Alleviation of Brain Edema and Restoration of Functional Independence by Bevacizumab in Brain-Metastatic Breast Cancer: A Case Report

Berghoff, Anna Sophie; Sax, Cornelia; Klein, Martin; Furtner, Julia; Dieckmann, Karin; Gatterbauer, Brigitte; Widhalm, Georg; Rudas, Margaretha; Zielinski, Christoph; Bartsch, Rupert; Preusser, Matthias

doi:10.1159/000360930

Cited by 24 publications

(14 citation statements)

References 22 publications

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“…A number of previous case studies with small sample sizes have shown that bevacizumab is effective for brain edema by blocking the binding of VEGF-A to its receptors. [ 7 – 10 ] Wang et al [ 11 ] reported that in 8 patients with brain metastasis and severe brain edema, using a combination therapy of bevacizumab and stereotactic radiosurgery (Cyberknife) decreased the edema area by 63.4% in MRI T2 images. Recently, our case series study of 10 patients showed that bevacizumab therapy effectively relieved serious brain edema associated with reirradiation in patients.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of bevacizumab treatment for refractory brain edema

Meng

Zhao²,

Ge³

et al. 2017

Medicine

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Objective:This retrospective study investigated the efficacy and safety of bevacizumab treatment for refractory brain edema.Methods:Between March 2009 and December 2015, bevacizumab was used to treat 59 cases of brain metastatic patients with refractory brain edema. The median dose of bevacizumab was 4.68 mg/kg (range 2.8–6.52 mg/kg). The clinical-pathological data, the efficacy, and the side effects of bevacizumab were recorded. Magnetic resonance imaging (MRI) was performed before and after bevacizumab treatment. Tumor and edema volumes were measured separately.Results:The clinical symptoms of 50 out of 59 cases (84.74%) improved the day after the bevacizumab treatment, and the edema volumes of 55 (93.22%) cases were reduced after the bevacizumab treatment. The average edema volume was significantly reduced after bevacizumab treatment from 125,583.43 ± 14,093.27 to 71,613.42 ± 9473.42 mm3 (Mann–Whitney rank test, P < .01), and the average edema index was significantly reduced from 25.66 ± 11.54 to 17.87 ± 6.87 (Mann–Whitney rank test, P < .01). One patient died from a hemorrhage due to a cancerous-ulcer of the maxillary sinus. The main complication observed was hypertension, which was observed in 11 cases (18.6%).Conclusion:The effective rate of bevacizumab for refractory brain edema is 84.74%. Hypertension was the main side effect of the bevacizumab treatment. Bevacizumab is an effective and relatively safe treatment for brain edema.

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of bevacizumab treatment for refractory brain edema

Meng

Zhao²,

Ge³

et al. 2017

Medicine

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“…Although the brain has long been considered an “immune-privileged” organ with limited capacity for inflammatory response, it is becoming clear that BM harbors an active inflammatory microenvironment that is capable of inducing prominent anti-tumor immune responses [43]. Because established BM contain considerable inflammatory infiltrates composed of various immune cells [44], the marked reduction of the large peritumoral edema on progressive NSCLC BM might reflect how silibinin-induced inhibition of STAT3 may increase the immunogenicity of BM cancer cells via cell-autonomous pathways and/or may favor the cell-nonautonomous reprogramming of the BM microenvironment (e.g., endothelial cells, tumor-associated macrophages, tumor-infiltrating lymphocytes) toward an immunostimulatory state [45–48]. …”

Section: Discussionmentioning

confidence: 99%

Response of brain metastasis from lung cancer patients to an oral nutraceutical product containing silibinin

et al. 2016

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Despite multimodal treatment approaches, the prognosis of brain metastases (BM) from non-small cell lung cancer (NSCLC) remains poor. Untreated patients with BM have a median survival of about 1 month, with almost all patients dying from neurological causes. We herein present the first report describing the response of BM from NSCLC patients to an oral nutraceutical product containing silibinin, a flavonoid extracted from the seeds of the milk thistle. We present evidence of how the use of the silibinin-based nutraceutical Legasil® resulted in significant clinical and radiological improvement of BM from NSCLC patients with poor performance status that progressed after whole brain radiotherapy and chemotherapy. The suppressive effects of silibinin on progressive BM, which involved a marked reduction of the peritumoral brain edema, occurred without affecting the primary lung tumor outgrowth in NSCLC patients. Because BM patients have an impaired survival prognosis and are in need for an immediate tumor control, the combination of brain radiotherapy with silibinin-based nutraceuticals might not only alleviate BM edema but also prove local control and time for either classical chemotherapeutics with immunostimulatory effects or new immunotherapeutic agents such as checkpoint blockers to reveal their full therapeutic potential in NSCLC BM patients. New studies aimed to illuminate the mechanistic aspects underlying the regulatory effects of silibinin on the cellular and molecular pathobiology of BM might expedite the entry of new formulations of silibinin into clinical testing for progressive BM from lung cancer patients.

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“…Bevacizumab is a monoclonal antibody that targets the VEGF ligand and inhibits vascular proliferation. At present, there are only preliminary results of using bevacizumab in the treatment of BC-related brain metastases [ 8 , 9 , 10 , 11 , 12 ]. Prolonged responses with neurological progression-free survival times varying from 2.8 to 11 months have been observed.…”

Section: Discussionmentioning

confidence: 99%

Prolonged Response and Restoration of Functional Independence with Bevacizumab plus Vinorelbine as Third-Line Treatment for Breast Cancer-Related Leptomeningeal Metastases

Rhun

Taillibert²,

Boulanger

et al. 2015

Case Rep Oncol

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Background: Survival of patients with leptomeningeal metastases (LM) and impaired functional status is limited to several months, and rarely does neurological function improve with treatment. Case Report: A 34-year-old female with hormone-negative and HER2-positive metastatic breast cancer was diagnosed with bulky radiographic LM 45 months after initial diagnosis. She was treated with intra-CSF trastuzumab followed by intra-CSF liposomal cytarabine; however, the cancer progressed 8 months after the diagnosis of LM. At the time of the third LM progression, the patient presented with a cauda equina syndrome and cerebellar impairment resulting in an inability to walk. She was treated with CNS-directed radiotherapy (lumbosacral and cerebellar) and bevacizumab plus vinorelbine. Rapid functional improvement occurred, and the patient regained the ability to walk and independently manage her daily activities. Twelve months later, she presented with rapid progression of the LM resulting in death within several weeks. Conclusion: In radiographically defined bulky LM, the combination of systemic therapy and CNS-directed radiotherapy likely is more active than intra-CSF therapy only. In lieu of the rapid and significant improvement in neurological function combined with the prolonged response, bevacizumab alone or in combination with chemotherapy and CNS-directed radiotherapy may be considered in select patients with radiographically bulky breast cancer-related LM.

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Alleviation of Brain Edema and Restoration of Functional Independence by Bevacizumab in Brain-Metastatic Breast Cancer: A Case Report

Cited by 24 publications

References 22 publications

Efficacy and safety of bevacizumab treatment for refractory brain edema

Efficacy and safety of bevacizumab treatment for refractory brain edema

Response of brain metastasis from lung cancer patients to an oral nutraceutical product containing silibinin

Prolonged Response and Restoration of Functional Independence with Bevacizumab plus Vinorelbine as Third-Line Treatment for Breast Cancer-Related Leptomeningeal Metastases

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