What is the significance of irradiation in the fight against cancer?
Today one of the oldest methods of cancer treatment belongs to the most innovative areas of oncological medicine – irradiation. Thanks to new technologies, scientists managed to develop such methods of radiotherapy that could not be imagined at the time of Wilhelm Conrad Roentgen. What techniques of radiation therapy are at the disposal of doctors for today? What awaits the patient during irradiation? Information from the Internet cannot replace a medical consultation. The following information is a general overview for patients.
Brief explanation of the basics
Enough rays of energy can infect tumor cells so much that they die. Healthy cells react less sensitively – most of them have recovery mechanisms that no longer have tumors with their rapid, excessive growth. In addition, modern techniques of radiotherapy allow you to direct the beam of energy precisely to the target: those severe side effects, which were feared earlier, are rare today.
Most people are familiar with the use of rays in the field of diagnostics – diagnostic methods include X-rays, computed tomography, and ultrasound or magnetic resonance imaging. The treatment of cancer with the help of rays with high energy potential refers to today to “radiation therapy” or “radiation oncology”. At the same time, within the framework of radiotherapy, the use of so-called ionizing rays is made. Today the use of electromagnetic waves of other frequency ranges, for example, for hyperthermia, or the use of ultrasonic waves for the treatment of tumors also broadly refer to radiation therapy.
Who performs the irradiation?
Doctors have the right to take responsibility for conducting radiotherapy for cancer patients only if they have completed an additional five-year training and received a diploma in radiation therapy. In addition to special knowledge in the field of medicine and physics, as well as practical exercises, the training program includes knowledge on the topic “Protection from exposure”.
Specialists in the field of radiation therapy work in clinics and medical practices. During treatment, patients are supervised by assistants in medical technical radiology (medical technical assistant in radiology). In larger institutions, in most cases, physicists or technicians with specialization in the field of medical physics also work.
Experts within the professional communities determine the importance to date of different methods of radiological treatment in oncological medicine. Based on the results of the examination, they constitute the current recommendations for the treatment of cancer patients. At the same time, specialists in the field of radiation therapy exchange information with specialists from other areas of oncological therapy.
Protection from exposure: no use without proper supervision
The use of radiation in medicine is strictly regulated by law because of the need to protect against radiation. At the same time, we are talking about the safety of patients on the one hand, and on the other – about the health effects of people who, in the course of their professional activities, deal with radiation or radioactivity daily.
In Germany, the Commission on Protection Against Radiation (www.ssk.de) is working in the framework of which the issues of safety of new technologies are discussed, and assistance is being provided in drafting legislation. It cooperates with the International Commission on Radiation Protection (www.icrp.org).
Radiation therapy of cancer diseases is more than a hundred years: The basis for it was published in 1895, the discovery by Wilhelm Conrad Roentgen of a “new kind of rays”, which he called X-rays. In his studies, he recognized the significance of these rays for diagnostics: X-ray radiation makes it possible to look inside the human body. Even before the onset of the new century, doctors began to use “X-rays” and to treat skin changes, as well as other diseases.
This text contains a brief overview of the physical principles of radiation therapy.
Radiation: what forms of radiation exist?
All forms of radiation therapy are based on the fact that radiation with a high energy potential permeates the tumor. In this case, we can talk about electromagnetic waves, as well as about particle flows. The deciding factor is how much energy is released into the tissue when the radiation is decelerated, how accurately this released energy hits the target, and determines the quality of the impact.
“Classical” forms of irradiation in oncological therapy use so-called ionizing rays. Their energy is high enough to cause changes in the cells where they penetrate, changes at the molecular level: ionization means the production of positively and negatively charged particles from electrically neutral atoms and molecules. These “ions” trigger biochemical and biological reactions in cells, and only the consequences of these reactions lead to the desired damage to tumor cells. Other forms of radiation, such as ultraviolet fractions of sunlight or infrared or thermal radiation, cannot achieve this effect, and therefore they are considered to be “non-ionizing rays”.
The question of which laws of physics form the basis of radiation therapy, whether tumors are destroyed by “rays”, “particles”, “waves” or simply energy”, most patients leave specialists – it is enough that their disease reacts to treatment. Nevertheless, it is important to understand some terms:
Physicists use for the irradiation both electromagnetic waves (this includes X-ray and gamma radiation), and particle flows, that is, the radiation of electrons, protons and ions. In medicine, the terminological separation of the various forms of radiation is often confusing: so beta or β-radiation means the same as electron radiation, alpha or α-radiation refers to ion beams, and the photon radiation that is most commonly used today corresponds to the super-hard ray radiation. Ion radiation is also called particle radiation or hadronic radiation.
Energy, the dose of energy: Gray or Sievert?
The dose of energy upon irradiation is indicated in units such as Gray (Gy). It corresponds to the released energy, which must be released in the tumor or in a certain thickness of tissue. For patients, this is the most important physical unit, since it indicates the dose that is planned for their treatment.
Instruments in radiation therapy
Today linear accelerators have the largest role in oncological medicine in terms of the number of applications.
In them, radiation is produced by very intense heating of the filament. This requires the presence of a few megavolts of electrical voltage in modern appliances (for comparison, in Germany, the usual voltage in the household electrical system is 230 volts). Due to high voltage, the filament releases electrons, that is, subatomic, negatively charged particles. In principle, they can be used directly for irradiation, however, they practically do not penetrate the skin into deeper tissues. Therefore, today, in most cases, electrons are subjected to “further processing” in a linear accelerator: in a vacuum tube, the device accelerates them almost to the speed of light. After that, the electrons collide with a water-cooled sheet of tungsten, which slows them down. In this case, energy is released in the form of photons, which is equivalent to super-hard X-ray radiation. They can penetrate the tissues deeper than electrons.
Devices for gamma irradiation or remote cobalt therapy devices work on a radioactive substance, usually on the same substance Cobalt-60.
These devices release not only the desired, relatively weak gamma radiation (about one megavolt), but also relatively poorly regulated alpha and beta rays. In addition, they hardly penetrate the skin. Cobalt devices are suitable, first, for the treatment of tumors located on the surface. Nevertheless, up to the 70-ies these were standard devices. To date, in Germany, they are almost completely replaced by linear accelerators. They are used only in radiosurgery in the so-called gamma-knife devices.
In those countries in which it is impossible to compensate for the huge energy consumption required for linear accelerators, gamma-irradiation devices are still widely used.
In various types of ion beam therapy, also called interstitial radiation therapy or particle therapy, a stake is made on the production of fast particles. These particles can form more distinct beams than other types of radiation. In addition, they release their energy only when they penetrate through the tissues, reduce their speed below a certain limit.
Thus, it is possible to direct the main dose directly to the tumor. On the tissues located above, a more sparing effect is carried out on the organs located below the tumor or behind it, the irradiation practically does not act.
To ionic radiation are photons as the nucleus of the atom and whole ions of carbon, helium and other types of ions in the so-called heavy ion therapy. Ion radiation therapy is expensive from a technical point of view; in many aspects it is still experimental and inaccessible to large-scale application. In particular, heavy ion therapy worldwide is conducted in only a few centers.
Percutaneous irradiation, brachytherapy
Linear accelerators, devices for remote cobalt therapy, as well as ion beam therapy, are usually used as external devices for “percutaneous” that is, penetrating through the skin, irradiation of internal tissues.
In so-called brachytherapy, the radiation sources are not located above the patient’s body, but are placed in the tumor as far as possible or in the immediate vicinity of it. They are either located in the body cavity, for example, when the esophagus tumors are irradiated, they are injected into the affected esophagus, or directly into the tumor itself with the help of a small surgical intervention, for example, they are placed in the affected prostate gland with prostate carcinoma.
In this case, as a rule, speech is about sources of radiation, which have a very short range of action and therefore should be in direct contact with the tissues of the tumor. For this reason, the term contact exposure is sometimes used. However, the radiation sources themselves are not involved in the patient's metabolism, as is the case with nuclear medicine methods.
Effects of rays with high-energy potential on tumor cells
What actually happens when the tumor is irradiated? The released energy affects many processes in the cell; it affects the genetic material of tumor cells and prevents the implementation of important metabolic mechanisms. Cells that carry the typical changes in cancer, respond to such a lesion is much more sensitive than healthy tissues.
This text contains a brief overview of the effects of radiation with a high-energy potential on the tumor.
The text contains links for more information or sources.
Target: energies affect cells
Ionizing radiation causes various biochemical and biological reactions in the tissues. They depend on the energy that is released upon penetration, and on the sensitivity of the corresponding tissue.
The highest doses, which are comparable to the doses in an atomic bomb explosion, due to heating and massive changes in the molecular structure lead directly to tissue destruction. In the treatment of cancerous tumors, such intensity of irradiation does not find application.
However, at high doses and within the framework of radiation therapy, tissue damage, so-called radiation necrosis, can occur. Physicians, if possible, try to prevent their development - severe necrosis could truly poison the body with cell debris and decomposition products, as it happens after a burn. At what dose of radiation the tissue can no longer recover depends on the type of tissue. Especially sensitive are the cells of the blood and the immune system, the roots of the hair, the kidneys and the lungs, and the eyes can also carry much smaller doses than, for example, the intestines or larynx. In addition, the effect of the rays strongly depends on how much tissue or organ was affected. Thus, even a single body irradiation with a dosage of only four Gy (Gy) can be fatal, since the immune system and the hematopoiesis system can no longer recover.
Despite the fact that easier damage is often cured, high doses of radiation still often leave vast changes in the genetic material of DNA, which could sometime lead to scar tissue restructuring or chronic inflammation. Ten or twenty years after high-dose radiation may increase the likelihood of developing so-called secondary cancers. The introduction of high doses in a single irradiation is possible only in a few special treatment situations. This is possible only if the course of the rays can be completely directed to small tumors, and healthy tissues are not affected.
Tissue tissues react differently
For most patients, instead of directly destroying cells, attempts are being made to induce indirect changes in important molecules in tumor cells. Thus, their death is provoked by a natural biological path: due to irradiation, aggressive molecules (so-called ions) appear, especially when the tumor tissue is well supplied with blood and oxygen. In particular, oxygen ions as "free radicals" affect the genetic material of tumor cells. Important enzymes and other molecules that play an important role in the rapid division of the tumor tissue are also affected by reactive molecules. After this, the cancer cell can no longer share and promote tumor growth. It is recognized by the body as an infected cell and is purposely destroyed. Current processes are more known to date, the most important of them is called programmed cell death or apoptosis.
What the patient feels in these biological processes depends on the dose and purpose of the irradiation, on the amount of damage to the healthy tissue, and on the general condition of the patient, the underlying disease and its symptoms. Many patients during treatment feel relatively well; others suffer, for example, from fatigue and lethargy or headaches.
Fractionation: “portioned” irradiation
Instead of the whole dose of radiation at a time, today, patients are irradiated, if possible, by repeated small “fractions” or portions from the planned total dose. The course of treatment is divided into several separate procedures over a period of several weeks.
Thanks to this, healthy tissues that are affected by treatment have time for regeneration, and the tumor is replaced by a kind of scar.
With regard to tumor tissue, fractionation, by contrast, leads to increased killing, until it completely withers. Often the tumor no longer has healthy, inherent in the cells, the mechanisms of recovery and is initially "in a stressful state" because of the typical for cancer of high-intensity cell division.
Due to fractionation, it is possible to give high doses to many patients without increasing the risk of developing long-term delayed complications. Conventional radiation therapy regimens include, for example, daily doses of about 2 Gray from Monday to Friday, repeated for many weeks.
Behind these schemes are still mostly practical considerations and a great clinical experience.
In rarer cases, there are possible forms of radiation therapy, in which so-called one-stage irradiation is performed. In these cases, the total dose of irradiation is actually introduced during one procedure. The prerequisite here is a tumor of a smaller size, the destruction of which will not be too aggravating, as well as the possibility of full preservation of healthy tissue, which is technically very difficult. Since here the rays are used as a scalpel or knife, in this case they talk about radiosurgery.
Techniques and examples of use
How exactly is the irradiation carried out? Why does every oncological patient receive different treatment? What devices do doctors use today, and how do they manage to connect rays with high-energy potential to the tumor and keep healthy tissue if possible?
Irradiation from the outside: percutaneous radiation therapy and radiation planning
Most people are familiar with the classical procedure of radiotherapy: when the patient is lying on a couch or a kind of table directly under the device for irradiation, which differs little from the familiar process of X-ray examination.
The irradiation usually takes not so much time – from a few seconds to several minutes. The actual duration of reception depends also on the necessary preparatory measures and the subsequent analysis of the results: discussions with doctors, location on the couch and exact placement in the radiation field, final calculations and, if necessary, subsequent discussion.
Today, most patients receive a total dose of radiation fractionated, that is, not in the same procedure, but in the form of several doses for many weeks.
Definition of the radial field: mobile devices, filters
The first devices for the treatment of cancer sent their rays through the body within a homogeneous field, while there was only a conditional possibility of changing its size and shape. In addition, remote cobalt therapy devices, like the predecessors of modern linear accelerators, were very heavy. Previously, they could be mounted permanently, which allowed for irradiation in the same direction - perpendicular to the patient. The preservation of healthy tissue was difficult.
The first attempts to locate the radial field not in a constant direction, but to correct it depending on the actual form of the tumor and, above all, its dimensions, were based on the use of filters. To date, in addition to extremely sophisticated technical filtration devices, there are a number of other possibilities to release the maximum dose of energy exclusively in the tumor, and not in the surrounding healthy tissues.
Modern linear accelerators are often equipped with moving elements – either a “beam gun” moves, which, with the aid of a mobile suspension, the so-called gantry, is suspended over the patient, or the table on which the patient is located moves.
Thus, the rays can be guided more easily, without affecting sensitive organs.
In addition, the angle from which radiation hits the tissues changes many times, the rays intersect only in the required target area. Due to the ability to irradiate from above, below or from different sides, the tumor is always exclusively affected, and not always the same healthy tissue.
The so-called collimators or moving radiation shields make it possible to make the radiation field not just circular or rectangular. These filters consist of shielding materials. Like lenses with visible light or diaphragms in the camera, they focus the rays and provide targeted irradiation. Thus, radiation fields are created which cover tumors even of a very irregular shape.
Marking, placement and fixation
In order that the radiation field does not “shift” after being placed on the table with the help of medical personnel, the patient cannot move - this is not always easy, but for most patients this is tolerable given the short duration of exposure. The place that should be irradiated during each procedure is marked on the skin by the doctors responsible for treatment in advance, for example, using water resistant markers. This marking must not be washed off. A newer method is tattooing tiny dots. They are hardly noticeable, and eventually they will turn pale and disappear. However, they are sufficient to identify reliably the radiation field. Advantage: if the skin condition in principle allows, then with such a tattoo, you can take a shower.
However, if the path of the rays cannot deviate from the target by any millimeter, for example, when irradiating brain tumors, even minimal involuntary movements should be avoided. In this case, it is not enough that the patient does not move.
For such cases, there are many fixation systems: one of the possibilities is an individual plaster cast, in which, in each treatment session, the patient lies in the same position as in the “shell”, or the patient receives a specially manufactured frame system in which the irradiated part of the body. With tumors of the brain, this frame system, under certain circumstances, can be fixed on the bones of the skull for the entire period of irradiation.
For fixing is also used a kind of inflatable or foam mattress, which tightly encircles the body.
None of these systems is very pleasant for patients. However, they provide protection for healthy organs and structures.
At present, scientists are engaged in examination of systems by means of which it is possible to “catch” even involuntary movements during breathing or movement of the intestine and by means of a lightning-fast automated change in the direction of the rays to compensate for these movements. Such devices for irradiation rely on a combination of visualization techniques, such as computed tomography, with a linear accelerator and an expensive computer system that immediately transmits the received images and corrects the radiation field and dose.
Planning and preparation with visualization diagnostics
In order to use the systems for irradiation most appropriate for each patient, the radiation is preceded by intensive planning and a large number of calculations. At the same time, an important role is played by X-ray images or images of computed tomography, magnetic resonance imaging, PET studies, and ultrasound imaging. They demonstrate how large the irradiated tumor is, what form it has, how healthy tissues are located in its environment, and which organs are located under or above the tumor, and what is the probability of their involvement in the radial field.
To date, such images can be analyzed by computers and converted directly into irradiation programs.
Glossary: terms from the field of percutaneous exposure
This term denotes all the techniques of irradiation, in which the radial field is most purposefully adapted to the shape of the tumor and its dimensions. The tumor has an irregular shape, and, first, it is never flat, what it looks like on X-rays, but in reality is three-dimensional. Therefore, a related concept is 3D or 3D-beam therapy. With conformational irradiation, adaptation to the tumor form is achieved by means of filters or diaphragms.
Planning of three-dimensional irradiation is advisable in those cases when the tumor should be destroyed, and the surrounding healthy tissues are preserved.
In the treatment of residual mammary gland tissue after resection in breast cancer, the single-angle angle is chosen so that the heart and lungs, if possible, do not fall into the radial field. It is also possible to add additional targeted irradiation to the former “tumor bed” using a smaller dose.
Radiation therapy with modulated intensity (IMRT)
Radiation therapy with modulated intensity, abbreviated IMRT, is a further modification of conformational irradiation.
At IMRT, the irradiation can be even more aiming, the healthy tissue is preserved thus even better. In addition to ray filtering, the single-angle angle changes many times. The beam always passes through the tumor, but every time through another healthy tissue. Thus, it is possible to “modulate”, that is, change the final achieved total dose even within the tumor. For example, in one area, a low intensity tumor is irradiated, since an organ at risk is located near it. In another area, the tumor is irradiated with a higher intensity, since here, for example, the tumor is very thick.
The IMRT method has already been extensively tested in clinical trials and in practice, by now, among experts, it is considered a routine procedure. However, due to large-scale preliminary planning, it requires much more time than conformational irradiation. Regarding the experience of using this new technique of treatment, now in most cases we are talking about patients with prostate cancer, tumors in the skull or head, mouth, larynx or throat, as well as patients with tumors of the gastrointestinal tract and genitals.
Stereotactic radiosurgery (SRS) and “gamma knife”
With this form of treatment, radiologists use radiation almost as a scalpel. They very accurately destroy the tumor with high doses of energy, so the result is comparable to surgical intervention. The term “stereotactic” is due to the analysis of the tumor from a spatial point of view – this method involves fixing (see above) the patient during irradiation in order to achieve even higher accuracy of treatment.
A typical area of application of stereotactic radiosurgery are brain tumors. More rarely stereotactic radiosurgery is considered as a treatment method for extracranial tumors, for example, for patients with certain forms of liver or lung tumors.
Stereotactic irradiation can be performed with the help of modern linear accelerators and corresponding fixation systems. However, the first stereotactic interventions were performed using the so-called “gamma knives”, which are still used today. They contain more than 200 single cobalt sources that send beams through a filter with tiny holes both through a helmet around the patient’s head.
Intraoperative radiosurgery (IOR)
In some situations, you can increase the chances of recovery if you irradiate the patient's tumor directly during surgery. Surgeons have already removed the tumor and have exposed the tissue that needs to be irradiated. The surrounding tissues, which would be endangered by traditional irradiation, can be pushed off for a short time. Intraoperative radiosurgery can be used, for example, with irradiation of the abdominal cavity, because in this way, it is possible to better protect the loops of the intestine, kidney or liver. However, in most cases, during the operation, patients receive only a fraction of the total radiation dose and after the operation the patients must undergo further, in this case, percutaneous irradiation.
Chemoradiotherapy, combination with drugs of purposeful action
Today, with certain tumor diseases, a combination of radiation and chemotherapy plays a big role. Such diseases include, in particular, carcinoma of the cervix (cancer of the cervix) or carcinoma of the rectum (cancer of the rectum). In these cases, the doctors thereby try to save patients from carrying out large-scale and mutilating operations.
In the framework of this form of treatment, oncologists rely on strengthening the effect. The cytotoxic agents used for chemotherapy act as so-called sensitizers, which increase the sensitivity to radioactive irradiation, since they make the tumor much more susceptible to radiation. A special role here is played by temporal synchronization and close integration of chemotherapy and irradiation in order to inflict the most targeted harm to cancer cells and not give them time for regeneration. Chemoradiotherapy refers to those forms of treatment that are severe for patients. Therefore, this combination is only used when patients can gain a significant advantage in controlling their disease.
At present, in many studies, the question is whether the combination of radiotherapy with new specific drugs against cancer is possible (“targeted therapies”, molecular-biological medicines).
Brachytherapy: internal irradiation
In brachytherapy, irradiation is not carried out through the skin, but by placing radiation emitting substances in the tumor or, at least, into the body cavity near the tumor.
Often, so-called seeds are used for this, as, for example, when irradiating prostate tumors. Seeds are tiny radioactive metal particles. The doctor enters them directly into the tumor through a hollow needle. Therefore, sometimes the term “sponging” is used in this case. The range is a few millimeters, and the half-life is too short. If the radiation stops, the seeds can safely remain in the body.
Theoretically, the intervention could be performed on an outpatient basis. However, in most cases it is easier to organize the necessary anesthesia during the introduction of seeds, as well as to control their location and the radiation emanating from them during a short stay in the hospital.
In the early days, patients should avoid too close physical contact with pregnant women and children, as experts in the field of radiation therapy advice. However, there is no need to isolate patients with such seeds. Visits, greeting with a handshake or a hug, staying in one room, etc. do not present any problem even immediately after treatment.
With the so-called afterloading, the radiologists apply more strongly