Tumor Vasculature Effects of High-Dose Radiation Therapy

Radiation therapy (XRT) is a form of cancer treatment that makes use of radiation, a high-powered beam, to kill tumor cells. Conventional fractionated XRT has been used for the longest time to treat varieties of tumors. In the past few years, an advanced method of XRT known as stereotactic radiosurgery (SRS) used for intracranial tumors and stereotactic body radiotherapy (SBRT) used for extracranial tumors has marked its success in the field of radiology. This form of treatment includes precise delivery of large doses to target the tumor volume given in a fewer number of fractions. As compared to a conventional, low dose per fraction XRT, a local tumor control of >80% has been reported using SBRT in several clinical trials. In spite of the success of SBRT in clinical settings, the actual mechanism by which this treatment modality eradicates tumor is still a controversial topic. Two divergent theories have been proposed and reported regarding this. Firstly, a direct tumor cell death caused by the accumulation of high radiation dose per fraction resulting in greater biologically effective dose. Secondly, an indirect tumor cell death caused by the damage of tumor vasculature following SBRT. In this chapter, we aim to discuss the characteristics of tumor vasculature and vascular changes upon high-radiation doses. The chapter will then be followed by the cellular targets and mechanisms of tumor cell death induced by high-dose XRT. Lastly, we also discuss vascular-targeted therapies for enhancing radiation-induced tumor response.