In situ Tumor Ablation with Radiation Therapy: Its Effect on the Tumor Microenvironment and Anti-tumor Immunity

The delivery of external beam radiation therapy (RT) for cancer with intent to cure has been optimized over the last 80 years and standardized to a protocol with doses fractionated into around 2 Gy amounts delivered daily five times per week to the tumor with a relatively homogeneous field and with the total dose being determined by what adjacent late responding normal tissues might tolerate. The radiobiological principles that underlie the success of such treatments have been elaborated with the most important being the relative sparing of tissues that turnover slowly (late responding tissues) compared with rapidly (acute responding tissues and many cancers) by small dose fractions. The aim of classical RT is therefore to preserve normal tissue function while curing cancer.