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  • Title: Radiation Therapy for WHO Grade 4 Adult-Type Diffuse Glioma
  • Society: American Society for Radiation Oncology (ASTRO)
  • Publish Date: June 25, 2025
  • Guideline Summary
  • Full-text

Video Transcription

Just published June 25th, 2025 - The American Society for Radiation Oncology’s newest guideline on Radiation Therapy for World Health Organization (WHO) Grade 4 Adult-Type Diffuse Glioma.

The objective of this guideline is 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 histological grade 4 glioblastoma.

There are 17 recommendations, so let’s get started:

  • For patients with WHO grade 4 diffuse glioma, fractionated radiation therapy (RT) after biopsy or resection is recommended. 
  • For patients with WHO grade 4 diffuse glioma who have undergone biopsy or resection, concurrent temozolomide (TMZ) with RT followed by adjuvant TMZ is recommended. 
  • For patients with supratentorial WHO grade 4 diffuse glioma who have undergone biopsy or resection and concurrent chemoradiation with TMZ, alternating electric field therapy for ≥18 hours per day starting during adjuvant TMZ is conditionally recommended. 
  • For patients age <70 years and Karnofsky performance status (KPS) of  ≥60 with WHO grade 4 diffuse glioma who have undergone biopsy or resection, partial brain irradiation with 6000 (centigray) in 30 fractions with concurrent and adjuvant TMZ is recommended. 
  • For patients age ≥70 years and KPS ≥50 with WHO grade 4 diffuse glioma who have undergone biopsy or resection, partial brain irradiation with 4005 centigray in 15 fractions with concurrent and adjuvant TMZ is conditionally recommended. 
  • For patients with WHO grade 4 diffuse glioma who are frail and have undergone biopsy or resection, partial brain irradiation alone using 3400 centigray in 10 fractions or 2500 centigray in 5 fractions is conditionally recommended. 
  • For patients with WHO grade 4 diffuse glioma who are very frail or with KPS ≤40, supportive care in lieu of RT and/or systemic therapy is conditionally recommended.
  • For patients with WHO grade 4 diffuse glioma, intensity modulated radiation therapy (IMRT) is recommended over 3-D conformal radiation therapy (CRT) to reduce toxicity. 
  • For patients with WHO grade 4 diffuse glioma, the following target volumes defined by MRI are recommended if cone-down/boost is desired:

GTV1 = resection cavity, residual enhancement on postoperative T1 postcontrast, and T2/FLAIR changes (non-enhancing tumor)

GTV2 = resection cavity and residual enhancement on postoperative T1 postcontrast

CTV1/2 = GTV1/2 + 10-20 mm expansion, modified to respect natural barriers to tumor spread (bone, dura, etc.)

PTV1/2 = CTV1/2 + 3-5 mm expansion

  • For patients with WHO grade 4 diffuse glioma, the following target volumes defined by MRI are recommended if no cone-down/boost is desired:

GTV = resection cavity and residual enhancement on T1 postcontrast

CTV = GTV + 10-20 mm expansion with additional expansion as needed to include T2/FLAIR signal changes (non-enhancing tumor) modified to respect natural barriers to tumor spread (bone, dura, etc.)

PTV = CTV + 3-5 mm expansion

  • For patients with WHO grade 4 diffuse glioma, a volumetric brain MRI with and without contrast preferably ≤14 days before starting RT is recommended for treatment planning. 
  • For patients with WHO grade 4 diffuse glioma receiving RT, daily image guidance is recommended to facilitate reduced CTV to PTV expansions.
  • For patients with suspected recurrent WHO grade 4 diffuse glioma, establishing the diagnosis by pathology or advanced imaging is conditionally recommended. 
  • For patients with recurrent WHO grade 4 diffuse glioma with a KPS ≥70, in-field RT interval of ≥6 months and/or focal tumor volume ≤6 cm3, reirradiation is conditionally recommended following a multidisciplinary, patient-centered discussion. 
  • For patients with recurrent WHO grade 4 diffuse glioma who elect reirradiation, the following treatment options are conditionally recommended: conventionally fractionated RT, hypofractionated RT, stereotactic radiosurgery, fractionated stereotactic RT, or brachytherapy. 
  • For patients with recurrent WHO grade 4 diffuse glioma who elect reirradiation, using a GTV defined as contrast enhancing tumor, non-enhancing tumor, and/or resection cavity based on MRI is conditionally recommended. 
  • For patients receiving reirradiation for recurrent WHO grade 4 diffuse glioma, concomitant bevacizumab is conditionally recommended to reduce toxicity. 

Make sure to check out the full guideline from The American Society for Radiation Oncology and other related clinical decision support tools at guidelinecentral.com.

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