Radiation Therapy for WHO Grade 4 Adult-Type Diffuse Glioma: An ASTRO Clinical Practice Guideline

The central nervous system World Health Organization (WHO) grade 4 adult-type diffuse glioma represents one of the most aggressive and challenging primary brain tumors. This guideline aims to provide evidence-based recommendations for the multidisciplinary management of these tumors, focusing on diagnosis, initial treatment, reirradiation, and health disparities, while acknowledging that present literature primarily represents historical histologic grade 4 glioblastoma.

The American Society for Radiation Oncology convened a task force to address 4 key questions focused on indications for radiation therapy (RT) and/or adjunctive therapies (eg, systemic therapy, alternating electric field therapy), appropriate regimens for external beam RT after initial biopsy/resection including variables such as pretreatment characteristics, target volumes, technique, dose, reirradiation indications and techniques, and health disparities. Recommendations are based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength.

Following maximum safe resection, molecular and pathologic diagnosis, and prognostic stratification of WHO grade 4 adult-type diffuse glioma, concurrent RT with temozolomide followed by adjuvant temozolomide is recommended for eligible patients and incorporation of alternating electric field therapy is conditionally recommended. In elderly patients, hypofractionated RT with concurrent and adjuvant temozolomide is conditionally recommended. In frail patients, supportive and palliative care is conditionally recommended following multidisciplinary, patient-centered discussion. Appropriate reirradiation techniques, with or without additional systemic therapies, can be considered and are conditionally recommended in patients following pathologic or advanced imaging confirmation of WHO grade 4 diffuse glioma recurrence. Health disparities exist in patients with WHO grade 4 adult-type diffuse glioma and attention is necessary to improve outcomes and increase clinical trial enrollment for underserved populations.

These evidence-based recommendations and current practice adoption patterns inform best clinical practices on the management of WHO grade 4 adult-type diffuse glioma. Future advancements in personalized medicine, biomarker discovery, and novel therapies are essential to improving outcomes. The integration of multidisciplinary care and participation in future clinical trials, especially in underserved populations, is crucial in addressing the poor outcomes among WHO grade 4 adult-type diffuse glioma.