Reflections on beam configuration optimization for intensity-modulated proton therapy.

Presumably, intensity-modulated proton radiotherapy (IMPT) is the most powerful form of proton radiotherapy. In the current state of the art, IMPT beam configurations (i.e. the number of beams and their directions) are, in general, chosen subjectively based on prior experience and practicality. Beam configuration optimization (BCO) for IMPT could, in theory, significantly enhance IMPT's therapeutic potential. However, BCO is complex and highly computer resource-intensive. Some algorithms for BCO have been developed for intensity-modulated photon therapy (IMRT). They are rarely used clinically mainly because the large number of beams typically employed in IMRT renders BCO essentially unnecessary. Moreover, in the newer form of IMRT, volumetric modulated arc therapy, there are no individual static beams. BCO is of greater importance for IMPT because it typically employs a very small number of beams (2-4) and, when the number of beams is small, BCO is critical for improving plan quality. However, the unique properties and requirements of protons, particularly in IMPT, make BCO challenging. Protons are more sensitive than photons to anatomic changes, exhibit variable relative biological effectiveness along their paths, and, as recently discovered, may spare the immune system. Such factors must be considered in IMPT BCO, though doing so would make BCO more resource intensive and make it more challenging to extend BCO algorithms developed for IMRT to IMPT. A limited amount of research in IMPT BCO has been conducted; however, considerable additional work is needed for its further development to make it truly effective and computationally practical. This article aims to provide a review of existing BCO algorithms, most of which were developed for IMRT, and addresses important requirements specific to BCO for IMPT optimization that necessitate the modification of existing approaches or the development of new effective and efficient ones.