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Planning. Clinical Aspects. Radiobiological Aspects. Delivery. Arthur Boyer Stanford University School of Medicine Stanford, California. Verification. Conventional planning. Time. IMRT planning. Complexity. Establish the Correspondence Between Output and Input. Output. Input.

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  • Clinical Aspects

  • Radiobiological Aspects

Delivery

Arthur Boyer

Stanford University School of Medicine

Stanford, California

  • Verification


Conventional planning

Time

IMRT planning

Complexity


Establish the Correspondence Between Output and Input

Output

Input

Specify quantities that describe a patient’s

quality of life (e.g., Karnofsky status)

Desired

output

Specify TCP and NTCP--biological model

Specify a dose distribution--dose based model


Procedures of Inverse Planning Computation

Optimal Input

Output

Construct an objective function

F = F (input parameters) = F (w1,w2,w3,….,wJ)

Optimize F and find the optimal beam profiles

Convert beam profiles into MLC leaf sequences


Dosimetric:

F = [Dc(1)-D0(1)]2 +[Dc(2)-D0(2)]2 + ...

w1

Beam profile

Dc(1)

D0(1)

Dc(2)

D0(2)


  • ~2000 pencil beam weights, non-linear system.

  • It should, ideally, include all of our knowledge of radiotherapy: dosimetry based and biological model based objective function.


  • Matrix Inversion

  • Iterative methods

  • Computer simulated annealing

  • Genetic optimization

  • Filtered backprojection


n=4

F = S [Dc(n)-D0(n)]2

Calculated dose

n=1

w3

w4

Prescribed dose

3

4

D3

D4

1.0

0.5

w2

1

2

D1

D2

w1

1.0

1.0


w “measurement” of radiation treatment.4

w3

n=4

F = S [Dc(n)-D0(n)]2

n=1

D3

D4

w2

D1

D2

w1

D1= w1 d11+ w2 d21 + w3 d31 + w4 d41

D2= w1 d12+ w2 d22 + w3 d32 + w4 d42

D3= w1 d13+ w2 d23 + w3 d33 + w4 d43

D4= w1 d14+ w2 d24 + w3 d34 + w4 d44

  • Direct Matrix Inversion


A Simple Iterative Algorithm “measurement” of radiation treatment.

Dose to point n:

1

dn = w1d1n + w2d2n + w3d3n

target

organ

2

3


Algebraic Iterative Method: “measurement” of radiation treatment.

Initial beam profiles

Calculate dose at a voxel n

Compare Dc(n) with D0(n)

n+1

Dc(n) > D0(n) ?

Yes

No

Decrease wi

Increase wi


Algebraic Iterative Method: “measurement” of radiation treatment.

n=6

F = S [Dc(n)-D0(n)]2

Calculated dose

n=1

0.5

0.5

Prescribed dose

1.0

1.0

1.0

1.0

0.5

1.0

0.5

1.0

1.0

0.5

1.0

1.0

1.0

1.0

0.5


Algebraic Iterative Method: “measurement” of radiation treatment.

Iteration step = 5

Iteration step = 1

0.51

0.45

0.50

0.49

1.01

0.95

0.50

0.99

1.00

0.50

0.95

0.99

0.90

0.44

0.97

0.49

1.02

1.01

0.99

1.00

0.50

0.50


Objective function “measurement” of radiation treatment.

Iteration step = 10

i=6

F = S [Dc(i)-D0(i)]2

0.30

0.51

0.42

i=1

0.25

0.20

0.15

0.10

0.51

1.02

0.92

0.05

0.91

0.41

0.82

0

20

40

80

60

1.02

0.92

100

0

0.51

Iteration step

Algebraic Iterative Method:


Planning parameters
Planning Parameters “measurement” of radiation treatment.

  • Number of beams

  • Beam/Coll orientation

  • Isocenter placement

  • Beamlet size

  • Intensity levels

  • Margins & Targets

  • Tuning structure


Beam orientation
Beam Orientation “measurement” of radiation treatment.

  • Coplanar vs Non-coplanar

    • Ease of setup

    • Ease of planning

    • Speed of treatment

  • Equi-spaced vs Selected angles

    • Entrance through table/immobilization device


Beam orientation1
Beam Orientation “measurement” of radiation treatment.

9 equi-spaced beams


Beam orientation2
Beam Orientation “measurement” of radiation treatment.

9 selected beams


Collimator orientation
Collimator Orientation “measurement” of radiation treatment.


Collimator orientation1
Collimator Orientation “measurement” of radiation treatment.

180o collimator angle


Collimator orientation2
Collimator Orientation “measurement” of radiation treatment.

Collimator angle


Isocenter placement
Isocenter Placement “measurement” of radiation treatment.

  • Issues

    • Can a better plan be achieved by isocenter placement ?

    • Dosimetry and/or QA

    • Patient setup


Isocenter placement1
Isocenter Placement “measurement” of radiation treatment.

Isocenter in geometric center of targets


Isocenter placement2
Isocenter Placement “measurement” of radiation treatment.

Isocenter in geometric center of GTV


Beamlet size
Beamlet Size “measurement” of radiation treatment.

Yi et al. 2000


Intensity levels
Intensity Levels “measurement” of radiation treatment.

Lehmann et al. 2000


Margins targets
Margins & Targets “measurement” of radiation treatment.


Tuning structure
Tuning Structure “measurement” of radiation treatment.

  • A structure added to control the dose distribution in IMRT plans

    • Reduce normal tissue dose

    • Reduce/Increase target dose


Tuning structure1
Tuning Structure “measurement” of radiation treatment.


Tuning structure2
Tuning Structure “measurement” of radiation treatment.


Summary of planning parameters
Summary of Planning Parameters “measurement” of radiation treatment.

  • Number of beams

  • Beam/Coll orientation

  • Isocenter placement

  • Beamlet size

  • Intensity levels

  • Margins & Targets

  • Tuning structure


Verification “measurement” of radiation treatment.


Planning System Commissioning “measurement” of radiation treatment.

a

b

c

d

e

f

specially designed intensity patterns


Planning System Commissioning “measurement” of radiation treatment.

90%

90%

50%

50%

40%

10%

20%

20%

40%

70%

70%

10%

80%

80%

90%

90%

30%

50%

30%

10%

10%

50%

90%

90%

Calculated Measured

specially designed intensity patterns


Patient Specific Field Verification “measurement” of radiation treatment.

Quantitative Comparison of Two Fluence Maps

  • Maximum difference in

  • pixel values---local quantity.

  • Correlation coefficient—

  • global quantity.


Quantitative film analysis

Film “measurement” of radiation treatment.

QUANTITATIVE FILM ANALYSIS

Courtesy, Tim Solbert


Quantitative Film Analysis “measurement” of radiation treatment.

White = measurement

Red = calculation

Courtesy, Tim Solberg


Quantitative film analysis profiles

Calculated “measurement” of radiation treatment.

Measured

Quantitative Film Analysis - Profiles

Horizontal and vertical profiles of measured data, calculated data, and  index.

Courtesy, Tim Solberg


40 cm “measurement” of radiation treatment.

1.5 cm

4.5 cm

30 cm

Measurement Tissue Equivalent Phantom


50% “measurement” of radiation treatment.

70%

90%

-1.8%

1mm

-3.5%

2mm

Cylindrical Phantom Dose Verification

Measured in Plane of Isocenter


BANG gel Dosimetry “measurement” of radiation treatment.

Courtesy, Tim Solberg


Periodic IMRT QA “measurement” of radiation treatment.


Periodic IMRT QA “measurement” of radiation treatment.

Test Pattern with Leaf Error

Test Pattern after leaf replacement and MLC calibration


IMRT MU Checks “measurement” of radiation treatment.

QUALITY ASSURANCE OF IMRT TREATMENT PLAN

DEPARTMENT OF RADIATION ONCOLOGY ,STANFORD UNIVERSITY SCHOOL OF MEDICINE

PATIENT NAME: xxx, xxxxxxx

PATIENT ID: xxx-xx-xx

TPS PLAN #: 2512

Treatment Machine: LA7

Beam Energy: 15 MV

Calibration Setup: SSD

Delivery Mode: Step and Shoot

Beamlet Size: 1.0 x 1.0 (cm x cm)

Calibration Factor: 1.000

Isocenter Dose Verification Report

Field MU x1 x2 y1 y2 SSD beam-dose

F 180-000 170 7.80 6.80 4.20 16.20 88.79 50.2

F 180-080 118 4.80 6.80 4.20 17.20 82.03 40.6

F 180-145 108 8.00 1.00 5.00 18.00 90.87 24.0

F 180-145a 101 1.00 8.00 4.00 18.00 90.87 17.9

F 180-215 80 9.00 0.00 3.00 18.00 90.49 1.6

F 180-215a 107 2.00 7.00 5.00 18.00 90.49 48.7

F 180-280 115 6.80 5.80 4.20 17.20 81.68 41.2


IMRT MU Checks “measurement” of radiation treatment.

Calculated Isocenter Dose: 224.2 cGy

TPS Isocenter Dose: 221.3 cGy

Percentage Difference: 1.3 (%).

Leaf Sequence Verification Report

Field ID Gantry Angle Correlation Coefficient Maximum Difference

1 0 1.0000 0.5112 (%)

2 80 1.0000 0.4017 (%)

3 145 1.0000 0.6799 (%)

4 215 1.0000 0.7275 (%)

5 280 1.0000 0.4034 (%)

Physicist: _________________________

DATE: 7/20/2001


Isocenter Setup Verification with DRRs “measurement” of radiation treatment.

Anterior Isocenter Verification


Isocenter Setup Verification with DRRs “measurement” of radiation treatment.

Lateral Isocenter Verification


Align DRR with EPID Image To Verify Patient Positioning “measurement” of radiation treatment.

DRR Image

AmSi EPID Image


DELIVERY OF IMRT BY COMPUTER CONTROLLED MLC “measurement” of radiation treatment.


1 cm “measurement” of radiation treatment.

m

1 cm

Tl,m,k

Beam Modulation Patterns



Velocity Modulation “measurement” of radiation treatment.

Fluence Profile Required for IMCRT


Velocity Modulation “measurement” of radiation treatment.

.

(x) =  (x) [tA(x) - tB(x)]

B

A


Velocity Modulation “measurement” of radiation treatment.

.

(x) =  (x) [tA(x) - tB(x)]

 (x)

.

(x) =

(x)

(x) = tA(x) - tB(x) > 0


Gradient Regions Between Extrema “measurement” of radiation treatment.

“Velocity” leaf sequencing


250 “measurement” of radiation treatment.

200

Leaf A

(x)

150

100

50

0

Leaf B

0

5

10

15

20

25

30

35

40

Position, X (cm)

Interpretation as Trajectories

“Velocity” leaf sequencing


250 “measurement” of radiation treatment.

200

150

(x)

100

50

0

0

5

10

15

20

25

30

35

40

Position, X (cm)

Reflection Operation to Remove Time Reversals

(x) = (x) - 

“Velocity” leaf sequencing


250 “measurement” of radiation treatment.

200

150

(x)

100

50

0

0

5

10

15

20

25

30

35

40

Position, X (cm)

Translation Operation to Remove Discontinuities

(x) = (x) + (x)

“Velocity” leaf sequencing


Reflection Operation to Remove Time Reversal “measurement” of radiation treatment.

250

200

150

(x)

100

50

0

0

5

10

15

20

25

30

35

40

Position, X (cm)

“Velocity” leaf sequencing


250 “measurement” of radiation treatment.

Leaf A

200

150

(x)

100

Leaf B

50

0

0

5

10

15

20

25

30

35

40

Position, X (cm)

Shear Operation to Remove Infinite Velocity

(x) = (x) + x/vmax

“Velocity” leaf sequencing


“measurement” of radiation treatment. (x)

.

(x) =

(x)

d(x) =

dx

d (x)/dx

.

(x)

Differentiation of Opening Time

“Velocity” leaf sequencing


Differentiation of Shear Operation “measurement” of radiation treatment.

(x) = (x) + x/vmax

d(x) = d(x) + 1

dx dx  vmax

d(x) = 1

dx v(x)

“Velocity” leaf sequencing


d “measurement” of radiation treatment. (x)/dx

1

1

.

+

=

vmax

v(x)

(x)

vmax

=

v(x)

d (x)/dx

.

vmax

1 

(x)

Substitutions to Obtain Velocity Relation

“Velocity” leaf sequencing


80 “measurement” of radiation treatment.

70

Leaf A

60

50

Time (sec)

40

30

20

Leaf B

10

0

0

5

10

15

20

25

30

35

Position (cm)

“Velocity” leaf sequencing


Step and Shoot “measurement” of radiation treatment.

“Step-and-Shoot” leaf sequencing


5.0 “measurement” of radiation treatment.

4.0

3.0

Intensity Level

2.0

1.0

12

13

0.0

14

-3

Leaf Pair

15

-2

-1

0

+1

+2

+3

x-Position


-3 -2 -1 0 +1 +2 +3

-3 -2 -1 0 +1 +2 +3

Leaf Pair 12

Leaf Pair 13

-3 -2 -1 0 +1 +2 +3

-3 -2 -1 0 +1 +2 +3

Leaf Pair 14

Leaf Pair 15


A +3

B

5

5

1

4

8

4

4

2

5

7

3

Levels

3

3

6

6

2

2

7

1

1

8

0

-3 -2 -1 0 +1 +2 +3

-

-

-

1

2

3

Position

Instance 1


A +3

B

5

5

1

4

8

4

4

2

5

7

3

Levels

3

3

6

6

2

2

7

1

1

8

0

-3 -2 -1 0 +1 +2 +3

-

-

-

1

2

3

Position

Instance 2


B +3

A

5

5

1

4

8

4

2

4

7

5

3

3

Levels

3

6

7

6

2

2

7

1

1

8

0

-3 -2 -1 0 +1 +2 +3

-

-

-

1

2

3

3

2

1

Position

Instance 3


B +3

A

5

5

1

4

8

4

2

4

7

5

3

3

Levels

3

6

7

6

2

2

7

1

1

8

0

-3 -2 -1 0 +1 +2 +3

-

-

-

1

2

3

3

2

1

Position

Instance 4


B +3

A

8

5

7

6

6

7

5

5

1

4

4

2

4

7

3

3

Levels

3

2

2

1

1

8

0

-3 -2 -1 0 +1 +2 +3

-

-

-

1

2

3

3

2

1

Position

Instance 5


B +3

A

5

5

1

4

8

4

2

4

7

5

3

3

Levels

3

7

6

6

2

2

7

1

1

8

0

-3 -2 -1 0 +1 +2 +3

-

-

-

1

2

3

3

2

1

Position

Instance 6


B +3

A

5

5

1

4

8

4

2

4

7

5

3

3

Levels

3

7

6

6

2

2

7

1

1

8

0

-3 -2 -1 0 +1 +2 +3

-

-

-

1

2

3

3

2

1

Position

Instance 7


B +3

A

5

5

1

4

8

4

2

4

7

5

3

3

Levels

3

7

6

6

2

2

7

1

1

8

0

-3 -2 -1 0 +1 +2 +3

-

-

-

1

2

3

3

2

1

Position

Instance 8


B +3

A

8

5

7

6

6

7

5

1

4

4

5

2

4

7

3

3

Levels

3

2

2

1

1

8

0

-3 -2 -1 0 +1 +2 +3

-

-

-

1

2

3

3

2

1

Position

Instance 9


B +3

A

5

1

4

8

4

5

2

4

7

5

3

3

Levels

3

7

6

6

2

2

7

1

1

8

0

-3 -2 -1 0 +1 +2 +3

-

-

-

1

2

3

3

2

1

Position

Instance 10


B +3

A

5

5

1

4

8

4

2

4

7

5

3

3

Levels

3

7

6

6

2

2

7

1

1

8

0

-3 -2 -1 0 +1 +2 +3

-

-

-

1

2

3

3

2

1

Position

Instance 11


B +3

A

5

5

1

4

8

4

2

4

7

5

3

3

Levels

3

7

6

6

2

2

7

1

1

8

0

-3 -2 -1 0 +1 +2 +3

-

-

-

1

2

3

3

2

1

Position

Instance 12


B +3

A

5

5

1

4

8

4

2

4

7

5

3

3

Levels

3

7

6

6

2

2

7

1

1

8

0

-3 -2 -1 0 +1 +2 +3

-

-

-

1

2

3

Position

Instance 13


B +3

A

5

5

1

4

8

4

2

4

7

5

3

3

Levels

3

7

6

6

2

2

7

1

1

8

0

-3 -2 -1 0 +1 +2 +3

-

-

-

1

2

3

Position

Instance 14


B +3

A

5

5

1

4

8

4

2

4

7

5

3

3

Levels

3

7

6

6

2

2

7

1

1

8

0

-3 -2 -1 0 +1 +2 +3

-

-

-

1

2

3

3

2

1

Position

Instance 15


B +3

A

5

5

1

4

8

4

2

4

7

5

3

3

Levels

3

7

6

6

2

2

7

1

1

8

0

-3 -2 -1 0 +1 +2 +3

-

-

-

1

2

3

3

2

1

Position

Instance 16


Leaf Pair 12 +3

Leaf Pair 13

Leaf Pair 14

Leaf Pair 15


15 +3

1&2

14

13

12


15 +3

3&4

14

13

12


15 +3

5&6

14

13

12


15 +3

14

13

7&8

12


15 +3

14

13

9&10

12


15 +3

14

13

11&12

12


15 +3

14

13

12

13&14


15 +3

14

13

12

15&16


15 +3

14

13

12

17&18


15 +3

14

12

13

19&20


File +3Structure


Static File Structure +3

File Rev = G

Treatment = Static

Last Name = Collimator

First Name = M.L.

Patient ID = 555-1212

Number of Fields = 13

Number of Leaves = 52

Tolerance = 0.3

Field = Left Lung

Index = 0.0

Carriage Group = 1

Operator = DNR

Collimator = 0.0

Leaf 1A = 0.00

Leaf 2A = 1.00

Leaf 3A = 2.00

Leaf 4A = 3.00

Leaf 5A = 4.00

Leaf 6A = 5.00

Leaf ...

For conventional MLC treatments, the STATIC mode is used.


Dynamic Treatment Files +3

File Rev = G

Treatment = Dynamic dose

Last Name = Patient

First Name = QA

Patient ID = 555-1212

Number of Fields = 12

Number of Leaves = 120

Tolerance = 0.3

Field = Shape1

Index = 0.000

Carriage Group = 1

Operator = DNR

Collimator = 0.0

Leaf 1A = 0.00

Leaf 2A = 1.00

Leaf 3A = 2.00

Leaf 4A = 3.00

Leaf 5A = 4.00

Leaf 6A = 5.00

Leaf ...

  • Identical file format and syntax as for static treatment

  • Each specified leaf pattern is correlated to value of some Clinac parameter

  • “Treatment = ” and “Index = ” file entries determine behavior

Field = Shape2

Index = 0.050

Carriage Group = 1

Operator = DNR

Collimator = 0.0

Leaf 1A = 0.00

Leaf 2A = 1.00

Leaf 3A = 2.00

Leaf 4A = 3.00

Leaf 5A = 4.00

Leaf 6A = 5.00

Leaf ...

Field = Shape3

Index = 0.072

Carriage Group = 1

Operator = DNR

Collimator = 0.0

Leaf 1A = 0.00

Leaf 2A = 1.00

Leaf 3A = 2.00

Leaf 4A = 3.00

Leaf 5A = 4.00

Leaf 6A = 5.00

Leaf ...


Treatment Field Index +3

File Rev = G

Treatment = Dynamic Dose

Last Name = John

First Name = Smith

Patient ID = 1234

Number of Fields = 20

Number of Leaves = 80

Tolerance = 0.1

Field = 1 of 20

Index = 0.0000

Carriage Group = 1

Operator = Physicist

Collimator = 180.0

Leaf 1A = 0.00

Leaf 2A = 0.00

Leaf 3A = 3.00

The file must specify the total number of instances that will be used.


Treatment Field Index +3

File Rev = G

Treatment = Dynamic Dose

Last Name = John

First Name = Smith

Patient ID = 1234

Number of Fields = 20

Number of Leaves = 80

Tolerance = 0.1

Field = 1 of 20

Index = 0.0000

Carriage Group = 1

Operator = Physicist

Collimator = 180.0

Leaf 1A = 0.00

Leaf 2A = 0.00

Leaf 3A = 3.00

Varian has 52-leaf, 80-leaf, and 120-leaf MLCs. The file must identify the MLC.


Treatment Field Index +3

File Rev = G

Treatment = Dynamic Dose

Last Name = John

First Name = Smith

Patient ID = 1234

Number of Fields = 20

Number of Leaves = 80

Tolerance = 0.1

Field = 1 of 20

Index = 0.0000

Carriage Group = 1

Operator = Physicist

Collimator = 180.0

Leaf 1A = 0.00

Leaf 2A = 0.00

Leaf 3A = 3.00

Tolerance parameter is in units of centimeters.


Treatment Field Index +3

File Rev = G

Treatment = Dynamic Dose

Last Name = John

First Name = Smith

Patient ID = 1234

Number of Fields = 20

Number of Leaves = 80

Tolerance = 0.1

Field = 1 of 20

Index = 0.0000

Carriage Group = 1

Operator = Physicist

Collimator = 180.0

Leaf 1A = 0.00

Leaf 2A = 0.00

Leaf 3A = 3.00

Dose (MU) fraction ranging from 0.0 (beginning of treatment) to 1.0 (end of treatment).


Treatment Field Index +3

File Rev = G

Treatment = Dynamic Dose

Last Name = John

First Name = Smith

Patient ID = 1234

Number of Fields = 20

Number of Leaves = 80

Tolerance = 0.1

Field = 1 of 20

Index = 0.0000

Carriage Group = 1

Operator = Physicist

Collimator = 180.0

Leaf 1A = 0.00

Leaf 2A = 0.00

Leaf 3A = 3.00

Dose (MU) fraction ranging from 0.0 (beginning of treatment) to 1.0 (end of treatment). Leaf positions (cm) are specified as a function of dose fraction.


File Footer - CRC +3

Leaf 51B = 2.25

Leaf 52B = 2.25

Leaf 53B = 1.75

Leaf 54B = -6.20

Leaf 55B = -6.20

Leaf 56B = -6.20

Leaf 57B = -6.20

Leaf 58B = -6.20

Leaf 59B = -6.20

Leaf 60B = -6.20

Note = 0

Shape = 0

Magnification = 0.00

CRC = CF95

â


File Structure +3

CRC

  • Ensures file data integrity

    • Against file corruption

    • Against unintentional editing outside of authorized data editing tools

  • Uses industry-standard algorithm


Step-and-shoot +3

Dynamic delivery

fMU=0.0

1st MLC

position

fMU=0.0

1st MLC

position

step

fMU=0.14

1st MLC

position

fMU=0.14

2nd MLC

position

shoot

fMU=0.14

2nd MLC

position

fMU=0.25

3rd MLC

position

step

fMU=0.25

2nd MLC

position

fMU=0.33

4th MLC

position

shoot



Planning +3

180o

140o

Immobilization

Aquaplast

Position Verification

Ximatron

Network File Management

Varis

Plan Verification

Wellhöfer

Structure Segmentation

AcQsim

Inverse Planning

Corvus

CT/MRI Acquisition

PQ 5000

240o

100o

260o

60o

300o

Delivery

20o

340o

Treatment Delivery

C-Series Clinac Dynamic MLC

IMRT Process



180 +3o

140o

220o

100o

260o

60o

300o

20o

340o

Example

9-field Head and neck Treatment


80% +3

90%

55%


85% +3

90%

55%


55% +3

80%

90%


80% +3

90%

55%


90% +3

55%

85%


80% +3

80%

90%

55%


Imrt clinical aims in prostate cancer
IMRT: Clinical Aims in +3Prostate Cancer

  • Improve conformality; dose escalation

  • Reduce high dose volumes in rectalwall & bladder

  • Reduced small bowel dose in nodal therapy


80 +3o

280o

320o

40o

0o

Prostate

Nodes

Irradiate Prostate and Nodal Region in Pelvis


Imrt prostate cancer
IMRT: Prostate Cancer +3

SV

CTV

Rectum

Bladder


GU or GI Toxicity +3

80

70

60

IMRT-Prostate and

50

Nodes

40

3D-Prostate and Nodes

30

20

10

0

0

1

2

3

P = 0.002

Maximum RTOG Score

Steven Hancock, 2002


IMRT: Prostate and Nodes +3

Intensity Modulated Plan

Field Intensity Maps


70% +3

50%

60%

80%

30%

20%

40%

10%

90%

40%


80% +3

50%

70%

30%

60%

20%

90%

10%

40%


80% +3

50%

70%

60%

90%

40%

30%

20%

10%


3d crt v imrt dose delivery prostate and seminal vesicles
3D-CRT v. IMRT: Dose Delivery +3Prostate and Seminal Vesicles

Organ 3D CRT IMRT

Mean±SD Mean Max Min

Small field:

Prostate: 74.0 ± 1.5 75.7 82.8 65.3

Seminal Vesicles: 50.0 ± 1.0 63.5 79.1 50.1

Large field:

Prostate: 50.0 ± 1.0 55.1 61.8

+ Boost: 70.0 ± 1.4 77.3 87.7

Nodes: 50.0 ± 1.0 54.2 63.5

Steven Hancock, 2002


P = 0.05 +3

Steven Hancock, 2002


Prostate imrt prescription doses
Prostate IMRT: Prescription Doses +3

MSKCC: Dose to 98 ± 2% of CTV: 81. Gy

Dose to 95% of PTV: 78. Gy

5% of Bladder > 83. Gy

25-30% Rectum > 75.6 Gy

Dose per fraction 1.8 Gy

2 yr risk of GI bleeding: 2% IMRT v. 10% 3D-CRT

Zelefsky et al. Radiother & Oncol 55:241


IMRT for Gynecological Cancers +3

  • CTV in a cervical cancer

  • pt s/p hysterectomy

  • Note the posteriorly and

  • laterally placed lymph

  • nodes regions

  • The central region is

  • where the small bowel

  • is now located

Mundt, 2002


Intensity Modulated-WPRT +3

100%

90%

70%

50%

Mundt, 2002


100 +3

90

80

70

60

50

40

30

20

10

0

Grade 0

Grade 1

Grade 2

Grade 3

Acute GI toxicity IM-WPRT vs. WPRT

IM-WPRT

WPRT

P = 0.002

Mundt et al. Int J Radiat Oncol Biol Phys 52:1330-1337, 2002


Chronic +3 GI Toxicity IM-WPRT vs. WPRT

90%

80%

70%

60%

50%

40%

30%

20%

10%

0%

0

1

2

3

IM-WPRT

WPRT

Multivariate analysis controlling for age, chemo, stage and site,

IMRT remained statistically significant ( p = 0.002)

Mundt et al. ASTRO 2002 (New Orleans)


SPECT-CT Image Fusion +3

Based on image fusion, highest intensity BM was contoured and used in planning process

Mundt, 2002


Isodose Comparison – Mid Pelvis +3

BM-Sparing Plan

100%

90%

70%

50%

100%

90%

70%

50%

IM-WPRT Plan

Mundt, 2002



Tumor Motion During Respiraton cone-beam CT.

Courtesy, David Faffray


Rt Lung cone-beam CT.

heart

cord

Lt Lung


Conclusions
Conclusions cone-beam CT.

  • IMRT with MLCs can be implemented in the clinic.

  • “Step-and-Shoot” or sliding window leaf sequence with dynamic MLCs can be used for IMRT.

  • Dose distributions can be computed and delivered that provide treatment options for particularly difficult presentations.

  • Imaging is required for variations in daily set-up.

  • Special procedures are required to compensation for respiration motion



Phenomenological Lyman Model for NTCP cone-beam CT.

(Note: The Lyman model does not explicitly take fraction size into consideration.)


Lyman Model for NTCP cone-beam CT.

For a biological target uniformly irradiated to dose D, the upper limit of integration is expressed as

where is the dose at which the complication probability is 50%, and m is a slope parameter.


Lyman Model for NTCP cone-beam CT.

For a uniformly irradiated partial volume,

define

then the upper limit of integration is


Lyman Model for NTCP cone-beam CT.

for n > 0

The ntcp curve moves to the right vs. D for partial volume irradiation.


Lyman Model : non-uniform irradiation cone-beam CT.

  • Multiple sub-volumes, at different doses di are each translated to effective sub-volumes at some reference dose, such as the maximum dose in a dvh or TD50(1).

  • The relationship must be reducible, i.e., the NTCP of two equal sub-volumes at a given dose must be the same as that of a single volume of twice the size at the same dose.

[Kutcher–Burman]


Equivalent Uniform Dose cone-beam CT.

Equivalent Uniform Dose (EUD) is the uniform dose that gives the same cell kill as a non-uniformly irradiated target.

(Niemierko, Med Phys. 24:103-110; 1997.)


For the simplest model of exponential cell kill, and uniformly distributed cells,

where really means the surviving fraction at dose Dref , which is often taken as 2 Gy


climbing the TCP curve uniformly distributed cells,

where we should be

Tumor Control Probability

where we are

complication curve

Dose


the unique biology of CaP uniformly distributed cells,

Striking similarities with slowly proliferating normal tissues

 Extremely low proportion of cycling cells (< 2.5%)

 Regression following RT is very slow

• PSA nadir times > 1 year

• regression of post-RT biopsies up to 3 years

 Potential doubling times

• median 40 days (range 15 – 170 days)

 PSA doubling times of untreated CaP

• median 4 years


Radiobiology 101 uniformly distributed cells,

Linear-Quadratic equation

s = exp(-ad-bd2)

s

cell survival curve

dose


Radiobiology 101 uniformly distributed cells,

Fractionated radiotherapy: n x d = D

S  s…s = s n

S = exp(-ad-bd2) n

S = exp(-aBED)

BED = D(1+ d/(a/b))

Biologic

Equivalent

Dose


Radiobiology 101 uniformly distributed cells,

BED = D(1+ d/(a/b))units of Gy

a  intrinsic radiosensitivity

b repair of sub-lethal damage

a/b sensitivity to dose-per-fraction


Radiobiology 101 uniformly distributed cells,

BED = D(1+ d/(a/b))

a/btumors > a/bNTLE

tumors a/b ~ 10

normal tissue late effects a/b ~ 3


tumors vs. NTLE uniformly distributed cells,

Tumors & early-

responding tissues

a/b ~ 10

Normal

Tissue late

effects

a/b ~ 3

surviving fraction

dose


tumor vs. NTLE uniformly distributed cells,

BED (Gy) = D(1+ d/(a/b))

D / d / n (Gy) BED a/b=10 BED a/b=3

tumorNTLE

74 / 2 / 37 88.8 123.3

70 / 2.5 / 28 87.5 128.3

69 / 3 / 23 89.7 138

64 / 4 / 16 89.6 149.3

NTLE: Normal Tissue Late Effects


the uniformly distributed cells,a/b ratio for CaP

series method a/b 95% CI

Brenner & Hall (1999) LDR / EBRT data 1.5 [0.8 – 2.2]

King & Fowler (2001) LDR / EBRT model 1.8/2

Fowler et al. (2001) LDR / EBRT data 1.49 [1.25 – 1.76]

Brenner et al. (2002) HDR data 1.2 [0.03 – 4.1]


36.25 / 7.25 / 5 211.5 123.8 62.5 uniformly distributed cells,

90 / 2 / 45 210 150 108

what if a/b is that low?

D (Gy) / d / n BEDa/b=1.5BEDa/b=3BEDa/b=10

tumorNTLE acute effects

74 / 2 / 37 172.6 123.3 88.8

NTLE: Normal Tissue Late Effects


why hypo-fractionate? uniformly distributed cells,

Hypo-fractionation for CaP will:

 escalate dose biologically

 reduce acute sequelae

 keep same normal tissue late-effects

 reduce overall treatment course


potential tumor control uniformly distributed cells,

100

90%

62%

SRS

hypo-fractionation

50

Tumor Control Probability

43%

0

50

60

70

80

90

100

Dose (Gy)


Radiobiology uniformly distributed cells,

Sensitivity to dose

fraction size

Other Tumors a/b ~ 10

Normal Tissues  a/b ~ 3

Prostate cancer  a/b ~ 1.5


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