4 D Igrt

4D‐IGRT: Certain Phase of Respiration Christopher D. Willey, MD, PhD Assistant Professor Department of Radiation Oncology The University of Alabama at Birmingham

Disclosures • I do occasional speaking/consultation for I do occasional speaking/consultation for Varian Medical Systems, Inc.

Learning Objectives Learning Objectives • Discuss rationale for IGRT Discuss rationale for IGRT • Understand the basic process involved in 4D IGRT • Learn about several gating/motion management strategies • Simulation and planning concepts for 4D treatment will be discussed.

Outline • Concepts • IGRT – D fi d Defined – Technologies • Applications UAB Women and Infants Center and Hazelrig-Salter R di ti Oncology Facility H l i S lt Radiation O l F ilit

Big Picture Concepts Big Picture Concepts • Radiation penetrates all tissues Radiation penetrates all tissues • Radiation can destroy all tissues (normal and tumor) and tumor) • Therapeutic ratio: Probability of tumor control Probability of normal tissue toxicity • Ideal: Maximize tumor kill, spare normal p tissue, and preserve function

Big Picture Concepts Big Picture Concepts • Factors involved in therapeutic ratio: • Tumor delineation: CT, PET, MRI, SPECT • Precision dose distribution: Brachy, SRS/SBRT, IMRT, Protons Adaptation p • Accurate Delivery: Immobilization and guidance (IGRT) • F ti Fractionation and Total dose ti dT t ld • Dose per fraction , , / , p • Dose rate: LDR, HDR, SRS/BT, RapidArc • Radiation modifiers: Radiation protectors and sensitizers • Tumor Type • Real Estate (Anatomical site): Location, location, location

Big Picture Concepts Big Picture Concepts Precision Accuracy • “Reproducibility” • “Veracity” • Narrow clustering of hits g • Closeness of hits to target Closeness of hits to target • Does not require accuracy • You must have some • Worry about geographic precision to be accurate miss • Worry about collateral damage High precision, low accuracy Precise and accurate High accuracy, low precision

• Distended rectum at time of CT was independently associated with associated with biochemical recurrence in prostate cancer and lower rectal toxicity t l t i it • With precise treatment, we need accurate deliveryy

Volumes – GTV gross tumor volume (gross disease) • Assumption: we can identify disease extent – CTV clinical target volume ( b l l l l (subclinical disease) ld ) • Assumption: we can predict subclinical disease extent – PTV planning target volume (setup/treatment uncertainty) • Assumption: we know our precision and accuracy • ICRU 62 – IM internal margin g • variations in size, shape, and position of the CTV in reference to the patient's coordinate system using anatomical reference points – ITV internal target volume g • CTV + IM Alternative is an IGTV that can then be expanded for CTV margins – SM set‐up margin • uncertainties in patient beam positioning in reference to the treatment p p g machine coordinate system

Change in Volume Definitions Change in Volume Definitions PTV ITV CTV IM “IGTV” IGTV GTV GTV GTV GTV SM SM ICRU50 ICRU62 “ICRU62”

Why do margins matter? Why do margins matter? • Volume = 4/3πr3 Volume = 4/3πr • Small margin reduction (5mm) decreases the volume of an orange by 1/2 the volume of an orange by 1/2

Big Picture Concepts Big Picture Concepts • How can we deal with our margins? – GTV/CTV: limited by our tumor detection • Relies on clinical judgment and our radiology colleagues – We can do something about PTV!!! IMPROVING PATIENT SETUP AND TX DELIVERY - Skin marks/weekly port films - Daily setup to bony anatomy - Immobilization and gating - Planar and volumetric image guidance and/or fiducials - Stereotactic delivery

In Search of Guidance In Search of Guidance • Effectively identify tumor and normal tissue Effectively identify tumor and normal tissue • Accurately align patient and precisely treat – Sh ld h l Should help with inter‐fraction motion i hi f i i • What about intra‐fraction motion? – Three general approaches: • Enlarge PTV margin • Prevent motion possible in some instances but not particularly comfortable • Track motion Track motion

Definitions • Image guided radiation therapy (IGRT) Image guided radiation therapy (IGRT). Two parts: – Use of modern imaging techniques for defining Use of modern imaging techniques for defining tumor and normal structures – Use of modern imaging techniques to accurately Use of modern imaging techniques to accurately and precisely deliver treatment

Broad Definition 6 D s of IGRT Broad Definition – 6 D’s of IGRT • Detection and diagnosis Detection and diagnosis • Determining biological attributes • Delineation of target and organs at risk l f d k • Dose distribution design • Dose delivery assurance • Deciphering treatment response through Deciphering treatment response through imaging Greco, Carlo and Clifton Ling, C.(2008)'Broadening the scope of Image-Guided Radiotherapy (IGRT)',Acta Oncologica,47:7,1193 — 1200

IGRT Tools IGRT Tools • Treatment planning: – PET/CT – MRI – 4D CT 4D CT • Treatment delivery: – Electromagnetic transponder (Calypso) Electromagnetic transponder (Calypso) – Ultrasound – Video – Planar (2D) – Volumetric (3D) – Gating (and immobilization)

Electromagnetic Transponder Electromagnetic Transponder

Ultrasound BATCAM SonArray I-Beam www.nomos.com www.varian.com www.cmsrtp.com

Video IGRT Video IGRT www.visionrt.com

Laser Surface Topography IGRT Laser Surface Topography IGRT www.LAP-LASER.com

On board Imager (Varian) On‐board Imager (Varian)

On board Fluoroscopic Imaging On‐board Fluoroscopic Imaging

Planar (2D) IGRT Planar (2D) IGRT Cyberknife ®(Accuray) C b k if ®(A ) Novalis ExacTrac X-Ray 6D Varian Trilogy OBI®/MV portal vision Elekta Synergy™ PlanarVie S nerg ™ PlanarView Siemens K-View™

Novalis Orthogonal X rays Novalis Orthogonal X‐rays Teh et al. Biomed Imag Interv J 2008

Volumetric (3D) IGRT Volumetric (3D) IGRT Varian Trilogy OBI® Novalis Tx™ Siemens CTVision™ Siemens Artiste™ KVision Elekta Synergy™ TomoTherapy® (HiART) Elekta Axesse™ VolumeView

Acuity (Varian) Acuity (Varian) • 2D simulation 2D simulation • 3D simulation with cone beam CT (KV) ( ) • Respiratory gating • Brachytherapy

Cone Beam CT (Varian) Cone Beam CT (Varian) www.varian.com

MV CT imaging MV CT imaging Siemens MVision™ (MV cone beam) TomoTherapy® (Hi-ART) (MV CT)

Prostate

The Problem with Motion The Problem with Motion • Motion is inevitable: Motion is inevitable: – Interfraction – Intrafraction • Example: Lung tumor motion with free breathing (Liu et al. IJROBP 2007) (Li t l IJROBP 2007) – 95% of patients will have motion less than… • 0 59 0.59 cm in the AP i h AP • 0.4 cm in the lateral • 1.34 cm in the SI

4D Motion 4D Motion Courtesy of Varian

Motion Management Options Motion Management Options • Ignore (ie, account for motion) • Prevent motion – Breath Hold/Breath Control – BodyFix (Elekta) p ( ) – Compression device (Elekta) • Track the motion – Cyberknife (Accuray) Cyberknife (Accuray) – ExacTrac X‐Ray 6D Adaptive Tracking (Varian/Novalis) – 4D CT and respiratory gating

Accounting for Motion Accounting for Motion • Traditional approach for lung tumors: – Free breathing CT simulation – ICRU50 defined GTV, CTV, and PTV plan – Verify patient on conventional simulator and use fluoro to confirm that tumor mass is contained within beam aperture i d i hi b • Modern approach: – Respiratory correlated CT imaging (4DCT) • Alternative: – Max excursion breath hold CT

Account for Motion (ITV) Account for Motion (ITV) • Do end expiratory and end inspiratory CT’s Do end expiratory and end inspiratory CT s – Fuse volumes to create Max Intensity Volume (MIV) – Project onto DRR to get Max Intensity Projection (MIP) Projection (MIP) • 4D‐CT with phases – Generate a MIP which gives the ITV for Generate a MIP which gives the ITV for contouring – Treat patient based on free breathing or “mean” Treat patient based on free breathing or mean CT

Accounting for Motion (4D CT) Accounting for Motion (4D CT) www.healthcare.philips.com www.gehealthcare.com

4D CT Approaches 4D CT Approaches • Helical (Philips CT scanner with bellows) – Retrospective or prospective respiratory correlated imaging – Image data at same respiratory phase is combined from multiple respiratory cycles • Cine (GE Lightspeed with Varian RPM) – Retrospective respiratory correlated imaging – Image data gathered for >1 respiratory cycle at each couch position

Retrospective Respiratory Correlation CT (4D Cine) • Acquire CT images at single couch position Acquire CT images at single couch position during a respiratory cycle (slightly longer) – Record amplitude and phase for each slice Record amplitude and phase for each slice • Move the couch the distance of the detector width and obtain CT images for respiratory idth d bt i CT i f i t cycle. • Fuse images based on phase of respiratory cycle • Generate 4D images

4D Cine Approach 4D Cine Approach From Chang et al. Journal of Thoracic Oncology 2008

Varian RPM Varian RPM MarkerBlock MarkerBlock-

4D Motion 4D Motion Courtesy of Varian

Artifacts in 4D CT Artifacts in 4D CT (From Yamamoto et al. IJROBP 2008)

Motion Management Options Motion Management Options • Ignore (ie, account for motion) • Prevent motion – Breath Hold/Breath Control – Inspiration based – BodyFix/Hexapod (Elekta) p ( ) – Compression device (Elekta) • Track the motion – Cyberknife (Accuray) Cyberknife (Accuray) – ExacTrac X‐Ray 6D Adaptive Tracking (Varian/Novalis) – 4D CT and respiratory gating – Expiration based

Immobilization • Abdominal Compression – Hof et al 2003: Hof et al. 2003: • Lung tumor motion: – cc 5.1 +/‐ 2.4 mm – Lat 2.6 +/‐ 1.4 – AP 3.1 +/‐1.5mm • B d Fi Body Fix • Hexapod www.elekta.com

Breathing Control Breathing Control • Breath Hold (Can be coupled with RPM) – Onishi et al 2003 Onishi et al. 2003 • Lung tumor motion is 2‐3 mm • Gives reduced lung density because is Gives reduced lung density because is end‐inspiration • Active Breathing Coordinator™ (Elekta) – 15‐30 sec breath hold – M Many studies show excellent limitation t di h ll t li it ti of tumor motion 1‐2 mm • High Frequency Jet Ventilation (HFJV) High Frequency Jet Ventilation (HFJV) (Acutronic Medical Systems)

Motion Management Options Motion Management Options • Ignore (ie, account for motion) • Prevent motion – Breath Hold/Breath Control – Inspiration based – BodyFix (Elekta) p ( ) – Compression device (Elekta) • Track the motion – Cyberknife (Accuray) Cyberknife (Accuray) – ExacTrac X‐Ray 6D Adaptive Tracking (Varian/Novalis) – 4D CT and respiratory gating – Expiration based

Respiratory Gating/Management Respiratory Gating/Management • Real‐time Position Management (RPM™) (Varian) • Synchrony (Accuray) • Tumor Tracking Varian/Novalis and Accuray • GateRT GateRT (VisionRT)

Respiratory Gating Respiratory Gating www.varian.com

Motion Tracking Motion Tracking www.varian.com

Cyberknife (Accuray) Cyberknife (Accuray) • Robotic arm containing LINAC tracks Robotic arm containing LINAC tracks motion

Precise Delivery (IMRT) Precise Delivery (IMRT) • Ix and Trilogy (Varian) and Trilogy (Varian) – RapidArc™ • Tx™ (Novalis‐Varian) T ™ (N li V i ) • Tomotherapy® (HI‐ART) • Synergy® (Elekta) • Artiste™ (Siemens) t ste (S e e s) • Compensator based methods • Add‐on serial tomotherapy (Best Nomos) Add on serial tomotherap (Best Nomos)

4D Verification 4D Verification • Imaging: – Bone alignment – MV or KV imaging – In‐phase KV imaging – with RPM – Fluoroscopy • Cine EPID • Cine KV – Active Markers – 4D DTS Emerging – 4D CBCT technologies • Tumor Tracking

Digital Tomosynthesis Digital Tomosynthesis (DTS) Zhang et al. IJROBP 2009 • DTS compared to CBCT for breast lumpectomy localization. – Oblique provided the best visualization Oblique provided the best visualization • Due to limited rotation, DTS may provide 4D information in less time with lower dose to the patient

Tumor Tracking 4D Verification Tumor Tracking 4D Verification • Novalis Tx – Near real time tracking with room g mounted xrays for image capture – Dynamic MLC for tracking – ex, Stanford • RTRT (Hokkaido University) RTRT (Hokkaido University) – Similar Approach as Novalis • Implantable transponders – Ex, Calypso – Many abstracts for this at ASTRO 2009 • Accuray Cyberknife – Room mounted xrays for image capture – Xsight® – soft tissue tracking – Synchrony® gating technology – Robotic arm tracks tumor

IMRT/IGRT at UAB IMRT/IGRT at UAB • 1999 Nomos Peacock Nomos Peacock • 2001 Varian DMLC • 2004 TomoTherapy® h • 2006 Cone Beam CT • May 2008 RapidArc™

UAB Technology

Respiratory Motion Management at UAB Managed Sites Management Options • Lung • End inspiratory and end • Breast p y g expiratory scans to get • Esophagus excursion • Liver/Gallbladder • 4D CT with RPM gating if ≥ 5mm motion in any plane 5mm motion in any plane • Pancreas – Select most stable gating window (ie, 30‐70) • Body‐fix immobilization • Breath‐hold/coaching

CT Imaging CT Imaging • Non‐4D approach • 4D CT • Mean (“slow CT”) ( ) – Free breathing like – Low resolution Low resolution – CT density is accurate we use this for p planning g • Maximum (“MIP”) – Represents ITV Represents ITV – Density is an overestimation

Non 4D Approach (Pancreas) Non‐4D Approach (Pancreas)

ITV Planning (Part 1) Non gating ITV Planning (Part 1) – Non‐gating • 4D CT scan performed on GE Lightspeed 4D CT scan performed on GE Lightspeed with Varian RPM. • Maximum Intensity Projection (MIP) is Maximum Intensity Projection (MIP) is transferred to Eclipse with free breathing CT. CT • Contouring of structures on MIP provides ITV information. ITV i f i • Contours are copied to free‐breathing CT for planning

ITV Planning (Part 2) ITV Planning (Part 2) – Gating • GE workstation does allow for contouring in 3D, but we g , prefer to measure excursion and selection of best phase on the workstation – Performed by dosimetrist with resident/attending Performed by dosimetrist with resident/attending • Ideally, we transfer only the phases to be used, but we can transfer entire dataset (VERY LARGE) • Contouring takes place on one of the phases and then we overlay it on other phases to expand the contour to generate the ITV (actually the IGTV) generate the “ITV” (actually the IGTV) • OAR will be contoured in a similar fashion. • Planning is performed based on average densities (MIP is Planning is performed based on average densities (MIP is not density correct)

ITV/Respiratory Phase Selection ITV/Respiratory Phase Selection

Combining PET with 4DCT Combining PET with 4DCT

Respiratory Gating Lung Respiratory Gating Lung

Respiratory Gating Lung (2) Respiratory Gating Lung (2)

Respiratory Gating Gallbladder Respiratory Gating – Gallbladder

Respiratory Gating Gallbladder Respiratory Gating Gallbladder

UAB Motion Management Studies UAB Motion Management Studies • ASTRO 2009 – E l E Early Experience with the Use of Gold Fiducial Markers in i ih h U f G ld Fid i l M k i IGRT of Pancreatic Cancers • Rojymon Jacob et al. • Conclusion: Additional margins of 0.4 cm(AP), 1.0 cm (SI), and 0.8 cm (Lat) are needed around the target for IMRT if skeletal registration is performed without fiducials – Respiratory Motion of Different Thoracic Regions Determined by Prospective Gated CT for Treatment Planning • S i Sh Sui Shen et al. t l • 95% Range of Motion of thoracic tumors/nodes were determined on 4D datasets from 90 patients with most significant motion seen in inferior, anterior and lateral lung regions i i f i t i dl t ll i

Hypofractionation The Kirklin Clinic at UAB

Radiobiology Rationale Radiobiology Rationale

Hypofractionation/SRS/SBRT Overview • We are finding that hypofractionation We are finding that hypofractionation schemes work as well if not better than standard fractionation. standard fractionation – More biological effect if given this way • Oft i Often involves tighter margins on tumor l ti ht i t – Precise Treatment – Less normal tissue toxicity potential • Absolute Requirement: – Accurate treatment IGRT

SBRT and SRS SBRT and SRS • Treatment planning considerations: – Is the patient comfortable? • Particularly, abdominal compression and bodyfix – How will respiratory motion be managed? • Is gating or respiratory suppression necessary? • Will affect margins – How will treatment setup be performed? • Fiducials • Optical tracking • Fluoro • Cone Beam CT

Lung SBRT Process Lung SBRT Process

LUNG SBRT LUNG SBRT

In Vivo Dosimetry at UAB? In Vivo Dosimetry at UAB? • 15‐20 Gy x 3 in 40 patients 15 20 Gy x 3 in 40 patients • ~75% treated for secondary metastases • 4D CT simulation with abdominal l h bd l compression – PTV = gated ITV plus 5 mm – < 5 mm tumor motion then no gating – Gated KV or CBCT image guidance – Most commonly 7‐13 beams Courtesy of John Fiveash and Chris Dobelbower

18 Gy 18 Gy Courtesy of John Fiveash and Chris Dobelbower

Acknowledgements • UAB – John Fiveash – Janice Carlisle – Chris Dobelbower – Heather Smith – Sui Shen h – Mark Hyatt • Vanderbilt – Rojymon Jacob R j J b – J i C Jostin Crass – John Stewart

4 D Igrt

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