Andrei GOLANOV, (c)
by Andrei GOLANOV, Dr. Sc. (Med.), Head of the Department of Radiology and Radiosurgery, Burdenko Research Institute of Neurosurgery (Moscow); Marina ZOTOVA, Valery KOSTYUCHENKO, medical physicists, Gamma-Knife Center (Moscow)
The Department of Radiology and Radiosurgery under Burdenko Research Institute of Neurosurgery since 2005, is equipped with the most sophisticated modern devices for precision radiotherapy. It is well known that the ideas of target use of various types of energy for treatment of pathologies of the brain have attracted the attention of physicians long ago. Today stereotaxic radiosurgery (SRS) and radiotherapy are the most important methods for treatment of tumors, vascular malformations, and functional diseases of the brain and spine.
ORIGIN OF STEREOTAXIC RADIOSURGERY
Various modes of radiation are used for the treatment of tumors—visceral, hemopoietic, ophthalmic, and even of the brain*—in virtually all spheres of medicine. Thus, during the first years after their discovery, X-rays were used for visualization and treatment mainly of skin diseases. Then they were used for the treatment of visceral tumors. At that time it was not so much radiotherapy (repeated exposure to low dose radiation), but rather radiosurgery (a single exposure to high-dose radiation) that was used.
Various types of irradiation are more and more widely used in the treatment of many diseases of the central nervous system. It is not only an important component of combined methods for the treatment of benign and malignant tumors, but also of metastatic involvement of the brain, arteriovenous malformations (congenital vascular abnormalities), functional disorders. In weak and elderly patients and in cases when the localization of the pathological process is difficult to determine, this method is an alternative to a direct surgical intervention.
For many years the treatment of diseases of the brain was impeded by difficulties in the spatial location of the focus. Introduction of stereotaxic technology (Greek stereos—spatial and taxis—location) helped solve this problem. In 1948, in Stockholm (Sweden), a well-known neurosurgeon Lars Leksell created an original device for reducing invasiveness** of the known functional operations on the brain in case of pain syndromes or motor abnormalities—hyperkinesias, including Parkinson's disease. The device consisted of a frame fixed on the patient's head, an arch with a mobile scale and a holder for instruments. This device was first used for evacuation of the contents of a deeply lying cyst. In 1951, Leksell suggested using X-rays for
* See: I. Shevelyov, "The Brain and Recognition of Visual Images", Science in Russia, No. 3, 2007. -Ed.
** Invasiveness is a degree of direct destructive impact on the object. -Ed.
Magnetic resonance imaging with contrast amplification in a patient with multiple metastases in the brain. During treatment and 3 months after radiosurgery on a Gamma-Knife unit.
destruction of the subcortical nuclei of the brain. He connected the X-ray tube to the stereotaxic frame. Moving it along the perimeter of the device arch and approximating the ionizing radiation to the thalamus, he destroyed the thalamic relay nuclei*, which helped the patient be saved from a severe pain syndrome. The scientist described this clinical case and called his method radiosurgery. Since then this term denotes a target (precise) one-moment exposure of a rather small volume of the pathological tissue inside the skull by means of stereotaxic technology to a sufficiently high dose of ionizing energy without trepanation.
RADIATION THERAPY TODAY
The list of indications for radiotherapy increased with the development of means and methods of neurovisual-ization. Due to X-ray angiography (a method for examining blood vessels after injection of a contrasting substance into them), it has become possible to carry out irradiation of vascular malformations. With the appearance of computer-aided tomography in the 1970s and of magnetic resonance tomography in the 1980s, it became possible to irradiate tumors of the brain. At present the indications for the use of radiotherapy and radiosurgery
* Thalamus is an area responsible for redistribution of information from organs of senses (except olfaction) to the cerebral cortex. It is transferred to the thalamic nuclei. The thalamic relay nuclei are specific nuclei through which the afferent (sensitive) pulses of certain modality are conducted. —Ed.
Hypofractionation treatment using a NOVALIS linear accelerator. Significant reduction of the tumor size after 2 months.
cover in fact the entire spectrum of neuro-oncological diseases, cerebrovascular diseases, functional disorders (parkinsonism, pain syndromes, epilepsy, etc.).
Linear electron or proton accelerators, sources of Co-60 (cobalt-60) gamma-radiation, serve as radiation sources for radiotherapy.
The proton bundle has been used as a source of longdistance ionizing irradiation since late 1950s. Scientific physical accelerators, not intended specially for medical application, were used for this purpose. The equipment for proton therapy is rather complex and expensive in comparison with commonly used devices for radiotherapy. From a physical viewpoint, it has some advantages in distribution of ionizing radiation in the target in comparison with photons.
Today studies of the use of heavy ion beams, for example, carbon C-12, are in progress. However, the use of this technology is fraught with difficulties, for example, in case of directing the beam to the patient, collimation (i.e. focusing of radiation beam), measurement of the active radiation energy, etc. It is easier to use linear accelerators. They consist of an electron radiation tube, in which the electrons are dispersed and then inhibited; these processes are accompanied by emission of photons, which after refraction, focusing, and collimation are directed to the target.
In 1984, radiosurgeons from Buenos Aires (Argentina) Oswaldo Betti and Victor-Eduardo Dereshinsky described the procedure of stereotaxic irradiation on a linear accelerator. Use of navigation systems for localiza-
Results of treatment of arteriovenous malformation by a Gamma-Knife unit 2 years after therapy.
tion of the target on linear accelerators with polypetalous collimators became the standard of modern therapy. Today there are four basic methods of irradiation using accelerators: multi-field exposure to static fields, the dynamic arch* technology, modulated intensity beams, and mobile irradiation by conical collimators.
The use of ionizing radiation in medicine became popular with the development of visualization means, such as MRT, CT, PET, and SPECT**. In contrast to traditional X-ray methods, tomography allows the three-dimensional reconstruction of the viscera on the basis of digital data characterizing the properties of biological tissue in a certain place. Due to the improvement of the methods and technologies of irradiation and introduction of navigation means, radiosurgery is used not only in neurosurgical diseases, but also for the treatment of tumors of other location.
Various visualization systems are used in modern irradiation technologies. These systems allow precise irradiation controlled by MRT, CT, etc. This is realized by "coupling" the three-dimensional tumor coordinate system and the coordinate system of the device (for example, Gamma-Knife) or making combined photos of the target and special labels or bone structures in the real time mode with images used for calculations (Cyber-Knife).
* Dynamic arches mean an irradiation technology, when the accelerator head (gantry) is rotating and at the same time is changing the position of the collimator petals in accordance with the program, worked out during irradiation planning. -Ed.
** MRT, CT, PET, SPECT—magnetic resonance, computer, positron emission, and single photon emission computer tomographs.—Ed.
Effects of ionizing radiation, leading to destruction (of different degree of reversibility) of bonds in a DNA molecule.
Histological diagnoses of patients treated at the Radiology and Radiosurgery Department of the Burdenko Research Institute of Neurosurgery.
THE "GOLDEN STANDARD" OF RADIOSURGERY
Today the procedures on the Gamma-Knife device are the "golden standard" of radiosurgery. The principle of its work consists in the use of multiple sources of gamma-radiation (radioactive cobalt-60) evenly distributed in the hemisphere with the patient's head in the center. The exposure to each of these sources separately does not affect the brain, but being focused in one point (in the isocenter), they give a summary radiation, which destroys the biological tissue. In contrast to the standard radiother-apeutic gamma-devices and linear accelerators, involving the movement of the massive headpiece (gantry) with the beam conduction systems, due to the fixed position of the sources, the only mobile object in the special automatic system in the Gamma-Knife is the stereotaxic frame fixed on the patient's head. Besides, the precision of exposure is fractions of a millimeter. Devices for radiotherapy and radiosurgery have to meet certain requirements: the dose delivery precision—3 percent, spatial resolution—1 mm, a system for fixation, navigation, and modeling, control equipment, possibility of multi-field non-complementary (not supplemented later on) irradiation, a system for formation of irregular fields of exposure, and relatively cheap sources of photon radiation (photon stream).
By now more than a million patients all over the world have been treated by the above method using the Gamma-Knife. Such diseases as epilepsy and some other mental disorders, intraorbital melanoma (a malignant tumor in the orbit, developing from melanocytes— pigmentary cells. -Ed.), glaucoma, etc., are now treated by the radiosurgical method.
A new Department of Radiology and Radiosurgery, equipped with the up-to-date devices, has been opened at Burdenko Institute of Neurosurgery in 2005. This equipment includes: a Gamma-Knife, the first in Russia cobalt device for radiosurgery, Novalis linear accelerators with the ExacTrac system and micro-polypetalous collimator, and a Cyber-Knife with specialized systems for navigation and treatment planning.
Approximately 5,000 patients with various diseases of the brain were treated since then by means of radiotherapy with the use of mask fixation and by radiosurgery with the use of stereotaxic frame. The results attained over 5 years indicate high efficiency and relative safety of the radiotherapeutic methods. Radiosurgery is carried out in an outpatient clinic, due to which patients return to usual life style virtually the next day after the procedure. Several targets are exposed in a single session of radiosurgery. This is particularly important for patients
Planning for a patient with meningioma of the skull base on a Cyber-Knife unit.
with multiple cancer metastases in the brain. In addition, repeated sessions of irradiation can be carried out with no additional risk, if necessary.
According to classical radiobiology, exposure to ionizing radiation leads to emergence of radicals, which damage the DNA and cell membranes. It has been established that the irradiation effect is realized through stimulation of cell apoptosis* and reduction of the cellular proliferative activity (rate of cell division). Exposure of blood vessels impairs their endothelium, which leads to development of cicatricial and adhesive changes, resulting in stenosis and obliteration (blocking) of the vascular lumen.
It must be emphasized that radiosurgical treatment can be carried out only on relatively small targets. Today it is well known that a single irradiation of a target with a maximum diameter of over 3 cm can lead to radiation injuries, such as necrosis and edema of adjacent tissues. The fractionation method is used in large tumors and in cases when the tumors are located in close proximity to functionally significant structures sensitive to ionizing radiation. Different tissues have different radiosensitivi-
* Apoptosis is a programmed death of a cell in response to external and internal signals. -Ed.
ty and rate of radiation injury recovery. This is explained by the rate of cell division: the process is rapid in malignant tumors, injuries accumulate at each stage, which eventually leads to the formation of nonviable cells. By contrast, the process is slow in normal tissues; the cells have time to recover. This process is effective if the dose absorbed by the cells is not very high. That is why the exposure in radiotherapy is carried out daily in low doses—parts (fractions) of the summary dose. It is assumed that an appreciable number of cells in normal tissues (but not tumor!) have time to recover between the sessions.
The standard protocol of radiotherapy consists of 20-30 fractions, more rarely refer to 4-10 sessions. The number of fractions and doses depends on the patient's state, histology, size and location of the tumor, as well as location of critical (functionally significant) structures.
At present complex therapy is widely used. It consists of radiotherapy after chemotherapy or irradiation of the site of operation after a surgical operation. The accumulated experience demonstrates higher efficiency of this approach.
As a rule, the patient's state does not improve instantly after the radiological treatment. After surgical removal of the tumor, its impact on normal surrounding tissues ceases at once, while during irradiation the tumor shrinks gradually. We usually speak about "tumor growth control" (analysis of changes, carried out on tomographs). Stabilization or shrinkage of the tumors are associated with the improvement of the patient's state and characterize the treatment efficiency. Surgical operation is used in cases of growing symptoms, progressive deterioration of the patient's state, signs of squeezing surrounding tissues. However, a radical intervention is fraught with a risk of progressive increase of the symptoms. For example, surgery for a vestibular schwannoma (benign tumor growing from the acoustic nerve myelin fibril membrane) can lead to a loss of hearing and facial nerve damage. But even a small part of remaining cells is fraught with continuing tumor growth and a relapse of the disease in future. Therefore, combination of its removal with subsequent target irradiation is rather promising.
In Russia more than 15,000 neuro-oncological patients with tumors of the brain are in need of radio-surgical care annually. Virtually all of them are in need of up-to-date target irradiation at some stage of treatment. It implies participation of neurosurgeons, oncologists, roentgenologists, medical physicists, radiobiolo-gists, and engineers. This allows to ensure a high level of treatment. New modern radiosurgical centers should be opened and qualified specialists trained for providing radiological care to patients.
Опубликовано на Порталусе 30 августа 2021 года
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