SBRT REQUIRES: STEREOTACTIC BODY RADIOTHERAPY STEREOTACTIC BODY RADIOTHERAPY (SBRT) (SBRT) What s s in a name? Stereotactic Body Radiotherapy

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INTRODUCTION TO STEREOTACTIC BODY RADIOTHERAPY: (I) Physics and Technology (II) Clinical Experience & (III) Radiobiological Considerations and Future Directions Stanley H. Benedict, Ph.D., Danny Song, MD, and Brian D. Kavanagh, MD, MPH STEREOTACTIC BODY RADIOTHERAPY (SBRT) Part 1: Physics and Technology Presented by Stanley H. Benedict, PhD Virginia Commonwealth University, Medical College of Virginia Hospitals Part 2: Overview of Clinical Experience Presented by Danny Song, MD Virginia Commonwealth University, Medical College of Virginia Hospitals Part 3: Radiobiological Considerations and Future Directions Presented by Brian Kavanagh, MD, MPH University of Colorado Health Sciences Center, Anschutz Cancer PavilionP STEREOTACTIC BODY RADIOTHERAPY (SBRT) What s s in a name? SBRT is the use of external beams to treat lesions of the body with surgical doses and high precision tumor identification and relocalization employing stereotactic image guidance or implanted fiducials. Extracranial stereotactic. Radioablation / Radiosurgery / Radiotherapy Surgery vs. Ablation vs. Therapy vs. According to the chief CPT code developer it will be called: Stereotactic Body Radiotherapy SBRT REQUIRES: Higher confidence in tumor targeting Reliable mechanisms for generating focused, sharply delineated dose distributions * Ability to shape the prescription isodose surface to the outline of the target volume surface itself. * This requires a relatively large number of non- opposing beams/arcs to avoid entrance/exit beam interactions, preferably non-coplanar. Specifically: Reliable accurate patient positioning accounting for target motion related to time dependent organ movement * Timmerman et al, Technology in Cancer Research and Treatment 2003 1

SBRT PHYSICS AND TECHNOLOGY 1. CT simulation: Assess tumor motion 2. Immobilization: Minimize motion, breathing effects 3. Planning: Small field dosimetry Inhomogeneity corrections, Hot spots in GTV Fixed fields, IMRT, Dynamic Arcs 4. Repositioning: High precision set-up: IR/LED Active and Passive markers, US, Video 5. Relocalization: Identify tumor in treatment field: * ASi, Dual KV Xray, Implanted markers and/or set-up fiducials * Motion tracking and gating systems, automated breathing control l systems * Real-time tumor tracking systems and EPID Image guidance systems for on- line treatment verification 6. Treatment delivery techniques High precision fixed fields, Novalis, Cyberknife, Cones, mmlc * Hadinger et al Med Phys.. 2002. * Hamilton et al, Stereotactic Funct Neurosurg,, 1996 * Lohr, et al Int J Radiat Oncol Biol Phys 1999 ACKNOWLEDGEMENTS A REVIEW OF SYSTEMS EMPLOYED TO INCREASE CONFIDENCE, PRECISION, AND VERIFICATION FOR ESRT. NO INSTITUTION EMPLOYS ALL OR EVEN THE SAME MEASURES! Sanford Meeks, PhD University of Iowa Tim Solberg,PhD UCLA Martin Murphy, PhD Accuray - CyberKnife Elekta Stereotactic Body Frame, Image Guidance Synergy Platform BrainLab ExacTrac IR patient positioning, Novalis Image Guidance Accuray Cyberknife Robotic image guided radiosurgical system Precise Therapeutics/Medical Intelligence- BodyFix immobilization NOMOS, Bat Ultrasound Guidance system Helical Tomotherapy Zmed Linac Scalpel System ELEKTA STEREOTACTIC BODY FRAME Reference indicators for CT /MR determination of target coordinates Diaphragm control attached to the frame minimizes respiratory movements. Horizontal positioning of the frame, in the scanner or on the treatment couch, Longitudinal alignment is controlled by skin marks over the tibia using a frame- mounted laser. Co-ordinates ordinates used for patient positioning can be easily read on the arc-ruler ruler and on the longitudinal ruler * Lax, Blomgren, Acta Oncologica 1994 * Blomgren, Lax, Acta Oncologica 1995 IMMOBILIZATION: Medical Intelligence - BodyFix: Integrated indexed patient positioning Minimizes respiratory motion Accurate Non-Invasive Repeat Positioning Dual vacuum technology: Custom-Mold and Patient Immobilization Radio-translucent materials 2

CT VERIFICATION PRIOR TO TX Day 1: CT Simulation Day 2: Treatment What is Optical Tracking? Optical tracking is a means of determining in real-time the position of an object by tracking the positions of either active or passive infrared markers attached to the object. The position of the point nt of reflection is determined using a camera system. Phantom precision on is sub-millimeter. Active markers Passive markers IR Camera Optical guidance for frameless stereotaxis For high-precision radiotherapy and frameless radiosurgery, optical guidance can track the patient position using passive markers BRAINLAB EXACTRAC REPOSITIONING VERIFICATION Reflective Body Markers for infrared Camera Technology Detection of patient position Video Camera for Independent Verification and Documentation Images 150 kv X-ray X sources - imaging of bony structures or implanted markers and amorphous silicon detector. * Soet, IJROBP 2002. * Wang Comput Biol Med. 2001 3

Visualization of internal anatomy at the treatment device Xray Tubes asi Detector X-Ray Acquisition & Comparison with DRRs Automatic Comparison of Live X-Ray Images with DRRs. Feedback to treatment couch and position automatically Computerized Generation of DRRs Setup Verification Spinal Radiosurgery Pos. 1 Pos. 2 (Slide Courtesy of Tim Solberg/UCLA) Live X- Rays Virtual DRRs Compare DRRs and Port Films (Slide Courtesy of Tim Solberg/UCLA) 4

(1) Real-time diagnostic imaging system with dual amorphous silicon detectors (2) Robotically-mounted 6MV X-X band LINAC with circular collimators (3) Control loop from imaging system to robot for automatic beam alignment & tracking (4) Cranial target localization based on bony anatomy (5) Spine target localization based on implanted fiducials (6) Soft tissue tumor localization based on implanted fiducials (7) Synchronous tracking of breathing motion at a few selected Beta test sites * Chang et al, Neurosurgery. 2003 CYBERKNIFE 1. Utilizes the skeletal structure of the body as a reference frame no invasive frame is needed. 2. Continually monitors and tracks patient position during treatment. 3. Ceiling-mounted KV X-ray X ray image patient's tumor treatment system correlates patient location detected by image guidance system with reconstructed CT scan and directs robot to adjust position accordingly 4. Compact linear accelerator mounted on a computer-controlled controlled robotic arm which adjusts position to maintain alignment with target, compensating for any small patient movement uses X-band X technology for mobility CyberKnife ACTIVE BREATHING CONTROL Active Breathing Coordinator Allows clinicians to pause a patient's breathing at a precisely indicated tidal volume and coordinate delivery with this pause. ABC has shown a median reduction of 12% lung mass in the irradiated field. By treating only when the heart is visibly out of the field, clinicians can reduce significantly or even eliminate irradiation of cardiac tissue. Sixel, et al Int J Radiat Oncol Biol Phys., 2001. tumor Beam ON Respiratory Gating tumor Slide courtesy of P. Keall/VCU Beam OFF tumor Beam ON 5

Respiratory Gating (Inhale vs Exhale) Varian RPM * Courtesy of P. Keall/VCU /VCU Gated tumor tracking with IR monitor allows maximum dose to tumor r & minimum dose to normal tissue. Varian's RPM Respiratory Gating system features the Predictive Filter F which analyzes the patient's respiration, establishes a baseline respiratory pattern, and detects any deviations from the expected pattern. Deviations from the "predicted" respiratory pattern result in ana n automatic hold of treatment delivery until the baseline respiratory pattern n is re- established. Med Tec preference frameless stereotaxy Implanted fiducial technology Tiny gold markers establish a permanent, accurate, internal patient reference system. Isoloc: Image-guided guided software verifies submillimeter localization accuracy for all setups. Gold Markers for bone are pure gold spheres placed during a simple 20- minute outpatient procedure under local anesthesia. Tools to facilitate marker placement include drill bits, guides, and a tool for holding the marker during implantation. The soft tissue marker surface is specially treated to prevent migration after implantation. The markers are implanted under ultrasound or CT guidance. * K. i-hwan i Kim IJROBP,, 2003 Inhomogeneity Considerations INHOMOGENEITY CONCERNS INHOMOGENEITY TISSUE/CALCULATIONS Very significant with lung/abdomen vs cranial interface effects are not accounted for with TPS using only a TMR LUT. Calculations with small/narrow fields require verification because of the complicated geometry, minimized lateral scatter, and loss of electronic equilibrium * Solberg 1998, Jones 2003, Rustgi 1998, Wang 2001 DOSE: HOT SPOT VERSUS UNIFORMITY Dose gradient within the target are acceptable for ESRT: targets contain no normal tissue. Higher target doses (hot spots) may be desirable if they facilitate ate steeper normal tissue dose fall-off outside of the target within normal tissue. Hot spots may be useful in treating hypoxic radioresitant cells in the tumor core. * Lax et al, Acta Oncol,, 1994 6

Clinical Implementation of ESRT These techniques are unusual in the high technology realm of radiation treatment in that they require more specialized training of physicians and physicists rather than specialized equipment. * Timmerman et al, Technology in Cancer Research and Treatment 2003 SUMMARY: Technical elements of QA SUMMARY: Clinical elements of ESRT QA A physician and physicist should carry out all clinical QA procedures: The physicist should be responsible for all technical QA procedures: Imaging equipment Localization and simulation equipment Treatment planning and evaluation system Treatment delivery equipment Treatment verification equipment Consistent target volume and organs at at risk delineation Quantitative assessment of target and organ motion during imaging and treatment Quantitative assessment of setup variation during imaging and treatment Patient specific QA NEED TO ESTABLISH TERMINOLOGY AND REPORTING CONVENTIONS Prescription considerations: GTV, margins, dose inhomogeneity/uniformity iformity Biological evaluations: EUD, NTCP, etc Dose and Fractionation strategy: (1 to 5 fractions, QOD, QD, etc) 7

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