Incidence of Brain Metastases in the Hippocampus and Feasibility of Hippocampal Avoidance Whole Brain Radiation in Patients With Hippocampal Involvement: Data From a Prospective Study

Abstract

Purpose: Among patients with brain metastases, hippocampal avoidance whole brain radiation (HA-WBRT) preserves neurocognitive function relative to conventional WBRT but the feasibility of hippocampal sparing in patients with metastases in/near the hippocampus is unknown. We identified the incidence of hippocampal/perihippocampal metastases and evaluated the feasibility of HA-WBRT in such patients. Methods: Dosimetric data from 34 patients randomized to HA-WBRT (30Gy/10 fractions) in a phase III trial (NCT03075072) comparing HA-WBRT to stereotactic radiation in patients with 5-20 brain metastases were analyzed. Patients with metastases in/near the hippocampi received HA-WBRT with prioritization of target coverage over hippocampal avoidance. Target coverage and hippocampal sparing metrics were compared between patients with targets in/near the hippocampus versus not. Results: In total, 9/34 (26%) patients had targets in the hippocampus and an additional 5/34 (15%) patients had targets in the hippocampal avoidance zone (HAZ, hippocampus plus 5mm expansion) but outside the hippocampus. Patients with targets within the hippocampus and those with targets in the HAZ but outside the hippocampus were spared 34% and 73% of the ipsilateral mean biologically equivalent dose, respectively. Of the latter cohort, 88% and 25% met conventional hippocampal sparing metrics of Dmin ≤9Gy and Dmax ≤16Gy, respectively. Among 11 patients with unilateral hippocampal/perihippocampal involvement, the uninvolved/contralateral hippocampus was limited to Dmin ≤9Gy and Dmax ≤17Gy in all cases. Conclusions: A substantial percentage of patients with 5-20 brain metastases harbor metastases in/near the hippocampus. In such cases, minimizing hippocampal dose while providing tumor coverage is feasible and may translate to neurocognitive protection.