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Radiosurgery is a medical procedure which allows non-invasive brain surgery, i.e., without actually opening the skull), by means of directed beams of ionizing radiation. It is a relatively recent technique (1951), which is used to destroy, by means of a precise dosage of radiation, intracranial tumors and other lesions that could be otherwise inaccessible or inadequate for open surgery. There are many nervous diseases for which conventional surgical treatment is difficult or has many deleterious consequences for the patient, due to arteries, nerves, and other vital structures being damaged.
Definition and applications
Radiosurgeons make use of highly sophisticated, highly precise and complex instruments, such as stereotactic devices, linear accelerators, computers and laser beams. In the last 20 years, radiosurgery has been used as a first approach, by exclusion or failure of other techniques or as supplements to them, such as other kinds of brain surgery, chemotherapy and radiotherapy. The highly precise irradiation of targets within the brain is planned by the surgeon with basis on images, such as computed tomography (CT), magnetic resonance imaging (MRI), and angiography of the brain. The radiation is applied coming from an external source, under precise mechanical orientation by a specialized apparatus. Multiple beams are directed (collimated) and centered at the intracranial lesion to be treated. In this way, healthy tissues around the target are preserved.
Patients can be treated within one day of hospital stay, or even as outpatients. By comparison, the average hospital stay for a craniotomy (conventional neurosurgery, requiring the opening of the skull) is about 15 days. Radiosurgery costs about the same as a conventional surgery, but it avoids mortality, pain and post-surgical complications, such as hemorrhage and infection. The period of recovery is minimal, and in the day following the treatment the patient may return to his or her normal life style, without any discomfort. Thus, the community gains many socio-economical benefits. The major disadvantage of radiosurgery in relation to open surgery (craniotomy) it is the duration of time required to achieve the desired effects, while its non-invasive character is perhaps its major advantage.
Radiosurgery has arisen as the result of many scientific developments which have occurred in the fields of neuroimaging and stereotactic surgery, continue to expand its application areas in neurosurgery, oncology (cancer), surgery of head and neck, and other specialties.
Radiosurgery started with Dr. Lars Leksell from the Karolinska Institute of Stockholm, Sweden, in 1959, in a joint development with Bjorn Larsson, a radiobiologist from Uppsala University. Leksell initially used heavy particles, protons from a to irradiate brain tumor lesions.
In 1968, they developed the "gamma knife", a new device exclusively for radiosurgery, which consisted of radioactive sources of Cobalt-60 placed in a kind of helmet with central channels for irradiation, using gamma rays. In the last version of this device, 201 sources of radioactive cobalt direct gamma radiation to the center of a helmet, where the patient's head is inserted.
In order to achieve high precision in the positioning of the patient's head, it is placed first on a rigid frame of reference called a stereotactic device. It uses a geometrical coordinate system for each structure of the brain, so the surgeon knows, by using a published atlas, precisely where is the point where the gamma rays must converge. The stereotactic frame then fits into the helmet.
The "Gamma-knife" is used nowadays in four continents for carrying out what is called functional stereotactic neurosurgery, and for the superselective irradiation of tumors and brain arteriovenous malformations .
Another type of radiosurgery which has enjoyed great dissemination in neurosurgery was introduced by Betti and Colombo, in the mid 80's, utilizing commercial medical linear accelerators available for radiation therapy in oncology (the so-called LinAc). High energy, narrowly focused beams of x-rays are employed.
This system differs from the Gamma Knife in the way the radiation beams are delivered to the patient's head. In a similar way, a stereotactic device is used to provide a geometric coordinates reference, but the radiation beams are emitted by a single source, which rotates slowly around the patient's head.
Finally, in advanced medical centers such as in Boston and in California, particle accelerators built for doing research in high energy physics are being used since the 60's for the treatment of brain tumors and brain arteriovenous malformations in humans. A still experimental type of radiosurgery, that utilizes a nuclear reactor for the nuclear fission of uranium, is the Neutron Capture Therapy (NCT) which was started in the United States at the nuclear reactor of the Massachusetts Institute of Technology (MIT) in the 60's, with promising results. Nowadays it is carried out as a promising advanced clinical research in several countries, due to the progress and to the results obtained in Japan by Dr. Hiroshi Hatanaka . He used NCT in more than 100 cases in the treatment of malignant tumors and of gigantic arterio-venous malformations.
How it works
The fundamental principle of radiosurgery is that of selective ionization of the tissue to be operated upon, by means of high-energy beams of radiation. Ionization is the production of inorganic ions which are usually deleterious to the cells, by forming free radicals that are harmful to the cellular and nuclear membranes, and even to the RNA and DNA chains of the cells, producing an irreparable damage to these structures and then the cell's death. Thus, biological inactivation is carried out in a volume of tissue to be treated, with a precise destructive effect. The radiation dose absorbed by the treated mass of tissue is what defines the degree of biological inactivation. It usually is measured in Gray units, where one Gray (Gy) is the absorption of one joule per kg of mass.
In order to perform optimal therapy, the neurosurgeon, assisted by physicists specialized in nuclear medicine and often in conjunction with a radiation oncologist, chooses the best type of radiation to be used, and how it will be delivered. Usually, the total dose of radiation required to kill a tumor, for example, is not delivered in a single, massive section, because this would cause undesirable effects on the patient. Instead, it is divided into several sessions of smaller duration and energy dose, in a procedure called dose fractioning . The aim of dose fractioning is to minimize the undesirable damage to healthy tissues, as healthy tissue cells are better than cancerous cells at repairing radiation induced damage between irradiations. In order to plan the radiation incidence and dosage, the physicists calculate a map portraying the lines of equal absorbed dose of radiation upon the patient's head (this is called a isodose map). Information about the tumor's location is obtained from a series of computerized tomograms, which are then feed to special planning computer software.
The first type of radiation is gamma rays, which are beams of high energy photons that interact with the corona of electrons of the atoms that compose the irradiated tissue, ionizing them. Gamma radiation is used in the "Gamma Knife" device, where they are produced by fixed sources of radioactive cobalt.
The second type of radiation, X-rays, are also high energy photons that are identical to gamma rays except for the way they are produced. Radiosurgery can be performed using a linear accelerator, the source being now a commercial medical device of universal use in radiotherapy. The Linac consists of a emitting tube of X radiation, with an energy of 4, 6, or 18 million electron-volts (MeV).
The emission head (called "gantry ") is mechanically rotated around the patient, in a full or partial circle. The table where the patient is lying, the 'couch,' can also be moved in small linear or angular steps. The combination of the movements of the gantry and of the couch makes possible the computerized planning of the volume of brain tissue which is going to be irradiated. Devices with an energy of 6 MeV are the most suitable for the treatment of the brain, due to the smaller volume to be irradiated. In addition, the diameter of the energy beam leaving the emission head can be adjusted to the size of the lesion by means of interchangeable collimators (an orifice with different diameters, varying from 5 to 40 mm, in steps of 5 mm). There are also multileaf collimators, which consist of a number of metal leaflets that can be moved dynamically during treatment in order to shape the radiation beam to conform to the mass to be ablated.
The third type of radiation, protons, is used in Proton Beam Therapy (PBT). Protons are produced by cyclotrons, extracting them from proton donor materials and accelerating them in successive travels through a circular, evacuated conduit, using powerful magnets, until they reach a high energy and are released toward the irradiation target, in the patient's body. Because of the Bragg peak effect , proton therapy has some advantages over other the other forms of radiation, since most of the proton's energy is deposited within a limited distance, and so tissue beyond this range is spared from the effects of radiation. This property of photons allows for highly conformal dose distributions to be created around even very irregularly shaped targets.
Neutrons, the fourth type of radiation, are used in Boron neutron capture therapy (BNCT). BCNT depends on the interaction of slow neutrons with boron-10 to produce alpha particles, another type of radiation. Patients are first given an intravenous injection of a boron-10 tagged chemical that preferentially binds tumor cells. The neutrons are created either in a nuclear reactor or by colliding high-energy protons into a Lithium target. The neutrons pass through a moderator, which shapes the neutron energy spectrum suitable for BNCT treatment. Before entering the patient the neutron beam is shaped by a beam collimator. While passing through the tissue of the patient, the neutrons are slowed by collisions and become low energy thermal neutrons. The thermal neutrons undergo reaction with the boron-10 nuclei, forming an unstable boron-11 nucleus which then undergoes spontaneous decay to lithium-7 and an alpha particle. Both the alpha particle and the lithium ion produce closely spaced ionizations in the immediate vicinity of the reaction, with a range of approximately 10 micrometres, or one cell diameter. This technique is advantageous since the radiation damage occurs over a short range and thus normal tissues can be spared. Also, there are two mechanisms for tumor selectivity, since both the boron compound is made to bind to tumor cells and the neutron beam is aimed at the location of the tumor. BNCT has been developed in only in an experimental basis, and it has not entered surgical routine.
The selection of the proper kind of radiation and device depends on many factors. Radiosurgery by Gamma-Knife is applied in isocenters of up to 30 mm of diameter, which therefore works better for small lesions. Linear accelerators achieve isocenters of up to 40 mm of diameter. With proton cyclotrons, the treatable lesions can have up to 100 mm of diameter; while in neutron-capture therapy, the field can be the whole head.
Latest generation Linacs are capable of achieving extremely narrow beam geometries, such as 0,15 to 0,3 mm. Therefore, they can be used for several kinds of surgeries which hitherto are carried out by open or endoscopic surgery, such as for trigeminal neuralgia, etc.
Radiosurgery of brain tumors
Radiosurgery has been especially helpful for the localized, highly precise treatment of brain tumors. Due to the steep fall of the irradiation fields (isodoses) from the center of the target to be destroyed, the biological inactivation happens only on it; while the brain, and other vascular and neural structures around it, are protected. This is achieved through the high mechanical precision of the radiation source, and the assured reproducibility of the target. The precision in the positioning of the patient, in the calculation of dosages, and in the safety of the patient, are all extremely high.
Radiosurgery is indicated primarily for the therapy of tumors of the brain and of the hypophysis. These tumors can be primary (i.e., they originated in the brain tissue itself) or metastatical (i.e., they originated from the spread of primary tumors growing in other parts of the body). Radiosurgery works equally well with benign or malignant tumors.
The non-interference with the quality of life of the patient in the post-operatory period competes with the inconvenience of the latency of months until the result of the radiosurgery is accomplished. Patients with a bad general state of health and those with tumors which are unreachable by conventional means, are specially helped.
The best results become evident three months after the treatment. Usually there is no new growth of tumors in the irradiated region. Radiosurgery has been used to treat many kinds of brain tumors, such as acoustic neuromas, astrocytomas, gliomas, germinomas , meningiomas, among others. Even highly fatal cancerous metastases in the brainstem can be reduced, leaving the patient neurologically intact. It has been demonstrated by the thousands of successfully treated cases, that radiosurgery can be a very safe and efficient method for the management of many difficult brain lesions, while it avoids the loss in quality of life associated to other more invasive methods. Patients are being treated for lesions which only radiosurgery can solve, or because they prefer it as a first treatment, after receiving complete information of its risks and benefits as compared to the conventional surgery, when the choice is available.
In the future, advanced computer methods, such as virtual reality, will be used to improve the accuracy and scope of radiosurgery. Three-dimensional (3D) reconstructed image of the tumor is visualized by the neurosurgeon, using special 3D goggles, as a projection onto the patient's head, with precise conservation of the spatial relations of one in relation to the other.
- Understanding Stereotactic Radiosurgery. University of Florida.
- Computer Assisted Neurosurgery, University of Alabama at Birmingham
- Proton-Beam Radiosurgery, Massachusetts General Hospital, Harvard University.
- Elekta Instruments AB Home Page: manufacturer of Leksell's Gamma Knife
- Siemens Corporation's Oncology Care Systems Home Page: manufacturer of linear accelerators and radiation planning systems.
- Varian Oncology Systems Home Page: manufacturer of linear accelerators
- Radionics Stereotactic Radiosurgery System: XKnife System
- BrainLAB Manufacturer of Novalis Radiosurgery System
Picture credits: Siemens Corporation (Oncology Care Systems), Elekta Instruments Ltd.; Varian Oncology Systems, Massachusetts General Hospital and Harvard University Dept. Neurosurgery, Singapore Gamma Knife Center.
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