What is the recommended radiation dose for central nervous system (CNS) lymphoma?

Radiation Dose for CNS Lymphoma

For primary CNS lymphoma (PCNSL), consolidation whole brain radiotherapy (WBRT) should be administered at 36-40 Gy in 20-22 fractions for patients who achieve complete response to high-dose methotrexate-based chemotherapy, with reduced-dose WBRT of 23.4 Gy as an alternative option for responsive disease. 1

Standard Consolidation Dosing

The most recent guideline-based recommendation is 36-40 Gy delivered in 20-22 fractions for consolidation WBRT in patients with responsive disease after induction chemotherapy. 1 This represents the current standard approach endorsed by the European Hematology Association (EHA) and European Society for Medical Oncology (ESMO) in 2024.

Key Dosing Considerations by Clinical Scenario:

• Young patients unsuitable for autologous stem cell transplant (ASCT): 36-40 Gy in 20 fractions is recommended as consolidation after chemotherapy 1
• Elderly patients: Consolidation WBRT at 36-40 Gy in 20-22 fractions should be avoided or deferred due to high risk of disabling neurocognitive impairment 1
• Reduced-dose option: 23.4 Gy is an alternative for patients with responsive disease after suitable induction chemotherapy, though longer-term cognitive effects remain undefined, especially in elderly patients 1

Palliative Treatment Dosing

For unfit patients unsuitable for high-dose methotrexate-based chemotherapy, palliative WBRT should be administered at 30-36 Gy in 10 or 15 fractions. 1 This lower-dose approach is appropriate when life expectancy and performance status are limited.

Evidence Supporting Dose Reduction

The shift toward lower radiation doses is driven by neurotoxicity concerns:

• Historical high-dose approach (45 Gy): A landmark RTOG 93-10 trial used 45 Gy WBRT after methotrexate-based chemotherapy, achieving median survival of 36.9 months, but 15% of patients experienced severe delayed neurologic toxicity 2
• Non-inferiority of omitting WBRT: The G-PCNSL-SG-1 trial demonstrated that omitting WBRT after high-dose methotrexate did not compromise overall survival (32.4 months with WBRT vs 37.1 months without), though progression-free survival favored WBRT (18.3 vs 11.9 months) 3
• Neurotoxicity reduction: Treatment-related neurotoxicity in complete responders was significantly higher with WBRT (49% by clinical assessment, 71% by neuroradiology) compared to chemotherapy alone (26% and 46%, respectively) 3

Special Situations

Partial Response After Chemotherapy

For patients achieving partial response (PR) with minimal residual unifocal disease <3 cm:

• Combined approach: Low-dose WBRT (23.4 Gy in 13 fractions) combined with stereotactic radiosurgery (12-12.5 Gy) to residual disease has shown efficacy with acceptable toxicity 4
• Dose reduction feasibility: Retrospective data suggest 36 Gy may be as effective as 45 Gy for PR patients, with 3-year overall survival of 100% vs 83.3% (p=0.313) and 3-year intracranial progression-free survival of 60% vs 66.7% (p=0.916) 5

Emergency/Resource-Limited Settings

During crisis situations (e.g., COVID-19 pandemic), hypofractionated regimens are acceptable alternatives, though specific CNS lymphoma dosing was not detailed in emergency guidelines 1

Critical Pitfalls to Avoid

• Avoid standard-dose WBRT (45 Gy) in elderly patients: This carries unacceptable neurocognitive toxicity risk, particularly in those >60 years 1, 3
• Do not use WBRT as monotherapy upfront: High-dose methotrexate-based chemotherapy (≥3 g/m²) should be the foundation of treatment, with WBRT reserved for consolidation or salvage 1
• Recognize the trade-off: WBRT improves progression-free survival but increases neurotoxicity risk; this balance must be weighed for individual patients 3
• Consider ASCT over WBRT when feasible: For fit patients, high-dose chemotherapy with autologous stem cell transplant is preferred over WBRT for consolidation to minimize neurotoxicity 1

Treatment Algorithm

1. Assess fitness for high-dose methotrexate: If fit → proceed with HD-MTX-based chemotherapy (≥3 g/m²) 1
2. Evaluate response after induction:
   • Complete response → Consider reduced-dose WBRT (23.4 Gy) or ASCT if fit 1
   • Partial response with minimal residual disease → Consider 36 Gy WBRT ± radiosurgery boost 4, 5
3. Age stratification:
   • <60 years and fit → ASCT preferred; if not candidate, 36-40 Gy WBRT acceptable 1
   • ≥60 years → Avoid or defer WBRT; consider watchful waiting or maintenance therapy 1
4. Unfit patients: Palliative WBRT 30-36 Gy in 10-15 fractions 1