Perils of Proton Therapy
Jatinder R Palta PhD
University of Florida
Department of Radiation Oncology
Gainesville, Florida
Are there any issues with these
illustrations?
J Johansson PhD Thesis 2006
Siemens Particle Therapy 2007
Proton spot scanning (from PSI home page, Pedroni et al)
Yes, they have made Proton Therapy prone to hyperbole
prone to hyperbole
“Proton therapy can strike a tumor with millimeter accuracy, yet spare
y tissue around the tumor and cause very
y few,, if any,
y, side
healthy
effects. In the Proton Therapy Center, we’re able to deliver energy
like never before.”
“It sounds like power belonging only to a superhero: a high-powered
beam that is able to zap a millimeter area within someone’s
someone s body,
and yet not harm the surrounding healthy cells. Heroic — yes,
but this is not in comic books. It’s happening in real life, in nearby
XXXXXX.”
When treated with Proton Beam Therapy
Therapy, radiation is controlled
“When
while inside the body, that enables the physician to deliver full
or higher doses while sparing surrounding healthy tissues and
organs. It allows to deliver necessary dose of radiation without
causing damage to healthy tissues
tissues.”
“With protons.. energy can be very precisely controlled to place the
Bragg peak within a tumor or other tissues that are targeted to
receive the radiation dose. Because the protons are absorbed at this
point normal tissues
point,
tiss es beyond
be ond the target receive
recei e very
er little or no
radiation”.
Promises of Proton Therapy
Compared to external beam photon therapy,
proton therapy:
•
•
•
•
Decreases the integral dose due to the “finite range” of
protons
Reduces the volume of normal tissue exposed to low
doses, potentially lowering the risk of second
malignancies This risk is notably higher for young
malignancies.
patients, as they are more at risk to future radiation
induced cancers.
Has demonstrated advantage for treating small tumor
volumes at shallow depths (eye tumors and CNS such as
chordomas and chondrosarcomas)
Has demonstrated advantage for treating a few select
cases in almost all disease site
Perils of Proton Therapy
1. Uncertainties:









Consequences off nuclear
C
l
iinteractions
i
((neutrons))
Multiple Coulomb scattering (lateral penumbra)
Intrinsic basic physics uncertainty (I-values)
CT numbers (stopping powers; range)
range),
Dose calculation errors due to complex inhomogeneities,
Intra-fractional organ motion,
Inter-fractional
Inter
fractional changes in anatomy and motion patterns
patterns,
Mis-registration of tissue compensators (passively
scattered proton beams,
Uncertainties in immobilization devices and patient
support devices
2. Evaluation of proton plans

How to evaluate a proton plan in the presence of various
uncertainties?


PTV?
Error bars of dose distributions?
Nuclear Interactions
About 20% (~1%/g
( 1%/g.cm
cm-2)of primary protons lost to interactions with
atomic nuclei
Effect on the depth dose curve
Effect on the lateral dose
distribution
Pristine
Bragg peak
Proton fluence
Secondary
particle
ti l flfluence
resulting from
nuclear
interactions
Primary
fluence
Resultant Bragg peak
Lomax : AAPM SS 2003
Proton Scattering
ips
 = f(w)
5
3
4
MCS
2
3
2
1
1
0
0
5
15
10
p in water ((cm))
Depth
20
Siigma MCS (m
mm)
Dosse per proton (nG
Gy)
A proton pencil beam
tott t = f(ips
i , MCS )
(80-20%) lateral dose
fall-offs at 10cm depth
Protons
– 5-8mm
6MV photons – 6mm
25
Lomax : AAPM SS 2003
Proton Depth
p Dose ((PDD))
Dose perr proton (nGy
y)
3
Peak-to-plateau
p
ratio 3-5
(depending on
width of energy
spectrum
p
)
2
1
0
dE
1

dX ( c)) 2
0
5
10
15
20
Width of peak
dependent on
range straggling in
medium and initial
energy spectrum;
typically 8 mm for
177 MeV p
25
Depth in water (cm)
Depth-dose curve for 177 MeV protons
PDD as a function of SOBP widths
G2_250MeV_RMW91_range28.5cm_mediumsnout@5cm
120
2
3
4
Excitation/ionization;
Nuclear interaction
Excitation/ionization
(Bragg Peaks);
Nuclear interaction
Range straggling and
energy spread
Neutrons from nuclear
i t
interactions
ti
2
100
1
80
PDD
1
60
40
20
0
0
50
SOBP 4 cm, Measured 4.2 cm
SOBP 10 cm, Measure 10.2 cm
SOBP 16 cm
cm, Measured 16
16.1cm
1cm
SOBP 12 cm, Measured 12.0 cm
SOBP 8 cm, Measured 8.1 cm
SOBP 6 cm,, Measured 6.1 cm
SOBP 14 cm, Measured 14.3 cm
100
150
200
3
4
250
Depth (mm)
Note increase in entrance dose with
increase in modulation.
300
350
Intrinsic basic physics uncertainty
(I l
(I-values)
)
P122 Iw67
P122 Iw75
P122 Iw80
P183 Iw67
P183 Iw75
P183 Iw80
P230 Iw67
P230 Iw75
P230 Iw80
3
Protons on water
I - dependence
w
The peak spread increases with
energ
energy
2
2
dE/dz (MeV/g cm ) per incid
dent partic
cle
4
1
0
0
5
10
15
20
25
30
35
2
depth in water (g/cm )
P Andreo, Phys Med Biol, 2009
122 MeV Protons on water: I - dependence
w
4
2
P122 I = 67eV
w
P122 I = 75eV
w
P122 I = 80eV
w
3
2
2
dE/dz (M
MeV/g cm ) per incident particlle
0.3 g/cm
1
Peak spread is .7 g/cm2
for 230 MeV protons
0
9.5
10.0
10.5
11.0
11.5
2
depth in water (g/cm )
Intrinsic basic ph
physics
sics uncertainty
ncertaint makes the
argument of “sub-millimeter precision” an issue,
which deserves careful consideration
P Andreo, Phys Med Biol, 2009
average I-values of various soft tissues
MUSCLE SKELETAL (ICRP)
LUNG (ICRP)
BLOOD (ICRP)
WATER LIQUID
TESTES (ICRP)
TISSUE SOFT (ICRU-33 4 comp)
HEART ADULT (BLOOD-FILLED)
MUSCLE STRIATED (ICRU)
HEART ADULT (HEALTHY)
GI TRACT (INTESTINE)
GI-TRACT
HEART ADULT (FATTY)
EYE LENS (ICRP)
BRAIN (ICRP)
UREA
SKIN (ICRP)
TISSUE SOFT (ICRP)
TISSUE SOFT (ICRU-44 MALE)
TISSUE SOFT (ICRU-44 FEMALE)
BREAST (WHOLE)-50/50
(WHOLE) 50/50
BREAST (WHOLE)-33/67
ADIPOSE TISSUE (ICRP)
62
64
66
68
70
72
74
76
I-value (eV)
P Andreo, Phys Med Biol, 2009
164 MeV protons on various tissues
(+/- 10% change in I-values)
2.5
0.7 g/cm
Peak spread
assuming 10%
uncertainty
in I-values
2
2.0
1.5
2
dE
E/dz (MeV c
cm /g) perr incident p
particle
30
3.0
1.0
P 164 muscle skeletal ICRP
P 164 tissue soft ICRU-44 F
P 164 water (I=75)
0.5
P 164 muscle skeletal ICRP
P 164 tissue soft ICRU-44 F
0.0
17.0
17.5
18.0
18.5
19.0
19.5
2
depth (g/cm )
P Andreo, Phys Med Biol, 2009
HU-Stopping Power Calibration Curve
2
Re
ealative Stopping Powe
er
1.8
16
1.6
1.4
1.2
1
0.8
Large phantom, Average position, 140kV,
400mAs, Big bore
0.6
Body phantom, Average position, 140kV,
400mAs, Big bore
Full head phantom
phantom, Average position,
position 140kV,
140kV
400mAs, Big bore
Empty head phantom, Average position, 140kV,
400mAs, Big bore
0.4
0.2
0
1000
-1000
-500
500
0
500
CT #
1000
1500
2000
S. Flampouri, UFPTI
Range
g uncertainty
y due to CT calibration is
generally taken as 3.5%. However, it can be
minimized with better calibration techniques.
HU‐Stopping Power Conversion Uncertainties Results in Range Uncertainties
Results in Range Uncertainties
S Flampouri, UFPTI, 2007
Impact of CT Hounsfield number
uncertainties on dose distributions
-3.5%
+3.5%
Dong/MDACC
0% uncertainty
Individualized patient determination of tissue composition
along the complete beam path
path, rather than CT Hounsfield
numbers alone, would probably be required even to reach
“sub-centimeter precision”
CT Artifacts and Hounsfield Numbers
“It is imperative that body-tissue compositions are not given
th standing
the
t di off physical
h i l constants
t t and
d th
their
i reported
t d
variability is always taken into account” (ICRU-44, 1989).
Proton treatment delivery
Passive scattering in practice
Aperture
Range
modulator
wheel
Compensator
Scatterer
Target
Patient
Range compensator
conforms dose to
distal edge target
volume; the aperture
shapes field in lateral
direction.
Brass aperture
Lucite range compensator
Misalignment of the compensator g
p
with Target Volume
Correct alignment of
(a)
the compensator and
target volume
Patient(b)
is
shifted left
Patient is
(c)rotated
clockwise
ICRU Report 78
Proton Range Uncertainty in the
Presence of heterogeneities
Soft
tissue
Soft
tissue
Rhom
Bone
Rinho
m
Lomax : AAPM SS 2003
Impact of Organ Motion on Proton Dose Di ib i
Distributions
Free breathing treatment
Tsunashima/MDACC
Dong: ASTRO 2008
Impact of Organ Motion on Proton
Dose Distributions
Prescription Dose Line
Treatment planned based
on single Free-breathing
Free breathing
(FB) CT image
(conventional approach)
The same treatment plan
calculated on 4D CT
images
Y. Kang et al. IJROBP. 67, 906-914 (2007)
Comparing Proton Therapy with IMRT
Protons Therapy
Ca Oropharynx
Photon IMRT
Yeung UFPTI
Ca Oropharynx
Concomitant Boost (7200 cGy)
(95% PTV receives prescription dose, 99% PTV receives 93% of prescription dose and
20% PTV receives <110% of prescription dose)
Tumor Coverage
Photon IMRT
PROTONS
95% of PTV 5400/7200
7320 (101.6%)
7178 (99.7%)
99% of PTV 5400/7200
7221 (100.3%)
6975 (96.7%)
20% of PTV 5400/7200
7722 (107.3%) 7243 cGy (106%)
Brain stem (0.1 c.c.)
5020
2685
Spinal cord (0.1 c.c.)
4400
546
Contralateral parotid
(mean dose  2600)
2529
1482
Contralateral
submandibular gland
(mean dose  2600)
6928
6148
Please note that this is ONLY a synthetic
comparison of two modalities of treatment
Yeung UFPTI
The Clinical Challenge
g
Accurately deliver ionizing radiation to the real
dynamic
y
p
patient
Intra‐Fraction Prostate Motion Due to Breathing and Bladder Filling
Due to Breathing and Bladder Filling
Rectal DVH from multiple post treatment PET/CT
p p
/
70 00
70.00
rectumRAOplan@104.5cc
rectumRAO#1@105.5cc
60.00
Uncertainties in Rectal V74
and V39
rectumRAO#2@135.4cc
rectumRAO#3@68.8cc
rectumLAOplan@104.5cc
50.00
rectumLAO#1@139.4cc
V o lu m e (% )
rectumLAO#2@116.1cc
40.00
Mean ±
Dev.
rectumLAO#3@60.7cc
30.00
V74 9.6%±7.2%
V39 25.2%±11.4%
20.00
10.00
Rel. Dev. ±
Dev.
73.9%±20.5%
42.1%±15.3%
0.00
10
20
30
40
50
60
70
80
90
100
110
Dose (%)
Yin: UFPTI, 2008
Anatomic Variations During Course of RT
Barker et al. Int J Radiat Oncol
Biol Phys 2004;59:960-970.
2004;59:960-970
Planning CT
Three Weeks into RT
Impact of Tumor Shrinkage on Proton
Dose
ose Distribution
st but o
D
Dose
recalculated
l l t d
Original Proton Plan
on the new anatomy
Bucci et al. ASTRO Abstract, 2007
Intensity Modulated Proton Therapy (IMPT)
The
e tthree
ee ‘orders’
o de s o
of p
proton
oto ttherapy
e apy co
compared
pa ed
Passive
scattering
Spot
scanning
IMPT
1 field
1 field
1 field
3 fields
3 fields
3 fields
Lomax/PSI
Plan DVH Evaluation (PTV)
What you see is not what you always get….
Photon DVH
Volume
Proton DVH
Dose
Plan DVH Evaluation (PRV)
What you see is not what you always get..
Volum
me
Proton DVH
Photon DVH
Dose
Plan Evaluation
What you see is not what you always get….
IMXT Plan
IMPT Plan
(with Confidence-weighted Isodose Distribution)
Lomax PSI
Ji UF
Jin
180 160 120 80 40 cGy
There is no easyy wayy to
show what patient will get
in proton therapy
Summary 1
• Proton beams stop ‐ no exit dose
– Although we don
Although we don’tt know exactly where they stop
know exactly where they stop
• Proton beams are more sensitive to
– CT Hounsfield number/Stopping Power accuracy
– Organ motion Organ motion
– Anatomy changes
• Proton plans are difficult to evaluate
– “What you see is not what is delivered”
y
• Protons demonstrate excellent low dose sparing
Summary 2
• IMPT shows additional benefits both in low dose sparing and high dose conformality
dose sparing and high dose conformality
• IGRT and Adaptive RT will play an important role
• Inter/Intra
Inter/Intra‐fractional
fractional variations have far more variations have far more
significant consequences in patients treated p
py
with proton therapy
– Approaches and data to deal with this issue is still lacking
• Minimize it and develop strategies to deal with the residual motion
Summary 3
Summary 3
• Empirical
Empirical approaches used in defining margins for approaches used in defining margins for
range uncertainties, smearing, and smoothing are q
questionable
– No real data exist to support any of these approaches
• Repeat imaging and reevaluation based on p
g g
deformable registration may be necessary
– In some cases repeat planning may be clinically beneficial
• Biologically Effective Dose
– Little published data on end of range RBE
General Observations Regarding P t Th
Proton Therapy Technology
T h l
•
State‐of the Art in Proton Therapy is still an accelerator with multi‐room configuration and scattered beam delivery system. These are far from “turnkey” systems
•
– Scanning and IMPT are still a works
Scanning and IMPT are still a works‐in‐progress
in progress.
– Subsystem integration is far from complete
• It impacts clinical workflow and throughput
•
Development of new proton beam production technologies are being f l d b th
fueled by the promise of proton therapy in normal tissue sparing.
i
f
t th
i
l ti
i
– Developing a technology is lot simpler and quicker than its seamless and safe integration in existing clinical work flow.
• Historically, routine application of new developments in radiation oncology has taken at least 5 years from the time its FDA approval (e g MLC IMRT IGRT etc )
taken at least 5 years from the time its FDA approval (e.g. MLC, IMRT, IGRT, etc.)
•
Promise of Proton Therapy will only hold if we take the most advantage of the state‐of‐the art in conventional radiation therapy
– We must not be satisfied with less than the best in technology available for i
immobilization, imaging, treatment planning, patient/target position bili i
i
i
l
i
i /
ii
verification, and treatment delivery.