Hypofractionation in Glioblastoma: An Overview of Palliative, Definitive, and Exploratory Uses

Simple Summary Despite ongoing medical advancements, glioblastoma remains a nearly uniformly fatal disease with a median survival of less than two years. This is largely attributable to its aggressive infiltration of surrounding brain parenchyma, which leads to a high risk of locoregional recurrence after the first line of therapy. Many strategies have been explored in an attempt to improve locoregional control, including hypofractionation. Here, we review a range of preclinical and clinical research on hypofractionation in the neoadjuvant, adjuvant, and recurrent or palliative setting. Additionally, we discuss novel hypofractionation strategies currently under investigation, such as FLASH radiotherapy.Abstract Glioblastoma (GBM) is the most common primary brain malignancy in adults, and its incidence is increasing worldwide. Its prognosis remains limited despite recent imaging and therapeutic advances. The current standard of care is maximal safe resection followed by conventionally fractionated radiotherapy with concurrent and adjuvant temozolomide (TMZ), with or without tumor-treating fields (TTF). However, hypofractionated radiotherapy (HFRT) has also been utilized for a variety of reasons. It is an established treatment option in the palliative setting, where shortened treatment duration can positively impact the overall quality of life for older patients or those with additional health or socioeconomic considerations. HFRT, and in particular stereotactic radiosurgery (SRS), has also been explored in both the pre- and post-operative setting for newly diagnosed and recurrent diseases. In this review, we summarize the ways in which HFRT has been utilized in the GBM patient population and its evolving role in the experimental space. We also provide commentary on scenarios in which HFRT may be indicated, as well as guidance on dose and fractionation regimens informed by our institutional experience.