Increasing the power of tumour control and normal tissue complication probability modelling in radiotherapy: recent trends and current issues(550 views)(PDF public150 views) Tommasino F, Nahum A, Cella L
Increasing the power of tumour control and normal tissue complication probability modelling in radiotherapy: recent trends and current issues
The release of a homogeneous high dose to the tumour region has been one
of the cornerstones of radiotherapy (RT) treatment since its early
days. According to the organ type and to the cancer histology, different
doses are required in order to inactivate malignant cells, thus
stopping proliferation. However, radiation-induced cell killing is a
stochastic process. Tumour control probability (TCP) models have been
developed in order to assign a success rate to a given RT treatment. At
the same time, there is the need to keep the risks of normal tissue
toxicity at an acceptable level. Normal tissue complication probability
(NTCP) models provide a means of doing this. Traditionally, TCP and NTCP
models combine clinical outcomes with dosimetric information in terms
of dose-volume histograms (DVH). Model parameters are derived by
mathematical fits to clinical observations and are subsequently used to
estimate the risk of tumour relapse or toxicity. In both types of
models, all of the patient dosimetric information is condensed into the
DVHs, which represents a potential limitation on their descriptive and
predictive power. This choice, related to historical and practical
reasons, does not allow the full complexity of the 3D dose distribution
in the patient to be taken into account. Neglecting these aspects might
be relevant in a modern RT setting, which often includes the presence of
high dose gradient regions. This has motivated research on ‘advanced’
TCP and NTCP models, able to tackle the problem by looking at a
different scale, e.g. in tumour sub-regions or at the single voxel
level. This is relevant not only from the purely dosimetric point of
view. Increasing evidence is reported on the heterogeneity of cancer
tissues, suggesting that non-uniform dose distributions could result in
improved survival, for instance if targeted to take into account sub
volumes with high clonogen density or hypoxic radioresistant regions.
Similarly, radiation-induced side effects are part of a complex
biological response, which depends not only on cell killing, but also on
the inflammatory response and in some cases on the interplay among
different organs. Obviously, conventional NTCP models cannot describe
this scenario, and the development of more advanced mathematical tools
is needed. This review will be focused on the discussion of recent
studies showing possible directions for moving the field of TCP and NTCP
modelling forward. Without diminishing the role and usefulness of
available models, the aim is to shed light on the benefits that might be
achieved by ‘enhanced’ modelling. This could represent an important
step in the gradual transition of radiation therapy towards a form of
precision medicine.
Increasing the power of tumour control and normal tissue complication probability modelling in radiotherapy: recent trends and current issues
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