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Whole-brain helical tomotherapy with integrated boost for brain metastases in patients with malignant melanoma – final results of the BRAIN-RT trial

Authors Hauswald H, Bernhardt D, Krug D, Katayama S, Habl G, Lorenzo Bermejo J, Debus J, Sterzing F

Received 10 February 2019

Accepted for publication 10 April 2019

Published 24 May 2019 Volume 2019:11 Pages 4669—4676

DOI https://doi.org/10.2147/CMAR.S204729

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 3

Editor who approved publication: Dr Antonella D'Anneo


Henrik Hauswald,1–4 Denise Bernhardt,1–3 David Krug,1–3,5 Sonja Katayama,1,2 Gregor Habl,1–3,5 Justo Lorenzo Bermejo,6 Jürgen Debus,1–4,7–8 Florian Sterzing1–4,9

1Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany; 2National Center for Radiation Research in Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), 69120 Heidelberg, Germany; 3National Center for Tumor Diseases (NCT), Heidelberg, 69120, Germany; 4Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; 5Radiologie München, 80331 München, Germany; 6Institute of Medical Biometry and Informatics, Heidelberg University Hospital, 69120 Heidelberg, Germany; 7Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, 69120, Germany; 8German Cancer Consortium (DKTK), Partner Site Heidelberg, Heidelberg, Germany; 9Department of Radiation Oncology, Hospital Kempten, 87439, Kempten, Germany

Background: Patients with multiple brain metastases (BMs) from malignant melanoma have a poor prognosis. Recent developments in radiation techniques allow simultaneous integrated boost (SIB) concepts while sparing organs at risk. Data on conventional versus dose-escalated radiation approaches in multiple BMs from malignant melanoma are warranted.
Methods: In this prospective, single-center, randomized two-armed study (trial ID: DRKS00005127), patients with multiple BMs from malignant melanoma were treated with either conventional whole-brain radiotherapy (WBRT) applying 30 Gy in 10 fractions (standard arm) or helical tomotherapy applying 30 Gy to the whole brain with an integrated boost to metastases of 50 Gy in 10 fractions and sparing of the hippocampus (HA-WBRT, experimental arm). The primary endpoint was treatment-related toxicity, while secondary endpoints were imaging response, intracerebral progression-free survival (PFS), overall survival (OS) and quality of life.
Results: The study was stopped early due to slow patient recruitment. A total number of 7 patients were enrolled (standard arm n=3, experimental arm n=4), and were followed-up for a median time of 5 months between August 2013 and July 2017. All patients were treated according to protocol. The median OS, intracerebral PFS and follow-up time were 5 months, 2 months and 5 months, respectively. The local control in every individual BM was significantly longer in the experimental versus the standard arm. No patient developed radiation-related high-grade toxicities.
Conclusion: HA-WBRT with SIB results in improved local control in the individual melanoma BMs without radiation-associated high-grade toxicities. Survival times were comparable to published data.

Keywords: melanoma, brain metastases, tomotherapy, hippocampal sparing, integrated boost

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