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  • 1. 4D‐IGRT: Certain Phase of Respiration Christopher D. Willey, MD, PhD Assistant Professor Department of Radiation Oncology The University of Alabama at Birmingham
  • 2. Disclosures • I do occasional speaking/consultation for I do occasional speaking/consultation for  Varian Medical Systems, Inc.
  • 3. 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.
  • 4. 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
  • 5. 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
  • 6. 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
  • 7. 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
  • 8. • 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
  • 9. 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
  • 10. Change in Volume Definitions Change in Volume Definitions PTV ITV CTV IM “IGTV” IGTV GTV GTV GTV GTV SM SM ICRU50 ICRU62 “ICRU62”
  • 11. 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
  • 12. 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
  • 13. 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
  • 14. 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
  • 15. 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
  • 16. 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)
  • 17. Electromagnetic Transponder Electromagnetic Transponder
  • 18. Ultrasound BATCAM SonArray I-Beam
  • 19. Video IGRT Video IGRT
  • 20. Laser Surface Topography IGRT Laser Surface Topography IGRT
  • 21. On board Imager (Varian) On‐board Imager (Varian)
  • 22. On board Fluoroscopic Imaging On‐board Fluoroscopic Imaging
  • 23. 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™
  • 24. Novalis Orthogonal X rays Novalis Orthogonal X‐rays Teh et al. Biomed Imag Interv J 2008
  • 25. Volumetric (3D) IGRT Volumetric (3D) IGRT Varian Trilogy OBI® Novalis Tx™ Siemens CTVision™ Siemens Artiste™ KVision Elekta Synergy™ TomoTherapy® (HiART) Elekta Axesse™ VolumeView
  • 26. Acuity (Varian) Acuity (Varian) • 2D simulation 2D simulation • 3D simulation with  cone beam CT (KV) ( ) • Respiratory gating • Brachytherapy
  • 27. Cone Beam CT (Varian) Cone Beam CT (Varian)
  • 28. MV CT imaging MV CT imaging Siemens MVision™ (MV cone beam) TomoTherapy® (Hi-ART) (MV CT)
  • 29. Prostate
  • 30. 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
  • 31. 4D Motion 4D Motion Courtesy of Varian
  • 32. 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
  • 33. 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
  • 34. 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
  • 35. Accounting for Motion (4D CT) Accounting for Motion (4D CT)
  • 36. 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
  • 37. 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
  • 38. 4D Cine Approach 4D Cine Approach From Chang et al. Journal of Thoracic Oncology 2008
  • 39. Varian RPM Varian RPM MarkerBlock MarkerBlock-
  • 40. 4D Motion 4D Motion Courtesy of Varian
  • 41. Artifacts in 4D CT Artifacts in 4D CT (From Yamamoto et al. IJROBP 2008)
  • 42. 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
  • 43. 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
  • 44. 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)
  • 45. 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 
  • 46. Respiratory Gating/Management Respiratory Gating/Management • Real‐time Position Management (RPM™)  (Varian) • Synchrony (Accuray) • Tumor Tracking Varian/Novalis and Accuray • GateRT GateRT  (VisionRT)
  • 47. Respiratory Gating Respiratory Gating
  • 48. Motion Tracking Motion Tracking
  • 49. Cyberknife (Accuray) Cyberknife (Accuray) • Robotic arm containing LINAC tracks Robotic arm containing LINAC tracks  motion
  • 50. 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)
  • 51. 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
  • 52. 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
  • 53. 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
  • 54. 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™
  • 55. UAB Technology
  • 56. 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
  • 57. 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
  • 58. Non 4D Approach (Pancreas) Non‐4D Approach (Pancreas)
  • 59. 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
  • 60. 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)
  • 61. ITV/Respiratory Phase Selection ITV/Respiratory Phase Selection
  • 62. Combining PET with 4DCT Combining PET with 4DCT
  • 63. Respiratory Gating Lung Respiratory Gating Lung
  • 64. Respiratory Gating Lung (2) Respiratory Gating Lung (2)
  • 65. Respiratory Gating  Gallbladder  Respiratory Gating – Gallbladder
  • 66. Respiratory Gating Gallbladder Respiratory Gating Gallbladder
  • 67. 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
  • 68. Hypofractionation The Kirklin Clinic at UAB
  • 69. Radiobiology Rationale Radiobiology Rationale
  • 70. 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
  • 71. 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
  • 72. Lung SBRT Process Lung SBRT Process
  • 74. 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
  • 75. 18 Gy 18 Gy Courtesy of John Fiveash and Chris Dobelbower
  • 76. 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