Abstract
This work aims to theoretically show the development of a nonequilibrium of radiation-induced bystander effect (RIBE) under steep dose gradient regions that typically occur in the field edges of a beam. We applied the kinetics model proposed by (McMahon et al. 2013) for in vivo conditions coupled with a hypothesis called “Layer-limited bystander signaling (LLBS)” to demonstrate 1) an enhancement in TCP (i.e. Enhanced TCP or ETCP) due to bystander signals, 2) the development of nonequilibrium of RIBE under steep dose gradient regions and 3) the reduction in ETCP in the surface of Clinical Target Volume (CTV) due to the non-equilibrium of RIBE. We incorporated the elements of RIBE directly in the existing Poisson LQ model available in Pinnacle3 TPS (Version 9.10.0) to compute the percentage reduction of ETCP in the tumor surface due to nonequilibrium of RIBE. The percentage improvement in TCP obtained in tumor surface by accounting for RIBE is about 46% lower than that obtained in the interior of the tumor. This suggests that relatively more number of cancerous cells might survive in the vicinity of tumor surface. The result obtained from the study is indicative of an additional uncertainty component associated with radiation treatment. Hence, this paper suggests that the radiation treatments employing steep dose gradients could be biophysically different in many ways.
Highlights
Intensity modulated Radiation Therapy (IMRT) allows for a highly conformal dose distribution to be planned for a target volume, while effectively sparing the surrounding healthy tissues or organs
We applied the kinetics model proposed by McMahon et al for in vivo conditions [12] coupled with a hypothesis called “Layer-limited bystander signaling (LLBS)” to quantitatively demonstrate 1) an enhancement in tumor control probability (TCP) (i.e. Enhanced TCP or enhanced tumor control probability (ETCP)) due to bystander signals, 2) the development of nonequilibrium of radiation-induced bystander effects (RIBE) under steep dose gradient regions and 3) the reduction in ETCP in the surface of Clinical Target Volume (CTV) due to the non-equilibrium of RIBE
We incorporated the elements of RIBE directly in the existing Poisson LQ model available in Pinnacle3 TPS (Version 9.10.0) to compute ETCP
Summary
Intensity modulated Radiation Therapy (IMRT) allows for a highly conformal dose distribution to be planned for a target volume, while effectively sparing the surrounding healthy tissues or organs. The reported advantages in IMRT arise from the ability to produce steep dose gradients between tumor surface and surrounding normal tissue. Many investigators have suggested methods to account for changes in radiation response of tumour cells when exposed to inhomogeneous dose distributions [1]-[3]. These models are based on the hypothesis that the probability of killing tumour cells at a given point is a function solely of the dose delivered to that point [4]. Recent studies have indicated that direct exposure to high doses of radiation does not mitigate signaling effects [9] [10]
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