The significant differences in dose deposition and scattering characteristics of protons and photons mean that many of the formalisms, algorithms and techniques used for photon treatment planning, optimization and plan evaluation are not extensible to protons. The finite range, sharp distal fall-off and scattering characteristics make proton dose distributions more sensitive to inter- and intra-fractional anatomy variations. The computed range of protons in patients is uncertain due to uncertainty in the transformation of Hounsfield Units (HUs) to stopping power ratios (SPRs). The conventional practice in photon therapy is to assign an adequate safety margin to the clinical target volume (CTV) to create a planning target volume (PTV) to ensure that the CTV will receive the prescribed dose in the face of treatment setup and anatomy variations over the course of radiotherapy. For protons, however, uncertainty in the range depends on the depth of point of interest and, therefore, on the direction of each proton beam. Furthermore, anatomic variations perturb the dose distribution within the target volume, not just near the boundaries. Consequently, the conventional practice of assigning CTV-to-PTV margins is not appropriate for the planning and evaluation of proton treatments. Similar margin issues exist for margins for organs at risk.
Another noteworthy difference between protons and photons is that an attenuator placed in the path of photons changes the intensity (number) of photons with only a small effect on the energy spectrum; whereas for protons, the attenuator changes their energy, and, therefore, their range, and has only a small effect on the number of protons.
For proton therapy in general, due to the lower dose proximally and distally to the target, the number of beams needed are typically much smaller than for photons. This is assumed to be an advantage for protons, though, in some aspects, e.g., robustness of dose distributions, it may be a detriment. Preferred beam directions for protons tend to be those that minimize passage through complex tissue heterogeneities and have shorter paths to the distal tumor edge. Furthermore, because of concern about higher biological effectiveness at the end of proton range and uncertainty in proton range, directions, which could potentially lead to higher biologically effective dose to a critical tissue, such as spinal cord, at or just beyond the distal edge of the target, are avoided.
For these reasons, alternative techniques have been and continue to be further developed. Techniques are different for passively-scattered protons and scanning beams and IMPT for reasons that may become apparent from the discussion below.
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