Proton radiotherapy represents a rapidly developing alternative to photon based treatment for specific types of cancer. The therapeutic use of protons is fundamentally motivated by an advantageous depth-dose profile characterised by the “Bragg peak". The limitation of damage to healthy tissues surrounding a treatment region using protons presents an inherent advantage over photons. However, even though there is extensive experience in the clinical use of protons, there remains much to be learned regarding the relative biological effectiveness (RBE) of protons in relation to photons. The shortcoming of current knowledge is manifested in the large uncertainties in the relationship between RBE and the proton linear energy transfer (LET), since many aspects must be considered when utilising current datasets (different experimental conditions, biophysical models etc.). As a result, current clinical practice adopts a constant RBE value of 1.1 across the entire treatment region, irrespective of size, beam modulation, depth, cellular radiosensitivity, and dose. Focussing on the key biological endpoints of cell survival and DNA damage, this work presents a comparative investigation of the biological effectiveness of clinical proton beams using normal and radioresistant human cells. Significant cell killing RBE and DNA damage response variations along the proton beam path were observed, particularly in the distal region, coinciding with a sharp rise in LET. Experimental RBE values were in excellent agreement with local effect model predicted values, indicating that dose-averaged LET is a suitable predictor of proton biological effectiveness. In addition, using the key clinical strategy of dose fractionation, variations in the cell killing RBE were also observed. The work presented has demonstrated that there is considerable potential for the optimisation of proton radiotherapy through the use of a variable RBE model as opposed to the currently adopted generic value of 1.1
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:707533 |
| Date | January 2016 |
| Creators | Marshall, Thomas |
| Publisher | Queen's University Belfast |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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