Intensity modulated radiotherapy : effect on dose distribution and scattered dose and implications for carcinogenesis

2017-02-27T05:32:12Z (GMT) by Ruben, Jeremy David
BACKGROUND : Intensity modulated radiotherapy (IMRT) produces highly complex and conformal radiation dose distribution at the cost of exposing more normal tissue to low isodoses and greater monitor unit (MU) requirements. Hence concerns have been raised regarding its increased carcinogenic potential. AIMS : Over four experiments, this thesis examines the effect of IMRT on radio-carcinogenic risk through its alteration of radiation dose distribution within the treatment portals as well as its effect on scattered dose to tissues beyond the beam edge. The thesis examines the implications of such altered dose distribution for carcinogenic risk using a range of credible dose-response relationships. Dose distribution from IMRT and resultant carcinogenic risks are compared to those of three-dimensional conformal radiotherapy (3DCRT) for beam energies and disease sites relevant to clinical radiotherapy. The thesis also investigates the influence of beam energy on individual components of out-of-field scatter for both modalities. METHODS : The first experiment analyses in-field dose distribution through dose volume histogram (DVH) analysis and measures out-of-field scatter in an anthropomorphic phantom using thermo-luminescent dosimeters, for various clinical scenarios. Carcinogenic risks are calculated using several credible dose-response relationships by dividing normal tissues into smaller volumes of homogenous dose and summating their proportional carcinogenic contributions. Its findings questioned previous assertions about IMRT’s effect on out-of-field scatter and prompted two further experiments investigating out-of-field scatter in detail. These experiments were performed for both IMRT and 3DCRT in a specially constructed water phantom using both low- and high-energy photon beams. They provide detailed information on the individual contributions of the constituent components of out-of-field dose, namely head leakage, collimator scatter and internally scattered radiation. They analyse the implications for carcinogenesis including the influence of photoneutrons. The fourth experiment described in the thesis is an extension of the first, and examines the effect of high energy pelvic IMRT on in-field dose distribution together with previously measured peripheral doses, so as to generate carcinogenic estimates for the entire body. This experiment also provides information regarding the clinically relevant area of gynaecologic IMRT which was not covered in the first experiment. OUTCOMES : IMRT is demonstrated to constrict high isodoses while spreading out lower ones. Thus the effect of IMRT on in-field risk is variably advantageous or disadvantageous depending on dose-response model used. IMRT is consistently demonstrated to increase overall out-of-field scatter because of excess collimator scatter, despite a reduction in internally scattered radiation. Head leakage contributes very little. IMRT thus invariably increases out-of-field carcinogenic risks but these increases are small in absolute terms. High-energy beams increase machine scatter, for both modalities but reduce internal scatter; the net effect on out-of-field photon dose approximates zero. Photoneutron production however is significant - especially for high-energy IMRT which produces roughly twice as many photoneutrons as 3DCRT. These carry a high radio-carcinogenic risk. Carcinogenic risks are almost always increased by IMRT although relative risks appear lower than initially feared, and small in absolute terms. The increase in risk varies with dose-response model used, MU demand relative to 3DCRT, anatomical site, beam arrangement and beam energy. Dose-response models reflecting ever-increasing risk with increasing dose (no plateau); and less inter-modality MU disparity favour IMRT. High-energy IMRT carries the highest carcinogenic risk.