Hippocampus-avoidance whole-brain radiation therapy with a simultaneous integrated boost for multiple brain metastases

Ilinca Popp; Stephan Rau; Mandy Hintz; Julius Schneider; Angelika Bilger; Jamina Tara Fennell; Dieter Henrik Heiland; Thomas Rothe; Karl Egger; Carsten Nieder; Horst Urbach; Anca Ligia Grosu

doi:10.1002/cncr.32787

Hippocampus-avoidance whole-brain radiation therapy with a simultaneous integrated boost for multiple brain metastases

Cancer. 2020 Jun 1;126(11):2694-2703. doi: 10.1002/cncr.32787. Epub 2020 Mar 6.

Authors

Affiliations

¹ Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
² Department of Neurosurgery, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
³ Department of Neuroradiology, 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, Partner Site Freiburg, German Cancer Research Center Heidelberg, Freiburg, Germany.

PMID: 32142171
DOI: 10.1002/cncr.32787

Abstract

Background: The current study was aimed at investigating the feasibility of hippocampus-avoidance whole-brain radiation therapy with a simultaneous integrated boost (HA-WBRT+SIB) for metastases and at assessing tumor control in comparison with conventional whole-brain radiation therapy (WBRT) in patients with multiple brain metastases.

Methods: Between August 2012 and December 2016, 66 patients were treated within a monocentric feasibility trial with HA-WBRT+SIB: hippocampus-avoidance WBRT (30 Gy in 12 fractions, dose to 98% of the hippocampal volume ≤ 9 Gy) and a simultaneous integrated boost (51 or 42 Gy in 12 fractions) for metastases/resection cavities. Intracranial tumor control, hippocampal failure, and survival were subsequently compared with a retrospective cohort treated with WBRT via propensity score matching analysis.

Results: After 1:1 propensity score matching, there were 62 HA-WBRT+SIB patients and 62 WBRT patients. Local tumor control (LTC) of existing metastases was significantly higher after HA-WBRT+SIB (98% vs 82% at 1 year; P = .007), whereas distant intracranial tumor control was significantly higher after WBRT (82% vs 69% at 1 year; P = .016); this corresponded to higher biologically effective doses. Intracranial progression-free survival (PFS; 13.5 vs 6.4 months; P = .03) and overall survival (9.9 vs 6.2 months; P = .001) were significantly better in the HA-WBRT+SIB cohort. Four patients (6.5%) developed hippocampal metastases after hippocampus avoidance. The neurologic death rate after HA-WBRT+SIB was 27.4%.

Conclusions: HA-WBRT+SIB can be an efficient therapeutic option for patients with multiple brain metastases and is associated with improved LTC of existing metastases, higher intracranial PFS, a reduction of the neurologic death rate, and an acceptable risk of radiation necrosis. The therapy has the potential to prevent neurocognitive adverse effects, which will be further evaluated in the multicenter, phase 2 HIPPORAD trial.

Keywords: brain metastases; hippocampus avoidance; neurocognitive function; whole-brain radiation therapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brain Neoplasms / mortality
Brain Neoplasms / radiotherapy*
Brain Neoplasms / secondary*
Cranial Irradiation / adverse effects*
Female
Hippocampus / radiation effects*
Humans
Male
Middle Aged