Radiation Biology of Lung Cancer

Radiobiology is central to an understanding of the principles of radiotherapy today. In the early twentieth century, the use of large, single doses of radiation, or hypofractionation, declined as evidence mounted that these doses caused considerable damage to normal tissues. Based on radiobiology, treatments then shifted toward smaller daily doses over a period of several weeks as a way to reduce this damage yet still achieve tumor control. A paradigm shift toward hypofractionation occurred again in the early twenty-first century as advances in technology now enable high-dose radiation to more precisely target the tumor while minimizing the amount of normal tissues exposed. In this chapter, we explore the basic tenets of radiation biology in order to understand the rationale behind these vastly different approaches as they apply specifically to the treatment of lung cancer. We also examine ways to exploit the radiobiology of lung cancer by using various strategies with a focus on moderate hypofractionation, stereotactic ablative radiation therapy, and tumor hypoxia. We conclude with a discussion on the biology of combining immunotherapy with radiation in lung cancer.