smaller gantry in size and weight can be more conveniently placed in the hospital building, and this will reduce the costs of construction work, maintenance and maintenance, and therefore reduce the cost of treatment.
Finally, it is worth telling about how the safety of treatment is ensured. Firstly, the accelerator and the patient are in different rooms. The latter is located in a separate, not scary-looking room (shown at the beginning of the post) on a bed that can be moved along seven axes to provide irradiation of any organ and at the same time maintain a comfortable position for the patient. The optimal position of the bed and the radiators, as we have already mentioned, is determined on the basis of a pre-made computed tomogram and X-ray scanning in real time immediately before the procedure.
The medical worker can observe the treatment using the beam monitoring system developed by Toshiba: while the irradiation is ongoing, the position of the beam and the flux density at each site of the irradiated tissues are displayed on the monitor screen in the hardware room in real time. The condition of the equipment is also constantly checked – this ensures the safety of the patient. If something goes wrong, a special blocking system will stop the flow of particles. The equipment management interface has been specially designed to minimize the possibility of error caused by the human factor and to give medical workers a sense of confidence and safety.
Is radiation therapy ruinous?
Like any new technology, in the development of which a lot of money and efforts of highly qualified specialists have been invested, radiation therapy cannot be cheap. For a patient, a course of treatment will cost on average more than a course of chemotherapy (exact calculations depend on the severity of each specific case).
The high cost is understandable: firstly, hospitals need to invest in the purchase of expensive equipment. Secondly, its maintenance will require additional costs. Thirdly, to work on it, you need personnel with a high level of qualification - you will also have to spend money on their training and maintenance.
As for the cost of the equipment itself, the scope is very wide. So, the simplest, not the newest, and possibly used linear accelerator abroad can cost up to $ 300 thousand. The price of newer systems rises to a million dollars and above. At the same time, the latest developments can be estimated at several million US dollars. In general, for a full-fledged radiotherapy clinic in the USA, for example, you will have to spend from $ 20 million to $ 150 million, and in some cases even more. It depends on the number of seats and other factors.
Nevertheless, any effective technology eventually goes the same way: it becomes mass, and as a result – more accessible. And we hope that the "terrible and dangerous" atom will clear its image in the near future and turn into the savior of humanity from one of its most terrible problems.
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