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Improving Radiation Therapy for Moving Tumors
Sarah Geneser
Improving Radiation Therapy for Moving Tumors
Outline
Brief description of current radiotherapy successes and challenges
Dual-Gating: Increasing delivery speed without sacrificing targeting accuracy-- Demonstration on a lung cancer case-- Demonstration on a phantom with varying degrees of motion
Examining the effect of deformable image registration on dose warping
Concluding remarks
Improving Radiation Therapy for Moving Tumors
Radiation Therapy
• destroy tumor cells using radiative energy
• goal: irradiate the tumor (improves tumor control) while limiting dose to surrounding healthy tissues (reduces side effects)
• new hardware makes it possible to shape the beam aperture and deliver high levels of dose to the tumor while keeping normal tissue dose low (highly-conformal therapy)
multi-leaf collimator
(Image courtesy of Varian)
fluence mapconformal dose
Improving Radiation Therapy for Moving Tumors
Motion Presents Challenges
• several types of motion exist that complicate radiation therapy:• intrafraction:
• respiratory motion - diaphragm displaces abdominal and thoracic organs• prostate motion - prostate can move during treatment (due to bladder and
rectal filling)• interfraction:
• bladder filling - difficult to ensure consistent bladder fill level for treatment• weight loss - can occur over the course of several treatments
• cannot accurately predict intrafraction and interfraction motion, so must develop methods to account for these types of motion• e.g. respiratory motion uses “motion envelope” or gated therapy
Improving Radiation Therapy for Moving Tumors
Treatment in the Presence of Respiratory Motion
• motion envelope• benefits: ensures tumor coverage, delivery throughout breathing cycle• drawbacks: increases radiation dose to surrounding tissues
• respiration-gating• benefits: reduces irradiation of dose to surrounding tissues• drawbacks: tumor coverage somewhat less certain, delivery during only a
portion of breathing cycle
beam enabled
beam held
exhale window!
Both methods turn the 4D problem into a 3D
problem
Improving Radiation Therapy for Moving Tumors
4D Therapy in the Presence of Respiratory Motion
• create individual dose plans for each respiratory phase by optimizing over all phases simultaneously
• benefits: ensures tumor coverage while limiting radiation dose to surrounding tissues, delivery throughout breathing cycle
• drawbacks: increases delivery complexity
4DRT work began in 2004, but has not entered the clinic because not
feasible with current linac hardwareRelated Publications:Keall, et. al, Phys. Med. Biol., 49(16), 2004. Rietzel, et. al, IJROBP, 61(5), 2005.Trofimov, et. al, Phys. Med. Biol., 50, 2005.Lee, et. al, Phys. Med. Biol., 54, 2008.
Improving Radiation Therapy for Moving Tumors
Can We Do Better? Delivering at Inhale and Exhale
• compromise between 4DRT and conventional gated therapy
• benefits: • ensures tumor coverage while limiting radiation dose to surrounding
tissues, • faster than conventional gated therapy• less complicated than than 4DRT delivery
• drawbacks: • more complicated than conventional gated therapy• slower than 4DRT delivery
Improving Radiation Therapy for Moving Tumors
Dual-Gated Alternating Delivery
inhale window
beam enabled
beam held
exhale window
exhale fluence inhale fluencealternate delivery of IMRT fields
Improving Radiation Therapy for Moving Tumors
Machine Dynamics: Implementing Dual-Gating
True-Beam XML: used for developing
novel delivery methods on the True-Beam linac
Enables control of the gating windows:
Improving Radiation Therapy for Moving Tumors
minimize
w
X
s
r
spM
s
kAs
w �D
s
k22
subject to 0 w w
max
Dmin
s
A
s
w Dmax
s
Conventional Treatment Planning Optimization
How do we model dose for dual-gated therapy?
minimum and maximum dose constraints
non-negative fluence constraint
prescribed dose
calculated dose
sum over structures of interest
relative importance weighting normalized by voxels in a structure
IMRT fluence map
Improving Radiation Therapy for Moving Tumors
Dose Warping and Accumulation
exhale fluence inhale fluence
inhale CTexhale CT
exhale dose
inhale dose
R
registeredinhale dose
R
+
summed dose
=
Dtotal
= R(Dinhale
) +Dexhale
Improving Radiation Therapy for Moving Tumors
Machine Dynamics
inhale window
beam enabled
beam held
exhale window
exhale fluence inhale fluenceMLCs must move to correct positions between phases
Improving Radiation Therapy for Moving Tumors
Leaf Motion Regularization
exhale fluence inhale fluence
�
NfX
f=1
NuX
u=2
NvX
v=2
(|wu,v,f,i � wu,v,f,e|) penalizes large pixel-wise differences between the inhale and exale IMRT maps
Improving Radiation Therapy for Moving Tumors
Dual-Gated Treatment Planning Optimizationdose matching term
leaf motion penalization term TVR term
non-negative fluence constraintminimum and maximum dose constraints
minimize
w1,2
X
s
�
s
kDinhale
+D
exhale
�D
prescribed
k22
+
0
@NfX
f=1
NuX
u=2
NvX
v=2
�(|wu,v,f,1 � w
u,v,f,2|) +2X
p=1
�(|wu,v,f,p
� w
u�1,v,f,p|+ |wu,v,f,p
� w
u,v�1,f,p|)
1
A
subject to 0 w w
max
Dmin
s
ˆ
A1,2,sw1,2 Dmax
s
Improving Radiation Therapy for Moving Tumors
Evaluate Dual-Gating on Lung Patient Case
Improving Radiation Therapy for Moving Tumors
Evaluating Dual-Gating Performance (1, 2, 3 cm Motion)
gafchromic film can be placed in the cedar cylinder perpendicular to motion
respiratory-motion stage translates the phanom in the SI direction
right lungheart
left lung
spinalcord
ptv
Improving Radiation Therapy for Moving Tumors
1 cm SI Translation Dose Plan
+
inhale dose exhale dose
total dose
=
Gy Gy
Gy
0246810
15
21
27
33
39
0246810
15
21
27
33
39
05101520
30
40
50
60
Improving Radiation Therapy for Moving Tumors
2 cm SI Translation Dose Plan
+
inhale dose exhale dose
Gy Gy
Gy
0246810
15
21
27
33
39
0246810
15
21
27
33
39
05101520
30
40
50
60
total dose
=
Improving Radiation Therapy for Moving Tumors
3 cm SI Translation Dose Plan
+
inhale dose exhale dose
Gy Gy
Gy
0246810
15
21
27
33
39
0246810
15
21
27
33
39
05101520
30
40
50
60
total dose
=
Improving Radiation Therapy for Moving Tumors
−1
−0.4
−0.1
0.1
0.4
−1
−0.4
−0.1
0.1
0.6
−1.4
−0.6
−0.10.1
0.8
Dose Differences
1 cm translation 2 cm translation
3 cm translation stationary dosedual-gated plan has greater dose than conventional plan
dual-gated plan has less dose than static plan
05101520
30
40
50
60
Improving Radiation Therapy for Moving Tumors
Dual-Gating: Conclusions
• produces conformal dose distributions for lung cancer patient and for phantom with up to 3cm motion
• provides 1.75 to 2.23 times speedup depending on patient breathing
• promising option for treating respiratory-gated patients
Improving Radiation Therapy for Moving Tumors
Dual-Gating: Limitations (and Potential Solutions)
• MLC maximum speed and patient breathing characteristics may complicate delivery and reduce efficiency gains -- possible to encourage brief pauses at inhale and exhale using respiratory coaching
•the treatment for inhale or exhale may finish sooner -- possible to incorporate patient breathing dynamics into optimization to weight one phase more heavily
Improving Radiation Therapy for Moving Tumors
But ... What About Image Registration?
• Image registration deformations are used to warp dose.
• What if deformations are inaccurate?
• How do these errors effect registered dose?
• How do we determine ground truth?
Improving Radiation Therapy for Moving Tumors
Neil Kirby’s 2D Deformable Phantom
deformable phantom with optical markers to measure deformations
Improving Radiation Therapy for Moving Tumors
Prostate Dose Warping and Accumulation
empty bladderfull bladder
What are the errors in the dose warping?
• HDR planned on full bladder and IMRT planned on empty bladder
• Would be useful to be able to sum the two plans to see total dose
1) register full bladder image to empty bladder2) apply transformation to full bladder dose
full bladder registered to empty bladder
R
0
5
10
15
20
25
30
35
40
45
50
55
Gy
Improving Radiation Therapy for Moving Tumors
Percent Dose Deviations using DIR
symmetric force Demons
−30
−20
−10
0
10
20
30%
%
%
%
%
%
%
MIMVista
−30
−20
−10
0
10
20
30%
%
%
%
%
%
%original Lucas Kanade
−30
−20
−10
0
10
20
30%
%
%
%
%
%
%
free form by Lu
−30
−20
−10
0
10
20
30%
%
%
%
%
%
%
Improving Radiation Therapy for Moving Tumors
Dose Underestimation and Overestimation
0 5 10 15
10−4
10−3
10−2
10−1
100
Underdosing [Gy]
Frac
tion
of v
oxel
s w
ith g
reat
er u
nder
dosi
ng
lucasKanadeOriginalhornAndSchunckOriginalhornAndSchunckInverseConsistencyiterativeOpticalFlowdemonsFastiterativeOpticalFlowFastdemonsFastWithElasticRegularizationfreeFormDeformationByLudemonsSymmetricForcelucasKanadeImprovedMIMVista
0 5 10 15
10−4
10−3
10−2
10−1
100
Overdosing [Gy]
Frac
tion
of v
oxel
s w
ith g
reat
er o
verd
osin
g
lucasKanadeOriginalhornAndSchunckOriginalhornAndSchunckInverseConsistencyiterativeOpticalFlowdemonsFastiterativeOpticalFlowFastdemonsFastWithElasticRegularizationfreeFormDeformationByLudemonsSymmetricForcelucasKanadeImprovedMIMVista
MIMVista
Improving Radiation Therapy for Moving Tumors
Lessons Learned
• even when image registration is visually excellent, deformations may still be inaccurate (you can’t necessarily trust the clinical software!)
• difficult for image registration tools to infer deformations in regions of homogeneous dose
• regions of high dose gradient perpendicular to deformation vectors produce large errors in dose
Improving Radiation Therapy for Moving Tumors
Next Steps?
• Calculate and determine the effect on the dose volume histogramss
• Examine 3D deformations
• Incorporate tissue mechanics into image registration methods. (e.g. Kristi Brock et. al. -- MORFEUS)
Improving Radiation Therapy for Moving Tumors
Acknowledgements• Dual-Gated Delivery: Lei Xing, Benjamin Fahiminan, Kayla Keilar
• Dose Warping Accuracy: Neil Kirby, Jean Pouliot
• Funding: National Cancer Institute (T32 CA09695)
Improving Radiation Therapy for Moving Tumors
Thanks! Questions?
inhale window
beam enabled
beam held
exhale window
0
5
10
15
20
25
30
35
40
45
50
55
+ = ??
−30
−20
−10
0
10
20
30
Improving Radiation Therapy for Moving Tumors
EXTRA SLIDES
Improving Radiation Therapy for Moving Tumors
Dose Accumulation
Ai,e,swi,e = [Ai,s Ae,s]
wi
we
�= [Ai,swi +Ae,swe]
= di + de
voxel-wise dose at inhale voxel-wise dose at exhale
Improving Radiation Therapy for Moving Tumors
Dose Operators
voxel-wise dose at inhale voxel-wise dose at exhale
d = di + de
to sum properly, doses must be voxel-wise consistent dose operators must also be voxel-wise consistent)Ii Ie
~xi
T (~xi)
T (Ii)
~xe
1) register images to obtain voxel-wise correspondence
original inhale system: original exhale system:reordered inhale system:
2
66664
3
77775
2
66664
3
77775
2
664
3
775 =
Ai widi 2
66664
3
77775
2
66664
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77775
2
664
3
775 =
Ai widi 2
66664
3
77775
2
66664
3
77775
2
664
3
775 =
Ae wede
inhale dose
at voxel ~xe
inhale dose
at voxel ~xi
exhale dose
at voxel ~xi
2) reorder dose operators according to the deformation mapping
Improving Radiation Therapy for Moving Tumors
Dual-Gated Treatment Planning Optimization
minimize
wi,e
X
s
�
s
k ˆ
A
i,e,s
w
i,e
�D
s
k
subject to 0 w w
max
Dmin
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inhale fluence
exhale fluence
wi,e =
wi
we
�Ai,e,s = [Ai,s Ae,s]
inhale dose operator exhale dose operator
Improving Radiation Therapy for Moving Tumors
−15
−10
−5
0
5
10
15
symmetric force DemonsGy
Warped Isodose Contours using DIR
−15
−10
−5
0
5
10
15
MIMVistaGy
−15
−10
−5
0
5
10
15
original Lucas KanadeGy
−15
−10
−5
0
5
10
15
free form by LuGy