Microdosimetry in hadron therapy as a bridge between ... · 7 The response of two different types...
22
© SCKCEN, 2018 Microdosimetry in hadron therapy as a bridge between physics and biology Alessio Parisi a,b , Olivier Van Hoey a , Filip Vanhavere a , Sabina Chiriotti a , Marijke De Saint Hubert a , Jérémie Dabin a , Werner Schoonjans a , Patrice Mégret b , Charlot Vandevoorde c , Philip Beukes c , Evan Alexander de Kock c , Julyan Symons c , Jaime Nieto Camero c , Jacobus Slabbert c , Emily Debrot d , David Bolst d , Anatoly Rosenfeld d a Belgian Nuclear Research Centre SCK•CEN, Mol, Belgium b University of Mons, Faculty of Engineering, Mons, Belgium c iThemba LABS, Cape Town, South Africa d University of Wollongong, Centre for Medical Radiation Physics, Wollongong, Australia BVS-ABR Young Scientist Event, Gent, 19/10/2018
-
Upload
truongtram -
Category
Documents
-
view
216 -
download
0
Transcript of Microdosimetry in hadron therapy as a bridge between ... · 7 The response of two different types...
© SCKCEN, 2018
Microdosimetry in hadron therapy as a bridge
between physics and biology
Alessio Parisi a,b, Olivier Van Hoey a, Filip Vanhavere a, Sabina Chiriotti a, Marijke De Saint Hubert a, Jérémie Dabin a,
Werner Schoonjans a, Patrice Mégret b, Charlot Vandevoorde c, Philip Beukes c, Evan Alexander de Kock c, Julyan
Symons c, Jaime Nieto Camero c, Jacobus Slabbert c, Emily Debrot d, David Bolst d, Anatoly Rosenfeld d
a Belgian Nuclear Research Centre SCK•CEN, Mol, Belgiumb University of Mons, Faculty of Engineering, Mons, Belgiumc iThemba LABS, Cape Town, South Africad University of Wollongong, Centre for Medical Radiation Physics, Wollongong, Australia
BVS-ABR Young Scientist Event, Gent, 19/10/2018
© SCKCEN, 2018
Cancer therapy
2
SURGERY CHEMOTHERAPY RADIOTHERAPY
The use of charged particle to treat cancer is increasing worldwide:
79 centers in operation, 45 in construction, 22 planned
Particle Therapy Co-Operative Group (PTCOG, https://www.ptcog.ch/)
© SCKCEN, 2018
Hadron therapy has superior physical proprieties than conventional radiotherapy
3Mayo Clinic, United States of America (https://www.mayoclinic.org)
X-rays of conventional radiotherapy irradiate organs both in front of and behind the tumor
on the other hand, charged particle energy deposition can be better controlled
this allows a reduction of the doses to the surrounding organs lower risk of secondary cancers
© SCKCEN, 2018
Charged particles are more effective in inducing lethal damages
4
cells exposed to photons (left) or charged particles (right)
figures from Cucinotta and Durante, 2006, Weyrather and Kraft, 2004
Surv
ival
fra
ctio
n
Absorbed dose [Gy]
𝑅𝐵𝐸 =𝐷𝑟𝑒𝑓𝑒𝑟𝑒𝑛𝑐𝑒 𝑟𝑎𝑑𝑖𝑎𝑡𝑖𝑜𝑛
𝐷𝑟𝑎𝑑𝑖𝑎𝑡𝑖𝑜𝑛 𝑢𝑛𝑑𝑒𝑟 𝑠𝑡𝑢𝑑𝑦
the relative biological effectiveness (RBE) is a parameter
indicating the effectiveness of a radiation in inducing a
determined effect in comparison to a reference radiation
© SCKCEN, 2018
Charged particles are more effective in inducing lethal damages
5
RBE is a complex function of particle type, its energy,
cell line, biological endpoint… currently, in proton therapy a constant RBE value of 1.1
in respect to photons is used
figures from Sorensen et al., 2011 and IAEA, 2008
© SCKCEN, 2018
Increased RBE at the distal part of treatment
6
recent evidences have proven the inadequacy
of using a constant factor, especially in the
distal edge region
this effect is due to the increased proton LET
and the creation of high LET secondary
fragments
increased risks of secondary tumors
figure adapted from Chaudhary et al., 2014
U87 radioresistant human glioma
AG01522 normal human skin fibroblasts
A novel method has been developed
to assess LET and RBE in proton therapy beams
using couples of thermoluminescent detectors
© SCKCEN, 2018
Methodology
7
The response of two different types of detectors was predicted as function of the proton energy
LiF:Mg,Ti and LiF:Mg,Cu,P thermoluminescent detectors
Microdosimetric d(z) Model (Parisi, 2018) – key ideas and experimental validation
The relative response of the two detectors was correlated with the proton RBE
Correlation between the expected response and the proton dose average LETD
Database of experimentally determined RBE values as function of the LETD (Paganetti, 2014)
Validation of the methodology through a comparison with cell survival studies in a clinical SOBP
iThemba LABS (South Africa) proton therapy room
Chinese hamster ovary (CHO-K1)
© SCKCEN, 2018
The luminescence phenomenon is explained as transition between a
ground state (valence band) and a excited state (condition band)
The radiation induced luminescent signal depends strongly on the
microscopic structure of the detector
different materials different trapping centers different luminescent
signal
Luminescence phenomenon
8
0.0
0.2
0.4
0.6
0.8
1.0
0.0
0.2
0.4
0.6
0.8
1.0
50 100 150 200 250 300 3500.0
0.2
0.4
0.6
0.8
1.0
LiF:Mg,Ti (MTS) detectors
LiF:Mg,Cu,P (MCP) detectors
Lum
ines
cen
ce in
ten
sity
[a.
u.]
LiF:Mg,Ti (MTT) detectors
Temperature [°C]
© SCKCEN, 2018
Microdosimetric d(z) Model – methodology
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9
mono-energetic beam
(i.e. 12C, 15 MeV/u)lithium fluoride target, 0.9 mm
9
Key ideas
the detector is supposed being composed by many independent
structures called targets which act as sensitive volumes for
measuring radiation
microdosimetric specific energy probability distributions are used
to quantify changes in the pattern of energy deposition
Efficiency evaluated for a lot of particle-energy combinations
ions from 1H to 132Xe, photons, muons, antimatter
energy from keV to TeV
𝜂𝑟𝑒𝑙 =0+∞
𝑑 𝑧 𝑟 𝑧 𝑑𝑧𝑟𝑎𝑑𝑖𝑎𝑡𝑖𝑜𝑛
0+∞
𝑑 𝑧 𝑟 𝑧 𝑑𝑧60𝐶𝑜 𝛾−𝑟𝑎𝑦𝑠
101
102
103
104
105
106
107
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1H ions, 1000 MeV/u
132
Xe ions, 3 MeV/u
z d(z
)
z in lithium fluoride [Gy]
© SCKCEN, 2018
Microdosimetric d(z) Model – HCPs, results for LiF:Mg,Ti (MTS) detectors
The results of the model are in very good agreement with
experimental data for all particles and energies
0.0
0.5
1.0
0.0
0.5
1.0
0.0
0.5
1.0
0.0
0.5
1.0
10-1
100
101
102
103
104
0.0
0.5
1.0
4He ions
12C ions
1H ions
16O ions
20Ne ions
Rel
ativ
e ef
fici
ency
LiF:Mg,Ti detectors
Microdosimetric d(z) Model, 40 nm
Experimental Data
Unrestricted LETF in water [keV/µm]
0.0
0.5
1.0
0.0
0.5
1.0
0.0
0.5
1.0
0.0
0.5
1.0
10-1
100
101
102
103
104
0.0
0.5
1.0
28Si ions
40Ar ions
84Kr ions
56Fe ions
Rel
ativ
e ef
fici
ency
Unrestricted LETF in water [keV/µm]
LiF:Mg,Ti detectors
Microdosimetric d(z) Model, 40 nm
Experimental Data
132Xe ions
10-1
100
101
102
103
104
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4 1H
4He
12
C
16
O
20
Ne
28
Si
40
Ar
56
Fe
84
Kr
132
Xe
LiF:Mg,Ti (MTS) detectors
Rel
ativ
e ef
fici
ency
Unrestricted LETF in water [keV/µm]
10
© SCKCEN, 2018
Microdosimetric d(z) Model – HCPs, results for LiF:Mg,Cu,P (MCP) detectors
As for LiF:Mg,Ti (MTS) detectors, the results of the model are
in very good agreement with experimental data
0.0
0.5
1.0
0.0
0.5
1.0
0.0
0.5
1.0
0.0
0.5
1.0
10-1
100
101
102
103
104
0.0
0.5
1.0
1H ions
4He ions
16O ions
12C ions
Rel
ativ
e ef
fici
ency
20Ne ions
LiF:Mg,Cu,P detectors
Microdosimetric d(z) Model, 40 nm
Experimental Data
Unrestricted LETF in water [keV/µm]
0.0
0.5
1.0
0.0
0.5
1.0
0.0
0.5
1.0
0.0
0.5
1.0
10-1
100
101
102
103
104
0.0
0.5
1.0
28Si ions
40Ar ions
56Fe ions
84Kr ions
Rel
ativ
e ef
fici
ency
LiF:Mg,Cu,P detectors
Microdosimetric d(z) Model, 40 nm
Experimental Data
132Xe ions
Unrestricted LETF in water [keV/µm]
10-1
100
101
102
103
104
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4LiF:Mg,Cu,P (MCP) detectors
1H
4He
12
C
16
O
20
Ne
28
Si
40
Ar
56
Fe
84
Kr
132
Xe
Rel
ativ
e ef
fici
ency
Unrestricted LETF in water [keV/µm]
11
© SCKCEN, 2018
Microdosimetric d(z) Model – photons, relative air kerma response
101
102
103
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
40 nm
Experimental Data
LiF:Mg,Ti (MTS) detectors
Rel
ativ
e ai
r ker
ma
resp
on
se
Photon energy [keV]
101
102
103
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
40 nm
Experimental Data
LiF:Mg,Cu,P (MCP) detectors
Rel
ativ
e ai
r ker
ma
resp
on
se
Photon energy [keV]
12
© SCKCEN, 2018
Microdosimetric d(z) Model – muons
13
100
101
102
103
104
105
106
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
Muon
LiF:Mg,Ti (MTS) detectors
Rel
ativ
e ef
fici
ency
Energy [MeV]
100
101
102
103
104
105
106
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
Muon
LiF:Mg,Cu,P (MCP) detectors
Rel
ativ
e ef
fici
ency
Energy [MeV]
© SCKCEN, 2018
Microdosimetric d(z) Model – muons and antimuons
14
100
101
102
103
104
105
106
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
Muon
Antimuon
LiF:Mg,Ti (MTS) detectors
Rel
ativ
e ef
fici
ency
Energy [MeV]
100
101
102
103
104
105
106
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
Muon
Antimuon
LiF:Mg,Cu,P (MCP) detectors
Rel
ativ
e ef
fici
ency
Energy [MeV]
© SCKCEN, 2018
A novel method to assess LET and RBE in proton therapy using TLD couples
15
1 10 100 10000.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
7LiF:Mg,Ti detectors
7LiF:Mg,Cu,P detectors
7LiF:Mg,Ti/
7LiF:Mg,Cu,P detector ratio
Proton energy [MeV]
Rel
ativ
e ef
fici
ency
1.0
1.5
2.0
2.5
3.0
3.5
7L
iF:M
g,T
i/7L
iF:M
g,C
u,P
det
ecto
r ra
tio
1 10 100 10000
5
10
15
20
25
Un
rest
rict
ed L
ET
D in
wat
er [
keV
/µ
m]
Proton energy [MeV]
1 2 30
5
10
15
20
25
Un
rest
rict
ed L
ET
D in
wat
er [
keV
/µ
m]
7LiF:Mg,Ti/
7LiF:Mg,Cu,P detector ratio
LETD - PHITS
Fit LETD
© SCKCEN, 2018
iThemba Labs measurement campaign
16
Combined dosimetry-radiobiology experimental campaign
iThemba Labs (South Africa, April 2017)
Belgian Nuclear Research Centre SCK•CEN , Centre for Medical Radiation Physics – University of Wollongong
protons accelerated up to 200 MeV using a separated sector cyclotron
© SCKCEN, 2018
iThemba Labs measurement campaign
17
Aim: study eventual RBE variations within a therapeutic SOBP with emphasis on the distal part of the treatment
SOBP: range = 120 mm, modulation = 50 mm, max proton energy = 198.5 MeV
thermoluminescent detectors exposed a different depths within the SOBP together with Chinese hamster ovary (CHO-K1) cells
PMMA phantom with positioning accuracy of 0.1 mm
0 20 40 60 80 100 120
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
O
O
OO
O
OOO
O
Rel
ativ
e ab
sorb
ed d
ose
in
wat
er [
mG
y]
Depth in water [mm]
Ionization chamber
© SCKCEN, 2018
iThemba Labs measurement campaign
18
0 20 40 60 80 100 120 1400
100
200
300
400
500
600
Ab
sorb
ed d
ose
in
wat
er [
mG
y]
Equivalent depth in water [mm]
Ionization chamber
7LiF:Mg,Ti (MTS-7) detectors
7LiF:Mg,Cu,P (MCP-7) detectors
0 20 40 60 80 100 120 140
1.0
1.5
2.0
2.5
Equivalent depth in water [mm]
7L
iF:M
g,T
i/7L
iF:M
g,C
u,P
det
ecto
r ra
tio
7LiF:Mg,Ti/
7LiF:Mg,Cu,P detector ratio
Relative absorbed dose profile
Rel
ativ
e ab
sorb
ed d
ose
in
wat
er [
mG
y]
1 2 30
5
10
15
20
25
Un
rest
rict
ed L
ET
in
wat
er [
keV
/µ
m]
7LiF:Mg,Ti/
7LiF:Mg,Cu,P detector ratio
LETD - PHITS
Fit LETD
© SCKCEN, 201819
iThemba Labs measurement campaign – RBE assessment, TLDs
0 20 40 60 80 100 120 1400
2
4
6
8
10
12
14
16
18
Equivalent depth in water [mm]
Un
rest
rict
ed L
ET
in
wat
er [
keV
/µ
m]
LETD - TLD couples
LETD - GEANT4
Relative absorbed dose profile
Rel
ativ
e ab
sorb
ed d
ose
in
wat
er [
mG
y]
CHO cell line (α/ß)ref = 11.5 ± 1.5 Gy
LETD < 15 keV/µm and (α/ß)ref > 9 Gy (Paganetti, 2014)
𝑅𝐵𝐸 (2 𝐺𝑦) = 0.132 𝐿𝐸𝑇𝐷 + 0.96
0 20 40 60 80 100 120 1401.0
1.2
1.4
1.6
1.8
2.0
2.2
2.4
2.6
Equivalent depth in water [mm]R
elat
ive
bio
logi
cal ef
fect
iven
ess
Relative absorbed dose profile
RBE - TLD couples
Rel
ativ
e ab
sorb
ed d
ose
in
wat
er [
mG
y]
© SCKCEN, 201820
iThemba Labs measurement campaign – RBE assessment, CHO cells
CHO cell line
reference radiation: 250 keV X-rays,
RBE relative to a clinical dose of 2 Gy
0 20 40 60 80 100 120 1401.0
1.2
1.4
1.6
1.8
2.0
2.2
2.4
2.6
Equivalent depth in water [mm]R
elat
ive
bio
logi
cal ef
fect
iven
ess
Relative absorbed dose profile
RBE - CHO cells
Rel
ativ
e ab
sorb
ed d
ose
in
wat
er [
mG
y]
© SCKCEN, 201821
iThemba Labs measurement campaign – RBE assessment, comparison
Very good agreement between the results of this new methodology and the in vitro cell survival study
0 20 40 60 80 100 120 1401.0
1.2
1.4
1.6
1.8
2.0
2.2
2.4
2.6
Equivalent depth in water [mm]
Rel
ativ
e b
iolo
gica
l ef
fect
iven
ess
Relative absorbed dose profile
RBE - TLD couples
RBE - CHO cells
Rel
ativ
e ab
sorb
ed d
ose
in
wat
er [
mG
y]
© SCKCEN, 201822
The Microdosimetric d(z) Model is a very powerful tool
very good agreement with experimental data for charged particles and photons
possibility of predicting detector efficiency for other type of radiation (exotic particles, antimatter…) and mixed fields
A new methodology has been proposed to correlate the relative light emission of two different crystals
with the radiation induced cell death
based on the Microdosimetric d(z) Model
LET and RBE in proton therapy beams using pairs of differently doped thermoluminescent detectors
very good agreement with and in vitro cell survival studies
Conclusions
![g]kfn ;/sf/ s[lif tyf ;xsf/L dGqfno s[lif ljefu s[lif k|;f ...vdd.gov.np/public/kcfinder/upload/files/Norms_Whole_2068.pdf · b'O{ zAb s[lif ljefusf] :yfkgf sfnb]lv g} s[lif k|;f/n]](https://static.fdocuments.net/doc/165x107/5ecbc4accdaccc4d425b8270/gkfn-sf-slif-tyf-xsfl-dgqfno-slif-ljefu-slif-kf-vddgovnppublickcfinderuploadfilesnormswhole2068pdf.jpg)
![[XLS]pulse.sgcib.com · Web viewRX LIF REXAM RY LIF ROYAL & SU RZ LIF RANDGOLD LIF STNDRD LIF LIF SMTH & NPH LIF SMITHS GRP S3 LIF STND CHRTD S4](https://static.fdocuments.net/doc/165x107/5aadecb77f8b9a59478b658c/xlspulsesgcibcom-viewrx-lif-rexam-ry-lif-royal-su-rz-lif-randgold-lif-stndrd.jpg)
