Page 96 - 2014 Printable Abstract Book
P. 96
the other hand, the clinical relevance of experimental RBE values in vitro and in vivo is often unclear,
specifically for normal tissue effects. Furthermore, clinical endpoints comparing proton and photon
treatments are based on differences in organ dose distributions. As RBE uncertainties are comparable to
RBE variations, practitioners are reluctant to modify the current clinical practice. Dose-averaged LET
values could potentially be used in biological treatment optimization even without knowing dose and
endpoint specific RBE values accurately. Specifically, it might be possible to increase the therapeutic ratio
in intensity-modulated proton therapy. This presentation will first summarize the current knowledge on
measured proton RBE values for cell survival and other endpoints in vitro and in vivo and discuss the
clinical evidence for a variable proton RBE. Next, the potential impact of RBE variations for certain
treatment sites in proton therapy will be outlined. Finally, uncertainties in proton RBE values and
shortcomings in the general RBE concept will be discussed and concepts for biological treatment
optimization in proton therapy will be presented.
(S2703) New biological models of radiation response - relevance to radiotherapy. Stephen McMahon,
Queen's University, Belfast, Ireland
The development of the linear-quadratic model was a major contribution to the development of
radiotherapy, and has formed the basis for a range of analyses of different treatment modalities and
outcome predictions. However, despite continuing improvements in our knowledge of fundamental
radio-biological responses, the translation of this knowledge to therapeutic modelling has been limited.
The need for improved translation is becoming increasingly pressing as technical advances in radiotherapy
delivery mean that highly conformal delivery can be supplemented with sub-volume dose painting and
there is increased flexibility in dose prescriptions. While computationally simple, direct dose-response
models are difficult to expand to encompass the range of underlying biological and physical processes
which may impact on biological outcomes. Although there are many examples dose correction factors
(such as the Oxygen Enhancement Ratio in hypoxia, or Relative Biological Effectiveness in hadrontherapy),
these are usually ad-hoc, generated with reference to a particular variable, and in most cases have seen
limited translation to the clinic. A more robust approach involves the development of models informed
by biological mechanisms at a fundamental level, enabling an explicit incorporation of a range of biological
processes which impact on cellular survival. When implemented on the sub-tissue or cellular level, these
models also enable the incorporation of environmental and signalling-driven factors which are typically
neglected in clinical practice. This talk will review progress in developing such a model, as well as
investigating some of the divergences which are observed between simple dose-based predictions and
the model's biologically-informed ones.
(S2704) New approaches in radiobiology impacting on advanced radiotherapy. Brian Marples, PhD and
Sarah A. Krueger, PhD, William Beaumont Hospital, Royal Oak, MI
The technical evolution of clinical radiotherapy has improved both the efficacy and safety of
radiation treatments for patients. The advent of computed tomography (CT)-based planning marked an
important shift toward target-directed treatment, and cone-beam CT images acquired prior to each
fraction compensate for any deviations from the simulation CT. In brain tumor studies, fusing CT-planning
images with positron emission tomography (PET) and magnetic resonance imaging (MRI) scans has further
94 | P a g e
specifically for normal tissue effects. Furthermore, clinical endpoints comparing proton and photon
treatments are based on differences in organ dose distributions. As RBE uncertainties are comparable to
RBE variations, practitioners are reluctant to modify the current clinical practice. Dose-averaged LET
values could potentially be used in biological treatment optimization even without knowing dose and
endpoint specific RBE values accurately. Specifically, it might be possible to increase the therapeutic ratio
in intensity-modulated proton therapy. This presentation will first summarize the current knowledge on
measured proton RBE values for cell survival and other endpoints in vitro and in vivo and discuss the
clinical evidence for a variable proton RBE. Next, the potential impact of RBE variations for certain
treatment sites in proton therapy will be outlined. Finally, uncertainties in proton RBE values and
shortcomings in the general RBE concept will be discussed and concepts for biological treatment
optimization in proton therapy will be presented.
(S2703) New biological models of radiation response - relevance to radiotherapy. Stephen McMahon,
Queen's University, Belfast, Ireland
The development of the linear-quadratic model was a major contribution to the development of
radiotherapy, and has formed the basis for a range of analyses of different treatment modalities and
outcome predictions. However, despite continuing improvements in our knowledge of fundamental
radio-biological responses, the translation of this knowledge to therapeutic modelling has been limited.
The need for improved translation is becoming increasingly pressing as technical advances in radiotherapy
delivery mean that highly conformal delivery can be supplemented with sub-volume dose painting and
there is increased flexibility in dose prescriptions. While computationally simple, direct dose-response
models are difficult to expand to encompass the range of underlying biological and physical processes
which may impact on biological outcomes. Although there are many examples dose correction factors
(such as the Oxygen Enhancement Ratio in hypoxia, or Relative Biological Effectiveness in hadrontherapy),
these are usually ad-hoc, generated with reference to a particular variable, and in most cases have seen
limited translation to the clinic. A more robust approach involves the development of models informed
by biological mechanisms at a fundamental level, enabling an explicit incorporation of a range of biological
processes which impact on cellular survival. When implemented on the sub-tissue or cellular level, these
models also enable the incorporation of environmental and signalling-driven factors which are typically
neglected in clinical practice. This talk will review progress in developing such a model, as well as
investigating some of the divergences which are observed between simple dose-based predictions and
the model's biologically-informed ones.
(S2704) New approaches in radiobiology impacting on advanced radiotherapy. Brian Marples, PhD and
Sarah A. Krueger, PhD, William Beaumont Hospital, Royal Oak, MI
The technical evolution of clinical radiotherapy has improved both the efficacy and safety of
radiation treatments for patients. The advent of computed tomography (CT)-based planning marked an
important shift toward target-directed treatment, and cone-beam CT images acquired prior to each
fraction compensate for any deviations from the simulation CT. In brain tumor studies, fusing CT-planning
images with positron emission tomography (PET) and magnetic resonance imaging (MRI) scans has further
94 | P a g e
