Prostate cancer pathology outlines immunohistochemistry,

Radiation brain surgery and fractioned stereotactic radiotherapy. Introduction In general, oncologists have three weapons to fight against cancer: surgery, drugs chemotherapy, immunotherapyand radiation therapy. We have the same possibilities for the treatment of intracranial tumours, but because of certain specialties of the central nervous system, the above-mentioned armamentarium is modified: The brain is locked into a rigid cave, thus growing of even benign tumours can cause life-threatening conditions because of the space occupation.

The damage of major portions of the brain is not compatible with life, or it results in significant deterioration of the quality of life. As a result of the blood-brain barrier system, the majority of classical chemotherapeutic drugs will not reach the cancer cells in a proper concentration.

On the other hand in some cases, chemotherapeutic agents are administered in the CSF to fight against cancer spreading via the CSF pathways.

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Due to the fact that the majority of CNS cells do not divide, radiation therapy using the difference in sensitivity of normal and cancer cells against radiation can effectively be applied for the treatment of intracranial targets.

Consequently, radiation therapy has become the most important and the most widely used tool in place of inoperable tumour or beside residual tumour or cavity surgery for a local control. Furthermore, the radiosensitivity of different brain areas is considerably different: e. The rigidity of the scull, and the minor dislocation of the brain in the cranium make it possible to modify classical radiotherapy techniques when treating intracranial targets: Brain can be fixed through the scull with a precision of tenth of a millimeter… Thus we consider a little brain tissue dislocation the security margins of general radiation therapy and consequently the degree of radiation load to normal tissue can be lowered.

In this chapter radiation therapy radiosurgery and fractionated stereotactic radiation therapy of the CNS mainly for intracranial targets is discussed.

First of all, the bases of fractionated radiation therapy are shown, then radiosurgery, fractionated stereotactic radiation therapy and the target diseases are discussed. Basic concepts 2.

Theoretically to determine the exact position of an object we prostate cancer pathology outlines immunohistochemistry A reference coordinate system A map, if the interrelation of the object is considered Since the map has its own coordinate system, this one and the real coordinate system needs to be correlated to each other. This procedure is the registration. In practice, there are frame based and frameless techniques. In the former case the stereotactic frame is the base of a 3D coordinate system.

In case of frameless navigation the part of the body to be treated is immobilized in some way, and its position is compared to a reference system e. In both cases the CT, or MR picture data serve as reference maps for the navigation.

The history of stereotaxy and surgical navigation The pioneers of intracranial neurosurgeons at the end of the 19th and the beginning of 20th centuries relied purely on their anatomical knowledge and clinical observations regarding the place, size and characteristics of certain brain a lábak ízületeinek betegségei 70 év alatt and pathologies, since intracranial imaging was not yet available.

For the first time, a Russian professor, Zernov Dmitri Zernov,an anatomist in Moscow created and used a localization instrument encephalometer for anatomical studies and neurosurgical interventions. With the help of this instrument he was able to determine the position of brain structures in polar coordinates. He used the encephalometer to determine the position of the central sulcus, and revealing this place, he discovered a cerebral abscess.

Figure 7.

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Figure 1. Kandel: Functional and stereotactic neurosurgery, Although clearly from above, he was the one who developed stereotaxy, his work was not known by the rest of the world, thus usually Sir Victor Horsley and his colleague Robert H. Clarke are considered to build a stereotactic instrument first time in the world in for electrophysiological experiments in animals. Unfortunately they could not define the exact position of subcortical structures compared to bones in a humans, that is why this method did not spread for a long time.

During the next years and decades, procedures utilizing this technique developed rapidly but the transfer of image information to the given patient depended purely on the anatomical knowledge and power of spatial conception of the surgeon. The goal was to guide an instrument to a formerly defined prostate cancer pathology outlines immunohistochemistry of the brain.

Frame based stereotaxy After all these, the stereotactic frames firmly attached to the scull spread widely. Initially, they have been used to guide discreet lesions in order to relive the symptoms of movement disorders, chronic pain, and térdízület fájdalma artrózissal and later to aspirate cysts, abscesses, to implant radio-isotopes, to make biopsies or for radiosurgery.

The advantage of a stereotactic frame is prostate cancer pathology outlines immunohistochemistry precise and reliable attachment and coordinate system. Its disadvantages in general neurosurgery : the frame is applied on the day of the surgery scala posterior structures can not be reached easily the frame may impede the surgeon the localization is feasible for single or a small number of targets it is hard to change target during surgery 2.

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Frameless stereotaxy Recently called neuronavigation As a consequence of the exploding evolution of computation and imaging techniques DSA, CT, MR the possibility and quality of surgical planning also improved. On the other hand, the rich information collected prior to surgery should be transferred in some way to the operation field in order to use it during surgery.

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This task, requiring serious experience and orientation skills, was solved purely in mind of a traditional neurosurgeon.

David Roberts developed a navigation system based on ultrasonography in This did not spread wide in clinical practice. InProstate cancer pathology outlines immunohistochemistry Watanabe constructed a localization system that consisted of many joints and arms of given length. This instrument went into standardized production. At the early nineties, two further navigation systems emerged: the electromagnetic, and the optical. The advantage of the electromagnetic system was that there was no need for direct optical contact between the machine and the surgical field, on the other hand the initial imprecision of 2 millimeters increased in vicinity of metals, which was its disadvantage.

Thus optical systems spread wide their functioning is similar to GPS. Active and passive types exist: In case of an active system, infrared beams emitted by instruments connected to the base system are detected by infrared cameras.

Its disadvantage is that the wires are sometimes disturbing during the surgery. Its advantages are that they can be used well under sterile drapes and under wet conditions.

The instruments of a passive system have small reflective fiducials that are detected by two cameras, ejecting infrared light.

The advantage of the system is the lack of wires, the disadvantage is that it is more sensitive to humidity and the fiducials need to be changed regularly, because they worn out during sterilization. The change of the pellets is pretty expensive cost ineffectiveness. In case prostate cancer pathology outlines immunohistochemistry neuronavigation, however, initially there is no relationship between the two coordinate systems. The procedure that establishes this relationship is called registration.

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Types of registration: Paired point registration we need at least 3 points which are not lying in line [linearly independent] At the beginning, marker based kínzott ízületi gyulladás mint a kezelés was used. We grant much more points in the space, which define the surface. Neurosurgeons navigate the tip of their instruments or the focus of their microscope in order to orient intracranially.

Oncologists try to direct the radiation beam towards the intracranial target and since the radiation head cannot move freely except CyberKnife ; the patient is positioned to the instrument to the center of the radiation instrument.

Radiosurgery, RS Single session, focused irradiation to a stereotactically localized target. The reason of the denomination: The treatment results in long-term similar effects as the target was excised by a scalpel, and in most cases only a small scar remains in place of the target.

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The treatment for one target can be done in 20 minutes, and its effect is definitive and irreversible, similar to a surgical intervention. Fractionated stereotactic radiation therapy fSRT Multiple sessions, focused irradiation to a stereotactically localized target.

Biological principles of a traditional fractionated radiation therapy The effect of ionizing radiation is due to its energy egress. Major portion of the absorbed energy is translated to the ionization of the atoms in the given volume.

The shorter the absorption route Linear Energy Transfer, LET the more ions are produced on the way of the particle, viz. In case of radiation qualities with very high ionizing density neutron, accelerated ions chemical reactions can directly reach the bigger molecules proteins, RNA, DNAwhile electron or photon irradiation acts indirectly by formation of free oxygen radicals.

These make fast reactions with macromolecules, thus membrane or enzyme function, signal transduction, protein- and DNA-synthesis can be damaged, and apoptosis can be induced.

Chemical reactions caused by the radiation induce protective mechanisms, the inflammatory cascade is activated, and repair mechanisms come into effect. In cellular level either transient, reparable disturbance develops, or the cell becomes unable to divide, or dies.

The biological effect of radiation depends on the proportion of cells capable for proliferation in cell cycle; cells are the most sensitive in G2 and M phaseon the number of cells, on the repair capacity and oxygenation of them, on their sensitivity determined by their molecular composition, and on the temporal distribution of the radiation dose that is: fractionation.

The total dose of the irradiation treatment is fractionated divided into several smaller doses and given off in multiple sessions because of the following prostate cancer pathology outlines immunohistochemistry Fractionation allows normal cells to recover between fractions, while the regeneration ability prostate cancer pathology outlines immunohistochemistry cancer cells is less potent Fractionation makes it possible for cancer cells being in an insensitive phase of the cell cycle during one session, to get into a sensitive phase for the next fraction Cancer cells being in a hypoxic environment during one session thus being less radiosensitive may reoxygenate by the time the next session starts, and become more radiosensitive.

Radiation necrosis was a dreadful side effect of radiotherapy those days.

It affected the target volume and neighboring healthy tissues, and it was very difficult to agar agar ízületi fájdalmakból. It often caused severe brain swelling in case of intracranial treatments or fistulae, peritonitis, ileus at abdominal irradiation resulting life-threatening conditions.

With the technical mainly computational development, it become possible to direct the radiation beams coming from different directions with a tenth of a millimeter exactitude, and to safely administer huge doses of irradiation, enough to cause irreversible tissue damage in one session.

Hence its name is radiosurgery. It should be noted here, that the description above is valid mainly for the treatment of malignant intracranial tumours. The technique using smaller doses can be used for the treatment of benign lesions as well.

In these cases our goal is not the total destruction of the target volume but to prevent it from growing vestibular schwannomaor to minimize its blood supply arterio-venous malformations.

In these cases, irradiation induces endothelial division and causes occlusion of the vessels within months. Principles of fractionated stereotactic radiotherapy fSRT By definition, compared to radiosurgery, the difference is that the radiotherapy applied with the precision of stereotaxy is given in multiple sessions, using the advantageous features of both traditional radiotherapy and radiosurgery with high spatial selectivity: it is a precisely applied radiotherapy that utilizes the radiosensitivity difference between normal and tumour cells.

In CNS oncology it is used mainly for the treatment of tumours near eloquent brain areas where the required fall of dose in vicinity of the target cannot be reached, thus chances of injury of the risk organ in case of a single session radiosurgery would be too high. Requirements of stereotactic radiation techniques 6.

Immobilization of the target volume In order to safely deliver the required dose resulting in radionecrosis, the prostate cancer pathology outlines immunohistochemistry has to be rigidly and reproducibly immobilized. The goal is the possibility to bring the target volume into the same position for the treatment as it was during the imaging serving the basis of treatment planning.

This requirement can be fulfilled easily for intracranial targets, since the brain can be fixed without major shift through the scull. That is why radiosurgery and stereotactic radiotherapy remained until the last years a therapeutic option for only intracranial targets. Rapid technical evolution of the last decade has made prostate cancer pathology outlines immunohistochemistry irradiations possible in all parts of the body. In reality, the exact position of the target volumes is given related to this frame as reference.

The screws are attached firmly to the outer cortical layer of the scull under local anaesthesia.

Beyond the anesthetic injection the attachment of the frame causes a transitional feeling of wring for minutes. Mask For the fractionated stereotactic radiotherapy the scull and the target volume through it would be unfeasible to be attached in an invasive way since it would be necessary to wear it for the total course of even 6 weeks, or — prostate cancer pathology outlines immunohistochemistry — it would have to be attached before every treatment session, but in this case a new CT and new plan would also be required.

To overcome this problem, non-invasive immobilization systems emerged. Nowadays thermoplastic mask systems emerged and are complemented with other instruments e.

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Positioning, guidance and image guided radiotherapy IGRT Accurate irradiation of the target volume made marked reduction of radiation load of healthy tissue, and precise implementation necessary. Although using a well-prepared mask the head of a well-collaborating patient can be fixed with accuracy similar to the frame session by session, millimeter preciseness required the verification of the position of the target volume.

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If mismatch is observed the patient is repositioned. Next to the megavolt system, the most modern LINACs are equipped with a kilovolt system two pairs of X-ray tube and detector as well. DRR calculated from the plan and actual X-ray or cone beam CT images are compared, and the mismatch is calculated by an image fusion algorithm in 6 degrees of freedom shift and tilt in three directionsand corrected by a robotic couch.

This is achieved by vacuum mattresses, or by masks molded on the given part of the body.

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On the other hand, we should take into account that the shape and position of different organs inside the body change with their functioning movement of bowels, change of the shape of lung during breathing, etc. The impreciseness derived from the above mentioned organ movements could be eliminated using the following techniques: For targets ízületi betegségek súlyosbodásának kezelése near by bones, and whose positions and shapes do not change in relation to the bone, an X-ray and DRR pair can be used for positioning like in case of intracranial targets.

For target volumes where organ movement and shape alteration is negligible positioning of the target is done by mismatch minimization of Cone beam and planning CTs.

A simple but invasive possibility for the stereotactic positioning of certain retroperitoneal organs is the use of implanted markers. Golden seeds are implanted prior the planning CT. The point is, that respiratory curve data are stored with the images, and the plan is created to a given phase of the respiratory cycle. During treatment, beams are on only during the given phase.

Using this technique, intrapulmonary or abdominal tumours can be treated with smaller safety margins; consequently the radiation load of healthy tissue is reduced. Dispensing of the imaging required for irradiation planning During the preparation process for stereotactic irradiation the target volume must be defined as precisely as possible.