New ASTRO Guidelines Highlight RT in WHO Grade 4 Adult-Type Diffuse Glioma

Updated guidelines from ASTRO recommend various radiation therapy techniques for patients with WHO grade 4 adult-type diffuse glioma.

The American Society for Radiation Oncology (ASTRO) has released updated clinical practice guidelines for World Health Organization (WHO)–classified grade 4 adult-type diffuse glioma, which were published in Practical Radiation Oncology.1

A total of 23 official peer reviewers reviewed and revised the document, with final approval given by the ASTRO Board of Directors. The study noted that this updated guideline will replace the 2016 ASTRO Guideline on Radiation Therapy for Glioblastoma because of changes from the 2021 WHO Classification of Tumors of the Central Nervous System. The task force consisted of radiation, medical, and surgical oncologists; a neuropathologist; a radiation oncology resident; a medical physicist; and a patient representative.

“As oncologists, high-grade gliomas are among the most challenging cancers we see, and radiation therapy plays a vital role in improving outcomes for these patients,” said Joseph A. Bovi, MD, chair of the guideline task force and a radiation oncologist at ThedaCare Regional Cancer Center in Appleton, Wisconsin.2 “This guideline brings together the best evidence across multiple disciplines to support coordinated care that includes surgery, radiation therapy, systemic therapies, alternating electric field therapy, and supportive care."

For this update, 4 key questions were assessed for this population:

What are the indications for radiation therapy and/or adjuvant therapies in this patient population?

• The panel found strong strength of recommendation and high quality of evidence for fractionated radiation therapy after biopsy or resection.
• If patients have undergone biopsy or resection, concurrent temozolomide (Temodar) and radiation followed by adjuvant temozolomide received a strong recommendation with high quality of evidence.
• If patients had supratentorial disease and had undergone biopsy or resection and concurrent chemoradiation with temozolomide, alternating between electric field therapy for 18 or more hours per day beginning in the middle of adjuvant temozolomide, the strength of recommendation was conditional, and the quality of evidence was moderate.

What are the appropriate dose-fractionation regimens for radiation therapy after biopsy/resection in patients with this disease, and how might treatment vary based on pretreatment characteristics?

1. For patients who are younger than 70 with a Karnofsky performance status (KPS) of 60 or more and have undergone biopsy/resection, partial brain irradiation with 6000 cGy in 30 fractions with concurrent and adjuvant temozolomide received a strong recommendation with high quality of evidence.
2. For patients who are 70 years or older, have a KPS of 50 or more, and have undergone biopsy or resection, partial brain irradiation with 4005 cGy in 15 fractions and concurrent adjuvant temozolomide received a conditional recommendation; the quality of evidence was moderate.
3. For patients who are frail and have undergone biopsy or resection, partial brain irradiation alone at 3400 cGy in 10 fractions or 2500 cGy in 5 fractions was recommended conditionally, and the quality of evidence was low.
4. For patients who are very frail or have a KPS of 40 or less, supportive care should be given instead of radiation therapy or systemic therapy. The recommendation was conditional, and the quality of evidence was based on expert opinion.

What are the appropriate target volumes and techniques for radiation therapy?

1. Intensity-modulated radiation therapy is recommended over 3D conformal radiation therapy to reduce toxicity based on a strong recommendation and moderate quality of evidence.
2. Target volumes assessed by MRI showed that a cone-down/boost is desired for:
   1. Gross tumor volume (GTV) 1, GTV2, clinical target volume (CTV) 1, CTV2, and planning target volume (PTV) 1/2 with a strong recommendation and low quality of evidence.
3. If no cone-down/boost is desired, the target volumes defined by MRI include GTV, CTV, and PTV with a strong recommendation and low quality of evidence.
4. A volumetric brain MRI with and without contrast conducted within 14 days before starting radiation therapy received a strong recommendation based on expert opinion.
5. If patients received radiation therapy, daily image guidance was suggested to help with CTV to PTV expansions with a strong recommendation and an expert opinion for the quality of evidence.

What are the indications and appropriate techniques for reirradiation in patients who have disease recurrence after completion of standard first-line therapy?

1. If establishing the diagnosis by pathology or advanced imaging, the strength of recommendation was conditional, and the quality of evidence was low.
2. For patients with a KPS of 70 or more and an in-field radiation therapy interval of 6 months or more and/or focal tumor volumes of 6 cm or less, reirradiation was conditionally recommended based on multidisciplinary and patient-centered discussions.
3. An implementation remark noted that patient enrollment in clinical trials or multi-institutional registries is encouraged, with the strength of recommendation being conditional and the quality of evidence as moderate.
4. If the patient selects reirradiation, conventionally fractionated radiation therapy, hypofractionated radiation therapy, stereotactic radiosurgery, fractionated stereotactic radiation therapy, or brachytherapy had a conditional strength of recommendation and a moderate quality of evidence.
5. If reirradiation is elected by the patient using a GTV defined as a contrast-enhancing tumor, non-enhancing tumor, and/or resection cavity based on MRI, the strength of recommendation was conditional, and the quality of evidence was moderate.
6. For those receiving reirradiation with concomitant bevacizumab (Avastin) to reduce toxicity, the strength of recommendation was conditional, and the quality of evidence was moderate.

Health disparities were also assessed as part of this guidelines update. However, since there was a lack of randomized controlled phase 3 trials in this area, the committee could not make a formal recommendation on this topic. The members created a call for action highlighting the need to include this in future directions.

“Our goal was to equip clinicians with a clear, robust framework for shared decision-making with their patients, while also highlighting areas where research is needed to move the field forward,” said Debra Nana Yeboa, MD, vice chair of the guideline task force and an associate professor of radiation oncology at the University of Texas MD Anderson Cancer Center in Houston.2 “Progress in personalized medicine, biomarker discovery, and advanced treatment techniques could help us change outcomes for patients, particularly those in underserved populations.”

References

1. Yeboa DN, Braunstein SE, Cabrera A, et al. Radiation therapy for WHO grade 4 adult-type diffuse glioma: an ASTRO clinical practice guideline. Pract Radiat Oncol. 2025. doi:10.1016/j.prro.2025.05.014
2. ASTRO updates guideline on radiation therapy for high-grade diffuse glioma, the most common primary brain tumor in adults. News release. ASTRO. June 26, 2025. Accessed July 1, 2025. https://tinyurl.com/mkvk76tx