Radiosurgery Revised

Radiosurgery: Overview R. Rick Bhasin, MD Department of Neurosurgery University of Florida

Outline
History
How does radiation work
Types of radiosurgery
Current available systems
Planning and Treatment
Targets
Dose Selection
Outcomes

Definitions
Stereotactic radiosurgery (SRS) treats brain disorders with a precise delivery of a single, high dose of radiation in a one-day session.
Fractionated stereotactic radiation therapy—which are received over a period of days or weeks—may be administered to the body with the assistance of removable masks and frames that achieve a lesser degree of immobilization.

History
1895, first use of radiation therapy in cancer
1946, Robert Wilson first proposed the clinical use of charged particle beams
1949, Lars Leksell, Professor of Neurosurgery in Lund, Sweden & later Karolinska Institute in Stockholm, developed a stereotactic apparatus based on the Cartesian coordinate system

More History
1951, Lars Leksell and Borje Larsson, a radiobiologist, realized that an x-ray tube could be the surgical tool placed on a stereotactic arc. They started with an x-ray tube and later applied proton beam therapy to human subjects at the Uppsala University. He called this therapy “stralkniven” (ray knives)

How does radiation work?
The fundamental principle of radiosurgery is that of selective ionization. Ionization is the production of ions and free radicals in tissue from water, which causes irreversible DNA damage.
The cells lose their ability to reproduce and retain fluids. The tumor reduction occurs at the rate of normal growth for the specific tumor cell.
In lesions such as AVMs radiosurgery causes the blood vessels to thicken and close off. The shrinking of a tumor or closing off of a vessel occurs over a period of time. For benign tumors and vessels, this will usually be 36 months. For malignant or metastatic tumors, results may be seen in a few months, because these cells are very fast-growing.

There are six types of irradiation available in radiation therapy:
1. Gamma rays - high energy photons produced by fixed sources of radioactive cobalt (cobalt-60)
2. X-rays - high energy photons produced by accelerating electrons and colliding them with a metal target, called Bremsstrahlung
3. Electrons - very similar characteristics to x-rays
4. Protons - protons are produced by a cyclotron
“ Bragg Peak Effect”
5. Neutrons - Boron neutron capture therapy depends on the interactions of slow neutrons with boron-10 to produce alpha particles, another type of radiation. Neutrons are produced by a nuclear reactor or by colliding protons with a Lithium target
6. Carbon ions

Proton Therapy

Proton Therapy
Proton therapy, like all forms of radiotherapy, works by aiming, energetic ionizing particles (protons) onto the target
All protons of a given energy have a certain range; no proton penetrates beyond that distance. Furthermore, the dosage to tissue is maximum just over the last few millimeters of the particle’s range, this maximum is called the Bragg Peak. This depth depends on the energy to which the particles were accelerated by the accelerator. It is therefore possible to focus the cell damage due to the proton beam at the very depth in the tissues where the tumor is situated; tissues situated before the Bragg peak receive some reduced dose, and tissues situated after the peak receive none.

Bragg Peak Effect While rapidly traveling through tissue, high-energy proton beams lose energy. As this energy is lost, the likelihood of the particle interacting with the tissue increases. This leads to deposition of most of the energy within a discrete band of spatial depth measuring roughly 12-20 mm.

Proton Beam Centers in the USA
The Northeast Proton Therapy Center at Massachusetts General Hospital
Loma Linda University Medical Center in Loma Linda, California (LLUMC)
UC Davis Proton Facility
Midwest Proton Radiotherapy Institute at Indiana University
M. D. Anderson Cancer Treatment Center, Houston, Texas
Florida Proton Therapy Institute at the University of Florida Shands Medical Center, Jacksonville, Florida

Proton Therapy

Proton Therapy
Current clinical applications of proton therapy include:
Choroidal melanoma - ocular tumors
Chondrosarcoma
Chordoma
Prostate cancer
Nasopharyngeal tumors
Pediatric tumors

The Gamma Knife

Development of the Gamma Knife
In 1968, Lars Leksell and Bjorn Larsson, developed a device which consisted of radioactive Cobalt-60 placed around a helmet with central channels for irradiation.
In order to achieve a high degree of precision, the patients head was placed in a stereotactic frame.
The first patient treated with the Gamma Knife was in 1967 for a craniopharyngioma at the Studsvik nuclear plant.
In 1968 the first patient treated at the Karolinska Institute was for intractable cancer pain.

Development of the Gamma Knife
The first Gamma Knife was designed to create small lesions used in functional neurosurgery, acoustic neuromas, pituitary adenomas, craniopharngiomas, and AVMs.
The first AVM treated by Lars Leksell and Ladislau Steiner in 1970 resulted in obliteration of the AVM two years later.
The first USA installation was at the University of Pittsburgh in 1987 (under Dade Lunsford)
Over the years there have been modifications of the gamma knife several times (models U, B, & C). The current model is the Eleckta Leksell Gamma Knife C
(201 beams)

Linear Accelerator Radiosurgery

History of LINAC Radiosurgery
Linear accelerators are the standard machine used to deliver radiation therapy treatments
Linear accelerators convert electricity into radiation
Terms: gantry, couch, collimator (multileaf or cone)
Linear accelerators were available during Leksell’s time, however they lacked accuracy

History of LINAC Radiosurgery
Betti, Derechinsky, and Colombo were the first to apply linear accelerator technology to radiosurgery in 1984
Winston and Lutz modified their LINAC in 1987 to treat neurosurgical patients (Boston)
Initial problem with this technique was a high degree of error in targeting, complicated dose planning and dose delivery
1986-1987: University of Florida developed a system to improve LINAC radiosurgery accuracy to 0.2 mm, which included a new floorstand, dose planning software & detailed phantom testing
UF Radiosurgery system licensed to Philips and Sofamor Danek (Zmed). The system is now incorporated by Varian as the Trilogy System

How LINAC Radiosurgery Works
University of Florida System
Reduced error to within 2/10 mm

5 Arcs per Isocenter, with 100 degrees of arc

The gantry of the LINAC rotates around the patient, producing an arc of radiation focused on the target. The couch in which the patient rests is then rotated in the horizontal plane, and another arc is performed. In this manner, multiple noncoplanar arcs of radiation intersect at the target volume and produce a high target dose, resulting in minimal radiation affecting the surrounding brain. This dose concentration method is exactly analogous to the multiple intersecting beams of cobalt radiation in the Gamma Knife.

Online Video

Stand mount versus couch mount
Frame-based intracranial positioning

Frameless intracranial positioning Used for fractionated radiotherapy

Current devices using linear accelerator sources include:
Novalis (BrainLab, Helmstetten, Germany)
Peacock (Nomos, Cranberry, PA)
X-Knife (Radionics, Burlington, MA)
Trilogy (Varian Medical Systems, Palo Alto, CA)
CyberKnife (Accuray, Sunnyvale, CA)

Trilogy
The Trilogy incorporates:
Image guidance technology - Locates tumor precisely with sub-millimeter accuracy, using on-board imaging that verifies positioning at each session.
Respiratory gating - Synchronizes dose delivery with the patient's breathing cycle to ensure accuracy and reduce radiation to healthy tissue.
Imaging adaptability - Offers adaptable modes of operation, including radiographic, cone beam CT and fluoroscopic for maximum flexibility.
Intensity-modulated beam delivery - Calculates dose distributions that conform to the three-dimensional shape of the target, including concave and complex shapes.
Stereotactic radiosurgery - Treats tumor with surgical precision, both cranially and extracranially.
Operates at least 60 percent faster than conventional accelerators

Intensity Modulated Radiotherapy (IMRT)
Intensity-modulated radiation therapy (IMRT) is an advanced form of three dimensional conformal radiotherapy (3DCRT). It uses sophisticated software and hardware (multileaf collimator) to vary the shape and intensity of radiation delivered to different parts of the treatment area
IMRT dose gradient not as steep as standard sphere packing

UF Radiosurgery Treatment Paradigm
1. Patient obtains volumetric MRI scan
2. Patient seen in clinic by both Neurosurgeon and Radiation Oncologist
3. Dose pre-planning performed day before treatment
4. Placement of stereotactic head ring followed by volumetric CT scan
5. Fusion of two sets of images
6. Dose Planning (with Neurosurgeon and Radiation Oncologist)
7. Dose Delivery (physicist): 15 minutes/isocenter

How to place a headring
See online video on resident website
Key points
Review films to locate tumor
Two people required
No prepping, local anesthetic
Generally, short pins in front &
long in back
Place ring below EAC
Check with localizer

Dose Planning
Concepts in Planning
Conformality
Maximum dose to target, minimum dose to surrounding tissues
Achieved by multiple isocenters, arc weighting, single arcing, arc spacing and collimator size
Sphere packing
Minimum collimator 5 mm
Treat to the 80% isodose line to maximize dose fall off
When multiple isocenters used treat to the 70% isodose line to avoid hotspots

Dose Falloff Curve

What do we treat with radiosurgery?
Brain metastases (up to 4 usually)
AVM
Vestibular Schwannoma
Meningioma
Recurrent GBM
Trigeminal Neuralgia
Spinal Radiosurgery
Others: Pituitary adenoma, Hemangioblastoma, Nasopharyngeal carcinoma

Radiation Doses Prescribed
Dose is selected to maximize dose, while minimizing complications
Mets: 15-20 Gy
AVM: 17.5-20 Gy
Meningioma: 12.5-15 Gy
Vestibular Schwannoma: 12.5 Gy
Trigeminal Neuralgia: 70-90 Gy
(need to keep max dose at visual apparatus less than 800 cGy)
Compare to WBRT, 30 Gy in 10 fractions

Brain Metastasis
UF 12 year experience from 1989 - 2001
393 patients
Types by frequency: lung, melanoma, breast, renal, GI
Actuarial 1 year local control rate was 75%
Median actuarial survival was 9 months
Ulm et al, Neurosurgery 55: 1076-1085, 2004

AVM
UF experience with AVM from 1989-1999
269 patients reviewed
For lesions less than <1 cc, 87.9 % radiological success
Submitted, UF experience with large volume AVMs from 1989 - 2005
90 patients reviewed
70% success rate with repeat radiosurgery
Bradshaw et al, Neurosurgery 52:296-308,2003

Vestibular Schwannoma
UF experience from 1988 to 1998
149 patients treated
Overall radiological tumor control rate was 93%
Median followup 36 months
5 year actuarial control rate was 87%
At lower doses (12.5 Gy) the incidence of facial and trigeminal neuropathies fell from 29% to 5 and 2%, respectively
Foote et al, J Neurosurg 95:440-449, 2001

Meningioma
UF experience from 1989-2001
Actuarial local control for benign tumors
100 % at 1 and 2 years, 96% at 5 years
Actuarial local control for atypical tumors
100% at 1 year, 92% at 2 years, 77% at 5 years
6.2% temporary complication rate, 2.3% permanent complication rate
Friedman et al, J Neurosrg 103:206-209, 2005

Glioblastoma Multiforme
RTOG-9305: Prospective randomized trial designed to evaluate upfront SRS followed by RT with BCNU compared to RT with BCNU
186 patients enrolled
Median survival for the two arms was 14.1 and 13.7 months
No difference in survival with upfront radiosurgery

Glioblastoma Multiforme
UF 12 year experience from 1989-2002
100 patients
Decreased survival for Class I/II,
Similar survival for Class III/IV
Increased survival for Class V
Some role for radiosurgery in recurrent GBM
Ulm et al, Neurosurgery 57:512-517, 2005

Spinal Radiosurgery
Initial treatments with Cyberknife
Patient immobilized on the couch, implantation of fiducials, followed by localizing orthogonal xrays
University of Pittsburgh experience, 2004

Cyberknife Outcomes
Intradural extramedullary lesions (schwannomas, neurofibromas, meningiomas)
Stanford experience 1999 - 2004: 51 patients treated
3/51 required surgery within one year because of worsening symptoms
28/51 have at least 24 months followup, 61% are stable in size, 39% are smaller in size
Dodd et al, Neurosurgery 58:674-85,2006

Spinal Radiosurgery with Trilogy
On board CT scanner to localize target with MRI (or CT) fusion
We will begin at UF in the fall

Trigeminal Neuralgia
University of Wisconsin LINAC Experience
28 patients treated with single fraction of 80 Gy to the trigeminal nerve root (treatment time 55 minutes)
57% had complete pain relief, 75% had some reduction in pain to 3 or less (out of 10)
Median time to pain relief was one month
Mehta et al, Neurosurgery: 57:1193-2000, 2005 .

Radiosurgery Revised

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