Using Task Group 137 to
Prescribe and Report Dose
Vrinda Narayana
The
Department of Radiation Oncology
University of Michigan
TG137
• AAPM Recommendations on Dose Prescription
and Reporting Methods for Permanent Interstitial
Brachytherapy for Prostate Cancer
R. Nath
W. S. Bice
W. M. Butler
Z. Chen
A. Meigooni
V. Narayana
M. J. Rivard
Y. Yu
2016 AAPM Spring 2
TG 137 Charge
• Review
– Prescription
– Reporting
– Radiobiological models
• Consensus
– Min requirements for prescription and reporting
• Pre implant
• Post implant
• Recommend
– Optimal requirements for prescription and reporting
• Pre implant
• Post implant
2016 AAPM Spring 3
Outline
Permanent Prostate Implants
• Impact of dose reporting based upon
–
–
–
–
Imaging modalities
Timing of imaging study
Treatment planning approaches
Interoperative planning strategies
• Biophysical models
– BED
– EUD
– TCP
2016 AAPM Spring 4
Bladde
r
History Dose Prescription
Prostate
Rectum
• Nomogram
based on a modified peripheral
loading
Zheng et al., Medical Dosimetry, 28, 185 - 188 (2003).
2016 AAPM Spring 5
History Dose Reporting
Bladde
r
Prostate
Rectum
D99 – Dose to 99% of target
mPD – minimum Peripheral Dose
US PROSTATE DVH
120
Isodose Surface
Volume %
100
80
Implant too deep
60
Implant too shallow
Best Fit
40
0.5 cm superior
1.0 cm superior
20
0.5 cm inferior
1.0 cm inferior
0
0
200
Dose Gy
400
600
2016 AAPM Spring 6
Plan evaluation today
• V100
– Vol that receives 100% of dose
– 90 % excellent implant
• D90
– Dose to 90 % of the volume
– Prescribed dose
2016 AAPM Spring 7
Today
• D90 – Dose to 90% of target
• V100- Volume that receives Rx dose
V100
Rx
D90
2016 AAPM Spring 8
• Dose calculation
• Imaging
2016 AAPM Spring 9
Today
• D90 – Dose to 90% of target
• V100- Volume that receives Rx dose
V100
Rx IDS
V100
D90
Rx
D90
2016 AAPM Spring 10
D90 issue
False Increase
D90
False Decrease
D90
CT Prostate
MR prostate
2016 AAPM Spring 11
Impact of Imaging Modality on Dose
Reporting
• Ultrasound Imaging
• CT Imaging
• MR Imaging
• Recommendations on Imaging
modality
2016 AAPM Spring 12
Imaging modalities
• Target delineation
www
2016 AAPM Spring 13
Prostate Anatomy
2016 AAPM Spring 14
2016 AAPM Spring 15
Imaging Modalities
Plane CT MRI
films
* Identification
++ + * Localization
++ 0
+
Prostate Delineation
-+ ++
Critical St Delineation
-+ ++
Comfort
+
+ Cost & Convenience
++ --
TRUS
--+
0
-+
2016 AAPM Spring 16
Ultrasound
• Prostate
• Urethra
• Rectal wall
2016 AAPM Spring 17
Ultrasound Apex / GUD Transition
Prostate
Apex
GUD
external sphincter
Bulbourethral Gland
H shaped External sphincter
2016 AAPM Spring 18
MRI Coronal vs. CT Coronal
2016 AAPM Spring 19
MR Anatomy
• Prostate
• Urethra
• Rectal wall
• Corpus
Cavernosum
• Pudendal Arteries
• Sphincter
• Neurovascular
bundle
2016 AAPM Spring 20
CT Prostate
• Apex – when do you stop
• Base – bladder neck oblitaration
2016 AAPM Spring 21
2016 AAPM Spring 22
Intra - lumen bladder density-small gland
2016 AAPM Spring 23
Figure 6
2016 AAPM Spring 24
Bladder Neck Obliteration
2016 AAPM Spring 25
MRI Coronal vs. CT Coronal
2016 AAPM Spring 26
MRI Coronal vs. CT Coronal
2016 AAPM Spring 27
CT Prostate – post implant
• Apex – when do you stop
• Base – bladder neck obliteration
• Seminal vesicles
• Rectal surface
2016 AAPM Spring 28
Axial CT
without Contour
Axial CT
with Contour
Axial MRI
without
Contour
Axial MRI
with Contour
2016 AAPM Spring 29
Variations without a Standard (Lee)
Observer 1
Vol
D90
V100
39 cc
142 Gy
93%
Observer 2
Observer 3
48 cc
123 Gy
86%
32 cc
155 Gy
99%
2016 AAPM Spring 30
Perils of CT contouring
Bladder
Anterior
CT base
Rectum
Prostate
CT apex
Saggital
McLaughlin et. al.
2016 AAPM Spring 31
CT
• Prostate
• Outer Rectum
• Inner Rectum – de-expansion 5 mm
• Urethra – Foley
Urethra
• Penile Bulb
Prostate
Rectum
Axial
2016 AAPM Spring 32
Why MR? EXPECT VARIATION
2016 AAPM Spring 33
CT contouring / 6 national experts
2016 AAPM Spring
McLaughlin
et.34al.
CT contouring
3.00
Wide margin implants
Observer/Std Volume
2.50
2.00
1.50
1.00
0.50
0.00
0
1
2
3
4
5
6
1.40
1.40
1.20
1.20
1.00
1.00
Observer/Std D90
Observer/Std V100
Study
0.80
0.60
0.80
0.60
0.40
0.40
0.20
0.20
0.00
0.00
0
1
2
3
Study
4
5
6
Narayana et. al.
0
1
2
3
4
5
2016 AAPM Spring 35
Study
6
Deviation from a Standard (6 experts)
MRI
36cc
Observer 1
Observer 2
34cc
38cc
Prostate Volume Agreement
2016 AAPM Spring 36
Deviation from a Standard (6 experts)
MRI
Observer 1
Observer 2
148 Gy
153 Gy
143 Gy
D90 Agreement
2016 AAPM Spring 37
Deviation from a Standard (6 experts)
MRI
95%
Observer 1
98%
Observer 2
92%
V100 Agreement
2016 AAPM Spring 38
bladder
seminal
vesicle
prostate
rectum
bone
external sphincter
Proximal penis
Prostate side view: Note labels on right. Prostate is not enlarged and does not extend
into the bladder. Urethra opening from the bladder is open (yellow arrow). Sphincter is
normal length and there is no bony restriction – note space between the bone and
prostate (purple arrows)
2016 AAPM Spring 39
Central = transition zone (TZ) = dark
Peripheral zone (PZ) = light
normal prostate - normal appearance with light peripheral zone where tumors form
and the dark central area called the transition zone – this enlarges with age
2016 AAPM Spring 40
Multiparameter Imaging
• T2
• DCE
• DWI
2016 AAPM Spring 41
Right side of the gland panel is normal prostate with clear PZ and TZ. On the
left side (red) note the dark area that extends into the TZ and from front to
back. This is tumor
2016 AAPM Spring 42
with contrast the area of concern on the left side of the panel is clearly seen, with
a suggestion of extension beyond the gland (arrow).
2016 AAPM Spring 43
Note the tumor on the left side of the panel (red) and possible extension beyond
the capsule
2016 AAPM Spring 44
Imaging Recommendations
• CT – 2/3 mm cuts
• Prostate – mindful of pitfalls
• Rectum outer – 1 cm sup and inf
• Rectal wall - 0.5 cm contraction
• Urethra
– Foley Day 0
– Foley Optional later scans
• Penial Bulb
2016 AAPM Spring 45
Imaging Guidelines MR
• T2 3 mm cuts (no rectal coil)
– immediately before or after CT
– Axial, coronal, sagittal
• Rectum – 1 cm above & below
• Bladder – axial MR
• Urethra – axial and Sag MR
• Register CT-MR around prostate only
• CT – seed positions
2016 AAPM Spring 46
Impact of timing of imaging on dose reporting
• Prostate edema
• Source displacement with time
• Optimal timing for post implant
dosimetry
• Recommendations on timing of
imaging
2016 AAPM Spring 47
Edema
? Needle insertion
? Bleeding – needle pentration
? General inflamation
2016 AAPM Spring 48
Edema Model
Volume
Vmax
VT
V0
T0
Tmax
T
Time
2016 AAPM Spring 49
Edema Model
? T max
? Different imaging modalities
? Prostate Volumes
2016 AAPM Spring 50
Edema
US
1m
80%
CT3
120%
CT1
14d
CT2
150%
Narayana et. al.
2016 AAPM Spring 51
Edema
CT
130%
US
14 d
MR
101%
McLaughlin et. al
2016 AAPM Spring 52
MR edema
MR
130%
3w
MR
Implant
3w
Chung et. al
2016 AAPM Spring 53
Edema Model
• Max – 1 day
• Longer to resolve than initial
swelling
• Quick resolution - 2 weeks
• Slow resolution – 2 to 4 weeks
• T1/2 ~ 10 d (4 to 25 days)
2016 AAPM Spring 54
Effect on post implant dosimetry
• Day 1 – edema large
– underestimate dose
• Day 100 – edema resolved
– overestimate dose
2016 AAPM Spring 55
Edema Model
• Assumes seeds move with the
prostate
– Seeds inside the prostate
? Stranded seeds
2016 AAPM Spring 56
McLaughlin et. al.
2016 AAPM Spring 57
2016 AAPM Spring 58
2016 AAPM Spring 59
2016 AAPM Spring 60
2016 AAPM Spring 61
By how much?
• Timing of imaging
• Magnitude of prostate swelling
• Rate of resolution
• Radioactive T1/2
↑ Short T1/2 & low energy
2016 AAPM Spring 62
Optimal time
•
131Cs
10+2 days
•
103Pd
16+2 days
•
125I
42+2 days
2016 AAPM Spring 63
Recommendation Timing of imaging
• Pre-Implant prostate volume
• Implant day dosimetry
– US immediate
– CT/MR 2 to 4 h
• Post-Implant dosimetry
– 131Cs 10+2 days
– 103Pd 16+2 days
– 125I 1month+1week
2016 AAPM Spring 64
The optimal timing for post implant
dosimetry is
20%
20%
20%
20%
20%
1.
2.
3.
4.
Immediately following the implant
2 weeks after the implant
1 month after the implant
10, 16 and 42 days for 131Cs, 103Pd, 125I
respectively
5. No post implant dosimetry is required
10
The optimal timing for post implant
dosimetry is
20%
20%
20%
20%
20%
1.
2.
3.
4.
Immediately following the implant
2 weeks after the implant
1 month after the implant
10, 16 and 42 days for 131Cs, 103Pd, 125I
respectively
5. No post implant dosimetry is required
Answer: 4
Reference: AAPM TG137, Nath et. al. 2009
10
Post implant prostate volume underor overestimation is a result of
20%
20%
20%
20%
20%
1.
2.
3.
4.
5.
The timing of dosimetry
Magnitude of preimplant prostate swelling
The rate of edema resolution
The radioactive decay half-life
All of the above
10
Post implant prostate volume underor overestimation is a result of
20%
20%
20%
20%
20%
1.
2.
3.
4.
5.
The timing of dosimetry
Magnitude of preimplant prostate swelling
The rate of edema resolution
The radioactive decay half-life
All of the above
Answer: 5
Reference: AAPM TG137, Nath et. al. 2009
10
Impact of treatment planning approaches on
dose reporting
• Planning techniques
• Choice of isotope
• Choice of source strength
• Calculation Algorithm
• Dose indices for target and normal
tissue
• Recommendations for planning and
dose reporting
2016 AAPM Spring 69
Peripheral loading?
Prostate, with error
120
120
100
Nomogram
Prostate + 0.5 cm margin, with
error
100
Nomogram
80
Differential
Differential
80
Volume %
Volume %
Periphery
60
Periphery
60
Spike
40
Spike
40
20
20
0
0
0
100
200
300
400
Dose (Gy)
500
600
0
Narayana et. al.
100
200
300
400
500
600
Dose (Gy)
2016 AAPM Spring 70
Loose seeds vs strands
• Loose Seeds
– Expand with the prostate
– Migrate to the lung
• Strands
– No migration
– May not track with the prostate
2016 AAPM Spring 71
Seed Drop off
• Stranded preloaded
• Mick applicator
• Thin stranded seeds
• Preloaded cartridge
2016 AAPM Spring 72
Seed Drop off
Rapid
Strand
Mick
applicator
Thin strand
Preloaded
cartridge
Prostate V100
%
96.5+2
93.2+5
93.4+4
94.1+3
Prostate D90
Gy
109+7
102+19
106+17
101+8
Rec wall D1cc
Gy
95+18
70.4+8
70+23
73+11
Rec wall D2cc
Gy
59+17
53+18
52+18
54+10
Urethra D10
Gy
156+25
163+36
164+21
158+31
2016 AAPM Spring 73
Choice of Isotope
•
131Cs
•
103Pd
•
125I
2016 AAPM Spring 74
I125
• I-125 vs. Pd-103
120
120
100
100
I-125
Vol + Error
Ideal
80
Volume %
Volume %
80
Pd-103
Vol + Error Error
60
60
40
40
Ideal
Error
20
20
0
0
0
0.5
1
1.5
2
2.5
3
Relative Prescription Dose
3.5
0
1
2
3
Relative Prescription Dose
4
2016
AAPM Spring
Narayana
et.75al
Seed Drop off
Rapid
Strand
Mick
applicator
Thin strand
Preloaded
cartridge
Prostate V100
%
96.5+2
93.2+5
93.4+4
94.1+3
Prostate D90
Gy
109+7
102+19
106+17
101+8
Rec wall D1cc
Gy
95+18
70.4+8
70+23
73+11
Rec wall D2cc
Gy
59+17
53+18
52+18
54+10
Urethra D10
Gy
156+25
163+36
164+21
158+31
2016 AAPM Spring 76
Source strength?
• Prospective Randomized Trial
– high vs. low mCi
– No sig diff
Transition
Zone
Prostate
2mm exp
Rectum
Narayana et. al
Axial
2016 AAPM Spring 77
Calculation Algorithm
2016 AAPM Spring 78
Recommendations
• GTV
• CTV – no posterior expansion
• PTV=CTV
• OAR
– Urethra
– Rectum
– Penile bulb
2016 AAPM Spring 79
Recommendations
• Dose clinical decision
– 131Cs 115 Gy ? (100-125 Gy)
– 103Pd 125 Gy
– 125I 145 Gy
2016 AAPM Spring 80
Recommendations Planning criteria
• CTV
– V100> 95% of CTV
– D90 > 100 % of Rx
– V150 < 50% of CTV
• Rectum D2cc < Rx dose
• Urethra
– D10 < 150% Rx dose
– D30< 130% of Rx dose
• Penile bulb - investigational
2016 AAPM Spring 81
Recommendations Dose Reporting
• DVH for target
– Primary, D90,V100, V150
– Secondary V200, V90,D100
• Urethra – D10
– Secondary: D0.4cc, D30, D5
• Rectum – D2cc,
– Secondary: D0.1 cc, V100
2016 AAPM Spring 82
Primary dose parameters for prostate
implant that should always be
reported are
20%
20%
20%
20%
20%
1.
2.
3.
4.
5.
D90
V100
D90 & V150
D90 V100& V150
D90 D100 V90 V100 & V150
10
Primary dose parameters for prostate
implant that should always be
reported are
20%
20%
20%
20%
20%
1.
2.
3.
4.
5.
D90
V100
D90 & V150
D90 V100& V150
D90 D100 V90 V100 & V150
Answer: 4
Reference: AAPM TG137, Nath et. al. 2009
10
Intraoperative treatment planning strategies
• Intraoperative preplanning
• Interactive planning
• Dynamic dose calculations
• Recommendations on Intraoperative
planning and evaluation
2016 AAPM Spring 85
Pre vs. OR planning
Pre
2 procedures
Reproducible setup
OR
Target Volume
Stress
Time pressure
# of seeds ordered
2016 AAPM Spring 86
Techniques
• Intraoperative
– Creation of plan in
OR just before the
implant
– Immediate
execution
• Interactive
– Stepwise
refinement
– Computerized dose
calculations based
on image feedback
• Dynamic
– Calculations constantly
updated using continuous
deposited-seed-position
feed back
2016 AAPM Spring 87
Recommendations
• Enhanced implant quality
• Post implant dosimetry
– Edema
– Seed migration
2016 AAPM Spring 88
Sector anaylsis
• Research setting
2016 AAPM Spring 89
Biophysical Models
• BED for prostate implants
• EUD calculations
• TCP
• Recommendations for reporting
radiobiological response
2016 AAPM Spring 90
.
BED
BED = D[1 + D /(α / β )]
BED = D(Teff ) RE (Teff ) − ln 2
Teff
αT p
D 0
β
1
2λ
− 2 λT
− ( µ + λ )T
×
−
−
−
RE (T ) = 1 + ( )
e
e
{
1
(
1
)}
− λT
α (µ − λ ) 1 − e
µ +λ
eff
eff
eff
Teff = Tavg ln[α ⋅ D ⋅
Tp
T1 / 2
]
2016 AAPM Spring 91
BED for inhomogeneous dose
BED = −
1
α
ln(∑ν i e −α ⋅BEDi )
i
D(Teff ) RE (Teff ) − ln 2
Teff
αT p
=−
1
α
ln(∑ν i e
−α ⋅ BEDi
)
i
2016 AAPM Spring 92
Equivalent uniform EBRT dose
EUDd =
− ln(∑ν i e
−α ⋅ BEDi
)
i
α + βd − γ ln 2 /(d ⋅ T p )
2016 AAPM Spring 93
TCP
TCP ( D) =
1
1 + (TCD50 / D )
k
TCP = exp[− N 0 exp(−α ⋅ BED)]
2016 AAPM Spring 94
Example
Radionuclide
Indices
125I
103Pd
131Cs
Dose (Gy)
145.0
125.0
120.0
BED (Gy)
110.9
115.4
117.3
EUD (Gy)
69.7
72.6
73.8
TCP (%)
74.1
85.9
89.2
Teff (day)
235.3
93.9
60.8
Calculated with: α = 0.15 Gy-1, β = 0.05 Gy-2, α/β = 3.0 Gy, Tp = 42
days, repair half-life of 0.27 hour, and N0 = 5x106
2016 AAPM Spring 95
Linear Quadratic Model

d 
ERD = Nd 1 +

α
β


• N= # fx
• D = dose/fx
• α/β = 3Gy
2016 AAPM Spring 96
Linear Quadratic Model

Rt 
ERD = NRt 1 + G

α
β


• R = dose rate
• t = time
2016 AAPM Spring 97
Linear Quadratic Model
GLDR
2
=
µt
(
− µt

1− e
−
1

µt

)


• µ = repair rate const

Rt 
ERD = NRt 1 + G
α β 

2016 AAPM Spring 98
Linear Quadratic Model
ERD IMP


R
= R / λ 1 +

(µ + λ )α β 

• R = dose rate
• λ = decay constant
• µ = repair rate constant
• α/β = tissue specific parameter
2016 AAPM Spring 99
Linear Quadratic Model
• Beam ?
• Brachy
– d = 2 Gy/fx
– R = 4.4 cGy/h
– α/β = 3Gy
– λ = 0.693/59.4 d-1
– α/β = 3Gy
– µ = .4 h-1

d 
ERD = Deq 1 +

 α β


R
ERD = R / λ 1 +

 (µ + λ )α β 
2016 AAPM Spring 100
Recommendations
• Adequate information
– BED
– EUD
– TCP
– Other
2016 AAPM Spring 101
Recommendation
• Model parameters should be
specified
• All parameters required to calculate
the biodose should be specified
• Encourage vendors to provide
models
2016 AAPM Spring 102
What is the cause of most
inconsistencies in dose reporting?
20%
20%
20%
20%
20%
1.
2.
3.
4.
5.
Identification of source positions
Dose calculations
Target delineation
Timing of the imaging study
Type of isotope used
10
What is the cause of most
inconsistencies in dose reporting?
20%
20%
20%
20%
20%
1.
2.
3.
4.
5.
Identification of source positions
Dose calculations
Target delineation
Timing of the imaging study
Type of isotope used
Answer: 3
Reference: AAPM TG137, Nath et. al. 2009
10