22 chap 20 intensity modulated radiation therapy
DESCRIPTION
TRANSCRIPT
1
Chapter 20Intensity Modulated Radiation Therapy
2
Goals of Conformal Radiation Therapy
Reduce normal tissue toxicity
• Conform dose to the tumor
•
• Tumor dose escalation
improve local tumor control
3
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
4
Outline
• Optimization (Inverse Planning)
• Delivery
• Quality Assurance
• Clinical Applications
5
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.
6
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.)
7
(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.)
8
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|.
9
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
10
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.
11
Examples of Optimization Methods
• Deterministic:
Gradient, Conjugate gradient (Eclipse,Konrad).
Maximum likelihood (Brainlab, nuclear medicine).
• Stochastic:
Simulated annealing (NOMOS).
Genetic algorithm (Brachy therapy).
12
5-field to 81 Gy
Prostate IMRT plan
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
Skin-Flash for Intensity-Modulated Field
Simple, flat extension
skin
28
Detection of unexpected hotspots
PTV
Beam II
Beam III
Beam I
A
BPTVCordHotspots > 120%location > 3 cm from PTV
29
• 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
30
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.
31
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.
32
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.
33
MIMiC
Multileaf
Intensity
Modulating
Collimator
34
Individual leaf controls opening
MIMiC
Multileaf
Intensity
Modulating
Collimator
35
Tomotherapy
36
Delivery of IMRT with a Multileaf Collimator (MLC)
MLC mounted on the head of a linac Close-up view of the leaves
37
directionof motion
Left-leafRight-leaf
beam-ontime
P
Delivery of IMRT with a Conventional MLCsliding window method
radiation
38
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 =
39
The Posterior Field in a Prostate Treatment
40
An Intensity-modulated Field Delivered with a Conventional MLC
For cord protection
41
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
42
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
43
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
44
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
45
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
46
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
47
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
48
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
51
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.
52
• 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)
• 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
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’
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
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
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
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
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
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.
61
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)
62
- 0.5 mm
+ 0.5 mm
- 0.2 mm
+ 0.2 mm
errors introducedFilm test
1 mm bands
63
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)
64
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)
65
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
66
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%.
67
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
68
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
69
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
72
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.
73
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
74
tonguegroove
BEAM
Between leaf transmission
BEAM
Tongue-and/or-groove effect
75
Ring-shaped Field
first segmentsecond segment
76
Varian Clinac-2100C MLC
tongue&
groove
77
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.
78
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
79
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
80
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
'')','()','(
),(
81
Pencil Beam Convolution
d1
d2
pencil beam
pencil beam kernel dose distribution
Intensity-modulated field
Dose Calculation Algorithm for IM Fields
82
Tongue-and-groove Between leaf transmission
Comparison Between Calculation and Measurement
Film Calc.
83
A Field used in a Nasopharynx Treatment
Ant Post
Sup
Inf
Film Plan
6 MVx
84
7-field Nasopharynx - cylindrical phantom/coronal
85Overlay Difference
PlanFilm
Dosimetry (Lung - PA field)
Film - Plan
2 cm
86
T&G Source
MLC scatter
Lung PA-field: Dose difference (film – calc.)
89
6-field to 72 Gy, 6 cone-down fields to 81 Gy
target
Rectal wall
bladderwall
81-Gy Prostate Plans – 3D Conformal Plan
90
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
91
81 Gy - Transverse
Conventional Plan
8640 7560 250050008100
IMRT Plan
92
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
93
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
94
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
95
NasopharynxTraditional Treatment
e e
50 Gy
70 Gy
77 Gy
PTV Cord, Brainstem
96
MSKCC Conformal Treatment
50 Gy
70 Gy
77 Gy
PTV Cord, Brainstem
97
IMRT Treatment
50 Gy
70 Gy
77 Gy
PTV Cord, Brainstem
98
Traditional Conformal IMRT
50 Gy 70 Gy 77 Gy
Comparison of nasopharynx treatment techniques
99
Posterior Field in a Nasopharynx Treatment
100
Nasopharynx IMRT
101
IMRT 3D Conformal Traditional
3D dose display of the 65 Gy isodose surface
Spinal cord/Brain stem Eye PTV
102
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
104
Fusion of CT, MRI, and PET Scans for IMRT Planning
105
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
106
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
107
IMRT for Nasopharynx – Hong Kong
Kam et al, IJROBP 60, 1440 (2004)
108
IMRT for Head/Neck - Finland
Saarilahti et al, Radiother Oncol 74, 251 (2005)
Stimulated secretion
109
108 104 105090100
IMRT
Wedged pair
Breast Plans - IMRT vs. Wedged Pair
110
0
20
40
60
80
100
0 20 40 60 80 100 120Dose (%)
Vo
lum
e (%
)
Standard
Intensity Modulated
DVH: Coronary Artery Region
111
DVH: Contralateral Breast
Standard
IMRT
Dose (%)
117
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
118
108 506090100
coronal sagittal
Whole Abdomen - Isodose Distributions
119
PTV
Liver
Kidneys
Bones
IMRTAP-PA
120
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.