Narrative review of palliative hypofractionated radiotherapy for high grade glioma

Abstract

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.

Radiotherapy of High-Grade Gliomas: First Half of 2021 Update with Special Reference to Radiosensitization Studies

“…As yet another confirmation, the expected improved survival has been observed in elderly patients treated with RT in comparison with those receiving the best supportive care alone, with similar survival for patients undergoing conv-FRT (60 Gy/30 fractions) and hypo-FRT (25-40 Gy in 5-15 daily fractions) [87]. Hence, while it has an undeniable role in improving cancer survival, RT has also various negative effects, ranging from mild to severe and including IR-induced meningioma, IR-induced glioma, cavernous malformation, enlarging perivascular spaces, leukoencephalopathy, stroke-like migraine after RT, Moyamoya syndrome, radiation necrosis, IR-induced labyrinthitis, optic neuropathy, retinopathy, and others [88].…”

Role of Borneol Induced Autophagy in Enhancing Radiosensitivity of Malignant Glioma

“…Despite advances in neurosurgery and the widespread use of chemotherapy and radiotherapy against newly diagnosed GBM, patient survival has improved only marginally. Radiotherapy is the primary treatment strategy for advanced glioma ( 25 , 26 ), although its outcomes are limited due to hypoxia-induced resistance. HIF-1α is activated in the hypoxic microenvironment of solid tumors, and promotes tumor cell survival by increasing glucose uptake and utilization.…”

PKM2 Is Overexpressed in Glioma Tissues, and Its Inhibition Highly Increases Late Apoptosis in U87MG Cells With Low-density Specificity

“…Glioma therapies mainly consist of surgical excision combined with radiotherapy and chemotherapy (3)(4)(5)(6). Patient survival rates are very low despite surgery in combination with postoperative chemotherapy and radiotherapy (1,3,4,6,7). Thus, new therapies for treatment of glioma are urgently needed.…”