Session Item

November 28
10:30 - 11:30
Clinical Stream 2
Proffered papers 4: CNS
Proffered Papers
10:50 - 11:00
Hippocampus-avoidance whole-brain irradiation with dose escalation on multiple brain metastases


Hippocampus-avoidance whole-brain irradiation with dose escalation on multiple brain metastases
Authors: Popp|, Ilinca(1)*[];Rau|, Stephan(1);Hintz|, Mandy(1);Schneider|, Julius(1);Bilger|, Angelika(1);Fennell|, Jamina T.(1);Heiland|, Dieter H.(2);Rothe|, Thomas(1);Egger|, Karl(3);Nieder|, Carsten(4,5);Urbach|, Horst(3);Grosu|, Anca L.(1,6);
(1)University Medical Center Freiburg, Department of Radiation Oncology, Freiburg im Breisgau, Germany;(2)Medical Center - University of Freiburg, Department of Neurosurgery, Freiburg im Breisgau, Germany;(3)Medical Center - University of Freiburg, Department of Neuroradiology, Freiburg im Breisgau, Germany;(4)Nordland Hospital, Department of Oncology and Palliative Medicine, Bodø, Germany;(5)Faculty of Health Sciences- University of Tromsø, Department of Clinical Medicine, Tromsø, Norway;(6)German Cancer Consortium DKTK- German Cancer Research Center DKFZ- Heidelberg- Germany, Partner Site Freiburg, Freiburg im Breisgau, Germany;
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Purpose or Objective

Whole brain radiation therapy (WBRT) is the standard treatment for multiple brain metastases. However, WBRT ensures a relatively poor local tumor control and can lead to a significant neurocognitive decline. The aim of the current study was to investigate the efficacy of a hippocampus-avoidance WBRT with simultaneous integrated boost on the metastases (HA-WBRT+SIB) in patients with multiple cerebral metastases.

Material and Methods

Between May 2012 and December 2016, 66 patients were prospectively enrolled and treated with HA-WBRT+SIB analog to the constraints of the experimental arm of the HIPPORAD trial protocol (DRKS00004598). The HA-WBRT+SIB was performed with 30 Gy in 12 fractions and D98% in hippocampus ≤ 9 Gy, D2% ≤ 17 Gy. A SIB (51/42 Gy) was applied on metastases (2-16) and/or resection cavities (0-2). The 66 patients were further analyzed regarding survival, tumor control, occurrence of metastases in the HA-area, and toxicity. After 1:1 propensity score matching analysis, 62 HA-WBRT patients and 62 additional patients having received conventional whole-brain irradiation (WBRT, mostly 10x3 Gy) were selected and compared.


Median follow-up time was 44.1 months (3.7 years) in the HA-WBRT+SIB group and was not reached in the WBRT group. The local tumor control of existing metastases was significantly higher in the HA-WBRT+SIB group (96% vs. 77% at 1 year, p=.004). At the last follow-up, from a total of 380 boosted lesions in the HA-WBRT+SIB cohort, 103 (27.6%) had a complete remission, 153 (40.3%) a partial remission, 47 (12.4%) were stable and 11 (2.9%) were progressive. The distant intracranial tumor control was significantly higher in the WBRT group (68% vs. 81% at 1 year, p=.016), corresponding to higher applied biologically effective doses (60.6 Gy vs. 42.1 Gy and 42.1 Gy vs. 37.5 Gy). Intracranial progression-free (12.8 vs. 5.8 months, p=.02) and overall survival (9 vs. 4.9 months, p=.0003) were significantly better in the HA-WBRT+SIB cohort. Five patients (7.6%) developed hippocampal or perihippocampal metastases after HA. The acute toxicity profile of HA-WBRT+SIB proved acceptable and derived primarily from the SIB. Serious adverse events within the first year of follow-up were comparable in type and frequency (6.1%) to those following radiosurgery alone. The neurologic death rate after HA-WBRT+SIB was 27.4%.


HA-WBRT with SIB is a safe and effective therapeutic option for patients with multiple brain metastases and shows improved local tumor control of existing metastases and overall intracranial progression-free survival compared to WBRT alone. The potential to avoid neurocognitive side effects is being further explored in the multicenter phase II HIPPORAD trial.