Dr Umesh V

Stereotactic Radiosurgery &

Stereotactic Radiotherapy

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

Stereotaxy (stereo + taxis – Greek, orientation in space) is a method which defines a point in the patient’s body by using an external three-dimensional coordinate system which is rigidly attached to the patient.

This results in a highly precise delivery of the radiation dose to an exactly defined target (tumor) volume.

Introduction

Stereotactic RadiotherapyThe delivery of multiple fractionated doses of

radiation to a definitive target volume sparing normal structure (both intra as well as extracranial)

Stereotactic RadiosurgeryThe delivery of a single, high dose of irradiation to a

small and critically located intracranial volume, sparing normal structure

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

Definitions

The intention of SRS 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 target volume.

The SRT combines the precision of target localization and dose application of SRS with the radiobiological advantage of fractionated radiotherapy, i.e., breaking the total dose into smaller parts and thus allowing repair of DNA damage in normal tissue during the time between fractions.

Time intervals of more than 6 h between fractions can significantly reduce the risk of side effects in normal tissue

Radiobiological Rationale

Conventional Stereotactic

coplanar setup non-coplanar setup

large volumes small volumes

less no. of fields more no. of fields

target volume delineation precise delineation

positional accuracy ± 5 mm positional accuracy ± 1 mm

Optical field, SSD indicator Target volumes preciselydelineated

Marking on patient.s skin Margins not necessary

Normal cells within the targetnegligible

Differences between Conventional and Stereotactic set up

The first one to combine stereotactic methodology with radiation therapy was the Swedish neurosurgeon Lars Leksell. Leksel performed the first treatment in 1951, at the Karolinska Institute, and called the new therapy approach radiosurgery (RS)

Leksel continued his work and built the first isotope radiation machine, in 1968, the Gamma knife

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 first published reports on clinical use of LINAC came from Buenos Aires and Vicenza

In India AIIMS started SRS/SRT on 27th May 1997

Historical Background

The stereotactic coordinates are a cartesian three-dimensional coordinates system attached to the stereotactic frame in a rigid relationship.

The origin of the stereotactic coordinates system is generally in the center of the volume defined by the stereotactic 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

Stereotactic Coordinates

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

3. Treatment planning4. Positioning of the patient for the stereotactic

radiation therapy5. Delivery of the irradiation6. Quality assurance

Stereotactic Irradiation Treatment

Stereotactic radiotherapy is based on the rigid connection of the stereotactic frame to the patient during CT, MRI, and angiography imaging

The stereotactic frame is the base for the fixation of the other stereotactic elements (localizer and positioner) and for the definition of the origin (point 0) of the stereotactic coordinates.

During the whole treatment procedure, from the performance of the stereotactic imaging to the delivery of the irradiation 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

Stereotactic Frame

For the treatment of cranial lesions by RS the frame system is neurosurgically fixed onto the patient’s skull

For SFR the head is fixed non-invasively in a relocatable thermoplastic mask attached on the stereotactic frame

There are different stereotactic frame systems described in detail in the literature:

the BRW system the CRW system the Leksell system the BrainLAB system Each system is different with regard

to material of the stereotactic frame, design, and connection with the localizer and positioner and accuracy of repositioning

Types Of Frames

Imaging is used in stereotactic radiotherapy for: (a) Localization and positioning; (b) Definition of target volume and organs at risk; and (c) Calculation and 3D representation of the isodose

distributionMRI describes the anatomical structures of soft tissue

with a high accuracyCT is important for the delineation of bone and soft

tissue Positron emission tomography (PET) and single photon

computed emission tomography (SPECT) offer additional information about tumor extension and biology

Angiography is essential for the visualization of the arterio-venous malformations

Imaging in SRS/SRT

Most stereotactic systems use CT for localizationDuring the CT investigation the localizer is attached to the frame The localizer is a box with CT-compatible fiducial markers on each

plane, which are visualized on CT on each scan; thus, the localizer defines 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 fixation system, and the localizer form a fix unit.

Definition of Target Volume and Organs at Risk

Definition of the Stereotactic Target Point

Planning of the Radiation Technique

3D Dose CalculationDose SpecificationVisualization of the Dose Distribution

Treatment Planning

The tumor-specific morphology, the growth pattern of the tumor, and the anatomical relationship to the normal tissue are essential parameters in defining 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 significant dose have to be delineated

Definition of Target Volume and Organs at Risk

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 defined interactively.

One or more target points can be defined. In stereotactic planning programs the coordinates of the

target points are related in such way that the resulting dose distribution meets the clinical requirements.

The planning system outputs the position of these points in stereotactic 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 treatment device is defined

Definition of the Stereotactic Target Point

The following parameters can be defined interactively in the process of radiation planning:

the number and position of the target points; the number of the radiation arcs and static

fields and their shape; the position of the gantry and radiation table;

and the radiation dose in the target point for each

field or arc. By combining these parameters the radiation plan is

developed.

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 collimators for circular or oval target volumes are attached to the tray holder of the LINAC. The diameter of the irradiated area is defined by the size of the circular collimators and varies usually between 1 and 35 mm

Micro-multileaf collimators have recently become available . The beam shape can be selected by computer or by hand. In this way the contours of the irradiation field can be adjusted individually to the tumor shape. Micro-multileaf collimators, in comparison with the traditional multi-leaf collimators, have the advantage of a decreased leaf width and therefore optimized the resolution (between 1 and 3 mm).

Convergent Radiation Techniques. The radiation techniques are in general isocentric and implemented by using a rotational technique (using circular collimators or dynamic fields) or a static-field technique; both can be combined with an isocentric table rotation.

In the rotational technique usually five 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 fields (usually 6–12 fields)

Most of the planning systems use CT images for the calculation of the correct dose.

The planning software converts the Hounsfield number of the CT data into an electron density.

Some planning software programs use MRI information only, by considering homogenous soft tissue density for the calculation of the dose.

Stereotactic radiation therapy can use simple dose-calculation algorithms because no large-density inhomogeneities are in the brain.

3D Dose Calculation

The prescribed dose, Do, is the isodose surface which is intended to completely encompass the PTV.

The minimal dose, Dmin, and the maximal dose, Dmax, in the PTV have to be specified 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.

The maximal dose in the area of risk structures has to be defined as well.

Dose Specification

The decision for the best radiation plan is made after evaluation of the dose distribution based on the isodose curves dose volume histograms, conformity index, or mathematical models for the normal tissue complication probability and tumor control probability, similar to the conventional 3D radiation.

The definitive 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.

Visualization of the Dose Distribution

The positioning of the patient on the LINAC is done by using a stereotactic positioner .

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

Patient positioning

After positioning the patient, the target instrument (positioner) is removed and the radiation can start.

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 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.

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

Delivery of Radiation

The essential requirement for the clinical use of the LINAC is quality control based on well-defined protocols

The quality-assurance protocols address the precision of the target volume and target point with CT, MRI, PET and angiography, the dosimetry, the planning of the irradiation, and especially with the calibration of the absolute dose and of the dose application.

For the quality-assurance assessment proper phantoms and specialized dosimetric instruments must be available.

Quality Assurance

Tumor volume — As the size of the target lesion for SRS increases, incidental irradiation to the surrounding normal tissue also increases. This may be important since a much higher dose of irradiation is administered with SRS compared to fractionated RT.

SRS was not recommended for lesions >4 cm because adequate control could not be achieved without an unacceptable level of radiation toxicity to surrounding normal tissue.

Proximity to cranial nerves — The proximity of a target to cranial nerves can cause radiation neurotoxicity, despite the steep decrease in dose outside the intended target  Fractionated RT should be considered when SRS may jeopardize cranial nerve function.

Cranial nerves II and VIII are more sensitive to radiation injury than the other cranial nerves. SRS is generally avoided if the maximal dose delivered to the optic nerve exceeds 10 Gy.

Location of the lesion — The risk of developing permanent damage following SRS varies dramatically with the location of the lesion in the brain. Fractionated RT is often preferred to SRS for the treatment of lesions in the deep gray matter or the brainstem

Choice between SRS/SRT

•Enhances clinical outcome

•Improves quality of life

•Time factor

Advantages of SRS/SRT

Clinical Outcome-Documented scientific data shows better or equal results compared with microsurgery, Fewer complications, Reproducible results ,Treatment solution for inoperable patients, Combined treatment with microsurgery and endovascular techniques extend the capabilities

Quality Of Life- Minimally invasive, Less trauma, Faster recovery, Minimal hospitalization, Fewer complications , Documented efficacy

Time Factor

Disadvantages of SRS/SRT

High cost of purchase and useRisk of neurological injuryRisk of mechanical inaccuracyPotential necessity of multiple visits

MalignantMeningiomaPituitary tumors Acoustic neuromasMetastatic brain

lesionsGlioma

Treatment- IndicationsNon MalignantVascularAVMFunctionalTrigeminal NeuralgiaResearch Areas. Movement Disorders. Intractable Pain. Epilepsy. Macular

Degeneration. Uveal Melanoma

Meningioma

Dose plan with 6 isocenters- Minimizing dose to optic chiasm

2 Years Post treatment

Pituitary Adenoma

Pre treatment 54 months post

Metastasis

Pre treatment 2 months post treatment

10 months post treatmentPre treatment

Brain Tumors- Astrocytoma

Arteriovenous Malformation

Pre Gamma Knife Surgery

2 years post Gamma Knife Surgery

AVM

Pre treatment Dose Plan 13 Months Post treatment

Acoustic Neuroma

Trigeminal Neuralgia

Gamma Knife RadiotherapyRotating Gamma System(RGS)Proton RadiosurgeryLINAC RadiosurgeryTomotherapyLINAC Image guided Radiotherapy

Various ways to deliver SRS/SRT

Gamma Knife- In 1999, the model C version of the gamma knife was introduced with the option to use robotic positioning to set treatment coordinates. This expedites execution of multiple-isocenter treatment plans. The model 4-C, introduced in 2005, was equipped with enhancements designed to improve workflow, increase accuracy, and provide integrated imaging capabilities. The Perfexion model introduced in 2006 uses a larger patient aperture and internally mounted secondary collimators

RGS-A radiosurgery device called the rotating gamma system (RGS) was developed in China. The rotating gamma system employs 30 cobalt-60 radiation sources in a revolving hemispherical shell. The secondary collimator is a coaxial hemispheric shell with six groups of five different collimators to produce spherical treatment volumes of different diameter

Proton Radiosurgery The chief advantage of charged

proton radiosurgery is that the beams stop at a depth related to the beam's energy.

The lack of an exit dose and the sharp beam profile of protons allow target irradiation with lower integral doses than are delivered with photon (Linac x-ray or cobalt-60 gamma) irradiation.

An unmodified proton beam irradiation deposits increased energy in the last couple of millimeters of the path length.

This area of increased ionization, where cell killing is even higher because of an increased radiobiologic effect, is termed the Bragg peak or Bragg-Gray peak

The first treatment of a malignant tumor by irradiation with a proton beam Bragg peak was carried out in 1957 and followed by functional neurosurgery for advanced Parkinson's disease in 1958.

LINAC RadiosurgeryMany LINAC-based systems such

as Xknife, Novalis, the Peacock System, and Cyberknife are commercially available

The Cyberknife combines a miniaturized LINAC mounted on an industrial robot with a system for target tracking and beam realignment

Cyberknife plans use multiple fixed-beam positions and multiple isocenters.

Before the radiation is delivered from any beam position, the target position is tracked using an integrated x-ray image processing system, consisting of two orthogonal diagnostic x-ray cameras and an optical tracking system.

Tomotherapy rapidly rotates the beam around the patient (and inside the housing of the unit), thus allowing the beam to enter the patient from many different angles in succession

Tomotherapy

The combination of the stereotactic radiation therapy of the LINAC with IMRT opens new perspectives for those entities where exact conformal and high doses must be delivered

The first analysis of RS with dynamic field shaping technique in comparison with conformal static beams and multi-isocentric non-coplanar circular arcs showed that the dynamic-arc technique combines simple planning, short treatment times, dose homogeneity within the target, and rapid dose falloff in normal tissue

A new method under development is robot-assisted RS. The LINAC in this device is mounted on a robotic arm with 6 degrees of freedom

In past years progress has been made in the field of frameless stereotactic radiation therapy.

For neuronavigation internal and external markers are used for positioning the patient with stereoscopic video cameras and X-ray machines

Future developments

AIIMS, New DelhiApollo Hospitals IndiaYashoda Hospital HyderabadHCG group of hospitals BangaloreAdyar Cancer Institute Dharamshila Hospital DelhiAnd many more.

India

References

Thank You

Lars Leksell.