Background
Dosimetric planning/feasibility study (not an RCT). Tested whether hippocampal-sparing whole-brain RT (HA-WBRT) could spare bilateral hippocampus to V40Gy <0.5 cm³ while delivering 30 Gy in 10 fractions to whole brain, using helical tomotherapy and LINAC-based IMRT.
Interventions and follow up
Arm A: Helical tomotherapy, 30 Gy in 10 fractions whole-brain RT with bilateral hippocampal sparing (hippocampal V40Gy <0.5 cm³)
Arm B: LINAC-based IMRT, 30 Gy in 10 fractions whole-brain RT with same hippocampal constraint
Primary endpoint: Feasibility — achievement of hippocampal dose constraint while maintaining brain target coverage
mFollow up: Dosimetric analysis only
Arm B: LINAC-based IMRT, 30 Gy in 10 fractions whole-brain RT with same hippocampal constraint
Primary endpoint: Feasibility — achievement of hippocampal dose constraint while maintaining brain target coverage
mFollow up: Dosimetric analysis only
Results
Hippocampal V40Gy achieved: <0.5 cm³ in all plans
Median max hippocampal dose: 12–17 Gy vs 33–36 Gy with standard WBRT
PTV coverage: Maintained ≥95% brain coverage in all plans
Both modalities feasible: Tomotherapy and LINAC-IMRT both achieved constraints
Median max hippocampal dose: 12–17 Gy vs 33–36 Gy with standard WBRT
PTV coverage: Maintained ≥95% brain coverage in all plans
Both modalities feasible: Tomotherapy and LINAC-IMRT both achieved constraints
Adverse events
Clinical toxicity: None — dosimetric study, no clinical toxicity endpoints
Caveat: HA-WBRT does not leave a sanctuary site at the hippocampus if metastases are present there; HA-WBRT trial eligibility requires no hippocampal metastases
Caveat: HA-WBRT does not leave a sanctuary site at the hippocampus if metastases are present there; HA-WBRT trial eligibility requires no hippocampal metastases
Conclusions
Hippocampal-sparing WBRT is technically feasible using IMRT, markedly reducing hippocampal dose and thus theoretically reducing radiation-induced neurocognitive decline. This feasibility work directly enabled the RTOG 0933 phase II trial and NRG CC001 phase III RCT.
Key Limitations
Dosimetric/planning study only — no clinical, neurocognitive, or survival endpoints. No patients treated; benefit is theoretical and required prospective validation (subsequently provided by RTOG 0933 and NRG CC001). Technique is contraindicated when hippocampal or perihippocampal metastases are present.
Clinical Context
Foundational planning work for hippocampal-avoidance WBRT, later validated by RTOG 0933 and NRG CC001 showing memory preservation. HA-WBRT (with memantine) is now a standard option for patients with brain metastases and no hippocampal involvement requiring whole-brain RT.