Choline PET based dose-painting in prostate cancer - Modelling of dose effects

Background: Several randomized trials have documented the value of
radiation dose escalation in patients with prostate cancer,
especially in patients with intermediate risk profile. Up to now
dose escalation is usually applied to the whole prostate. IMRT and
related techniques currently allow for dose escalation in
sub-volumes of the organ. However, the sensitivity of the imaging
modality and the fact that small islands of cancer are often
dispersed within the whole organ may limit these approaches with
regard to a clear clinical benefit. In order to assess potential
effects of a dose escalation in certain sub-volumes based on
choline PET imaging a mathematical dose-response model was
developed. Methods: Based on different assumptions for alpha/beta,
gamma 50, sensitivity and specificity of choline PET, the influence
of the whole prostate and simultaneous integrated boost (SIB) dose
on tumor control probability (TCP) was calculated. Based on the
given heterogeneity of all potential variables certain
representative permutations of the parameters were chosen and,
subsequently, the influence on TCP was assessed. Results: Using
schedules with 74 Gy within the whole prostate and a SIB dose of 90
Gy the TCP increase ranged from 23.1% (high detection rate of
choline PET, low whole prostate dose, high gamma 50/ASTRO
definition for tumor control) to 1.4% TCP gain (low sensitivity of
PET, high whole prostate dose, CN + 2 definition for tumor control)
or even 0% in selected cases. The corresponding initial TCP values
without integrated boost ranged from 67.3% to 100%. According to a
large data set of intermediate-risk prostate cancer patients the
resulting TCP gains ranged from 22.2% to 10.1% (ASTRO definition)
or from 13.2% to 6.0% (CN + 2 definition). Discussion: Although a
simplified mathematical model was employed, the presented model
allows for an estimation in how far given schedules are relevant
for clinical practice. However, the benefit of a SIB based on
choline PET seems less than intuitively expected. Only under the
assumption of high detection rates and low initial TCP values the
TCP gain has been shown to be relevant. Conclusions: Based on the
employed assumptions, specific dose escalation to choline PET
positive areas within the prostate may increase the local control
rates. Due to the lack of exact PET sensitivity and prostate
alpha/beta parameter, no firm conclusions can be made. Small
variations may completely abrogate the clinical benefit of a SIB
based on choline PET imaging.