Radiation Therapy for Glioblastoma

Publication Date: August 1, 2016
Last Updated: March 14, 2022

Guideline statements

1. When is radiation therapy indicated after biopsy/resection of glioblastoma and how does systemic therapy modify its effects?

Fractionated radiation therapy improves overall survival compared with chemotherapy or best supportive care alone following biopsy or resection of newly diagnosed glioblastoma (HQE). Whether radiation therapy is indicated in a particular individual may depend on patient characteristics such as performance status (see 2.). (Strong)
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Adding concurrent and adjuvant temozolomide to fractionated radiation therapy improves overall survival and progression free survival compared to fractionated radiation therapy alone, with a reasonably low incidence of early adverse events and without impairing quality of life (HQE). The guideline panel endorses fractionated radiation therapy with concurrent and adjuvant temozolomide as the standard of care following biopsy or resection of newly diagnosed glioblastoma in patients up to 70 years of age (see KQ2 for recommendations regarding patients older than 70). (Strong)
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Adding bevacizumab to standard therapy for newly diagnosed glioblastoma (ie, fractionated radiation therapy with concomitant and adjuvant temozolomide) does not improve overall survival and is associated with a higher incidence of early adverse events (HQE). Bevacizumab may, however, prolong progression free survival (MQE). The panel does not recommend the routine addition of bevacizumab to standard therapy for newly diagnosed glioblastoma outside of a clinical trial. (Strong)
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The addition of other systemic therapies to conventional radiation therapy with or without temozolomide remains investigational. (Strong)
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2. What is the optimal dose-fractionation schedule for external beam radiation therapy after biopsy/resection of glioblastoma and how might treatment vary based on pretreatment characteristics such as age or performance status?

For patients younger than age 70 with good performance status (KPS ≥60), the optimal dose-fractionation schedule for external beam radiation therapy following resection or biopsy is 60 Gy in 2-Gy fractions delivered over 6 weeks (HQE). Numerous other dose schedules have been explored without definitive benefit. Care should be taken to keep dose to critical structures (eg, brainstem, optic chiasm/nerves) within acceptable limits. (Strong)
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Older age and poor performance status are associated with shorter survival in GBM patients (MQE). Prognostic considerations should help guide treatment recommendations for individual patients. (Strong)
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Among elderly patients (≥70 years of age) with fair-good performance status (KPS ≥50), the panel recommends external beam radiation therapy following biopsy or resection because radiation therapy (compared with supportive care alone) improves overall survival without impairing quality of life or cognition (HQE). The efficacy of concurrent and adjuvant temozolomide in this population has not been evaluated in a randomized trial, but may be considered for selected patients (LQE). (Strong)
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Among elderly patients, there is no evidence that conventionally fractionated radiation therapy (60 Gy in 30 fractions over 6 weeks) is more efficacious than hypofractionated radiation therapy (eg, 40 Gy in 15 fractions over 3 weeks) (HQE). Compared with conventionally fractionated radiation therapy, hypofractionated radiation therapy has been associated with superior survival and less corticosteroid requirement (MQE). (Strong)
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Given the absence of proven superiority for conventionally fractionated radiation therapy, the panel recommends hypofractionated radiation therapy for elderly patients with fair-good performance status (HQE). Temozolomide monotherapy is an efficacious alternative for elderly patients with MGMT promoter methylation (HQE), but the panel does not recommend temozolomide monotherapy as first-line therapy for patients with unmethylated MGMT promoters (MQE). Temozolomide monotherapy confers a higher risk of adverse events than radiation therapy, particularly with respect to hematologic toxicity, nausea, and vomiting (MQE). (Strong)
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Among elderly patients with good performance status, adding concurrent and adjuvant temozolomide to hypofractionated radiation therapy appears to be safe and efficacious without impairing quality of life (LQE). In such patients, the panel recommends consideration of concurrent and adjuvant temozolomide. The combination of hypofractionated radiation therapy and temozolomide may be particularly efficacious in those with a methylated MGMT promoter (LQE). (Strong)
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Reasonable options for patients with poor performance status include hypofractionated radiation therapy alone, temozolomide alone, or best supportive care (LQE). (Strong)
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3. What are the ideal target volumes for curative-intent external beam radiation therapy of glioblastoma?

Although glioblastoma is thought to be diffusely infiltrative, partial brain radiation therapy leads to no worse survival than whole brain radiation therapy (HQE). The panel endorses partial brain radiation therapy as the standard treatment paradigm for glioblastoma. (Strong)
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Several strategies for target volume definition produce similar outcomes (LQE). All confer a low risk of isolated marginal or distant failure, with a high risk of local failure as a component of disease progression (MQE). Acceptable strategies include but are not limited to the following:

  • Two-phase: (1) primary target volume encompasses edema (hyperintense region on T2 or FLAIR on MRI) and gross residual tumor/resection cavity; (2) boost target volume encompasses gross residual tumor/resection cavity. A range of acceptable clinical target volume margins exists.
(Strong)
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  • One-phase: single target volume includes gross residual tumor/resection cavity with wide margins, without specifically targeting edema.
(Strong)
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Reducing target volumes allows less radiation to be delivered to radiographically normal brain. Delivering less radiation to normal brain should result in less late toxicity (LQE), but this remains to be validated. (Weak)
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4. What is the role of reirradiation among glioblastoma patients whose disease recurs following completion of standard first-line therapy?

In younger patients with good performance status, focal reirradiation (eg, stereotactic radiosurgery, hypofractionated stereotactic radiation therapy, brachytherapy) for recurrent glioblastoma may improve outcomes compared with supportive care or systemic therapy alone (LQE). Tumor size and location should be taken into account when deciding whether reirradiation would be safe (LQE). (Weak)
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HQE, high-quality evidence; KPS, Karnofsky performance status; LQE, low-quality evidence; MQE, moderate-quality evidence.

Recommendation Grading

Overview

Title

Radiation Therapy for Glioblastoma

Authoring Organization

Publication Month/Year

August 1, 2016

Last Updated Month/Year

April 13, 2023

Supplemental Implementation Tools

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Document Objectives

To present evidence-based guidelines for radiation therapy in treating glioblastoma not arising from the brainstem.

Target Patient Population

Patients with glioblastoma

Inclusion Criteria

Female, Male, Adolescent, Adult, Older adult

Health Care Settings

Ambulatory, Hospital, Outpatient, Radiology services

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Management, Treatment

Diseases/Conditions (MeSH)

D018787 - Radiation Oncology, D011827 - Radiation, D005909 - Glioblastoma

Keywords

cancer, radiation therapy, Adjuvant Radiation Therapy, glioblastoma