What are the normal brain constraints for Stereotactic Radiosurgery (SRS) in brain metastases (brain mets)?

Normal Brain Dose Constraints for SRS in Brain Metastases

For stereotactic radiosurgery of brain metastases, the critical normal brain constraint is maintaining brain mean dose ≤3 Gy per fraction (equivalent to one fraction of standard WBRT), which allows treatment of approximately 12-13 metastases while limiting V12 (volume receiving >12 Gy) to approximately 2.2 cc per tumor. 1

Hippocampal Dose Constraints

The most rigorously defined normal tissue constraints for brain SRS are derived from the RTOG 0933 hippocampal-sparing protocol, converted to biologically effective dose:

• Hippocampal D100 (minimum dose): ≤421 cGy 2
• Hippocampal Dmax (maximum dose): ≤665 cGy 2

Risk Factors for Exceeding Hippocampal Constraints

• Distance of nearest metastasis <8-10 mm from hippocampus significantly increases risk (OR 1.14,95% CI 1.04-1.26) 2
• Total target volume >5.5 cm³ increases risk of constraint violation (OR 1.14,95% CI 1.00-1.32) 2
• Approximately 19% of hippocampi exceed dose constraints in multi-metastasis SRS, but 83% can be successfully re-optimized while maintaining target coverage 2

Brainstem Dose Constraints

For metastases within or directly abutting the brainstem:

• Margin dose ≥16 Gy is associated with superior local control (87.3% at last follow-up) with acceptable toxicity 3
• Grade 3-5 toxicity occurs in only 1.8% of cases when treating brainstem metastases with SRS 3
• Median margin dose of 18 Gy prescribed to 50% isodose line demonstrates safety 3

Planning Target Volume Margins

Use 0-2 mm PTV margins for intact metastases to minimize normal brain exposure while accounting for setup uncertainty 4

For post-operative cavities:

• Add 0.3-0.5 cm margin to CTV to create PTV, accounting for setup uncertainties and treatment delivery variations 5
• Minimize setup margin through accurate patient positioning with reproducible immobilization and digital imaging 5

Dose-Volume Considerations by Number of Metastases

The relationship between number of metastases and normal brain dose follows a predictable pattern:

• Treating 12-13 tumors delivers brain mean dose equivalent to one 3 Gy fraction of WBRT 1
• Mean V12 per tumor: 2.2 cc when treating multiple metastases 1
• No significant difference in hippocampal constraint violations between 4-5 versus 6-10 metastases (27% vs 21%, p=0.409) 2

Prescription Isodose Line

The prescription isodose line is typically 50% (range 20-90%) for optimal dose conformality and normal tissue sparing 6

Common Pitfalls to Avoid

• Do not assume all plans automatically spare hippocampi - approximately 19% will exceed constraints and require re-optimization 2
• Metastases within 10 mm of hippocampus require careful planning to avoid excessive hippocampal dose 2
• Single metastases can exceed hippocampal constraints in 50% of cases when located near hippocampus, even without other targets 2
• Total target volume >5.5 cm³ increases risk of violating normal tissue constraints regardless of number of lesions 2

Re-optimization Strategy

When hippocampal constraints are exceeded:

• Re-optimization achieves hippocampal sparing in 83% of cases without compromising PTV coverage (99.6% vs 99.0%, p=0.17) or conformality (CI 1.47 vs 1.4, p=0.78) 2
• Maintain focus on distance from hippocampus and total target volume as modifiable risk factors 2