Radiosurgery

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.

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Definition and applications

Doctors 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 and medical physicist with basis on images, such as computed tomography (CT), magnetic resonance imaging (MRI), and angiography of the brain. The radiation is applied 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. The major disadvantage of radiosurgery in relation to open surgery (craniotomy) is the duration of time required to achieve the desired effects, while its non-invasive character is perhaps its major advantage.

History

Radiosurgery started with Dr. Lars Leksell from the Karolinska Institute of Stockholm, Sweden, in 1949, in a joint development with Bjorn Larsson, a radiobiologist from Uppsala University. Leksell initially used protons from a cyclotron 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 a high degree of precision, the patient's head is placed on a rigid frame of reference called a stereotactic frame that is inserted into a metal helmet. The device utilizes a coordinate system for each structure of the brain. By consulting a published cranial 'atlas', the surgeon knows the precise point of gamma ray convergance.

Gamma Knife surgery is used for stereotactic surgery as a relatively safe and selective method to irradiate tumors and arteriovenous malformations of the brain. The Gamma Knife requires only a single treatment session on a single day. In fact, the Gamma Knife surgery is so established that all insurance providers cover it and Medicare has given it its own authorization code.^{[citation needed]}

LINAC is another type of radiosurgery which has enjoyed great dissemination in neurosurgury. It was developed at the University of Florida College of Medicine and introduced by Betti and Colombo in the mid 1980's and utilizes a linear accelerator. 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, at some medical centers such as in Boston and in California, particle accelerators built for doing research in high energy physics have been used since the 1960's for the treatment of brain tumors and arteriovenous malformations of the brain 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.^[1] 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 ions and free radicals which are usually deleterious to the cells. These ions and radicals, which may be formed from the water in the cell or from the biological materials can produce 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 grays, where one gray (Gy) is the absorption of one joule per kilogram of mass. A unit that attempts to take into account both the different organs that are irradiated and the type of radiation is the sievert, a unit that describes both the amount of energy deposited and the biological effectiveness.

In order to perform optimal therapy, the neurosurgeon, assisted by physicists specialized in radiation therapy 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 an isodose map). Information about the tumor's location is obtained from a series of computerized tomograms, which are then fed to special planning computer software.

There are six types of irradiation currently used in radiosurgery: electromagnetical waves (gamma rays and x-rays), subatomic particles ( electrons, protons and neutrons), and carbon ions.

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 Gamma Knife treatment is the gold standard in brain tumor and arteriovenous malformation radiosurgery.

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 an electron accelerator. Electrons from the accelerator can collide with a solid target to create X-radiation.

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, electrons, will have very similar characteristics to that of gamma or X-rays. The depth of penetration is less than that of the above-mentioned photon sources.

The fourth type of radiation, protons, is used in Proton Beam Therapy (PBT). Protons are produced by a medical synchrotron, extracting them from proton donor materials and accelerating them in successive travels through a circular, evacuated conduit, using powerful magnets, until they reach sufficient energy (usually about 200 MeV) to enable them to approximately traverse a human body, then stop. They are then released toward the irradiation target which is region in the patient's body. In some machines, which deliver only a certain energy of protons, a custom mask made of plastic will be interposed between the initial beam and the patient, in order to adjust the beam energy for a proper amount of penetration. Because of the Bragg Peak effect, proton therapy has advantages over other the other forms of radiation, since most of the proton's energy is deposited within a limited distance, so tissue beyond this range (and so some extent also tissue inside this range) is spared from the effects of radiation. This property of protons, which has been called the "depth charge effect" allows for conformal dose distributions to be created around even very irregularly shaped targets, and for higher doses to targets surrounded or backstopped by radiation-sensitive structures such as the optic chiasm or brainstem. In recent years, however, so-called "intensity modulated" techniques have allowed for similar conformities to be attained using linear accelerator radiosurgery.

Neutrons, the fifth 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 including lesion type, size and location in relation to critical structures. Data suggests that similar clinical outcomes are possible with all of these methods. More important than the device used are issues regarding indications for treatment, total dose delivered, fractionation schedule and conformity of the treatment plan.

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, vascular lesions and functional disorders. Significant clinical judgment must be used with this technique and considerations must include lesion type, pathology if available, size, location and age and general health of the patient. General contraindications to radiosurgery include excessively large size of the target lesion or lesions too numerous for practical treatment.

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 especially helped.

Outcome may not be evident for months after the treatment. Since radiosurgery does not remove the tumor, but results in a biological inactivation of the tumor, lack of growth of the lesion is normally considered to be treatment success. 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. For many indications, such as acoustic neuroma, brain arteriovenous malformations and skull base tumors, radiosurgery has emerged as the treatment of choice.

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 intensity-modulated radiosurgery will be used to improve the accuracy and scope of radiosurgery. For now, the Gamma Knife is the standard for brain tumor treatment. Gamma Knife only takes one treatment session and is the most accurate surgery on the market.

See also

• Radiation therapy
• Neurosurgery
• Nuclear medicine
• Stereotactic surgery
• History of medicine

Notes

References

• Radiosurgery, by Elson A. Montagno, MD, PhD and Renato M.E. Sabbatini, PhD, in Brain & Mind Magazine
• The Basics of Boron Neutron Capture Therapy.

Manufacturers

• Elekta Instruments AB Home Page: manufacturer of Leksell's Gamma Knife
  • Video: How Gamma Knife Works. University of Pennsylvania Gamma Knife Radiosurgery
  • How Gamma Knife Works (Video)
• Accuray, Makers of the CyberKnife System
• BrainLAB Manufacturer of Novalis Radiosurgery System
• 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
• TomoTherapy Home Page Manufacturer of the TomoTherapy Hi·Art System
• Gammastar Home Page Manufacturer of the Gyro Knife - new generation of gamma knife