Brain microischemic phenomena in a woman receiving bevacizumab treatment: a case report
© Quattrocchi et al; licensee BioMed Central Ltd. 2011
Received: 1 April 2010
Accepted: 27 February 2011
Published: 27 February 2011
Several adverse events have been associated with the use of bevacizumab during the treatment of neoplasms such as colorectal cancer, breast cancer, non-small cell lung cancer, pancreatic cancer and renal cell carcinoma. The present case demonstrates how focal neurological symptoms lead to the magnetic resonance imaging-based differential diagnosis between focal parenchymal metastases and microischemic phenomena, with crucial implications for patient management.
We describe the case of a 37-year-old Italian Caucasian woman with metastatic colon cancer who developed focal neurological symptoms during a chemotherapy regimen involving the use of bevacizumab. Brain magnetic resonance imaging examination revealed millimetric lesions with restricted diffusion without perilesional edema or contrast enhancement after gadodiamide intravenous injection, suggestive of acute microischemic phenomena. This complication is very rare but clinically significant.
The differential diagnosis in patients with cancer undergoing bevacizumab treatment should include microischemic phenomena.
We describe the case of a patient with metastatic colon cancer who developed focal neurological symptoms during a chemotherapy regimen including bevacizumab. Some millimetric lesions were detected by a first magnetic resonance imaging (MRI) examination and were not detectable on the MRI examination performed six months later. In patients with cancer undergoing bevacizumab treatment, the occurrence of neurological focal symptoms leads to an MRI differential diagnosis between focal parenchymal metastases and microischemic phenomena, with crucial decisions that must be made for patient management.
A 37-year-old Italian Caucasian woman underwent a colonscopy that revealed a polypoid formation 28cm from the external anal margin. The biopsy showed areas of adenocarcinoma in the context of tubulovillous and villous adenoma with mild to severe dysplasia. Computed tomography (CT) staging was negative for regional or distant metastases. Surgical removal was performed by partial colectomy. The tumor histology confirmed the diagnosis of adenocarcinoma with infiltration of the serosa and pathological TNM staging of pT4pN1M0.
A follow-up CT examination three months later revealed eight focal hepatic lesions distributed throughout both lobes. Chemotherapy treatment with the folinic acid, fluorouracil and oxaliplatin (FOLFOX) scheme was started, and the patient showed a partial response after the fourth course of treatment. She underwent surgical resection of metastases localized at hepatic segments IV and V. CT examination showed disease progression in the lung and liver parenchyma six months later. Several lines of treatment were started, including XELOX (capecitabine plus oxaliplatin), FOLFIRI (folinic acid, fluorouracil and irinotecan) and radiofrequency thermoablation, with no response. CT showed a partial hepatic response after 12 courses of cetuximab and irinotecan therapy, but hepatic progression was observed after 24 courses. Therefore, chemoimmunotherapy with bevacizumab (Avastin; Genentech, South San Francisco, CA, USA) and FOLFOX was started, but it was suspended after nine cycles as the patient developed left hemiparesis, hemifacial left anesthesia and right-hand paresthesia.
An ultrasound Doppler study was obtained, which showed normal morphology of supraaortic vessels. In addition, the patient's electrocardiogram and echocardiogram were normal.
Low-molecular-weight heparin (6,000 IU twice daily), edema therapy (8 mg of dexamethasone twice daily) and antiplatelet therapy (200 mg/day aspirin) were administered, resulting in complete resolution of the patient's neurological symptoms.
Bevacizumab, a humanized antibody directed against the vascular endothelial growth factor (VEGF) that is used as an angiogenesis inhibitor, has been examined in combination with chemotherapeutic agents in several clinical trials in patients with advanced colorectal cancer , even as a first-line treatment . The addition of bevacizumab increased the overall response rate and extended median survival. In the past four years, bevacizumab has been used with increasing frequency for the treatment of other neoplasms, such as breast cancer, non-small cell lung cancer, pancreatic cancer and renal cell carcinoma.
Several adverse events have been associated with the use of bevacizumab: hypertension (the most common side effect), gastrointestinal perforation, wound-healing complications, hemorrhage, arterial thomboembolic events, proteinuria, congestive heart failure, leukopenia and diarrhea . Arterial thromboembolic events have been observed in 0.9% of the cases in the BEATrial  and in 2.1% of the cases in the BRiTE Registry . The mechanism of concurrent thrombosis and bleeding during bevacizumab treatment is not clear, being related to the role of VEGF in maintaining a healthy endothelium.
Vascular events involving the central nervous system have been reported as reversible posterior leukoencephalopathy syndrome following a bevacizumab or FOLFIRI treatment regimen for metastatic colon cancer, which are likely related to high systolic blood pressure levels . Furthermore, as thromboembolic events and microischemic phenomena are a well-known complication of bevacizumab chemotherapeutic treatment , the occurrence of neurological focal symptoms leads to an MRI-based differential diagnosis between focal parenchymal metastases and microischemic phenomena, which lead to crucial decisions for patient management.
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
- Meyerhardt JA, Mayer RJ: Systemic therapy for colorectal cancer. N Engl J Med. 2005, 352: 476-487. 10.1056/NEJMra040958.View ArticlePubMedGoogle Scholar
- Saif MW, Merritt J, Robbins J, Stewart J, Schupp : Phase III multicenter randomized clinical trial to evaluate the safety and efficacy of CoFactor/5-fluorouracil/bevacizumab versus leucovorin/5-fluorouracil/bevacizumab as initial treatment for metastatic colorectal carcinoma. Clin Colorectal Cancer. 2006, 6: 229-234. 10.3816/CCC.2006.n.042.View ArticlePubMedGoogle Scholar
- Van Cutsem E, Michael M, Berry S, Dibartolomeo M, Rivera F, Kretzschmar A, Mazier M, Lutiger B, Cunningham D: Preliminary safety and efficacy of bevacizumab with first-line FOLFOX, XELOX, FOLFIRI, and capecitabine for mCRC: First BEATrial. Presented at the 2007 Gastrointestinal Cancers Symposium, Orlando, FL, USA, [Abstract 346]Google Scholar
- Kozloff M, Hainsworth J, Badarinath S, Cohn A, Flynn P, Steis R, Dong W, Suzuki S, Sugrue M, Grothey A: Efficacy of bevacizumab plus chemotherapy as first-line treatment of patients with metastatic colorectal cancer: updated results from a large observational registry in the US (BRiTE). Presented at the 2006 ASCO annual meeting proceedings, Part I (Abstract 3537). J Clin Oncol. 2006, 24 (18S):Google Scholar
- Glusker P, Recht L, Lane B: Reversible posterior leukoencephalopathy syndrome and bevacizumab. N Engl J Med. 2006, 354: 980-981. 10.1056/NEJMc052954.View ArticlePubMedGoogle Scholar
- Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T: Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009, 27: 4733-4740. 10.1200/JCO.2008.19.8721.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.