Impact of microscopic disease extension, extra-CTV tumour islets, incidental dose and dose conformity on tumour control probability

The impact of microscopic disease extension (MDE), extra-CTV tumour islets (TIs), incidental dose and dose conformity on tumour control probability (TCP) is analyzed using insilico simulations in this study. MDE in the region in between GTV and CTV is simulated inclusive of geometric uncertainties (GE) using spherical targets and spherical dose distribution. To study the effect of incidental dose on TIs and the effect of dose-response curve (DRC) on tumour control, islets were randomly distributed and TCP was calculated for various dose levels by rescaling the dose. Further, the impact of dose conformity on required PTV margins is also studied. The required PTV margins are similar to 2 mm lesser than assuming a uniform clonogen density if an exponential clonogen density fall off in the GTV-CTV is assumed. However, margins are almost equal if GE is higher in both cases. This shows that GE has a profound impact on margins. The effect of TIs showed a bi-phasic relation with increasing dose, indicating that patients with islets not in the beam paths do not benefit from dose escalation. Increasing dose conformity is also found to have considerable effect on TCP loss especially for larger GE. Further, smaller margins in IGRT should be used with caution where uncertainty in CTV definition is of concern.