Hippocampal Sparing in Whole Brain Radiation for CNS Lymphoma
Hippocampal sparing during whole brain radiation therapy (WBRT) for CNS lymphoma is generally NOT recommended as routine practice, as nearly half of recurrences occur in or near the hippocampus, though it may be considered in highly selected patients with lesions >15mm from the hippocampus. 1
Key Evidence Against Routine Hippocampal Sparing
The most recent and directly relevant study demonstrates that routinely sparing the hippocampus is not feasible in CNS lymphoma patients 1:
- 45.7% of recurrences occurred in the hippocampus or within 5mm of it 1
- At initial presentation, 13.6% of lesions involved the hippocampus directly, and 16.7% were within 5mm 1
- Only 54.5% of primary lesions were situated >15mm from the hippocampus 1
- Recurrences occurred out-of-field in 60% of cases, frequently involving previously spared hippocampal regions 1
The Neurotoxicity Problem
While the rationale for hippocampal sparing is compelling given the severe neurocognitive consequences of WBRT, the evidence shows:
- WBRT combined with chemotherapy causes cognitive impairment in most CNS lymphoma patients, particularly affecting attention, executive functions, memory, and psychomotor speed 2
- Patients treated with WBRT plus high-dose methotrexate had significantly worse cognitive outcomes compared to chemotherapy alone, with over 50% unable to work due to illness 3
- Neurotoxicity is the most frequent complication among long-term survivors 2
Current Treatment Paradigm Shift
The modern approach increasingly avoids or defers WBRT entirely rather than attempting hippocampal sparing 4, 5:
- High-dose methotrexate-based chemotherapy alone has become preferred first-line treatment to avoid neurotoxicity 4
- WBRT is increasingly reserved for salvage therapy rather than upfront treatment 4
- Reduced-dose WBRT (when used) shows stable cognitive function up to 24 months post-treatment 6
When Hippocampal Sparing Might Be Considered
Hippocampal sparing could be considered only in highly selected patients where 1:
- Primary lesion is >15mm from the hippocampus
- No multifocal disease near hippocampal regions
- Patient has good performance status and life expectancy justifying the approach
Critical Caveat
For brain metastases, Class II evidence suggests hippocampal avoidance may reduce neurocognitive decline 2, but this evidence cannot be extrapolated to CNS lymphoma given the diffuse, infiltrative nature of lymphoma and its predilection for periventricular and deep brain structures including hippocampal regions 1.
Practical Recommendation
The safest approach is to avoid WBRT entirely in favor of intensive chemotherapy regimens when feasible, reserving WBRT for salvage therapy 4, 5. If WBRT must be used upfront, standard whole-brain fields without hippocampal sparing remain the evidence-based standard, as the risk of undertreating disease in hippocampal regions (45.7% recurrence rate) outweighs potential cognitive benefits 1.