Narrative review of palliative hypofractionated radiotherapy for high grade glioma

High grade gliomas (HGG) include World Health Organization (WHO) grade III anaplastic astrocytoma (AA) and WHO grade IV glioblastoma (GBM). As genomic alterations are prognostic, even WHO grade II, IDH-wildtype gliomas may be considered as HGG. Current management of HGG include best supportive care (BSC), surgery, radiation therapy (RT), chemotherapy, and a combination. Elderly patients (defined here as age ≥65) with GBM have significantly worse survival compared to younger patients. Similarly, patients with poor performance status [defined as Karnofsky performance status (KPS) <60 or ECOG performance status (PS) >2], regardless of age have worse outcomes. The standard of care for treatment of HGG involves surgery and chemoradiation. However, the optimal treatment in terms of efficacy, safety and maintaining quality of life (QoL), remains a matter of debate in the elderly and/or poor performing patients due to their worse prognosis. Less aggressive interventions are usually reserved for these patients despite surgery providing a survival and neurologic benefit. Improved survival has been noted in elderly patients treated with RT in comparison with those receiving best supportive care (BSC) alone, with similar survival for patients undergoing standard RT (60 Gy/30 fractions) and hypofractionated RT (25-40 Gy in 5-15 daily fractions). An alkylating agent, temozolomide (TMZ), represents a safe and effective option in select patients with promoter methylation of O6-methylguanine-DNA-methyltransferase (MGMT) gene. A recent phase III randomized trial for GBM patients (age ≥65 years, ECOG PS 0-2) demonstrated a significant improvement in progression-free survival (PFS) and overall survival (OS) with hypofractionated RT (40 Gy/15 fractions) with concurrent and adjuvant TMZ vs. RT alone, without adversely impacting either QoL or functional status. Despite chemoradiation becoming the recommended treatment in GBM patients who are elderly but fit, several questions remain unanswered. This includes the survival impact of chemoradiation in patients with severe comorbidities or with ECOG PS >2 or a combination of poor prognostic features such as male gender, poor neurocognition, biopsy only and lack of MGMT methylation. Personalized management of patients with HGG is warranted in the modern era as we attempt to balance the benefit of efficacious treatment with potential toxicity while appreciating the many nuances associated with multiple prognostic factors on anticipated survival. Here, we aim to review the palliative management options available for HGG patients with an emphasis on the role of RT.