4D-IGRT involves accounting for tumor motion during radiation therapy delivery. It uses 4D computed tomography (4D CT) imaging, which captures tumor position at different respiratory phases. This allows delineation of an internal target volume (ITV) that encompasses the full range of tumor motion. Treatment can then be delivered over the entire respiratory cycle or gated to a specific phase such as end-exhalation using respiratory tracking systems. The goal is to ensure accurate radiation delivery while minimizing doses to surrounding healthy tissues.

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
www.nomos.com www.varian.com www.cmsrtp.com

19. Video IGRT
Video IGRT
www.visionrt.com

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

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)
www.varian.com

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)
www.healthcare.philips.com www.gehealthcare.com

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

40. Varian RPM
Varian RPM
MarkerBlock
MarkerBlock-

41. 4D Motion
4D Motion
Courtesy of Varian

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

43. 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

44. 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

45. 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)

46. 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

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

48. Respiratory Gating
Respiratory Gating
www.varian.com

49. Motion Tracking
Motion Tracking
www.varian.com

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

51. 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)

52. 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

53. 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

54. 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

55. 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™

56. UAB Technology

57. 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

58. 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

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

60. 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

61. 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)

62. ITV/Respiratory Phase Selection
ITV/Respiratory Phase Selection

63. Combining PET with 4DCT
Combining PET with 4DCT

64. Respiratory Gating Lung
Respiratory Gating Lung

65. Respiratory Gating Lung (2)
Respiratory Gating Lung (2)

66. Respiratory Gating Gallbladder
Respiratory Gating – Gallbladder

67. Respiratory Gating Gallbladder
Respiratory Gating Gallbladder

68. 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

69. Hypofractionation
The Kirklin Clinic at UAB

70. Radiobiology Rationale
Radiobiology Rationale

71. 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

72. 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

73. Lung SBRT Process
Lung SBRT Process

74. LUNG SBRT
LUNG SBRT

75. 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

76. 18 Gy
18 Gy
Courtesy of John Fiveash and Chris Dobelbower

77. 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