The Era of Modern Radiation Therapy: Innovations to Spare Normal Tissues

Abstract

The incidence of cancer is increasing worldwide with more than 14 million new cases per year (GLOBOCAN. Cancer incidence and mortality worldwide: IARC cancer base no. 11. GLOBOCAN 2012 v10, 2012). About 50% of cancer patients are treated with radiation therapy (RT), making it, after surgery, the most important contributor to cancer cure. In the era of targeted therapies, RT remains one of the most precise and powerful targeted treatments. Thanks to major advances in physics, imaging, and ballistics, high-precision dose delivery is successful in safely reducing the volume of irradiated normal tissues. New and very appealing RT approaches using high or very high dose per fraction (hypofractionation), such as stereotactic body radiotherapy (SBRT), also called stereotactic ablative radiotherapy (SABR) or stereotactic radiosurgery (SRS), are increasingly used, both in early-stage cancers and in some oligometastatic patients. In parallel, the particular dose distribution of protons and heavy ions is being therapeutically exploited with the aim to efficiently spare sensitive organs and enhance tumor cure. Increasing tumor sensitivity to irradiation, increasing normal tissue tolerance to radiation, and optimally avoiding normal tissue while distributing curative doses to tumors are the major paths toward improving the therapeutic index of radiotherapy. In this review, we will discuss the current status of normal tissue complications, their management, as well as the current status and future opportunities for clinical implementation of novel strategies to prevent, mitigate, and cure radiation injuries based upon the molecular understanding of cell and tissue responses to ionizing radiation.