Tips-06 Advancing Beyond the Hippocampus to Preserve Cognition for Patients With Brain Metastases: Dosimetric Results From a Phase 2 Trial of Memory-Avoidance Whole Brain Radiotherapy

Abstract

Recent advances to preserve neurocognitive function in patients treated for brain metastases include stereotactic radiosurgery (SRS), hippocampal avoidance whole brain radiation therapy (HA-WBRT), and memantine administration. The hippocampus, corpus callosum, fornix, and amygdala are key neurocognitive substructures with a low propensity for brain metastases. Herein, we report our preliminary experience using a “memory-avoidance” WBRT (MA-WBRT) approach that spares these substructures for patients with >15 brain metastases. Ten consecutive patients treated with MA-WBRT on a phase 2 clinical trial were reviewed. In each patient, the hippocampi, amygdalae, corpus callosum, and fornix were contoured. Patients were not eligible for MA-WBRT if they had metastases in these substructures. A memory- avoidance region created using a 5mm volumetric expansion around these substructures. Hotspots were avoided in the hypothalamus and pituitary gland. Coverage of brain metastases was prioritized over memory avoidance dose constraints. Dose constraints for these avoidance structures included a D100% ≤ 9Gy and D0.03cc ≤ 16Gy (variation acceptable to 20Gy). LINAC-based volumetric modulated arc therapy (VMAT) plans were generated for a prescription dose of 30 Gy in 10 fractions. On average, the memory avoidance structure volume was 37.1 ccs (Range: 25.2-44.6 ccs), occupying 2.5% of the entire whole brain target volume. All treatment plans met the D100% dose constraint, and 8/10 plans met the D0.03cc constraint, with priority given to tumor coverage for the remaining 2 cases. Target coverage (D98% >25Gy) and homogeneity (D2% ≤ 37.5Gy) were achieved for all plans. Modern VMAT techniques allow for sparing of the hippocampus, amygdala, corpus callosum, and fornix with good target coverage and homogeneity. After enrollment is completed, quality of life and cognitive data will be evaluated to assess the efficacy of MA-WBRT to mitigate declines in quality of life and cognition after whole brain radiation.

Unilateral hippocampal sparing during whole brain radiotherapy for multiple brain metastases: narrative and critical review

“…Indeed, in the NRG CC001 study, approximately 50% of patients treated with HA-WBRT and memantine experienced neurocognitive decline ( 34 ). It is conceivable that sparing more than just the hippocampi is necessary, as is being explored in the concept of Memory Avoidance WBRT, currently under evaluation in an ongoing phase II clinical trial ( 39 ). The Memory Avoidance region encompasses the left and right hippocampus, left and right amygdala, fornix, and corpus callosum, with constraints set at D100% ≤ 9 Gy and D0.03 cm3 ≤ 16 Gy in standard prescription of 30Gy in 10 fractions.…”