Reports of glioblastoma (GBM) progression following treatment with bevacizumab indicate that a subset of patients develop disseminated, often minimally enhancing tumors that differ from the typical pattern of focal recurrence. We have reviewed our institutional experience with bevacizumab for GBM to evaluate the prognostic factors and outcomes of patients with disseminated progression.
Patients and methods:
Medical records of patients treated for GBM at the University of California San Francisco from 2005 to 2009 were reviewed. Patients receiving bevacizumab for focal disease were evaluated and imaging was reviewed to identify patients who progressed in a disseminated pattern. Tumor and treatment factors were compared between focal and disseminated progressors to identify predictive factors for dissemination. Clinical outcomes were compared between progression groups.
Seventy-one patients received adjuvant bevacizumab at some point in their disease course in addition to surgical resection and standard chemoradiotherapy. Of these, 12 patients (17%) had disseminated progression after bevacizumab. There were no differences in patient demographics, surgical treatment, or bevacizumab administration between disseminated and focal progressors. Length of bevacizumab treatment for disseminated progressors trended toward increased time (7.4 vs. 5.4 months) but was not statistically significant (p=0.1). Although progression-free survival and overall survival did not differ significantly between progression groups (median survival from progression was 3.8 vs. 4.6 months, p=0.5), over 30% of focal progressors had a subsequent resection and enrollment in a surgically based clinical trial, whereas none of the disseminated progressors had further surgical intervention. Compared to previously published reports of GBM dissemination with and without prior bevacizumab treatment, our patients had a rate of disease dissemination similar to the baseline rate observed in patients treated without bevacizumab.
The risk of dissemination does not appear to be considerably increased due to the use of bevacizumab, and the pattern of disease at progression does not affect subsequent survival. Therefore, the risk of dissemination should not influence the decision to treat with bevacizumab, especially for recurrent disease.
[Show abstract][Hide abstract] ABSTRACT: The presence of angiogenesis is a hallmark of glioblastoma (GBM). Vascular endothelial growth factor (VEGF), which drives angiogenesis, provides an additional target for conventional therapy. The authors conducted a prospective clinical trial to test the effectiveness of bevacizumab, an inhibitor of VEGF, in newly diagnosed GBM.
From 2006 through 2010, 51 eligible patients with newly diagnosed GBM were treated with involved-field radiation therapy and concomitant temozolomide (75 mg/m(2) daily for 42 days) along with bevacizumab (10 mg/kg every 2 weeks), starting 29 days after surgery. This was followed by 6 cycles of adjuvant temozolomide therapy (150 mg/m(2) on Days 1-7 of a 28-day cycle) with bevacizumab administered at 10 mg/kg on Days 8 and 22 of each 28-day cycle.
The 6- and 12-month progression-free survival (PFS) rates were 85.1% and 51%, respectively. The 12- and 24-month overall survival (OS) rates were 85.1% and 42.5%, respectively. Grade III/IV toxicities were noted in 10 patients (19.6%). No treatment-related deaths were observed. Asymptomatic intracranial bleeding was noted in 5 patients.
The addition of bevacizumab to conventional therapy in newly diagnosed GBM appears to improve both PFS and OS in patients with newly diagnosed GBM, with acceptable morbidity. A shift toward diffuse relapse was noted in a significant number of patients. Ongoing Phase III clinical trials will show the true benefit of this antiangiogenic approach.
Journal of Neurosurgery 02/2012; 116(2):341-5. DOI:10.3171/2011.9.JNS11656 · 3.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Glioblastoma multiforme (GBM) remains one of the most devastating tumors, and patients have a median survival of 15 months despite aggressive local and systemic therapy, including maximal surgical resection, radiation therapy, and concomitant and adjuvant temozolomide. The purpose of antineoplastic treatment is therefore to prolong life, with a maintenance or improvement of quality of life. GBM is a highly vascular tumor and overexpresses the vascular endothelial growth factor A, which promotes angiogenesis. Preclinical data have suggested that anti-angiogenic treatment efficiently inhibits tumor growth. Bevacizumab is a humanized monoclonal antibody against vascular endothelial growth factor A, and treatment has shown impressive response rates in recurrent GBM. In addition, it has been shown that response is correlated to prolonged survival and improved quality of life. Several investigations in newly diagnosed GBM patients have been performed during recent years to test the hypothesis that newly diagnosed GBM patients should be treated with standard multimodality treatment, in combination with bevacizumab, in order to prolong life and maintain or improve quality of life. The results of these studies along with relevant preclinical data will be described, and pitfalls in clinical and paraclinical endpoints will be discussed.
Cancer Management and Research 09/2014; 6:373-87. DOI:10.2147/CMAR.S39306
[Show abstract][Hide abstract] ABSTRACT: Malignant glioma treated with anti-vascular endothelial growth factor (VEGF) bevacizumab show progression patterns that vary with different mechanisms of resistance. We evaluated the clinico-radiological data of 71 patients with progressive malignant glioma treated with bevacizumab to determine the prognostic value of the differential outcome of each progression pattern. Progression patterns were categorized as three types based on the initial response to bevacizumab and serious changes of MR images i.e., non-enhancing infiltration, flare-up of contrast enhancement (CE) and primary non-responder progression. We analyzed the clinical outcome in each type of progression using Kaplan-Meier survival analysis. Analysis of progression patterns showed that incidence of non-enhancing infiltration progression (28.1 %) was less common than flare-up of CE or primary non-responder pattern. The time from initiation of bevacizumab to development of non-enhancing infiltration or flare-up of CE progression was longer than for progression in primary non-responders. There was no significant difference of overall survival, progression-free survival from start of bevacizumab therapy, survival after bevacizumab failure between non-enhancing infiltration and flare-up of CE patterns. However, in the non-enhancing infiltration pattern, early appearance of enhancement was observed after bevacizumab was discontinued, resulting in poor survival, as compared to flare-up of CE pattern (P = 0.01). Although the appearance of non-enhancing infiltration after bevacizumab does not imply a worse prognosis, discontinuation of therapy can aggravate the clinical course.
Journal of Neuro-Oncology 05/2015; 124(1). DOI:10.1007/s11060-015-1808-z · 3.07 Impact Factor
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