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

Haley K Perlow; Ansel P Nalin; Alex R Ritter; Mark Addington; Aubrie Ward; Michal Liu; Collin Nappi; Dukagjin M Blakaj; Sasha J Beyer; Evan M Thomas; John C Grecula; Raju R Raval; Rupesh Kotecha; Daniel Boulter; Erica L Dawson; Wesley Zoller; Joshua D Palmer

doi:10.1016/j.adro.2023.101337

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

Adv Radiat Oncol. 2023 Aug 10;9(2):101337. doi: 10.1016/j.adro.2023.101337. eCollection 2024 Feb.

Authors

Haley K Perlow¹, Ansel P Nalin², Alex R Ritter¹, Mark Addington¹, Aubrie Ward¹, Michal Liu¹, Collin Nappi¹, Dukagjin M Blakaj¹, Sasha J Beyer¹, Evan M Thomas¹, John C Grecula¹, Raju R Raval¹, Rupesh Kotecha³, Daniel Boulter⁴, Erica L Dawson⁵, Wesley Zoller¹, Joshua D Palmer¹

Affiliations

¹ Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, Ohio.
² College of Medicine, The Ohio State University, Columbus, Ohio.
³ Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida.
⁴ Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, Ohio.
⁵ Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, Ohio.

Abstract

Purpose: Recent advances to preserve neurocognitive function in patients treated for brain metastases include stereotactic radiosurgery, hippocampal avoidance whole brain radiation therapy (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.

Methods and materials: 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 was created using a 5-mm 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% ≤ 9 Gy and D0.03 cm³ ≤ 16 Gy (variation acceptable to 20 Gy). LINAC-based volumetric modulated arc therapy plans were generated for a prescription dose of 30 Gy in 10 fractions.

Results: On average, the memory avoidance structure volume was 37.1 cm³ (range, 25.2-44.6 cm³), occupying 2.5% of the entire whole brain target volume. All treatment plans met the D100% dose constraint, and 8 of 10 plans met the D0.03 cm³ constraint, with priority given to tumor coverage for the remaining 2 cases. Target coverage (D98% > 25 Gy) and homogeneity (D2% ≤ 37.5 Gy) were achieved for all plans.

Conclusions: Modern volumetric modulated arc therapy 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.