PT with its physical characteristics of superior dose deposition in a given tumor and reduced radiation dose to surrounding normal tissues offers an inherent geometric advantage. Lower entrance doses as well as sharp dose falloff at the distal edge of the beam result in a significant higher conformality in comparison to photons. The main disadvantage of the proton beam is the worse lateral dose falloff and the range of uncertainties when treating tissues of different densities especially if there are inter- and intra-fractional changes during treatment (Fig. 1).

According to the International Commission on Radiation Units and Measurements (ICRU) report 78 (ICRU 2007) the radio-biological effectiveness (RBE) of protons is comparable with the RBE of photons. Dose units expressed as physical dose have a difference of about 10 % in favor of protons (Paganetti et al. 2002). The usually constant RBE of 1.1 in comparison to photons is an advantage of the proton beam. Nevertheless, one has to estimate a higher RBE at the distal edge of the proton beam. Also, the intensity of the linear energy transfer (LET) influences the RBE (see also the following chapter “There is Evidence of the Superiority of Protons or Heavy Ions, Pro”). Comparable proton or photon doses have a similar cell-killing effect on tumors and similar toxic effects on normal healthy tissues (Paganetti et al. 2004). This results in an excellent estimation of expected toxicities in comparison to applied doses during the treatment planning process. Established tolerance doses in RT are generally transferable to PT. All available publications on treatments with protons confirmed it. No publication has raised the issue of unexpected acute or late toxicity. Any described incidence of late toxicity was related to high dose escalation rather than use of protons. The initial concept of physical dose distribution and effectiveness has not been called into question by clinical results. However, no phase III trials were available comparing protons and photons. Most proton radiation therapy data were based on retrospective reviews and only for a few indications data were based on phase I/II trials of single institution experiences. Multi-institutional collaboration was very limited.