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.