Radiotherapy Dose in Primary Central Nervous System Lymphoma
Recommended Dose Based on Response to Chemotherapy
For patients achieving complete response (CR) after high-dose methotrexate-based induction chemotherapy, reduced-dose whole brain radiotherapy (WBRT) of 23.4 Gy in 13 fractions is recommended as consolidation, while patients with partial response or stable disease should receive 36-40 Gy in 20-22 fractions. 1, 2
Dose Selection Algorithm
For Fit Patients Eligible for Consolidation
- Complete responders after induction: 23.4 Gy in 13 fractions is the preferred reduced-dose option 1, 2
- Partial responders or stable disease: 36-40 Gy in 20-22 fractions is recommended 2
- Important caveat: The RTOG1114 trial demonstrated improved progression-free survival with reduced-dose WBRT (23.4 Gy) added to chemotherapy, though full neuropsychological assessment data remain pending 1
For Elderly Patients (≥60 Years)
- Standard-dose WBRT (45 Gy) should be avoided in elderly patients due to unacceptably high risk of disabling neurocognitive impairment 2
- If WBRT is used, 23.4 Gy in 13 fractions for patients in complete remission represents the maximum tolerable dose with encouraging survival rates and minimal cognitive decline 1, 2
- Consolidation with WBRT should be deferred or avoided entirely in patients >60 years when possible, favoring high-dose chemotherapy with autologous stem cell transplantation (ASCT) instead 1, 2
For Unfit/Palliative Patients
- 30-36 Gy in 10-15 fractions is recommended for patients unsuitable for high-dose methotrexate-based chemotherapy 1, 2
- This palliative dose applies to frail patients with poor performance status or significant comorbidities 1
Critical Evidence Regarding Dose De-escalation
A significant concern exists with reduced-dose WBRT: A prospective Indian phase II trial found that patients receiving 23.4 Gy after CR had higher recurrence rates compared to those receiving 45 Gy, with reduced-dose WBRT being a negative prognostic factor for progression-free survival (p=0.02) 3. However, this conflicts with the more recent EHA-ESMO guidelines that support dose tailoring based on response 1.
The strongest current guideline recommendation from the 2024 EHA-ESMO Clinical Practice Guideline states that no randomized trials have directly compared different WBRT doses, but response-adapted dosing is the consensus approach 1.
Technical Considerations
- Whole brain must be irradiated rather than focal radiotherapy, as PCNSL is multifocal in ~40% of cases and conventional MRI underestimates disease extent 1
- Stereotactic radiotherapy, radiosurgery, and hippocampal sparing should only be used within clinical trials due to lack of prospective safety data 1
Neurotoxicity Risk Factors
- Age >60 years is the strongest predictor of chronic neurotoxicity following WBRT 1, 2
- Doses >30 Gy significantly increase neurotoxicity risk, particularly when combined with concurrent systemic therapy 1
- Historical data with 45 Gy WBRT showed late neurotoxicity in 50% of patients ≥60 years versus 0% in younger patients 4
Preferred Consolidation Strategy
High-dose chemotherapy with ASCT is now preferred over WBRT for fit patients to minimize neurotoxicity while maintaining efficacy, with 3-year progression-free survival of 79% versus 53% with non-myeloablative chemotherapy 1, 2. WBRT remains a valid alternative for patients with insufficient stem cell harvest, those refusing ASCT, or those with residual disease after ASCT 1.