On the Nonequilibrium of Radiation-Induced Bystander Effects in Tumor Surface and Its Implications in Radiation Therapy


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.

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Vaitheeswaran, R. and Maria Das, K. (2015) On the Nonequilibrium of Radiation-Induced Bystander Effects in Tumor Surface and Its Implications in Radiation Therapy. International Journal of Medical Physics, Clinical Engineering and Radiation Oncology, 4, 208-214. doi: 10.4236/ijmpcero.2015.43025.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Kallman, P., Agren, A. and Brahme, A. (1992) Tumour and Normal Tissue Responses to Fractionated Non-Uniform Dose Delivery. International Journal of Radiation Biology, 62, 249-262.
[2] Ebert, M.A. and Hoban, P.W. (1996) Some Characteristics of Tumour Control Probability for Heterogeneous Tumours. Physics in Medicine and Biology, 41, 2125-2133.
[3] Niemierko, A. and Goitein, M. (1993) Implementation of a Model for Estimating Tumor Control Probability for an Inhomogeneously Irradiated Tumor. Radiotherapy and Oncology, 29, 140-147.
[4] Hall, E.J. and Giaccia, A.J. (2006) Radiobiology for the Radiologist. Lippincott Williams & Wilkins.
[5] Mothersill, C. and Seymour, C.B. (1998) Cell-Cell Contact during Gamma Irradiation Is Not Required to Induce a Bystander Effect in Normal Human Keratinocytes: Evidence for Release during Irradiation of a Signal Controlling Survival into the Medium. Radiation Research, 149, 256-262.
[6] Nagasawa, H. and Little, J.B. (1999) Unexpected Sensitivity to the Induction of Mutations by Very Low Doses of Alpha-Particle Radiation: Evidence for a Bystander Effect. Radiation Research, 152, 552-557.
[7] Suchowerska, N., Ebert, M.A., Zhang, M. and Jackson, M. (2005) In Vitro Response of Tumour Cells to Non-Uniform Irradiation. Physics in Medicine and Biology, 50, 3041-3051.
[8] Butterworth, KT., McGarry, C.K., O’Sullivan, J.M., Hounsell, A.R. and Prise, K.M. (2010) A Study of the Biological Effects of Modulated 6 MV Radiation Fields. Physics in Medicine and Biology, 55, 1607-1618.
[9] Butterworth, K.T., McGarry, C.K., Trainor, C., O’Sullivan, J.M., Hounsell, A.R., et al. (2011) Out-of-Field Cell Survival Following Exposure to Intensity-Modulated Radiation Fields. International Journal of Radiation Oncology*Biology*Physics, 79, 1516-1522.
[10] Butterworth, K.T., McGarry, C.K., Trainor, C., McMahon, S.J., O’Sullivan, J.M., et al. (2012) Dose, Dose-Rate and Field Size Effects on Cell Survival Following expoSure to Non-Uniform Radiation Fields. Physics in Medicine and Biology, 57, 3197-3206.
[11] Bromley, R., et al. (2009) Predicting the Clonogenic Survival of A549 Cells after Modulated X-Ray Irradiation Using the Linear Quadratic Model. Physics in Medicine and Biology, 54, 187.
[12] McMahon, S.J., et al. (2013) A Kinetic-Based Model of Radiation-Induced Intercellular Signaling. PloS One, 8.
[13] McMahon., S.J., et al. (2013) Implications of Intercellular Signaling for Radiation Therapy: A Theoretical Dose-Planning Study. International Journal of Radiation Oncology*Biology*Physics, 87, 1148-1154.
[14] Belyakov, O.V., Mitchell, S., Parikh, D., Randers-Pehrson, G., Marino, S., et al. (2005) Biological Effects in Unirradiated Human Tissue Induced by Radiation Damage up to 1 mm Away. Proceedings of the National Academy of Sciences of the United States of America, 102, 14203-14208.

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