Bevacizumab-based treatment as salvage therapy in patients with recurrent symptomatic brain metastases

Author:

Berghoff Anna Sophie123,Breckwoldt Michael Oliver4,Riedemann Lars35,Karimian-Jazi Kianush4,Loew Sarah35,Schlieter Franziska12,Furtner Julia26,Cinci Marc7,Thomas Michael8,Strowitzki Moritz J9,Marmé Frederik10,Michel Laura L10,Schmidt Thomas9,Jäger Dirk7,Bendszus Martin4,Preusser Matthias12,Wick Wolfgang35,Winkler Frank35

Affiliation:

1. Department of Medicine I, Medical University of Vienna, Vienna, Austria

2. Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria

3. Clinical Cooperation Unit Neuro-Oncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany

4. Department of Neuroradiology, University Hospital Heidelberg, Heidelberg, Germany

5. Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany

6. Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria

7. Department of Medical Oncology and Internal Medicine VI, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany

8. Department of Thoracic Oncology, University Hospital Heidelberg and Translational Lung Research Center Heidelberg, Heidelberg, Germany

9. Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany

10. National Center for Tumor Disease, Gynecologic Oncology, University Hospital Heidelberg, Heidelberg, Germany

Abstract

Abstract Background Salvage treatment for recurrent brain metastases (BM) of solid cancers is challenging due to the high symptomatic burden and the limited local treatment options. Methods Patients with recurrent BM with no option for further local therapies were retrospectively identified from BM databases. Bevacizumab-based treatment was initiated as a salvage treatment. Radiological imaging before and after bevacizumab-based treatment was reevaluated for treatment response using the Response Assessment in Neuro-Oncology (RANO) BM criteria. Results Twenty-two patients (36.4% male) with recurrent BM from breast cancer (40.9%), colorectal cancer (31.8%), or lung cancer (27.3%) were identified. Previous BM-directed therapies were radiosurgery in 16/22 (72.7%) patients, whole-brain radiotherapy in 8/22 (36.4%), and neurosurgical resection in 11/22 (50.0%). Time since BM diagnosis to initiation of bevacizumab treatment was 16.5 months. Of 22 patients 14 (63.6%) received concurrent systemic therapies. Neurological symptom improvement could be achieved in 14/22 (63.6%) and stabilization in 6/22 (27.3%) patients, resulting in a clinical benefit in 20/22 (90.9%) patients. Steroids could be reduced or stopped in 15/22 (68.2%) patients. Rate of improvement on T1-weighted imaging was 15/19 (78.9%; median reduction: −26.0% ± 32.9) and 19/20 (95%; median reduction: −36.2% ± 22.2) on T2-weighted FLAIR imaging. According to RANO-BM best response was partial response in 7/19 (36.8%), stable disease in 9/19 (47.3%), and progressive disease in 3/19 (15.7%) patients. Median CNS-specific progression-free survival was 8 months and median overall survival after initiation of bevacizumab treatment was 17 months. Conclusions Bevacizumab-based treatment had clinically relevant intracranial activity in the vast majority of patients suffering from recurrent, symptomatic BM. The data supports a prospective clinical trial of bevacizumab as a salvage treatment in BM.

Funder

Deutsche Krebshilfe

Schrödinger Scholarship

Novartis Foundation

Else Kröner-Fresenius-Stiftung

Physician Scientist Fellowship

Publisher

Oxford University Press (OUP)

Subject

Electrical and Electronic Engineering,Building and Construction

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