What are the guidelines for contouring Glioblastoma Multiforme (GBM)?

GBM Contouring Guidelines for Radiation Therapy

For newly diagnosed glioblastoma, the clinical target volume (CTV) should be defined as the surgical bed plus residual tumor on T1-weighted post-contrast imaging with a 1.0-2.0 cm margin, modified to include T2/FLAIR abnormalities and constrained by anatomical barriers, with a planning target volume (PTV) margin of 0.3-0.5 cm added for setup uncertainties. 1

Pre-Treatment Imaging Requirements

Minimum MRI sequences required for contouring include:

• T2-weighted imaging 1, 2
• FLAIR sequences 1, 2
• Pre- and post-gadolinium contrast-enhanced T1-weighted imaging 1, 2
• Diffusion-weighted imaging (DWI) should be included as part of standard sequences 1, 2

Additional imaging that may assist in target delineation:

• Perfusion-weighted MRI can help distinguish tumor from edema 2
• Amino acid PET (11C-methionine or 18F-FET) has been evaluated but is not currently standard practice 1
• CT imaging can provide information about calcification or hemorrhage 2

Target Volume Definition: Step-by-Step Approach

Gross Tumor Volume (GTV)

The GTV consists of: 1

• Surgical bed/resection cavity
• Residual enhancing tumor on T1-weighted post-contrast sequences
• T2/FLAIR abnormalities representing edema and microscopic invasion

Critical consideration: The EORTC-based approach focuses on T1 enhancement plus surgical cavity, with T2/FLAIR abnormalities included in the CTV expansion rather than routinely in the GTV 3, 4

Clinical Target Volume (CTV)

Standard CTV margin: 1, 3

• Add 1.0-2.0 cm isotropic margin to the GTV
• Modify this margin to include T2-weighted or FLAIR signal abnormalities (edema)
• Constrain to anatomical barriers: ventricles, tentorium, falx, skull

Alternative approach supported by recent data: 4

• Initial CTV margin of 15 mm from GTV (T1 enhancement + cavity)
• Boost CTV margin of 5-7 mm
• This approach showed 93% coverage with GTV + 7 mm and 98% coverage with GTV + 15 mm on interim MRI

Important caveat: A single CTV definition without cone-down is currently recommended based on EORTC consensus 3

Planning Target Volume (PTV)

PTV margin: 1, 3

• Add 0.3-0.5 cm margin to account for setup uncertainties and treatment delivery variations
• The specific margin depends on your immobilization system and image-guided radiotherapy (IGRT) capabilities
• Typically 3-5 mm with modern IGRT procedures 3

Radiation Dose and Fractionation

Standard fractionation for patients <70 years with good performance status: 1, 5

• 50-60 Gy in 1.8-2.0 Gy daily fractions
• Most commonly 60 Gy in 2 Gy fractions over 6 weeks
• No benefit demonstrated for doses >60 Gy 1

Hypofractionated regimens for elderly patients (>65-70 years) or poor prognosis (KPS <70): 1, 5

• 15 × 2.67 Gy (40.05 Gy total)
• 34 Gy in 10 fractions
• Other abbreviated schedules as appropriate

Organs at Risk (OARs) to Delineate

Structures requiring delineation to minimize toxicity: 1

• Optic nerves
• Optic chiasm
• Retinae
• Lenses
• Brainstem
• Pituitary gland
• Cochleae
• Hippocampi

Risk factors for late complications (radionecrosis, leukoencephalopathy): 6

• Age >50 years
• Previous vascular disease (hypertension, diabetes, hyperlipidemia)
• High radiation dose per fraction

Technical Considerations

Immobilization and positioning: 1, 3

• Reproducible immobilization system required
• Digital imaging during treatment for accurate positioning
• Essential for highly conformal techniques

Treatment techniques: 1

• Intensity-modulated radiotherapy (IMRT) for newly diagnosed tumors provides superior target coverage and normal tissue sparing
• Stereotactic radiotherapy/radiosurgery for recurrent tumors
• Proton or heavy ion therapy may be considered for tumors near critical structures, though RCTs are needed

Special Situations and Adaptations

When T1 enhancement and T2 abnormality are identical (Group A): 4

• Standard approach applies
• No additional considerations needed

When T2 abnormality extends beyond T1 enhancement (Group B): 4

• Omitting routine inclusion of all T2 abnormality from GTV may not compromise disease control
• The CTV margin adequately covers microscopic extension
• Patterns of failure similar to other groups

When tumor lacks enhancement (Group C): 4

• T2/FLAIR abnormality should be included in GTV definition
• Occurs in approximately 18% of cases

Timing and Follow-Up Imaging

Baseline imaging: 6, 5

• MRI within 72 hours after surgical intervention to assess residual tumor
• This serves as the basis for radiation planning

Post-radiation baseline: 1

• MRI scan 3-4 weeks after completion of radiotherapy
• Provides new baseline to monitor disease course

Surveillance imaging: 6, 5

• Clinical and MRI follow-up every 2-3 months
• MRI preferred over CT for detecting progression

Common Pitfalls to Avoid

Pseudoprogression: 6, 5, 7

• MRI changes within 6-9 months after radiotherapy may represent pseudoprogression rather than true progression
• Clinical and/or radiological deterioration within 2 months after radiotherapy should be interpreted with caution
• Consider advanced imaging (perfusion MRI, amino acid PET) if uncertain 6, 5

Margin errors: 3, 4

• Avoid arbitrary reduction of margins near eloquent structures without careful consideration
• Anatomical barriers (ventricles, falx, tentorium) are appropriate boundaries for CTV modification
• Ensure adequate coverage of surgical cavity and any residual enhancement

Inadequate imaging sequences: 1, 2

• Failure to include diffusion-weighted imaging misses important diagnostic information
• Relying solely on T1 post-contrast without T2/FLAIR assessment is insufficient