21 Stereotactic Radiotherapy/Radiosurgery Anca-Ligia Grosu, Peter Kneschaurek,

21 Stereotactic Radiotherapy/Radiosurgery

Anca-Ligia Grosu, Peter Kneschaurek, and Wolfgang Schlegel

A.-L. Grosu MD; P. Kneschaurek, PhD

Department of Radiation Oncology, Klinikum rechts der Isar, Technical University, Ismaningerstrasse 22, 81675 Munich, Germany

W. Schlegel, PhD

Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69121 Heidelberg, Germany

21.1

Introduction

Stereotactic radiotherapy dates back more than 50 years; however, this form of treatment has entered the domain of radiation oncology only in the past 10–15 years. Initially an exotic technique, stereotactic radiotherapy has become an established, widespread treatment approach, characterized by the delivery of the irradiation with a very high geometrical preci- sion. The method is especially used for benign and

malignant cranial tumors but has lately been adapted to the body.

Stereotactic coordinates are used in the method- ology of different irradiation techniques: implanta- tion of seeds; Bragg-Peak irradiation; irradiation with gamma knife (Co60) or with linear accelerator (LINAC or X-Knife). This chapter focuses on the de- scription of the technique of stereotactic tele-ther- apy (percutaneous stereotactic radiotherapy) with LINAC, also known as stereotactic convergent beam irradiation. This is the most widespread irradiation technique using stereotactic coordinates.

21.2 Defi nition

Stereotaxy (stereo + taxis – Greek, orientation in space) is a method which defi nes a point in the pa- tient’s body by using an external three-dimensional coordinate system which is rigidly attached to the patient. Stereotactic radiotherapy uses this technique to position a target reference point, defi ned in the tumor, in the isocenter of the radiation machine (LINAC, gamma knife, etc.) with a high accuracy. This results in a highly precise delivery of the radiation dose to an exactly defi ned target (tumor) volume. The aim is to encompass the target volume in the high- dose area and, by means of a steep dose gradient, to spare the surrounding normal tissue. This allows the defi nition of the planning target volume (PTV) without, or with only a very small (1–2 mm), safety margin around the gross tumor volume (GTV) or the clinical target volume (CTV). Stereotactic radiother- apy is performed in various treatment techniques, including gamma-knife units using 60 Co photons, heavy charged particles, or neutron beams units and modifi ed LINAC units.

Treatment can be administered in a single fraction (radiosurgery, RS) or as multiple fractions (stereotac- tic fractionated radiotherapy, SFR). Some authors use the term stereotactic radiotherapy for the fraction-

CONTENTS

21.1 Introduction 267 21.2 Defi nition 267

21.3 Historical Background 268 21.4 Stereotactic Coordinates 268

21.5 Method of Stereotactic Irradiation Treatment 269 21.5.1 Stereotactic Frame 269

21.5.2 Imaging for Stereotactic Irradiation Treatment 270

21.5.3 Treatment Planning 272 21.5.3.1 Defi nition of Target Volume and

Organs at Risk 272

21.5.3.2 Defi nition of the Stereotactic Target Point 272 21.5.3.3 Planning of the Radiation Technique 272 21.5.3.4 3D Dose Calculation 273

21.5.3.5 Dose Specifi cation 273

21.5.3.6 Visualization of the Dose Distribution 273 21.5.4 Positioning 273

21.5.5 Delivery of the Radiation 273 21.5.6 Quality Assurance 274 21.6 Future Developments 274 21.7 Conclusion 274

References 275

ated delivery of the radiation; however, we consider it as a general term for all the irradiation treatments which are characterized by the integration of stereo- tactic coordinates in the treatment planning and de- livery, including the RS and the SFR.

The intention of RS is to produce enough cell kill within the target volume in a single fraction in order to eradicate the tumor. This single high irradiation dose can produce considerable side effects in normal tissue located close to the tumor or within the tar- get volume. The SFR combines the precision of target localization and dose application of RS with the ra- diobiological advantage of fractionated radiotherapy, i.e., breaking the total dose into smaller parts and thus allowing repair of DNA damage in normal tis- sue during the time between fractions. Time intervals of more than 6 h between fractions can signifi cantly reduce the risk of side effects in normal tissue (Hall and Brenner 1993; Schlegel et al. 1993).

21.3

Historical Background

The fi rst one to combine stereotactic methodology – which up to that point was used only in neurosurgery – with radiation therapy was the Swedish neurosur- geon Lars Leksell. He had the idea that X-ray could be used to treat certain neurological functional diseases instead of stereotactically guided needles used in neu- rosurgery. Leksel performed the fi rst treatment in 1951, at the Karolinska Institute, and called the new therapy approach radiosurgery (RS). The patient was fi xed in a stereotactic ring and irradiated with a precisely guided roentgen tube using 200-kV Röntgenbremsstrahlung (Leksell 1951). Bragg-peak studies with protons were begun in Uppsala, Boston, and Berkeley (Kjellberg et al. 1968; Larsson et al. 1958; Lawrence et al. 1962).

In Berkeley Bragg-peak RS using helium ion beams was also developed (Lyman et al. 1977). Leksel con- tinued his work and built the fi rst isotope radiation machine, in 1968, the gamma knife.

The gamma-knife unit consists of 201 Co-60 sources arranged on the surface of a hemispherical shell, each aiming at an isocenter in a uniform dis- tance of 40 cm. Each source is collimated by a fi xed primary collimator and subsequently by a helmet, which consists of 201 collimators to which the patient and frame are attached and which is docked with the primary collimator array at the time of treatment.

The helmets defi ne an approximately spherical dose distribution at the isocenter with nominal diameters

of 4, 8, 14, or 18 mm. The physical point of interest inside the patient is positioned at the isocenter of this distribution before treatment, and, if required, a sequence of treatment at different isocenters, with possibly different diameter helmets, are used to pro- duce a conformal dose distribution. Multiple isocen- ters treatments are required when the target shape is irregular. By combining several spherical dose distributions of smaller diameter in the appropriate location, it is possible to create a sum of isodose dis- tributions similar to the target volume. As a result the dose to the target itself is inhomogeneous, with larger number of isocenters leading to higher mean target doses. To date, the radiobiological consequences of dose inhomogeneity in tumor tissue cannot be eval- uated yet, but the advantages of dose escalation in the tumor and dose reduction in the normal tissue are undisputed (Lindquist et al. 1995; Verhey and Smith 1995).

The stereotactic radiation therapy with LINAC started in the early 1980s: the Swedish physicist Larsson proposed to use the LINAC instead Co 60 or protons (Larsson et al. 1974). The fi rst published reports on clinical use of LINAC came from Buenos Aires (Betti and Derechinsky 1983), Heidelberg (Hartmann et al. 1985), and Vicenza (Colombo et al. 1985), the authors of which all had developed the concept to deliver a single-dose radiation with con- vergent non-coplanar dynamic irradiation. Many clinical investigators made use of this technology all over the world in a very short time, showing, in comparison with the gamma-knife RS, comparable clinical results (Engenhart et al. 1989, 1992; Mehta et al. 1995; Becker et al. 1996; Debus et al. 1999).

Further progress was made in LINAC stereotactic ra- diotherapy due to the development of non-invasive, replaceable head-fi xation systems, which allow the implementation of the dose fractionation (Schlegel et al. 1992, 1993; Stärk et al. 1997). Another impor- tant development is the micro-multileaf collimator which permits the adoption of the irradiated area to irregular-shaped target volumes (Schlegel et al.

1997) and the extension of the stereotactic irradia- tion technique to the head and neck (Gademann et al. 1993) and the body (Herfarth et al. 2000).

21.4

Stereotactic Coordinates

The key idea of all stereotactic radiation therapy

techniques is the use of stereotactic coordinates to

defi ne the volume which has to be irradiated three dimensionally; therefore, target volume and anatomi- cal structures are localized in the space defi ned by the stereotactic coordinates system. Computed tomogra- phy (CT) or magnetic resonance imaging (MRI) are used for defi ning the anatomical structures which are of crucial importance for radiation therapy. The stereotactic localizer which is imaged simultaneously allows transfer of the image coordinates into the ste- reotactic coordinates system. During the planning of the radiation therapy a target point in the stereotactic space is defi ned. Before onset of radiation the patient is positioned in such a way that this target point is placed in the isocenter of the radiation machine with the help of the stereotactic positioning system.

In general, the stereotactic coordinates are a carte- sian three-dimensional coordinates system attached to the stereotactic frame in a rigid relationship. The origin of the stereotactic coordinates system is gen- erally in the center of the volume defi ned by the ste- reotactic frame: the x and y axes correspond to the lateral and frontal side of the frame and the z axis to the cranio-caudal direction (Fig. 21.1).

3. Treatment planning

4. Positioning of the patient for the stereotactic radi- ation therapy

5. Delivery of the irradiation 6. Quality assurance

21.5.1

Stereotactic Frame

Stereotactic radiotherapy is based on the rigid con- nection of the stereotactic frame to the patient during CT, MRI, and angiography imaging (Figs. 21.2, 21.3).

The stereotactic frame is the base for the fi xation of the other stereotactic elements (localizer and posi- tioner) and for the defi nition of the origin (point 0) of

Fig. 21.1 The stereotactic coordinates defi ne three-dimension-

ally the space which has to be irradiated

21.5

Method of Stereotactic Irradiation Treatment

The main steps in the planning and delivering of stereotactic irradiation treatment are:

1. Rigid application of the stereotactic frame to the patient

2. Imaging (CT, MRI, angiography) of the patient with the frame and localizer attached to the frame

Fig. 21.3 Non-invasive repeat head fi xation with the mask sys-

tem and upper jaw support

Fig. 21.2 Head-ring fi xation. A Carbon fi ber posts. B, E Artifact-

free fi xation pins with ceramic tips. C Robust and lightweight

frame. D Two torque wrenches for pressure adjustment of

pins

the stereotactic coordinates. The constant geometri- cal relationship between the stereotactic frame and anatomical structures, including the PTV, is realized by fi xation of the frame to the patient. During the whole treatment procedure, from the performance of the stereotactic imaging to the delivery of the ir- radiation treatment, the stereotactic frame must not be removed from the patient. In case of relocatable frames it must be assured that the position of the patient is exactly the same relative to the frame after reapplication of the relocatable frame.

For the treatment of cranial lesions by RS the frame system is neurosurgically fi xed onto the patient’s skull (Fig. 21.2). For SFR the head is fi xed non-invasively in a relocatable thermoplastic mask attached on the ste- reotactic frame (Fig. 21.3).

There are different stereotactic frame systems de- scribed in detail in the literature: the BRW system (Brown 1979; Heilbrun et al. 1983); the CRW system (Couldwell and Apuzzo 1990; Spiegelmann and Friedman 1991); the Leksell system (Leksell and Jernberg 1980; Leksell et al. 1985); the Leibinger- Fischer system (Riechert and Mundinger 1955;

Sturm et al. 1983); and the BrainLAB system (Stärk et al. 1997; Auer et al. 2002). Each system is differ- ent with regard to material of the stereotactic frame, design, and connection with the localizer and posi- tioner and accuracy of repositioning (Kortmann et al. 1999).

21.5.2

Imaging for Stereotactic Irradiation Treatment

Imaging is used in stereotactic radiotherapy for: (a) localization and positioning; (b) defi nition of target volume and organs at risk; and (c) calculation and 3D representation of the isodose distribution.

Most stereotactic systems use CT for localization.

During the CT investigation the localizer is attached to the frame (Fig. 21.4). The localizer is a box with CT-compatible fi ducial markers on each plane, which are visualized on CT on each scan; thus, the localizer defi nes the link between the stereotactic coordinates and the imaging coordinates, so that for any point in the imaging the 3D stereotactic coordinates can be determined. The stereotactic frame, the patient fi xa- tion system, and the localizer form a fi x unit. They have to be compatible with the radiological investiga- tions and offer an accurate visualization of the tumor and of the critical structures, without artifacts. The use of MRI for localization and positioning needs a high homogeneity of the magnetic fi eld to avoid spa- tial distortions artifacts, which could disturb the geo- metrical correlation between the stereotactic coordi- nates system and imaging coordinates system.

Non-invasive imaging techniques are a central component of treatment planning in radiation oncol- ogy. The information gained from different imaging modalities is usually of a complementary nature: (a)

Fig. 21.4 The localizer compatible with the

head ring and mask system (upper left). The

target positioner (right) and the printed

fi lms (lower) attached to target positioner

with isocenter markers for laser setup (red

beam angle for conformal beam verifi ca-

tion with LINAC light fi eld (blue arrow)

MRI describes the anatomical structures of soft tis- sue with a high accuracy; (b) CT is important for the delineation of bone and soft tissue; (c) positron emis- sion tomography (PET) and single photon computed emission tomography (SPECT) offer additional infor- mation about tumor extension and biology; and (d) angiography is essential for the visualization of the

arterio-venous malformations; thus, the defi nition of tumor extension and critical structures is character- ized by the correct integration of multiple different investigational tools, by using specialized image fu- sion software (Figs. 21.5, 21.6; Grosu et al. 2003).

The calculation and 3D representation of the iso- dose distribution is discussed in the next chapter.

Fig. 21.5 The images left show the rotational stereotactic technique using six radiation arcs and conical collimators. The images right present the dose distribution for the radiosurgery treatment of a brain stem metastases on MRI (upper) and the CT/MRI

image fusion (lower)

Fig. 21.6 Stereotactic irradiation using eight static fi elds and micro-multileaf

collimator in a patient with acoustic neuroma treated with stereotactic frac-

tionated radiotherapy. The MRI/CT image fusion and the conformal dose dis-

tribution is shown in the two lower images

21.5.3

Treatment Planning

21.5.3.1

Defi nition of Target Volume and Organs at Risk

The delineation of the target volume is a complex interactive process in which all the information of the imaging tools and the clinical information (op- eration, histopathology, other treatment approaches, etc.) are considered. The tumor-specifi c morphology, the growth pattern of the tumor, and the anatomical relationship to the normal tissue are essential param- eters in defi ning the target volume.

Of major importance for the stereotactic radiation therapy is the delineation of the organs at risk. All the organs at risk which may get signifi cant dose have to be delineated.

21.5.3.2

Defi nition of the Stereotactic Target Point

The target point is the point in the target volume that must be positioned with exact precision in the isocenter of the LINAC. The position of the target point can be defi ned interactively. One or more tar- get points can be defi ned. In stereotactic planning programs the coordinates of the target points are related in such way that the resulting dose distribu- tion meets the clinical requirements. The planning system outputs the position of these points in stereo- tactic coordinate. Prior to therapy, these coordinates will be used to correctly position the patient. This is performed with a positioner, a device attached to the stereotactic frame, which allows the connection of the stereotactic coordinate system to the room coordinate system, where the isocenter of the treat- ment device is defi ned (Fig. 21.4).

21.5.3.3

Planning of the Radiation Technique

The stereotactic radiation is characterized by a very steep dose fall-off on the margin of the target volume.

The steep dose gradient is achieved by the use of appropriate collimators and a multitude of radiation directions.

Stereotactic Collimators. Tertiary stereotactic col- limators for circular or oval target volumes are at- tached to the tray holder of the LINAC. The diam- eter of the irradiated area is defi ned by the size of the circular collimators and varies usually between 1 and 35 mm (Fig. 21.7). For irregular target volumes

different individual apertures may be used, but the production and the use thereof is very cumbersome.

Only recently have micro-multileaf collimators become available (Fig. 21.8). The beam shape can be selected by computer or by hand. In this way the con- tours of the irradiation fi eld can be adjusted individu- ally to the tumor shape. Micro-multileaf collimators, in comparison with the traditional multi-leaf colli- mators, have the advantage of a decreased leaf width and therefore optimized the resolution (between 1 and 3 mm). Computer-controlled micro-multileaf

Fig. 21.8 Micro-multileaf collimator: 3-mm fi ne leaves at cen-

ter; 4.5-mm intermediate leaves; and 5.5-mm outside leaves.

Maximum fi eld size is 10×10 cm

collimators offer the possibility of a dynamic fi eld adjustment during irradiation and permit the imple- mentation of the intensity-modulated radiotherapy (IMRT; Bortfeld et al. 1994a, b) and of the fi eld shaping by dynamic arcs (Solberg et al. 2001).

Convergent Radiation Techniques. The radia- tion techniques are in general isocentric and imple- mented by using a rotational technique (using cir- cular collimators or dynamic fi elds) or a static-fi eld technique; both can be combined with an isocentric table rotation. In the rotational technique (Fig. 21.5) usually fi ve to ten radiation arcs are used. The size and the angle between the arcs are variable and are responsible for the conformal isodose distribution.

The stereotactic irradiation with the micro-multileaf collimator is done with multiple static irradiation fi elds (usually 6–12 fi elds; Fig. 21.6).

The following parameters can be defi ned interac- tively in the process of radiation planning: the num- ber and position of the target points; the number of the radiation arcs and static fi elds and their shape;

the position of the gantry and radiation table; and the radiation dose in the target point for each fi eld or arc. By combining these parameters the radiation plan is developed.

21.5.3.4

3D Dose Calculation

The stereotactic radiation techniques are composed of complex rotation or multi-fi eld irradiation. During the stereotactic radiation therapy planning the dose has to be calculated three-dimensionally on the basis of CT images. Most of the planning systems use CT images for the calculation of the correct dose. The planning software converts the Hounsfi eld number of the CT data into an electron density. Some plan- ning software programs use MRI information only, by considering homogenous soft tissue density for the calculation of the dose. In comparison with 3D planning systems, the stereotactic radiation therapy can use simple, but clearly quicker, dose-calculation algorithms because no large-density inhomogene- ities are in the brain. This simplifi cation does not infl uence the precision of the dose calculation due to the use of a high number of subfi elds.

21.5.3.5

Dose Specifi cation

The stereotactic dose distribution is defi ned as abso- lute or normalized dose distribution. The prescribed dose, Do, is in this case the isodose surface which

is intended to completely encompass the PTV. The minimal dose, D

, and the maximal dose, D

, in the PTV have to be specifi ed as well. In the radiation plan, based on ICRU 50, different volumes have to be considered as well: PTV, treated volume, as well as the percentage of the target volume which will be irradiated with a dose higher than Do. In addition to the information on the target volume, the maximal dose in the area of risk structures has to be defi ned as well.

21.5.3.6

Visualization of the Dose Distribution

The decision for the best radiation plan is made af- ter evaluation of the dose distribution based on the isodose curves (Figs. 21.5, 21.6), dose volume histo- grams, conformity index, or mathematical models for the normal tissue complication probability and tumor control probability, similar to the conventional 3D radiation. The defi nitive decision for the best treatment plan must be made by the physician, using clinical judgment, after the rigorous evaluation of the dose distribution in the complete 3D data base.

21.5.4 Positioning

The positioning of the patient on the LINAC is done by using a stereotactic positioner (Fig. 21.4). This instrument allows to project the coordinates of the target point onto orthogonal planes attached to the stereotactic frame. By the use of this projected target point, the patient can be positioned in a way that the target point and the isocenter of the LINAC overlap exactly. The position of the isocenter is indicated by a room-based laser positioning system.

21.5.5

Delivery of the Radiation

After positioning the patient, the target instrument

(positioner) is removed and the radiation can start. It

is important to know that the mechanical stability and

precision of the LINAC has to be much better than

in the conventional radiation treatment. The most

important requirement for the use of the isocentric

LINAC for RS and stereotactic radiation therapy is

the accuracy of the isocenter: under ideal conditions

the axis of the gantry rotation, the central axis of

the beams and the rotation axis of the rotation table

convert in one point, the isocenter. In practical terms these requirements cannot be achieved. In general, it is acceptable that the three axes – gantry rotation axis, central axis, and table rotation axis – meet in a sphere which coincides with the isocenter and has a diameter of approximately 1 mm. The amount of inaccuracy in the LINAC isocenter is similar to the imprecision of target volume and target point defi ni- tion with modern radiological techniques. Despite the high weight of the LINAC and of the patient ta- ble, these mechanical requirements can be achieved.

They must be constantly controlled during regular quality-control procedures.

21.5.6

Quality Assurance

The essential requirement for the clinical use of the LINAC is quality control based on well-defi ned pro- tocols (Report of Task Group 42, 1995, DIN 6827-1, 2001). These quality requirements are different from those needed in conventional radiotherapy (ICRU Report 50, 1984). The quality-assurance protocols address the precision of the target volume and target point with CT, MRI, PET and angiography, the dosim- etry, the planning of the irradiation, and especially with the calibration of the absolute dose and of the dose application. For the quality-assurance assess- ment proper phantoms and specialized dosimetric instruments must be available. Excellent documenta- tion of quality-control requirements have been pub- lished by Hartman (1995).

21.6

Future Developments

The stereotactic radiation therapy originated from RS and has been further developed into a fraction- ated stereotactic radiation therapy. The use of this method at present is still limited predominantly to central nervous system lesions. The use of stereotac- tic radiation therapy for other regions of the body (paravertebral tumors as well as in tumors of the liver, lung, and pelvis) is under development. The fi rst clinical results are promising (Herfarth et al. 2000;

Zimmermann et al. 2004).

The combination of the stereotactic radiation therapy of the LINAC with IMRT opens new perspec- tives for those entities where exact conformal and high doses must be delivered (Khoo et al. 1999).

The fi rst analysis of RS with dynamic fi eld shap- ing technique in comparison with conformal static beams and multi-isocentric non-coplanar circular arcs showed that the dynamic-arc technique com- bines simple planning, short treatment times, dose homogeneity within the target, and rapid dose fall- off in normal tissue (Solberg et al. 2001; Stärk et al. 2004).

A new method under development is robot-as- sisted RS. The LINAC in this device is mounted on a robotic arm with 6 degrees of freedom. This Cyber- Knife at this time point can only be used for static radiation, but principally it can be developed for dy- namic fi elds as well (Yu et al. 2004; Gerszten et al.

2004).

In past years progress has been made in the fi eld of frameless stereotactic radiation therapy. This method aims at delivering stereotactic radiation therapy without the stereotactic frame and thus does not use an invasive fi xation system, but is still re- quired to deliver the radiation dose with a precision of 1 mm. Frameless stereotactic therapy originated in neurosurgery. For neuronavigation internal and ex- ternal markers are used for positioning the patient with stereoscopic video cameras and X-ray machines.

Despite the high potential of frameless stereotactic treatments, the stereotactic frame will remain the standard. In stereotactic radiation therapy the frame is not only used for target localization but also for the exact positioning of the patient on the LINAC and for patient immobilization during the treatment.

21.7 Conclusion

Both RS and SFS have gained eminent positions in radiation oncology and have become established modalities in the treatment of cranial lesions. Most leading radiation departments offer this technique and their numbers have grown signifi cantly in the past decade.

The LINAC RS and gamma knife RS are equiva- lent techniques; however, technological and physical differences between these two methods have led to some confusion. Considering the RS, comparative clinical studies have documented that both therapeu- tic methodologies can be used with similar results.

In comparison with gamma knife, the use of LINAC

technology offers the possibility of dose fraction-

ation, which has substantial clinical implications. The

quality control of the complex LINAC is higher than

of gamma knife and requires a specialized team of medical physicists and radiation oncologists. On the other hand, it is undisputed that stereotactic radiation therapy with isocentric LINAC has a high potential for further developments. Examples in this direction are the introduction of computer-guided micro-mul- tileaf collimators which allows the delivery of a con- form dose distribution with only one isocenter, using static fi elds or dynamic arcs and the implementation of the stereotactic intensity-modulated radiotherapy.

These new technologies amplify substantially the po- tential of the stereotactic modality.

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