Abstract
Despite increasing use of proton therapy (PBT), several systematic literature reviews show limited gains in clinical outcomes, with publications mostly devoted to recent technical developments. The lack of randomised control studies has also hampered progress in the acceptance of PBT by many oncologists and policy makers. There remain two important uncertainties associated with PBT, namely: (1) accuracy and reproducibility of Bragg peak position (BPP); and (2) imprecise knowledge of the relative biological effect (RBE) for different tissues and tumours, and at different doses. Incorrect BPP will change dose, linear energy transfer (LET) and RBE, with risks of reduced tumour control and enhanced toxicity. These interrelationships are discussed qualitatively with respect to the ICRU target volume definitions. The internationally accepted proton RBE of 1.1 was based on assays and dose ranges unlikely to reveal the complete range of RBE in the human body. RBE values are not known for human (or animal) brain, spine, kidney, liver, intestine, etc. A simple efficiency model for estimating proton RBE values is described, based on data of Belli et al. and other authors, which allows linear increases in α and β with LET, with a gradient estimated using a saturation model from the low LET α and β radiosensitivity parameter input values, and decreasing RBE with increasing dose. To improve outcomes, 3-D dose-LET-RBE and bio-effectiveness maps are required. Validation experiments are indicated in relevant tissues. Randomised clinical studies that test the invariant 1.1 RBE allocation against higher values in late reacting tissues, and lower tumour RBE values in the case of radiosensitive tumours, are also indicated.
Highlights
Radiotherapy has evolved empirically, with progressive technical improvements, most of which have contributed to better clinical outcomes as either a better cure rate, or reduced complication rate, or both.Early and late tissue side effects are important and do frequently limit presently prescribed doses, as may changes in tissue radiation tolerances due to surgery, concomitant medical conditions, and various forms of chemotherapy
With increasing recognition that late vascular damage is responsible for many chronic effects of radiation and that the relative risk of radiation induced coronary artery disease is estimated to be around 7.5% per Gray [2], as well as the established cancer induction risks of at least 5% per Sievert [3], leads to a logical requirement for radiation beams that can markedly reduce integral dose and so the amount of tissue traversed. This can be achieved with positively charged particle beams such as protons and light ions, due to their reduced path length in tissues caused by the Bragg peak (BP) effect
The experiments of Belli et al [11] have shown that proton linear energy transfer (LET) and relative biological effect (RBE) rise sharply at much
Summary
Radiotherapy has evolved empirically, with progressive technical improvements, most of which have contributed to better clinical outcomes as either a better cure rate, or reduced complication rate, or both.Early and late tissue side effects are important and do frequently limit presently prescribed doses, as may changes in tissue radiation tolerances due to surgery, concomitant medical conditions, and various forms of chemotherapy. With increasing recognition that late vascular damage is responsible for many chronic effects of radiation and that the relative risk of radiation induced coronary artery disease is estimated to be around 7.5% per Gray [2], as well as the established cancer induction risks of at least 5% per Sievert [3], leads to a logical requirement for radiation beams that can markedly reduce integral dose and so the amount of tissue traversed. This can be achieved with positively charged particle beams such as protons and light ions, due to their reduced path length in tissues caused by the Bragg peak (BP) effect
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