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Igrt In Gynecologic Malignancies
1. IGRT in Gynecologic Malignancies
Arno J. Mundt MD
Professor and Chair
Department of Radiation Oncology
University of California San Diego
La Jolla CA
2. Image-Guided RT?
“Image guided” is non-informative
RT has always been guided by images
Definition of IGRT is not standardized and
is open to various interpretations
Global definition might include any aspect
of RT involving imaging, from fluoroscopic
simulation to CT-based planning, to
weekly port films
3. RTOG Research Plan 2002-2006
IGRT Committee Report
Michalski J, Purdy JA, Gaspar L, et al.
Int J Radiat Oncol Biol Phys 2001;51:60-5
“IGRT refers broadly to treatment delivery using
modern imaging methods, such as CT, MRI, PET and
Ultrasound, in target and non-target structures and in
RT definition, design and delivery…”
“IGRT includes, but is not limited to, 3DCRT, IMRT,
stereotactic radiosurgery, stereotactic RT, and
brachytherapy….”
4. Introduction
Recommend a more focused definition
Highlight the 2 most important roles of
imaging in modern RT:
Improved Target Delineation
Improved Treatment Delivery
5. IGRT Definition
Use of modern imaging modalities, especially those
incorporating functional or biological information, to
augment target delineation
and
Use of imaging, particularly in-room approaches, to
adjust for target motion and positional uncertainty,
and, potentially, to adapt treatment to tumor
response
6. New Frontier
Image-Guided Radiotherapy
Strong rationale in gynecologic tumors,
particularly when IMRT is used
CT is not ideal for imaging tumors and
normal tissues
Gynecology patients often difficult to setup
Considerable organ motion exists
Tumors shrink rapidly
7. Target Delineation
Traditional method planar (flouroscopic)
x-rays
External beam fields based on
visualized bony anatomy
Contrast used to define normal tissues
Brachytherapy doses prescribed to
specified “Points” based on applicator
position
8. 2D planning → Poor target coverage and excess normal
tissue exposure compared to 3D planning
Red
Journal
2006
43 cervical cancer pts
Evaluated adequacy of coverage of pelvic vessels
Surrogate for lymph nodes
Adequate: >15 mm vessel to block edge
41/43 (95%) inadequate coverage with 2D based
fields
24/43 (56%) too generous (> 2 cm)
Excess normal tissue exposure
9. Beyond CT Imaging
Interest now focused on more
sophisticated imaging for treatment
planning
Magnetic Resonance Imaging (MRI)
With ultra-small iron oxide particles (USPIO)
Positron Emission Tomography (PET)
18F-Deoxyglucose (FDG)
Or combined PET/CT units
10. Fe Oxide nano-particle
Taken up in benign lymph
nodes by macrophages
7 mm margin around
vessels encompassed 99%
of pelvic nodes
Red Journal (2005)
11. FDG-PET particularly useful to identify involved nodes
Boost to higher doses with IMRT
Mutic Red Journal (2003)
PET+ Nodes: 59.4 Gy/1.8 Gy fx
PET- Nodes: 50.4 Gy/1.53 Gy fx
Ahmed Red Journal (2004)
PET+ nodes: 60 Gy/2.4 Gy fx
PET- nodes: 45 Gy/1.8 Gy fx
12. More Advanced Imaging
Dynamic-Contrast MRI
(tumor hypoxia)
Cooper et al. Radiother
Oncol (2000)
1H-MR spectroscopy
(tumor vs normal tissue)
Okada et al. J MRI
Okada (2001)
(2001)
13. Alternative PET Tracers
Metabolic Abnormalities or Hypoxia
11C-Choline (tumor vs normal tissue)
11C-Methionine (amino acid transport)
60Cu-ATSM (hypoxia)
MRI FDG-PET 11C-Choline PET
Less uptake in normal tissues Torizuka J Nucl Med (2003)
11C-Choline imaging
14. Tumor hypoxia inversely
correlated with DFS and
OS
3y PFS normoxic (71%)
and hypoxix (28%)
Could be used to dose
paint during external
beam and brachytherapy
15. Normal Tissue Delineation
Novel imaging techniques also valuable
for normal tissue delineation
Roeske (2003)
MR-Spectroscopy to identify active
(red) marrow sites
Roeske (2005)
SPECT also useful for
active bone marrow delineation
17. T2* Pulse Echo MRI
“Fat Fraction”
Used to differentiate between red
and yellow marrow
Information then used to dose paint
IMRT plans minimizing red marrow
irradiation
Loren Mell MD
UC San Diego
ASCO Young Investigator
Award
18. Image-Guided Target Delineation
Brachytherapy
Growing interest in using imaging to
break away from Point A
Most attention on MRI
Radiother Oncol (2006)
19. PET-Guided Brachytherapy
Malyapa
Red Journal (2002)
Intravenous FDG
+ FDG inserted into
tandem and ovoids
20. Used to conform
dose to shape of the
cervix and uterus
Excellent correlation
with MRI
21. Image-Guided
Treatment
Delivery
Cancer Center Corridor
23. Rationale
All 3 issues are a problem for IMRT
Rapid dose gradients very unforgiving
Inaccurate setup, organ motion and
regression all may lead to underdosage
of the tumor and overdosage of the
normal tissues
IGRT has the potential to overcome all
three problems
25. Ultrasound-Based IGRT
Cervical Cancer
Little data
Surprising given popularity in prostate cancer
But useful for difficult implants
Bad
Good
26. Video-Based IGRT
Cervical Cancer
No data
Appealing given ability to monitor intra-fraction
patient position in real-time without x-rays
Clinical trial planned at UCSD
Align RT system
Ceiling-mounted cameras
Real-time 3D surface image
Popular in breast and lung cancer
27. Planar-Based IGRT
Cervical Cancer
Most studied IGRT approach in cervical cancer
Long history using electronic portal imaging
devices (EPID) to monitor patient setup
MV image of bony anatomy or implanted
markers
Antonuk (2002)
28. EPID-Based IGRT
Implanted Fiducials on Cervix
Kaatee (2002)
10 cervical cancer pts
Radiopaque tantalum markers
on cervix
Used to track cervix position
Image quality good-excellent
½ lost before end of RT
29. Red J (2000)
14 gynecology pts
On-line EPID IGRT
Based on boney landmarks
Action level > 4 mm
57% re-positioned
Average time ~ 3 minutes
Acquisition and adjustment
↓PTV margins to 5 mm
30. Real-Time Tumor Tracking
(RTRT)
Four sets of diagnostic x-ray
tubes and imagers
1.5 MHU x-ray tube and a fixed
floor-mounted collimator
Corresponding ceiling-mounted
imager
Mitsubishi Electronics Co Ltd, Tokyo, Japan
http://global.mitsubishielectric.com/
31. RTRT System
During treatment,
2 of the 4 x-ray systems
Track an implanted marker
Using motion tracking software
Tracking is continuous
If the marker coordinates are
within a permitted distance,
the beam is triggered on
Marker position calculated
0.03 seconds
Harada (2002)
32. Green Journal (2004)
10 gynecology patients with implanted fiducials
Necessary CTV-PTV margin using real-time RTRT
tracking:
6.9 mm (right-left), 6.7 mm (sup-inf), 8.3 mm (ant-post)
No data using other popular planar systems
(CyberKnife, Novalis)
33. Planar-IGRT Systems
Several vendors have mounted kV sources
on gantry opposite amorphous silicon (aSi)
flat panel detectors
Capable of generating high quality kV planar
images
Better image quality and less dose than EPID
Emerging data using both approaches
None focused solely on gynecology patients
34. Commercial Gantry-Mounted Systems
Planar IGRT
Varian On-Board Imaging (OBI)
www.varian.com
EPID aSI Detector
kV Source
Elekta Synergy
www.elekta.com
35. Planar kV Commercial
Systems
Varian OBI planar-IGRT
system
On-line patient setup correction
based on bony landmarks
Variety of tumor sites including
gynecology
Feasible
Entire process < 1 additional
minute
37. Process Flow
Planar IGRT (Gynecology-Pelvis)
Day 1
MD and RTTs meet at console
Discuss anatomy, special issues, etc.
Day 2 thru Completion
Other shifts
All shifts ≤ 1 mm LR shift > 15 mm
SI or AP shift > 15 mm
Any concerns
Make all shifts
Make no shifts
Call MD and treat
and treat
38. Planar kV Commercial Systems
Offer the potential to track
Implanted fiducials
Analogous to on-line
techniques popularized in
prostate cancer
Potentially useful to deliver
a high dose conformal
boost in patients unable to
receive brachytherapy
39. Volumetric-Based IGRT
Interest is now turning to volumetric
IGRT
Several vendors offer volumetric
solutions using the MV treatment beam
Tomotherapy, Siemens
Others generate kV cone-beam CT
(CBCT) scans by reconstructing
multiple planar kV images
Varian, Elekta
40. Volumetric-IGRT
High quality kV CBCT
scans can be
produced
Useful now to monitor
target coverage
In future, opens door
to adaptive RT
41. On-Line Planar, Off-line Volumetric IGRT
Cervical Cancer
Planar KV Imaging
Align boney anatomy
(↓CTV-PTV margins around Nodes
Generous margins around cervix)
↓
Video Imaging
Monitor Patient Position during Tx
↓
Volumetric Imaging
Off-line monitoring of target Coverage
Adjust margins if necessary
42. Day 2
Day 1
Day 2
Day 1
Day 3 Day 4
Day 4
Day 3
Day 5
Day 5
43. Day 2
Day 1
Day 1 Day 2
Day 3
Day 4
Day 3 Day 4
Day 5
95%
90%
Day 5
85%
80%
44. Volumetric-based IGRT
Cervical Cancer
Off-line monitoring of target coverage is
very useful
Particularly important if modest margins
are used around the cervix and fundus
We used 1.7 cm margins
Modifications are still common to ensure
coverage
45. CBCT Cervical Cancer Study
Margin % Fx Volume Location
(mm) CTV Missed Missed Fundus Cervix
0 100% 45.3 cc 100% 95.2%
3 98.7% 24.8 cc 89.0% 79.5%
5 95.4% 20.3 cc 83.6% 65.1%
7 87.2% 13.9 cc 71.2% 50.0%
10 59.3% 9.3 cc 54.0% 35.6%
15 32.1% 4.0 cc 24.0% 18.5%
20 19.3% 1.7 cc 11.6% 10.9%
25 14.0% 0.7 cc 7.5% 6.9%
30 6.7% 0.3 cc 4.1% 0.7%
46. Image-Guided
Adaptive RT
Aerial View, Inner Garden
and Cafe
47. Adaptive IGRT
Tumors shrink
And often quite quickly with
chemotherapy plus RT
Shrinkage is a double-edged sword
Reduces the Reduces the
chance of a conformity of the
geographic miss original plan
48.
49. Tumor Response
Many investigators have quantified the rate of
response in cervical cancers
University of Utah used physical exam
measurements and found by 30.8 Gy tumors
reduced by 50%
MD Anderson used weekly conventional CT
and noted a mean reduction of 64%
Others have used IMRT to better calculate
tumor regression
Lee et al. Red Journal 2005;58:625
Beadle et al. ASTRO 2006
Mayr et al. Am J Roentgenol 2006;187:65
Van de Bunt et al. Red Journal 2006;64:189
50. 14 cervical cancer patients
MRI prior to RT and after 30 Gy external beam
GTV decreased (on average) by 46%
Decrements in CTV and PTV were 18% and 9%
51. Does Re-Planning Help?
Re-optimizing the IMRT plan at 30 Gy
improved the sparing of the rectum
Average rectal volume receiving ≥ 95%
of the prescription dose
75 cc (range, 20-145 cc) (No Re-planning)
67 cc (range, 15-106 cc) (Re-planning)
P = 0.009
Improved bowel sparing seen in women
with bulky (> 30 cc) tumors
52. Does Re-Planning Help?
Currently analyzing a large dataset of
daily CBCT in cervical cancer patients
undergoing IMRT and chemotherapy
Daily imaging data allows us to not only
ask whether re-planning helps, but the
optimal frequency and timing of re-
planning
53. Adaptive IGRT
Many technical obstacles stand in the
way of adaptive IGRT, particularly if
performed on-line
New software tools: image deformation
and automated segmentation
Better quality CBCT imaging
New rapid, accurate QA approaches
54. Adaptive IGRT
Once technical obstacles are overcome,
numerous clinical questions remain
Does adaptive IGRT help? Does it hurt?
Should it be performed on-line or off-line?
How often should it be done? Weekly?
Daily?
Such questions can only be addressed
in carefully designed clinical trials
56. Adaptive IGRT
Necessary tools being developed at
UCSD in collaboration with the San
Diego Super-Computer Center and
Varian Medical Systems
57. On-Line Setup, Off-Line Adapt On-Line Setup, On-Line Adapt
Setup to Marks
On-Line
Planar IGRT
On-Line
Deliver Treatment CBCT
Real-time Video
IGRT
Re-plan if necessary
Off-Line Deliver Treatment
Analysis Real-time Video
Re-Plan as IGRT
needed
58. “Re-Plan If Necessary”
Need to decide on the table within
minutes!
Not an simple task
Could involve target and normal tissue
delineation, re-planning and evaluating
potential benefit
A more elegant solution may be to use
the CBCT image itself
Analyzed using Machine Learning
61. On-Line Adaptation
Deform simulation CT anatomy into all
potential anatomical changes
Generate 1000+ IMRT plans using
supercomputer computational power
Image patient on the table each day and
select most similar plan
Treat with new plan
62. Daily Re-Planning
High speed computer processing is
essential
Need to move from sequential
processing to parallel processing
Never been applied to radiation oncology
