What factors determine the choice between whole‑brain radiation therapy and focal stereotactic radiosurgery for treating brain metastases?

Decision Factors for Whole-Brain Radiation Therapy vs Stereotactic Radiosurgery

Stereotactic radiosurgery (SRS) alone should be favored over whole-brain radiation therapy (WBRT) for most patients with brain metastases to preserve cognitive function and quality of life, with the primary decision based on cumulative tumor volume (<7 mL) rather than lesion number. 1

Primary Selection Criteria

Tumor Volume (Most Critical Factor)

Total cumulative tumor volume is the single most important prognostic factor determining treatment selection, superseding lesion number. 1

• SRS is recommended when cumulative volume is <7 mL, regardless of lesion number (even >4 metastases) 1, 2
• Patients with cumulative volume <7 mL and <7 brain lesions achieve median survival of 13 months vs 6 months for those exceeding these thresholds 1
• Total treatment volume <13 cc with no single metastasis >3 cc predicts equivalent survival for patients with >4 metastases compared to 1-4 metastases 1

Lesion Size

Individual lesion size determines feasibility and fractionation strategy for SRS. 1, 2

• Lesions <3 cm: Single-fraction SRS is optimal with local control rates of 85% at 1 year 1, 2
• Lesions >3 cm: Fractionated SRS (27 Gy in 3 fractions or 30 Gy in 5 fractions) is mandatory to achieve 91% 1-year local control while reducing radiation necrosis from 20% to 8% 1, 2
• Lesions >3 cm in diameter should prompt consideration of surgical resection first 1, 2

Number of Metastases

Lesion number alone should not determine treatment choice when volume criteria are met. 1, 3

• 1-4 metastases: SRS alone is the standard of care 1, 4
• >4 metastases: SRS alone is recommended if cumulative volume <7 mL 1
• No survival difference exists between patients with >4 metastases vs 1-4 metastases when total volume <13 cc 1

Patient Performance Status

Good performance status (KPS >70) is essential for aggressive local therapy with either modality. 1, 2

• KPS <70 patients should receive best supportive care only, as median survival is <2 months regardless of radiation approach 2
• RPA Class I-II patients benefit most from SRS 1

Tumor Location and Eloquence

Deep-seated lesions in eloquent brain regions favor SRS over surgery. 2, 4

• Eloquent location lesions up to 30 mm can be treated with SRS 5
• Non-eloquent location lesions up to 40 mm are acceptable for SRS 5
• Posterior fossa lesions with brainstem compression require surgical decompression regardless of size 2

Clinical Presentation

Mass effect requiring immediate decompression mandates surgery, not radiation. 2

• Obstructive hydrocephalus requires surgical intervention 2
• Symptomatic lesions causing progressive neurologic deterioration favor surgery 2
• Asymptomatic lesions favor SRS to avoid surgical morbidity (5-23% permanent deficit risk) 2

Primary Tumor Histology and Systemic Disease Status

Radiosensitive histologies and controlled extracranial disease favor SRS. 1

• Favorable histologies (breast cancer, melanoma, renal cell carcinoma) achieve good local control with SRS regardless of metastasis number 1
• Controlled primary tumor and absence of extracranial disease predict longer survival with SRS (43 vs 10.5 months) 6
• Patients with CNS-penetrating systemic therapies available may benefit from selected-lesion SRS approach 5

Prior Treatment History

Prior WBRT is an absolute contraindication to repeat WBRT; salvage SRS is the only radiation option. 2, 5

• 44% of patients develop distant brain recurrences after initial SRS at median 16 months, requiring salvage therapy 6
• Only 30.7% ultimately require salvage WBRT, sparing 70% from WBRT-associated neurotoxicity 6

Critical Decision Algorithm

1. Assess cumulative tumor volume:

   • <7 mL → SRS alone 1

   • 7 mL → Consider WBRT or selected-lesion SRS 5

2. Evaluate individual lesion sizes:

   • All <3 cm → Single-fraction SRS 1, 2
   • Any >3 cm → Fractionated SRS (27 Gy/3 fx or 30 Gy/5 fx) or surgery 1, 2

3. Check for surgical indications:

   • Mass effect/herniation → Surgery required 2
   • No mass effect → Proceed with SRS 2

4. Verify performance status:

   • KPS >70 → Proceed with treatment 1
   • KPS <70 → Best supportive care only 2

Common Pitfalls to Avoid

Never use WBRT upfront when SRS criteria are met, as this causes irreversible neurocognitive decline without survival benefit. 1

• Combining WBRT + SRS has detrimental effects on cognitive function and quality of life compared to SRS alone 1
• WBRT should be reserved exclusively for salvage therapy after SRS failure 1, 2
• Do not refuse SRS based solely on lesion number if volume criteria are satisfied 1, 3
• Never attempt single-fraction SRS for lesions >3 cm due to 20% radiation necrosis risk 1, 2