Page 205 - 2014 Printable Abstract Book
P. 205
damage. In this work the initial damage and subsequent repair of DNA is studied in details. Moreover,
biological models for cell survival are used to calculate the RBE of proton beams.
Monte Carlo simulations with FLUKA and MCNPX were used to calculate proton dose distributions in
water phantoms. High-resolution energy spectra of proton beams were calculated for use in biological
models. Damage frequency including single strand breaks, and double strand breaks (DSB) was calculated
using the Monte Carlo Damage Simulation code (MCDS). DSBs along the depth of the Bragg curve were
subjected to a mechanistic repair model in order to calculate DSB-repair kinetics. The repair model
considers the recruitment of non-homologous end joining (NHEJ) and homologous recombination (HR)
repair proteins at the site of the DSB. All DSBs were initially subjected to NHEJ repair, while complex type
DSBs were further repaired with HR. The repair-misrepair-fixation (RMF) model was subsequently used to
calculate the RBE along the Bragg peak. The results demonstrated that LET, microdosimetric parameters
(e.g. dose-mean lineal energy), number of DSBs, complexity of DSBs, and RBE are constant along the
plateau region of the Bragg curve, while all parameters increase around the Bragg peak. DSB repair
kinetics illustrate that the repair of DSBs in the Bragg peak area are delayed due to enhanced complex
type DSBs. The RBE for V79 cell lines is close to 1 along the plateau of the proton depth dose but increases
by up to 40% at the distal edge. These data illustrate the need for revisiting the current generic RBE value
of 1.1 used in the clinic.
2
1
(PS3-27) Proton RBE for Fractionated exposures. Giuseppe Schettino, PhD MInstP ; Thomas Marshall ;
1
2
2
Pankaj Chaudhary ; and Kevin M. Prise NPL, Teddington, United Kingdom and Queen's University Belfast,
2
Belfast, United Kingdom
Fractionation is a key radiotherapy strategy to maximize dose delivered to cancer cells whilst
allowing healthy tissue to repair radiation damage. In conventional photon megavoltage radiotherapy,
reduced dose per fraction results in lower biological consequences in normal tissues compared to the
tumor. However, extrapolation of the clinical experience accumulated with conventional radiotherapy to
charged particles beams is not straightforward; scarce clinical database and errors in adapting photon-
based treatments could undermine the benefits of proton and hadrontherapy. One of the potential
advantages of charged particle beams is the increased efficiency for cell killing which is quantified by the
Relative Biological Effectiveness (RBE) parameter. It is well known that the RBE varies inversely with dose
and along the particle path in a non-linear trend as a function of the Linear Energy Transfer (LET). Recently
we have mapped the RBE variations at high resolution across a pristine and spread out Bragg peak for
clinically relevant proton doses in a range of cell lines with different radiosensitivity. We are now
investigating the impact of fractionation on the RBE with particular focus on the position along the beam
(i.e. LET dependency). Experimental measurements are combined with theoretical modelling adopting the
Linear Quadratic (LQ) formulation to analyze the RBE for clinically relevant fractionation treatments.
Impact of repopulation and redistribution is considered with reference to the greater yield of unrepairable
DNA damage caused at high LET. Fractionation data are used to critically evaluate the model prediction
of increase in RBE for large dose per fractions in contrast to the expectations from single-dose
experiments. Furthermore, we investigate the impact of intrinsic radiosensitivity with the aim of assessing
hyper- and hypo-fractionation schemes for proton therapy. Different number of fractions and dose per
fractions between photon and ion beams need to be both considered in calculating biological equivalent
plans. Data and model prediction highlight how changes of the RBE with dose per fraction and differential
203 | P a g e
biological models for cell survival are used to calculate the RBE of proton beams.
Monte Carlo simulations with FLUKA and MCNPX were used to calculate proton dose distributions in
water phantoms. High-resolution energy spectra of proton beams were calculated for use in biological
models. Damage frequency including single strand breaks, and double strand breaks (DSB) was calculated
using the Monte Carlo Damage Simulation code (MCDS). DSBs along the depth of the Bragg curve were
subjected to a mechanistic repair model in order to calculate DSB-repair kinetics. The repair model
considers the recruitment of non-homologous end joining (NHEJ) and homologous recombination (HR)
repair proteins at the site of the DSB. All DSBs were initially subjected to NHEJ repair, while complex type
DSBs were further repaired with HR. The repair-misrepair-fixation (RMF) model was subsequently used to
calculate the RBE along the Bragg peak. The results demonstrated that LET, microdosimetric parameters
(e.g. dose-mean lineal energy), number of DSBs, complexity of DSBs, and RBE are constant along the
plateau region of the Bragg curve, while all parameters increase around the Bragg peak. DSB repair
kinetics illustrate that the repair of DSBs in the Bragg peak area are delayed due to enhanced complex
type DSBs. The RBE for V79 cell lines is close to 1 along the plateau of the proton depth dose but increases
by up to 40% at the distal edge. These data illustrate the need for revisiting the current generic RBE value
of 1.1 used in the clinic.
2
1
(PS3-27) Proton RBE for Fractionated exposures. Giuseppe Schettino, PhD MInstP ; Thomas Marshall ;
1
2
2
Pankaj Chaudhary ; and Kevin M. Prise NPL, Teddington, United Kingdom and Queen's University Belfast,
2
Belfast, United Kingdom
Fractionation is a key radiotherapy strategy to maximize dose delivered to cancer cells whilst
allowing healthy tissue to repair radiation damage. In conventional photon megavoltage radiotherapy,
reduced dose per fraction results in lower biological consequences in normal tissues compared to the
tumor. However, extrapolation of the clinical experience accumulated with conventional radiotherapy to
charged particles beams is not straightforward; scarce clinical database and errors in adapting photon-
based treatments could undermine the benefits of proton and hadrontherapy. One of the potential
advantages of charged particle beams is the increased efficiency for cell killing which is quantified by the
Relative Biological Effectiveness (RBE) parameter. It is well known that the RBE varies inversely with dose
and along the particle path in a non-linear trend as a function of the Linear Energy Transfer (LET). Recently
we have mapped the RBE variations at high resolution across a pristine and spread out Bragg peak for
clinically relevant proton doses in a range of cell lines with different radiosensitivity. We are now
investigating the impact of fractionation on the RBE with particular focus on the position along the beam
(i.e. LET dependency). Experimental measurements are combined with theoretical modelling adopting the
Linear Quadratic (LQ) formulation to analyze the RBE for clinically relevant fractionation treatments.
Impact of repopulation and redistribution is considered with reference to the greater yield of unrepairable
DNA damage caused at high LET. Fractionation data are used to critically evaluate the model prediction
of increase in RBE for large dose per fractions in contrast to the expectations from single-dose
experiments. Furthermore, we investigate the impact of intrinsic radiosensitivity with the aim of assessing
hyper- and hypo-fractionation schemes for proton therapy. Different number of fractions and dose per
fractions between photon and ion beams need to be both considered in calculating biological equivalent
plans. Data and model prediction highlight how changes of the RBE with dose per fraction and differential
203 | P a g e
