let dependence of cell survival parameters in normal human
TRANSCRIPT
Yukari Yoshida*, Mayu Isono, Kensuke Mizohata, Tomoko Yakoh,
Koichi Ando, Tatsuya Ohno, Tatsuaki Kanai, Takashi Nakano,
Gunma University Heavy Ion Medical Center 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, JAPAN
LET dependence of cell survival
parameters in normal human skin cells
PTCOG53 2014.6.12 (Shanghai)
Ph
ys. d
ose
[G
y]/B
iol./C
lin. d
ose
[G
yE
]
0.0
1.0
2.0
3.0
4.0
5.0
6.0
0 50 100 150 200 250 300
Depth [mm]
Clinical dose
Biological dose
Physical dose Absolute dose [Gy]
Absolute dose x Experimental RBE [GyE]
Biological dose x Scaling factor [GyE]
Design of the SOBP at NIRS and GHMC
Background and purpose
The Linear-Quadratic (LQ) parameters α and β
for a mono-energetic He-ion and C-ion beams were
derived from the empirical LET-α and LET-β tables.
The 10% surviving fraction (D10)
was estimated by a method that
is based on the LQ model.
Survival curves of human salivary gland
(HSG) cells for He- and C-ion beams.
Furusawa Y, et al. Radiat Res, 2000
The experimental RBE
was estimated using the D10.
The treatment planning for
all of the tissues in patient is performed
based on experimental data with
radiosensitivity of HSG cells.
It is recommended that
fundamental data other than HSG model
be obtained for more effective radiotherapy.
Materials and Methods
Materials
Methods
Cell line
normal human dermal fibroblast (NHDF)
Irradiation
LET 13~80 keV/mm
The facility of Gunma University Heavy Ion Medical Center
(290 MeV/n, 60 mm SOBP or mono)
LET 100 keV/mm~
Japan Atomic Energy Agency Takasaki, TIARA (18.3 MeV/n, mono)
Reference beam
X-ray 200kVp, 14.6 mA
Analysis
Clonogenic assay
RBE values were estimated from the radiation dose survival curves fitted by
linear quadratic (LQ) model, and defined in vitro as follows.
LQ model: SF = EXP (-αD-βD2)
X-ray dose (Gy) as reference giving 90% cell killing
Radiation dose (Gy) of interest giving 90% cell killing RBE =
Cell survival curves in NHDF
0.0001
0.001
0.01
0.1
1
0 1 2 3 4 5 6 7
X-raySOBPcenter
C108C80C70
C60C40C13
Su
rviv
ing fra
ctio
n
Dose [Gy]
keV / µm
keV / µm
keV / µm
keV / µm
keV / µm
keV / µm
LET dependence of RBE, a and b parameters in NHDF
0
1
2
3
4
5
0 20 40 60 80 100 120
RB
E
LET [keV/mm]
RBE
0
0.5
1
1.5
2
2.5
0 50 100 150
alp
ha [
Gy
-1]
0
0.5
1
0 50 100 150
be
ta [
Gy
-2]
LET [keV/mm]
a parameter
b parameter
LET dependence of RBE, a and b parameters in NHDF and HSG
These analyzed data were taken from previously paper*.
*Furusawa Y, Fukutsu K, Aoki M, et al.
Radiat Res 154: 485-496, 2000
a parameter
0
0.5
1
1.5
2
0 20 40 60 80 100 120
alp
ha
[G
y-1
]
LET [keV/mm]
-3
-2.5
-2
-1.5
-1
-0.5
0
0.5
1
0 20 40 60 80 100 120
be
ta [
Gy
-2]
b parameter
RBE
0
1
2
3
4
5
0 20 40 60 80 100 120
RB
E
LET [keV/mm]
NHDF
NHDF
NHDF
HSG
HSG
HSG
Ando K, Koike S, Uzawa A, et al. J Radiat Res 46: 51-57, 2005
Ando K, Yoshida Y. Jpn J Cancer Clin 56: 457-461, 2010
LET dependence of a and b parameters
in skin reaction and murine fibrosarcoma in vivo
NFSa
skin
b parameter a parameter
Summary and Conclusion
1) The a and b parameter in NHDF increased with LET.
2) Referring the data of HSG cells previously obtained,
the a parameter increased with LET,
while the b parameter decreased with LET.
3) The LET dependence of RBE was observed in both NHDF and
HSG.
4) The LET dependence or independence of a and b parameters
here obtained in vitro was consistent with the in vivo data
previously reported for mouse skin reaction and tumor growth
delay assay.
These data imply that the biological dose of SOBP may be
homogeneous irrespective of difference in RBE values between
two tumors; one tumor possesses large RBE like NHDF and
another tumor does small RBE like HSG.