What is the percentage of radiation necrosis in patients undergoing Whole Brain Radiation Therapy (WBRT) versus Stereotactic Radiosurgery (SRS) versus fractionated Stereotactic Radiosurgery (fSRS)?

Radiation Necrosis Rates: WBRT vs SRS vs fSRS

Radiation necrosis occurs in 5-35% of patients after single-session SRS, compared to approximately 5% after WBRT, with fractionated SRS (fSRS) reducing necrosis rates to 8% versus 20% for single-session SRS in large lesions. 1

Comparative Radiation Necrosis Rates by Modality

Single-Session SRS (sSRS)

• The reported incidence ranges from 5% to 35% in various retrospective series, with this wide variation reflecting inconsistencies in diagnostic criteria and institutional delivery patterns 1
• For large lesions (>3 cm), single-session SRS carries a 20% radiation necrosis rate compared to 8% with multisession approaches 1
• In clinical practice, symptomatic radiation necrosis occurs in approximately 10% of patients receiving brain SRS 2
• One study reported 20.5% clinically significant radiation necrosis with single-session SRS at median follow-up of 320 days 3
• Radiation necrosis occurred at 5.4% of treated tumors at 6 months in patients with multiple brain metastases 4

Fractionated SRS (fSRS)

• Multisession SRS reduces radiation necrosis to 8% versus 20% with single-session for large lesions (p=0.004) 1, 5
• Using 27 Gy in 3 fractions achieves 91% 1-year local control with only 8% radiation necrosis 1, 5
• In one study, fSRS showed 18.8% radiation necrosis compared to 20.5% for single-session SRS, though this difference was not statistically significant 3
• For malignant gliomas, fSRS showed comparable 18.8% radiation necrosis despite treating significantly larger target volumes (19.3 cc vs 5.9 cc) 6

Whole Brain Radiation Therapy (WBRT)

• WBRT alone carries approximately 5% radiation necrosis risk based on the Society for Neuro-Oncology consensus 7
• WBRT is associated with more diffuse cognitive dysfunction rather than focal radiation necrosis, which is the primary toxicity concern distinguishing it from stereotactic approaches 1

Critical Factors Influencing Radiation Necrosis Risk

Volume-Dependent Risk

• For every 10-unit increase in volume, the odds ratio for radiation necrosis is 3.1 (95% CI: 1.0-9.6), making volume the most significant predictor 3
• Postoperative SRS/SRT to resection cavities carries relatively high necrosis rates due to typically large volumes, generous expansions, and interdigitation with normal brain 1

Dose-Response Relationship

• Maximum dose did not appear associated with radiation necrosis risk in paired analysis of simultaneous treatments 3
• However, dose escalation with hypofractionation demonstrates improved control without proportional increases in necrosis when properly fractionated 1

Algorithmic Approach to Minimize Radiation Necrosis

For Lesions <3 cm

• Use single-session SRS with standard dosing (24 Gy for <2 cm, 18 Gy for 2-3 cm) as radiation necrosis risk remains acceptable at 5-10% 1, 5

For Lesions >3 cm

• Prioritize fractionated SRS using 27 Gy in 3 fractions or 30 Gy in 5 fractions to achieve superior local control (91% at 1 year) while minimizing necrosis (8%) 1, 5, 8
• Consider surgical resection first for very large lesions to minimize radiation necrosis risk from high-volume irradiation 1, 5, 8

For Postoperative Cavities

• Expect higher necrosis rates with postoperative SRS/SRT due to large treatment volumes 1
• Multiple prospective trials are evaluating preoperative stereotactic radiation to decrease necrosis rates compared to postoperative approaches 1

Common Pitfalls and Management

Diagnostic Challenges

• Radiation necrosis typically develops 3 months to 3 years after treatment and requires histopathologic confirmation or advanced imaging (MR spectroscopy, perfusion, or PET) to distinguish from tumor recurrence 1

Treatment of Established Radiation Necrosis

• Corticosteroids achieve complete response in 50% and partial response in 33% of symptomatic radiation necrosis cases 2
• Bevacizumab achieves complete response in 50% and partial response in 18% of cases 2
• Surgical resection achieves 100% complete response but is reserved for refractory cases 2
• Age ≥54 years is associated with better response to non-surgical management (OR=8.40, p=0.027) 2

Critical Avoidance Strategies

• Never use single-fraction doses <18 Gy for large lesions, as this results in <50% local control without reducing necrosis risk 1, 5
• Do not attempt single-fraction SRS for lesions >3 cm due to prohibitive 20-23% necrosis risk 1, 5
• Fractionation does not directly lower necrosis rates but reduces the magnitude of risk in large-volume lesions 3