ESTRO 2020

Session Item

Saturday

November 28

10:30 - 11:30

Clinical Stream 2

Proffered papers 4: CNS

Session Code: 1200

Session Type: Proffered Papers

Track: Clinical

10:50 - 11:00

Hippocampus-avoidance whole-brain irradiation with dose escalation on multiple brain metastases

Ilinca Popp, Germany

Presentation Number: OC-0093

Abstract

Abstract Title:

Hippocampus-avoidance whole-brain irradiation with dose escalation on multiple brain metastases

Authors: Angelika Bilger.(University Medical Center Freiburg, Department of Radiation Oncology, Freiburg im Breisgau, Germany), Karl Egger.(Medical Center - University of Freiburg, Department of Neuroradiology, Freiburg im Breisgau, Germany), Jamina T. Fennell.(University Medical Center Freiburg, Department of Radiation Oncology, Freiburg im Breisgau, Germany), Anca L. Grosu.(German Cancer Consortium DKTK- German Cancer Research Center DKFZ- Heidelberg- Germany, Partner Site Freiburg, Freiburg im Breisgau, Germany), Anca L. Grosu.(University Medical Center Freiburg, Department of Radiation Oncology, Freiburg im Breisgau, Germany), Dieter H. Heiland.(Medical Center - University of Freiburg, Department of Neurosurgery, Freiburg im Breisgau, Germany), Mandy Hintz.(University Medical Center Freiburg, Department of Radiation Oncology, Freiburg im Breisgau, Germany), Carsten Nieder.(Faculty of Health Sciences- University of Tromsø, Department of Clinical Medicine, Tromsø, Norway), Carsten Nieder.(Nordland Hospital, Department of Oncology and Palliative Medicine, Bodø, Germany), Ilinca Popp.(University Medical Center Freiburg, Department of Radiation Oncology, Freiburg im Breisgau, Germany), Stephan Rau.(University Medical Center Freiburg, Department of Radiation Oncology, Freiburg im Breisgau, Germany), Thomas Rothe.(University Medical Center Freiburg, Department of Radiation Oncology, Freiburg im Breisgau, Germany), Julius Schneider.(University Medical Center Freiburg, Department of Radiation Oncology, Freiburg im Breisgau, Germany), Horst Urbach.(Medical Center - University of Freiburg, Department of Neuroradiology, Freiburg im Breisgau, Germany)

Show Affiliations

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.

Results

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%.

Conclusion

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.