Page 295 - 2014 Printable Abstract Book
P. 295
simulations, it has been possible to demonstrate the clinical impact of a variable RBE in terms of
biologically weighted dose, extended biological range, dose scatter and the treatment of hypoxic regions.
In particular, the ability to compare and contrast clinical consequences of a variable RBE allows the
optimization of physical dose plans to deliver well defined, homogeneous biological doses to treatment
regions. 1. Chaudhary & Marshall et al. - “RBE variation along monoenergetic and modulated Bragg peaks
of a 62 MeV therapeutic proton beam: a pre-clinical assessment.” Accepted pending minor revision,
March 2014 - International Journal of Radiation Oncology, Biology, Physics.
(PS5-15) A mechanistic mathematical model for the repair of base lesions and single-starnd breaks
1
2
induced by ionizing radiation of different quality. Shirin Rahmanian ; Reza Taleei ; and Hooshang
1
1
Nikjoo , Karolinska Institutete, Stockholm, Sweden and University of Texas MD Anderson Cancer Center,
2
Houston, TX
The aim of this study is to model mechansitically the repair of oxidized base damage (BDs) and
single-strand breaks (SSBs) produced by ionizing radiations (IR) of different LET (linear energy transfer). In
mamailian cells BDs and SSBs are repaired via the base excision repair (BER) pathway. The BER pathway
can proceed either via short-patch repair (SPR), which involves single nucleotide incorporation, or via the
long-patch repair (LPR) subpathway, which involves incorporation of several nucleotides. A hallmark of
ionizing radiation is the production of closely spaced lesions. The frequency of these clustered lesions is
increased with use of higher LET ions. BD and SSB are defined as complex if there is one or more lesions
within 10 bp proximity. While it is known that DSB kinetics is characterized by fast and slow components,
this characteristic is also observable with IR induced BDs and SSBs. We hypothesize that simple BDs and
SSBs are repaired via the short-patch repair with fast kinetics and complex base damages are repaired via
the long-patch repair subpathway with a much slower kinetics. In order to test the repair of these lesions
we used Monte Carlo track simulation (MCTS) to obtain the initial spectrum of DNA damage for different
particles including electrons, protons and alpha particles. Using the MCTS code KURBUC system the
energy depositions events and reactions of water radicals in the nucleobases were scored in a model cell
nucleus and the types of damages in the human genome were determined. Next, the initial induced BDs
and SSBs were subjected to our BER model. The repair model consist of a system of nonlinear ordinary
differential equations describing the repair process step by step and have been verified in comparison to
experimental measurements. Using our mechanistic repair models for BDs and SSBs, we present how
spatial distribution of these lesions with respect to one another and in presence of DSBs affects the repair
kinetics.
(PS5-16) Monte-Carlo assessment of glioblastoma (GBM) clinical target volume (CTV) efficacy based on
calculated cell survival following external beam radiotherapy for heterogeneous and hypoxic GBM
2
tumours. Leyla Moghaddasi 1; 2 ; Eva Bezak, PhD 1; 2 ; and Wendy Harriss-Phillips University of Adelaide,
2
Adelaide, Australia and Royal Adelaide Hospital, Adelaide, Australia
1
Aim: Determination of optimal CTV is complex and remains uncertain. The aim of this study is to
develop a microscopic-scale tumour model to be used for evaluation of CTV practices for GBM currently
applied in external radiotherapy. Method: The GBM model was structured in three parts: a micro-
dosimetry model (Geant4) was developed to calculate the dose deposited in GBM cells (a cubic water
293 | P a g e
biologically weighted dose, extended biological range, dose scatter and the treatment of hypoxic regions.
In particular, the ability to compare and contrast clinical consequences of a variable RBE allows the
optimization of physical dose plans to deliver well defined, homogeneous biological doses to treatment
regions. 1. Chaudhary & Marshall et al. - “RBE variation along monoenergetic and modulated Bragg peaks
of a 62 MeV therapeutic proton beam: a pre-clinical assessment.” Accepted pending minor revision,
March 2014 - International Journal of Radiation Oncology, Biology, Physics.
(PS5-15) A mechanistic mathematical model for the repair of base lesions and single-starnd breaks
1
2
induced by ionizing radiation of different quality. Shirin Rahmanian ; Reza Taleei ; and Hooshang
1
1
Nikjoo , Karolinska Institutete, Stockholm, Sweden and University of Texas MD Anderson Cancer Center,
2
Houston, TX
The aim of this study is to model mechansitically the repair of oxidized base damage (BDs) and
single-strand breaks (SSBs) produced by ionizing radiations (IR) of different LET (linear energy transfer). In
mamailian cells BDs and SSBs are repaired via the base excision repair (BER) pathway. The BER pathway
can proceed either via short-patch repair (SPR), which involves single nucleotide incorporation, or via the
long-patch repair (LPR) subpathway, which involves incorporation of several nucleotides. A hallmark of
ionizing radiation is the production of closely spaced lesions. The frequency of these clustered lesions is
increased with use of higher LET ions. BD and SSB are defined as complex if there is one or more lesions
within 10 bp proximity. While it is known that DSB kinetics is characterized by fast and slow components,
this characteristic is also observable with IR induced BDs and SSBs. We hypothesize that simple BDs and
SSBs are repaired via the short-patch repair with fast kinetics and complex base damages are repaired via
the long-patch repair subpathway with a much slower kinetics. In order to test the repair of these lesions
we used Monte Carlo track simulation (MCTS) to obtain the initial spectrum of DNA damage for different
particles including electrons, protons and alpha particles. Using the MCTS code KURBUC system the
energy depositions events and reactions of water radicals in the nucleobases were scored in a model cell
nucleus and the types of damages in the human genome were determined. Next, the initial induced BDs
and SSBs were subjected to our BER model. The repair model consist of a system of nonlinear ordinary
differential equations describing the repair process step by step and have been verified in comparison to
experimental measurements. Using our mechanistic repair models for BDs and SSBs, we present how
spatial distribution of these lesions with respect to one another and in presence of DSBs affects the repair
kinetics.
(PS5-16) Monte-Carlo assessment of glioblastoma (GBM) clinical target volume (CTV) efficacy based on
calculated cell survival following external beam radiotherapy for heterogeneous and hypoxic GBM
2
tumours. Leyla Moghaddasi 1; 2 ; Eva Bezak, PhD 1; 2 ; and Wendy Harriss-Phillips University of Adelaide,
2
Adelaide, Australia and Royal Adelaide Hospital, Adelaide, Australia
1
Aim: Determination of optimal CTV is complex and remains uncertain. The aim of this study is to
develop a microscopic-scale tumour model to be used for evaluation of CTV practices for GBM currently
applied in external radiotherapy. Method: The GBM model was structured in three parts: a micro-
dosimetry model (Geant4) was developed to calculate the dose deposited in GBM cells (a cubic water
293 | P a g e
