hadrontherapy beams Mario Carante John Tello and Francesca Ballarini mariopietrocarante01ateneopvit 15th NRM Varenna 2018 University of Pavia and INFN Italy Healthy tissue Healthy ID: 914124
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Slide1
A radiobiological database produced by the BIANCA model to predict the biological effectiveness of
hadrontherapy
beams
Mario Carante
, John Telloand Francesca Ballarini
mariopietro.carante01@ateneopv.it
15th NRM, Varenna 2018
University of Pavia and INFN, Italy
Slide2Healthy
tissue
Healthy
tissue
Tumour
Spread Out
Bragg
Peak
Slide3Physical
dose (
Gy)Biological dose
(GyRBE*)Depth (mm)Dose (Gy)
0 50 100 150 200 250
0.5 1 1.5 2 2.5 3 3.5 4
Carbon
Physical
dose and
biological
dose
Slide4Energy
depositions
D N A
Chromosome
Nucleus
Cell
DNA Cluster
Lesions
(CL)
Lethal
chromosome
aberrations
Cell
death
The BIANCA model
BI
ophysical
AN
alysis
of
C
ell
death
and
chromosome
A
berrations
Version
developed
within
the INFN
"
ETHICS"
project
Slide5Yield
of DNA Cluster
Lesions (CL)
Mainly dependent on particle
type
and energy
(
tuned for each
radiation
quality
and
kept
unvaried
with
varying dose)
Only two adjustable
parameters:
Model
parameters
Chromosome
fragment
un-
rejoining
probability
(f)
Mainly
dependent
on the target
cell
features
(
fixed
by
comparison
with
photon
data
and
kept
unvaried
with
varying
LET)
Protons
Increasing
CLs
Dose (
Gy
)
Surviving
fraction
LET
(
keV
/µm)
7.7
11.0
17.8
27.6
(Carante and Ballarini 2016,
Frontiers
in
Oncology
)
Exp
data from Belli et al 1998,
Folkard
et al 1996
V79
cells
Slide7He
ions
V79
cells
Increasing
CLs
Dose (
Gy
)
Surviving
fraction
LET
(
keV
/µm)
18.6
29.9
50.0
73.9
90.8
Exp
. data
fits
from
Furusawa
et al 2000
Simulations
Exp
. data
fits
16 LET
values
:
18.6
-
90.8
keV
/µm
(Carante et al. 2018,
Physics
in Medicine and
Biology
)
Slide8C
ions
V79
cells
Increasing
CLs
Surviving
fraction
Dose (
Gy
)
LET
(
keV
/µm)
22.5
102
137
360
Exp
. d
ata
fits
from
Furusawa
et al 2000
Surviving
fraction
Dose (
Gy
)
LET
(
keV
/µm)
31
78.5
206
Simulations
Exp
.
data fits
28 LET
values
: 22.5 – 502
keV
/µm
(Carante et al. 2018,
Physics
in Medicine and
Biology
)
Slide9LET (
keV
/µm)
CL/
µm
Protons
He
ions
CL/
µm
LET (
keV
/µm)
CL/
µm
LET (
keV
/µm)
Carbon
ions
CL/µm
yield
well
fitted
by a 2
parameter
linear-
quadratic
function
(y=aL+bL
2
)
before
the over-
killing
region
CLs
as
a
function
of LET (V79
cells
)
Slide10LQ
fits
of simulated
survival curves
Surviving
fraction
Dose (
Gy
)
Protons
(
example
at
15
keV
/µm)
Simulations
LQ
fit
We
perform
simulations
for the
different
particles
(up to
now
: p, He, C)
at
many
LET
values
, and
we
fit
them
with a Linear-
Quadratic
function
S=
exp
(
-
α
D-
β
D
2) (
α, β
)
Slide11α
and
β
for protonsLET (
keV/µm)
Alpha Beta
LET (
keV
/µm)
Alpha Beta
We
obtain
a set of
many
α
and
β
points
as
a
function
of LET
β
values
β
fit
α
values
α
fit
Unpublished
Slide12α
and
β for
helium ions
LET (keV
/µm)
Alpha Beta
LET (
keV
/µm)
Alpha Beta
We
obtain
a set of
many
α
and
β
points
as
a
function
of LET
β
values
β
fit
α
values
α
fit
Unpublished
Slide13α
and
β
for carbon ionsLET (
keV/µm)
Alpha Beta
LET (
keV
/µm)
Alpha Beta
For
every
LET
value
we
have
α
and
β
β
values
β
fit
α
values
α
fit
Unpublished
Slide14Interface with FLUKA
Fluka
3D dose
profile
Particle
LET
Dose
For
mixed
fields
We
provide
tables
of
α
and
β
values
for
different
ions
within
a wide
energy
range
Slide15Biological
profile
for protons
Depth (cm)
Relative
quantities
Dose
Cell
death
V79
cells
(
low
α
/
β
ratio)
Preliminary,
unpublished
Slide16α
and
β for
chromosome aberrations
LET (
keV
/µm)
Alpha Beta
β
values
β
fit
α
values
α
fit
These
kind
of
aberrations
may
induce
secondary
tumors
(
healty
tissue
damage
)
Protons
Dose (
Gy
)
Aberrations
/
cell
Preliminary,
unpublished
Slide17Biological
profile
for protons
Depth (cm)
Relative
quantities
Dose
Aberrations
V79
cells
(
low
α
/
β
ratio)
Preliminary,
unpublished
Slide18AG
cells
(high α/β
ratio)
Dose
Cell
death
Biological
profile
for
protons
Depth (cm)
Relative
quantities
Preliminary,
unpublished
Slide19Acknowledgments
Funding:
INFN
(projects “ETHICS” and “MC-INFN/FLUKA”)FLUKA collaboration
A.
Ferrari, A.
Mairani e G.
Aricò for cooperation and useful discussions
Slide20Backup
Slide21Physical
dose (
Gy)
Biological dose(GyRBE*)Depth (mm)Dose (Gy)
0 50 100 150 200 250
0.5 1 1.5 2 2.5 3 3.5 4
Carbon
Which
biological
effect
?
Dose (
Gy
)
Fraction
of
surviving
cells
Protons
Normal
cells (AG) ->
normal
tissue
Increasing
CLs
Surviving
fraction
Dose (
Gy
)
LET
(
keV
/µm)
1.1
4.0
7.0
11.9
18.0
22.6
(Carante and Ballarini 2016,
Frontiers
in
Oncology
)
Exp
data from
Chaudary
et al 2014
Slide23LET (
keV
/µm)
CL/µm
All
Protons
Helium
ions
Moving
from
one
particle
to
another
?
Carbon
ions
Slide24LET (
keV
/µm)
CL/µm
Carbon
ions
T
he
overkilling
region
A
function
of the
form
: y=
c·arctg
(aL+bL
2
)
works
better
Slide25α
and
β
for protonsLET (
keV/µm)
Alpha Beta
LET (
keV
/µm)
Alpha Beta
We
obtain
a set of
many
α
and
β
points
and
we
fit
them
β
values
β
fit
α
values
α
fit
Slide26α
and
β for
helium ions
LET (
keV/µm)
Alpha Beta
β
values
β
fit
α
values
α
fit
We
use a+bx
+
cx
2
for
α
and a+bx
-
cx
2
for
β
Slide27α
and
β
for carbon ions
LET (keV
/µm)
Alpha Beta
For
every
LET
value
we
have
α
and
β
β
values
β
fit
α
values
α
fit
Slide28LET (
keV
/µm)
CL/µm
Protons
CL/µm V79
LQ
fit V79
Moving
from
one
cell
line to
another
CL/µm AG
X 2.9
Slide29LET (
keV
/µm)
CL/µm
Helium
ions
CL/µm V79
LQ
fit
V79
Moving
from
one
cell
line to
another
CL/µm AG
X 1.5
Slide30LET (
keV
/µm)
CL/µm
Carbon
ions
CL/µm V79
LQ
fit V79
Moving
from
one
cell
line to
another
CL/µm AG
X 1.3
Slide31Goal 2:
predictions
for other
cell
lines
LET (
keV
/µm)
CL/
µm
Protons
Helium
ions
LET (
keV
/µm)
CL/
µm
Carbon
ions
LET (
keV
/µm)
CL/
µm
May
the
multiplying
factors
be
derived
from the
differences
in
radiosensitivity
to
photon
exposure
?
With the
calibration
curves
for V79
cells
and the
photon
survival
curve for
another
cell
line
, BIANCA
could
predict
the
response
of
that
line to
charged
particles
at
any
LET
Slide32Proton
fits
LET (
keV
/µm)
CL/
µm
Linear
CL/
µ
m
LQ
fit
LET (
keV
/µm)
Quadratic
Slide33Helium
fits
LET (
keV
/µm)
CL/
µm
Linear
CL/
µ
m
LQ
fit
LET (
keV
/µm)
Quadratic
Slide34Carbon
fits
LET (
keV
/µm)
CL/
µm
Linear
CL/
µ
m
LQ
fit
LET (
keV
/µm)
Quadratic
Slide35Biological
profile
for protonsDepth (cm)
Dose (
Gy
)
Dose*RBE
Dose*1.1
Dose
Slide36α
and
β
for protonsLET (
keV/µm)
Alpha Beta
LET (
keV
/µm)
Alpha Beta
We
obtain
a set of
many
α
and
β
points
and
we
fit
them
β
values
β
fit
α
values
α
fit
α
β
Giovannini et al 2015
Slide37FLUKA input
Slide38Bolzer
et al 2015
Reality
Simulations
Photons
:
CLs
distributed
uniformly
in the
cell
nucleus
S
L
ight
ions
(
like
p
and He
of
low
energy
):
CLs
distributed
along
the
particle
traversals
<n> = D
S/(0.16
LET)
h
S
’
> S
H
eavier
ions
(
like
C):
Delta
rays
Targets and
irradiation
Cell
nucleus
with the
various
chromosomes
Slide39R
max [
μm]=0.05E[MeV
/u]1.7(Scholz and Kraft, 1992; Kiefer and Straatch, 1986)
Radial
shift
r
(nm)
p
(r)