Hypofractionated radiotherapy treatment preserves immune function and improves tumor control vs. hyperfractionated treatment.

Abstract

Abstract Radiotherapy is one of the most effective means of treating solid tumors in cancer patients. The radiation acts in two ways to control tumor growth. First, by inducing cell death due to direct damage to the DNA, then by the dying tumor cells releasing cellular signals that boost antitumor immunity. Unfortunately, radiotherapy may also damage the healthy tissue surrounding the tumor, causing adverse side effects in patients. To limit this damage, radiotherapy in the clinic is generally delivered as multiple small doses (hyperfractionation) over the course of several weeks. However, in preclinical radiotherapy studies, radiation is often given as a single or a few high ablative doses (hypofractionation). We previously observed improved tumor growth control and an increased number of tumor infiltrating lymphocytes (TIL) in tumors given an ablative dose when compared to a hyperfractionated scheme. As TILs are radiosensitive, we hypothesize that the multiple doses of a hyperfractionated scheme may result in increased killing of the TILs, reducing the effectiveness of the anti-tumor immune response. To further investigate this, we compared the responses of the mouse Colon38 tumor model to a hypofractionated vs. a hyperfractionated scheme, using doses based on current clinical protocols. In vitro, the hypofractionation treatment was more effective at killing tumor cells and inducing the tumor cells to produce IL-1β, TNFα, IL-6 and IP-10. In vivo, the hypofractionated treatment also resulted in a significant delay in tumor outgrowth and improved survival rates when compared to the hyperfractionated treatment. Therefore, hypofractionated radiotherapy may increase immunity and be more beneficial in tumor control. Funded by NIH R01CA28332.