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

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.

Keywords: FLASH; elderly; glioblastoma; hypofractionation; palliation; radiomics; radiotherapy; recurrence; stereotactic.

Figure 1

Hypofractionated adjuvant radiation plan in a patient with resected GBM. Volumetric arc therapy (VMAT) photon plan for a 62-year-old patient who developed left hemiplegia approximately 3 weeks after initial gross tumor resection and was found with radiographic recurrence of GBM, treated to 25 Gy in 5 fractions. Red delineates gross tumor volume (GTV), purple delineates clinical target volume (CTV), and green delineates planning target volume (PTV). A 50% isodose line is shown. Axial, sagittal, and coronal views seen from left to right, respectively. After radiation, this patient completed 3 months of palliative Avastin and passed away from their disease 7 months after initial diagnosis.

Figure 2

A case of Gamma Knife SRS, a patient with resected GBM. Gamma Knife SRS plan for a 57-year-old patient who developed asymptomatic multifocal recurrence of GBM 2 months after completing gross total resection and 60 Gy/30 fx chemoradiation. Given their unresectable nature, the individual lesions were treated to 17–18 Gy in 1 fraction. Red delineates gross tumor volume (GTV). A 17 Gy isodose line is shown. Axial, sagittal, and coronal views seen from left to right, respectively. The red line denotes the target.