Implementation of hypoxia PET imaging in radiation therapy planning

Hypoxia has historically been relevant to radiation oncology as it relates to radioresistance, poor response to therapy and unfavorable patient's outcome in many solid tumors. In that regard, the recent advances in imaging, computation and radiation delivery techniques have been offering new perspectives to prescribe and deliver radiation dose in accordance with the spatial distribution of hypoxia mapped with molecular or functional imaging modalities, i.e., the so-called dose painting (DP). At first glance, the concept of dose painting appears promising and let foresee likely improvement in tumor local control at an acceptable clinical cost. However, adapting radiotherapy planning and delivery according to hypoxia imaging implicitly assumes: 1) that the imaging variable actually correlates with a local biological property associated with individual therapy outcome; 2) that the spatial distribution of the imaging parameter can be adequately converted into dose; and 3) that an irradiation device can actually deliver such a heterogeneous dose in fractionated RT treatments. In that regard, many uncertainties and difficulties remain at each step of the DP process, mainly related to the limitations of the current imaging techniques and the treatment fractionation. This paper will thus review the state of the art of DP with a specific focus on hypoxia, going from cancer biology to adaptive dose delivery. It will address the technological challenges and the clinical validation, which are both essential to translate an intuitively appealing concept into a clinically meaningful practice.