Feasibility of hippocampal avoidance whole brain radiation in patients with hippocampal involvement: Data from a prospective study

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. Materials/Methods Dosimetric data from 34 patients randomized to HA-WBRT (30 Gy/10 fractions) in a phase III trial (NCT03075072) comparing HA-WBRT to stereotactic radiation in patients with 5 to 20 brain metastases were analyzed. Patients with metastases in/near the hippocampi received HA-WBRT with prioritization of tumor 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 of 34 (26%) patients had targets in the hippocampus and an additional 5 of 34 (15%) patients had targets in the hippocampal avoidance zone (HAZ, hippocampus plus 5 mm 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 prescription dose, respectively. Of the latter cohort, 88% and 25% met conventional hippocampal sparing metrics of Dmin ≤ 9 Gy and Dmax ≤ 16 Gy, respectively. Among 11 patients with unilateral hippocampal/perihippocampal involvement, the uninvolved/contralateral hippocampus was limited to Dmin ≤ 9 Gy and Dmax ≤ 17 Gy in all cases. Conclusions In this study, a substantial percentage of patients with 5 to 20 brain metastases harbored metastases in/near the hippocampus. In such cases, minimizing hippocampal dose while providing tumor coverage was feasible and may translate to neurocognitive protection.