22 chap 20 intensity modulated radiation therapy
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Transcript of 22 chap 20 intensity modulated radiation therapy
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Chapter 20Intensity Modulated Radiation Therapy
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Goals of Conformal Radiation Therapy
Reduce normal tissue toxicity
• Conform dose to the tumor
•
• Tumor dose escalation
improve local tumor control
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target
Conventional Conformal Therapy and IMRT
Conventional Conformal TherapyField shape conforms to the outline of the target, uniform intensity across the field
IMRTNon-uniform intensity inside the field to achieve optimum dose distribution
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Outline
• Optimization (Inverse Planning)
• Delivery
• Quality Assurance
• Clinical Applications
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organ
xj
itarget
Inverse Planning Problem
xj is the intensity of the j-th pencil beam.
Find the optimum distribution of xj’s (i.e., the optimum intensity distribution) that will give the best target coverage and critical organ protection.
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Optimization (Inverse Planning)
Purpose: To find the ‘optimum’ intensity distribution for all beams involved in a plan that will best meet the planner’s requirements.
What are the requirements? Objective functionsdose, dose/volume - based,biological indices - based: TCP, NTCP
How to find the optimum solution? Search algorithmsdeterministic methodsstochastic methods
(*Optimization is conceptually separated from delivery, so in this step we don’t need to be concerned about how it’s to be delivered.)
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(Recent development)
Direct Aperture Optimization:
To optimize a set of apertures (shape and weight) to achieve the best dose distributions.
Advantage: eliminates the step of leaf-sequencing; optimized results = deliverable results.
(In fluence optimization, the optimal fluence distribution may not be deliverable, due to limitations of leaf transmission.)
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Objective Functions
based on Dose, Dose/Volume
• Examples of commonly used objective functions:target: (D-P)2
critical organs: (D-Dc)2, (D-Dc) if D>Dc
dose volume conditions:
no more than p% of the volume to exceed dose q.
• Reasonable and mathematically convenient.
• No fundamental physical basis.
• Could be any other forms such as |(D-P)m|.
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Objective Function Based on Dose and Dose/Volume
P Pul
target
w (D-P )2
uu
w (D-P )2
l l
Serial type Normal tissue
Dc
(D-Dc)2
D
VNo more than p% of the volume to exceed dose q.
p%
q
Parallel type Normal tissue
Dose constraint Dose/volume constraint
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Objective Functions
based on Biological Indices
• Maximize TCP, minimize NTCPs.
• Used in place of or in conjunction with dose-, dose/volume-based objective functions.
• At present, clinical data are scarce and models not well-established yet.
• Not available on commercial system at present.
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Examples of Optimization Methods
• Deterministic:
Gradient, Conjugate gradient (Eclipse,Konrad).
Maximum likelihood (Brainlab, nuclear medicine).
• Stochastic:
Simulated annealing (NOMOS).
Genetic algorithm (Brachy therapy).
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5-field to 81 Gy
Prostate IMRT plan
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The ‘Skin-Flash’ Problem in Inverse Planning
PTV
Conventional:
Margin added to field edge to allow for uncertainties.
IMRT:
Intensity remains at 0 outside PTV. No skin-flash
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Skin-Flash for Intensity-Modulated Field
Simple, flat extension
skin
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Detection of unexpected hotspots
PTV
Beam II
Beam III
Beam I
A
BPTVCordHotspots > 120%location > 3 cm from PTV
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• IMRT may produce hotspots outside the PTV– Can be at large distances from the PTV.
• Hotspots may not be appear at the standard three orthogonal planes used for plan evaluation– May be worse for non-coplanar beams
• Proposed solution:– Use volume display to detect possible hotspots
– “Rind” = annular region around the PTV
– “Rest-of-body” = “irradiated body” - PTV - OARs
– Efficiency issues: “Rest-of-body” is a large structure and fine calculation grid is required
Detection of unexpected hotspots
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Summary - Optimization
• Objective functions may be based on dose, dose/volume conditions, or biological indices.
• Optimization methods may be stochastic or deterministic.
• Local minima may exist, but there is no easy way to tell whether a solution is at a global or local minimum, regardless of which optimization method is used.
• Optimized intensity distribution should give better dose distribution than conventional conformal plans.
• A typical case involving 103 rays, and 104 points, takes about 3 to 10 minutes of computer time with the gradient method.
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Summary – Optimization (practical considerations)
• smoothing is necessary to reduce unnecessary fluctuations in intensity distribution.
• skin flash is needed to account for treatment uncertainties (breast, head/neck).
• beware of unexpected hot spots.
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Delivery of IMRT
• Compensator: less efficient (fabrication, re-entry into the room between fields).
• Fixed field with conventional MLC:continuous leaf motion,step-and-shoot.
• Rotational field:conventional MLC,NOMOS/MIMIC, Tomotherapy.
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MIMiC
Multileaf
Intensity
Modulating
Collimator
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Individual leaf controls opening
MIMiC
Multileaf
Intensity
Modulating
Collimator
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Tomotherapy
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Delivery of IMRT with a Multileaf Collimator (MLC)
MLC mounted on the head of a linac Close-up view of the leaves
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directionof motion
Left-leafRight-leaf
beam-ontime
P
Delivery of IMRT with a Conventional MLCsliding window method
radiation
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Methods - Sliding Window TechniquesDynamic vs. Segmental (step-and-shoot)
X
Bea
m-o
n-T
ime
Right-leaf
Left-leaf
delivered intensity
Dynamic
P
T
a
b
c
d
X
Right-leafLeft-leaf
delivered intensity
Segmental
P
T
a
bc
d
max
11
vvx
t
v =
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The Posterior Field in a Prostate Treatment
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An Intensity-modulated Field Delivered with a Conventional MLC
For cord protection
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Maximum leaf speed - approx. 2.5 cm/sec on Varian MLC Leaf transmission - approx. 1.5% on Varian MLC Leaf edge effect - rounded leaf end on Varian MLC Source distribution - variation of output with field size & shape Tongue & groove effect Maximum leaf protrusion/retraction on each side - 14.5 cm on Varian MLC very low intensities not deliverable
Practical Considerations
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BEAM
50%
tonguegroove
Tongue-and-groove Effect
• Varian MLC employs a tongue-and-groove design to reduce leakage between leaves
• Leaf synchronization
– Van Santvoort 1996
– Webb 1997
– Longer beam-on time
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Splitting Large IM fields
• Maximum Varian DMLC width ~ 15 cm
• Larger fields (e.g. NP) split into 2 or 3 subfields
• Considerations:
– Smoothness of profiles; no discontinuities
– Split along a straight line or a low intensity region
– Use feathering to reduce effects of uncertainties
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0
5
10
15
20
25
-8 -6 -4 -2 0 2 4 6 8
x (cm)
inte
nsity
(M
U)
Desired and Delivered Intensity Profiles
desired delivered
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DMLC:
• accurate delivery of the desired intensity profiles.
SMLC or Step-and-shoot:• User more comfortable - resembles multi-segment conventional treatment.
• Shorter beam-on-time (MU) compared to DMLC.
• Longer delivery time (min.) compared to DMLC. (on some machines)
• Loss of spatial & intensity resolution
Comparison of DMLC and SMLC Methods
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Continuous intensity profile
Equispaced multi-level intensity profile
Conversion from continuous to discrete intensity profiles
Resolution : x = 2 mm intensity = continuous
Resolution depending on the number of levels
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0
20
40
60
80
100
120
0 20 40 60 80 100 120
dose (%)
volu
me
(%)
DVH comparison between DMLC and a 5-level SMLC delivery for a prostate case
PTV
rectum
bladder
femur
DVH Comparison
DMLC
5-levelSMLC
x-grid = 2 mm
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DVH comparison between DMLC and a 5-level SMLC delivery for a head/neck case
0
20
40
60
80
100
120
0 20 40 60 80 100 120
dose (%)
volu
me
(%)
DVH comparison
PTV
cord
0
5
10
15
20
25
30
-10 -8 -6 -4 -2 0 2 4 6 8 10
x (cm)
inten
sity (
MU)
Delivered profile
DMLC 5-level SMLC x-grid = 2 mm
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Summary - Delivery
• Intensity-modulated field can be delivered with a conventional MLC using the Sliding Window Technique, either in dynamic (DMLC) or segmental (SMLC or step-and-shoot) mode.
• Capable of delivering (almost) any shape of intensity profile, but limited by leaf speed, transmission, etc.
• Need to account for leaf transmission, rounded leaf end, and head scatter.
• Split large field into 2 or more segments, if necessary.
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• Loss of beam-on-time efficiency relative to conventional fields due to small field openings.
prostate : 2~3 times nasopharynx: 3~4 times breast: about the same
• Treatment time equal or less than conventional treatment, e.g., 5-field prostate treatment < 8 min. (excluding patient setup).
• Delivery with SMLC requires less beam-on-time (MU), but longer delivery time (min) than that with DMLC (on some machines).
• Delivery with SMLC should avoid segments of short beam-on-time for concerns of beam stability.
Summary - Delivery (cont’d)
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• For conventional treatment, the entire treatment field is exposed during a fraction.
• For IMRT, the treatment field is divided into many sub-fields, of which only one sub-field is exposed at a time. Consequently, if there is organ motion during treatment, portions of the treated volume may move in and out of the sub-field during a fraction.
• Since leaf sequence is designed based on a static geometry, the presence of organ motion will cause the actual delivered intensity profile to be different from the planned one.
The Effects of Intra-Fraction Organ Motion on the Delivery of Intensity-Modulated Fields with a Multileaf Collimator
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Organ Motion Relative to Leaf Motion
X
Bea
m-o
n-T
ime
Right-leafLeft-leaf
Desired intensity
Parallel
P
Y
Perpendicular
P
T
a
b
c
d
a’
b’
c’
d’
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Intra-fraction Breathing Motion (Breast Treatment) A = ±3.5 mm, = 4 sec. organ motion leaf motion
Single fraction Averaged over 30 fraction
Leaf pair #14: average gap = 4.51 cm.
planned profile******* delivered profile, motion averaged over 30 fx
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Intra-fraction Breathing Motion (Breast Treatment)A = ±3.5 mm, = 4 sec. organ motion leaf motion
105 103 100 50
IMRT static IMRT motion averaged over 30 fx
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1 cm
Intra-fraction Breathing Motion (Lung Treatment)A = ±7.0 mm, = 4 sec. organ motion leaf motion
planned profile******* delivered profile, motion averaged over 30 fx
planning images acquired
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Intra-fraction Breathing Motion (Lung Treatment)A = ±7.0 mm, = 4 sec. organ motion leaf motion
105 100 90 50 20planning images acquired
IMRT static IMRT motion averaged over 30 fx
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staticmotion
0
20
40
60
80
100
120
0 20 40 60 80 100 120
lungs
PTV
GTV
Dose (%)
volu
me
(%)
Intra-fraction Breathing Motion (Lung Treatment)A = ±7.0 mm, = 4 sec. organ motion leaf motion
planning images acquired
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Summary of Effects of Intra-fraction Organ Motion
• Effects of intra-fraction organ motion can be calculated, provided the pattern of motion is known.
• Effects can be calculated for single or multiple fractions.
• For breast treatment, if the amplitude < 3 ~ 5 mm, effects appear to be insignificant over multiple fractions.
• Penumbra broadening at field edge is common to both conventional and intensity-modulated fields.
• If in-field effects significant, alternative means will be needed, e.g., compensator, breath hold, gating.
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Quality Assurance
• Machine Performance (DMLC):
Film test
Gap test
• Machine Performance (Step-and-Shoot):
Dose/MU vs. MU
Flatness, symmetry vs. MU
• Patient Dosimetry:
Record & verify, file check-sums (each fraction)
Independent MU check, portal image (each patient)
Log file analysis, chamber measurement, film dosimetry (periodically or new software, technique, or site)
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- 0.5 mm
+ 0.5 mm
- 0.2 mm
+ 0.2 mm
errors introducedFilm test
1 mm bands
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Gap error Dose error
0.0
5.0
10.0
15.0
20.0
0 1 2 3 4 5
Nominal gap (cm)
% D
ose
erro
r
Range of gap width
2.01.0
0.50.2
Gap error (mm)
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Gap Test100 MU
chamber
5mm gapGap error Dose error
0.0
5.0
10.0
15.0
20.0
0 1 2 3 4 5
Nominal gap (cm)
% D
ose
erro
r
Range of gap width
2.01.0
0.50.2
Gap error (mm)
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0-090-0270-0180-090-90270-90
0.97
0.98
0.99
1.00
1.01
1.02
1.03
Oct-97
Nov-97
Jan-98
Apr-98
Jun-98
Aug-98Oct-
98
Date
445
Date
Rel
ativ
e ou
tput
0.97
0.98
0.99
1.00
1.01
1.02
1.03
Oct-97
Nov-97
Jan-98
Apr-98
Jun-98
Aug-98Oct-
98
2450.2 m
m
DMLC Output vsGantry / Collimator Angles
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Beam Stability: Dose per MU
• Iso-centric setup, farmer-type ion chamber, in solid water phantom
• Checked both short and long term stability.
• For > 2MU, dose per MU is within +/- 2%. For > 2MU, dose per MU is within +/- 2%.
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Beam Stability: Flatness, Symmetry
Sym
metry
-0.05
0.00
0.05
0.10
GUN-TARGET DIRECTIONCROSS-PLANE DIRECTION
Total MUs Delivered1 10 100
Fla
tness
-0.05
0.00
0.05
0.10
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Measured vs CalculatedSum of 5 IMRT fields
Patient #
Dm
eas
/ Dca
lc
Linac-1
Linac-2
0.95
0.96
0.97
0.98
0.99
1.00
1.01
1.02
1.03
0 100 200 300 400
mean = 0.993, s = 0.008
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Use left leaves of first segment and right leaves of last segment as the port film field.
Port filmIMRT field
Port Film for Intensity-Modulated Field
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input
Calculate deliveredintensity distribution
Calculate dose
Leaf sequence file, beam-on-time,jaw settings, machine data table.
Including effects of scattered source,rounded leaf end, mid-leaf & between-leaf transmission, tongue-and-groove effect, and scatter from the leaves.
Calculate dose (cGy) .
Independent Verification of IMRT
A good QA practice. In the US, it may also be a regulatory requirement. For IMRT, hand calculation is impractical, an independent verification program is needed.
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Calculation of Delivered Intensity Distribution
Leaf sequencing file: describes leaf positions as a function of beam-on time (MU).
+ + + +
+ + + +
Step-and-shoot
dynamic
• • • • • • • • •
T1 T2 T3 T4
T0
time
Leaf positions
time
Leaf positions
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tonguegroove
BEAM
Between leaf transmission
BEAM
Tongue-and/or-groove effect
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Ring-shaped Field
first segmentsecond segment
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Varian Clinac-2100C MLC
tongue&
groove
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0
0.2
0.4
0.6
0.8
1
-0.4 -0.2 0 0.2 0.4 0.6 0.8 1
inte
nsit
y
distance from the leaf-end (cm)
under mid-leaf
direct exposure
under tongue or groove
under the leaf
Rounded leaf-end
mid-leaf
tongue or groove
beam
Intensity distribution in the penumbra region as a function of the distance from the rounded leaf end.
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Isocenterplane
MLCplane
Sourceplane
MLCopening
Variation of Output with Field Shape/SizeBackprojection to the Source Plane
(x,y)
'')','()','(' source ii dydxyyxxSyxO
S
dydxyyxxSyxsource
'')','()','('
openingoutsideyxif
openinginsideyxifyxOi ),(0
),(1),(
'')','()','(' source ii dydxyxSyxO
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Scattered Intensity from the MLC
– For large fields can contribute up to 5%
transmission
leaf
Distance from pencil beam
inte
nsity
1.5 to 2%
0 55 1010
Pencil beam
Scatter from the leaf
transmission
Scatter from the leaf
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Isocenterplane
MLCplane
Sourceplane
MLCopening
Scattered Intensity from the MLC
openingoutsideyxif
openinginsideyxifyxBi ),(1
),(0),(
Distance from pencil beam
intensity
0 55 1010
Scattered intensity from the leaf Smlc
i
ii tyxByxB ),(),(
mlcmlc
planeisocenter
mlc
mlc
SB
dydxyyxxSyxB
yx
'')','()','(
),(
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Pencil Beam Convolution
d1
d2
pencil beam
pencil beam kernel dose distribution
Intensity-modulated field
Dose Calculation Algorithm for IM Fields
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Tongue-and-groove Between leaf transmission
Comparison Between Calculation and Measurement
Film Calc.
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A Field used in a Nasopharynx Treatment
Ant Post
Sup
Inf
Film Plan
6 MVx
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7-field Nasopharynx - cylindrical phantom/coronal
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PlanFilm
Dosimetry (Lung - PA field)
Film - Plan
2 cm
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T&G Source
MLC scatter
Lung PA-field: Dose difference (film – calc.)
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6-field to 72 Gy, 6 cone-down fields to 81 Gy
target
Rectal wall
bladderwall
81-Gy Prostate Plans – 3D Conformal Plan
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3D Conformal Plan - Prostate 81 Gy
0
25
50
75
100
Vol
ume
(%)
0 25 50 75 100Dose (Gy)
femurs
bladder
target
rectum
D=77GyV=90%
D=75GyV=30%
D=72Gy
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81 Gy - Transverse
Conventional Plan
8640 7560 250050008100
IMRT Plan
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Prostate 81-Gy Plans
0
25
50
75
100V
olum
e (%
)
0 25 50 75 100
optimized
standard
0
25
50
75
100
0 25 50 75 100
0
25
50
75
100
70 80 90rectum
target
0
25
50
75
100
Vol
ume
(%)
0 25 50 75 100Dose (Gy)
bladder
0
25
50
75
100
0 25 50 75 100Dose (Gy)
femur
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0
20
40
60
80
100P
erce
nt P
SA
Rel
apse
-fre
e Su
rviv
al
0 12 24 36 48 60 72 84 96 108
Months
75.6 Gy (193)
81 Gy (65)
64.8-70.2 (134)
UnfavorableT1-3PSA >10; Gleason >7
p=0.05
p=0.006
21%
66 %
43%
PSA Relapse-free Survival in Unfavorable Patients by Dose
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80
85
90
95
Per
cen
t G
rad
e 2
Rec
tal T
oxic
ity
0 24 48 72 96 120
Months
5
10
15
20
p< 0.001
81 Gy IMRT (171)
64.8-70.2 Gy (364)
81 Gy (61)
75.6 Gy (446)
Grade 2 Rectal Toxicity by Dose
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NasopharynxTraditional Treatment
e e
50 Gy
70 Gy
77 Gy
PTV Cord, Brainstem
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MSKCC Conformal Treatment
50 Gy
70 Gy
77 Gy
PTV Cord, Brainstem
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IMRT Treatment
50 Gy
70 Gy
77 Gy
PTV Cord, Brainstem
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Traditional Conformal IMRT
50 Gy 70 Gy 77 Gy
Comparison of nasopharynx treatment techniques
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Posterior Field in a Nasopharynx Treatment
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Nasopharynx IMRT
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IMRT 3D Conformal Traditional
3D dose display of the 65 Gy isodose surface
Spinal cord/Brain stem Eye PTV
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0
20
40
60
80
100
0 2000 4000 6000 8000DOSE (cGy)
%V
OL
UM
E
Conf .Trad .IMRT
PTV CORD
0
20
40
60
80
100
0 2000 4000 6000 8000DOSE (cGy)
%V
OL
UM
E
Conf .Trad .IMRT
0
20
40
60
80
100
0 2000 4000 6000 8000DOSE (cGy)
Conf .Trad .IMRT
MANDIBLE
0
20
40
60
80
100
0 2000 4000 6000 8000
DOSE (cGy)
Conf.Trad.IMRT
PAROTID
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Fusion of CT, MRI, and PET Scans for IMRT Planning
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30 36 42 48 54 Gy
PTV54 Parotid
30 36 42 48 54 Gy30 36 42 48 54 Gy
PTV54 Parotid
Parotid Sparing in Parotid Sparing in N0 diseaseN0 disease
PTV
0
20
40
60
80
100
0 20 40 60 80
Dose (Gy)
%V
olu
me
No PS
PS
PAROTID
0
20
40
60
80
100
0 20 40 60 80
Dose (Gy)
%V
olu
me
No PS
PS
54
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PTV70 PTV54
40 47 55 63 70 Gy40 47 55 63 70 Gy
Cochlea
0
20
40
60
80
100
0 20 40 60 80
Dose (Gy)
% V
olu
me
Optimization Parameters and Target -Normal Tissue Proximity
PTV70
Lt. Cochlea
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IMRT for Nasopharynx – Hong Kong
Kam et al, IJROBP 60, 1440 (2004)
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IMRT for Head/Neck - Finland
Saarilahti et al, Radiother Oncol 74, 251 (2005)
Stimulated secretion
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108 104 105090100
IMRT
Wedged pair
Breast Plans - IMRT vs. Wedged Pair
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0
20
40
60
80
100
0 20 40 60 80 100 120Dose (%)
Vo
lum
e (%
)
Standard
Intensity Modulated
DVH: Coronary Artery Region
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DVH: Contralateral Breast
Standard
IMRT
Dose (%)
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Whole Abdomen Treatment (planning study only)
Target: whole abdomen.
Critical Organs: bones, kidneys, liver.
conventional
AP-PA
Extended distance
IMRT
Standard distance
Two isocenters
Nine fields
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108 506090100
coronal sagittal
Whole Abdomen - Isodose Distributions
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PTV
Liver
Kidneys
Bones
IMRTAP-PA
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Summary
• Optimized IMRT plans can produce better dose distributions than conventional conformal plans, in terms of both target coverage and normal organ sparing.
• Delivery of IMRT with a conventional MLC is practical, either in continuous or in step-and-shoot mode.
• Comprehensive QA is needed, for machine performance and patient-specific dosimetry.
• IMRT has been implemented for prostate, head/neck, breast and other sites. Early experience on prostate and nasopharynx thus far show encouraging results.