Hippocampus-Avoidance Whole-Brain Radiation Therapy Is Efficient in the Long-Term Preservation of Hippocampal Volume

Ilinca Popp; Alexander Rau; Elias Kellner; Marco Reisert; Jamina Tara Fennell; Thomas Rothe; Carsten Nieder; Horst Urbach; Karl Egger; Anca Ligia Grosu; Christoph P Kaller

doi:10.3389/fonc.2021.714709

Hippocampus-Avoidance Whole-Brain Radiation Therapy Is Efficient in the Long-Term Preservation of Hippocampal Volume

Front Oncol. 2021 Aug 19:11:714709. doi: 10.3389/fonc.2021.714709. eCollection 2021.

Authors

Affiliations

¹ Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
² Department of Neuroradiology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
³ Medical Physics, Department of Radiology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁴ Department of Oncology and Palliative Medicine, Nordland Hospital, Bodø, Norway.
⁵ Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
⁶ German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Abstract

Background and purpose: With improved life expectancy, preventing neurocognitive decline after cerebral radiotherapy is gaining more importance. Hippocampal damage has been considered the main culprit for cognitive deficits following conventional whole-brain radiation therapy (WBRT). Here, we aimed to determine to which extent hippocampus-avoidance WBRT (HA-WBRT) can prevent hippocampal atrophy compared to conventional WBRT.

Methods and materials: Thirty-five HA-WBRT and 48 WBRT patients were retrospectively selected, comprising a total of 544 contrast-enhanced T1-weighted magnetic resonance imaging studies, longitudinally acquired within 24 months before and 48 months after radiotherapy. HA-WBRT patients were treated analogously to the ongoing HIPPORAD-trial (DRKS00004598) protocol with 30 Gy in 12 fractions and dose to 98% of the hippocampus ≤ 9 Gy and to 2% ≤ 17 Gy. WBRT was mainly performed with 35 Gy in 14 fractions or 30 Gy in 10 fractions. Anatomical images were segmented and the hippocampal volume was quantified using the Computational Anatomy Toolbox (CAT), including neuroradiological expert review of the segmentations.

Results: After statistically controlling for confounding variables such as age, gender, and total intracranial volume, hippocampal atrophy was found after both WBRT and HA-WBRT (p < 10^-6). However, hippocampal decline across time following HA-WBRT was approximately three times lower than following conventional WBRT (p < 10^-6), with an average atrophy of 3.1% versus 8.5% in the first 2 years after radiation therapy, respectively.

Conclusion: HA-WBRT is a therapeutic option for patients with multiple brain metastases, which can effectively and durably minimize hippocampal atrophy compared to conventional WBRT.

Keywords: MRI; WBRT (whole-brain radiation therapy); atrophy; cognitive function; hippocampus.