Thrombotic events in patients with cancer receiving antiangiogenesis agents.
ABSTRACT Tumor-associated neoangiogenesis has recently become a suitable target for antineoplastic drug development. In this overview, we discuss specific drug-associated hemostatic complications, the already known pathogenetic mechanisms involved, and the effect of varying antithrombotic strategies. Multiple agents with angiogenic inhibitory capacity (thalidomide, lenalidomide, bevacizumab, sunitinib, sorafenib, and sirolimus) have obtained US Food and Drug Administration approval, and many others have entered clinical trials. Arterial and venous thromboembolism and hemorrhage have emerged as significant toxicities associated with the use of angiogenesis inhibitors. We present a detailed analysis of the literature on thrombotic complication of antiangiogenic drugs. Close attention to hemostatic complications during antiangiogenic treatment is warranted. Further studies are required to better understand the pathophysiologic mechanisms involved and to define a safe prophylactic strategy.
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ABSTRACT: Neoadjuvant therapy (NAC) is commonly used in operable breast cancer. Previous studies have suggested a high rate of postoperative complications after NAC. We prospectively evaluated the surgical complications in a cohort of patients who underwent mastectomy following neoadjuvant adriamycin/cytoxan/taxol (AC/T) plus bevacizumab (bev) and compared the rate of complications to a matched cohort of neoadjuvant AC/T without bev. One hundred patients with HER2-negative breast cancer enrolled in a single-arm trial of neoadjuvant AC/T plus bev (cohort 1), 60 of these patients underwent mastectomy and were matched with 59 patients who received standard neoadjuvant AC/T (cohort 2) over a similar time period in the same healthcare system. All patients underwent mastectomy with or without reconstruction. Fisher's exact tests were used to compare complication rates, with p < 0.05 considered significant. Patients were matched well in terms of demographics. The overall complication rate was 32 % in cohort 1 and 31 % in cohort 2 (p value = 1, Table 1). In cohort 1, 7 of 23 (30 %) patients who underwent immediate expander/implant reconstruction had complications, including 2 patients who had explantation of their reconstructions. In cohort 2, 0 of 8 (0 %) had complications (p value = 0.15). Nearly a third of patients undergoing NAC with AC/T with or without bev developed a postoperative complication after mastectomy. The use of bev was not associated with a significant increase in surgical complications, although this is a nonrandomized data set with a small sample size. As larger data sets become available with the use of neoadjuvant bevacizumab with mastectomy, further refinement may be necessary.Breast Cancer Research and Treatment 09/2013; · 4.47 Impact Factor
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ABSTRACT: Purpose To compare the capability to aid prediction of clinical outcome measures, including progression-free survival (PFS) and overall survival (OS), between volumetric estimates from contrast material-enhanced (CE) T1-weighted subtraction maps and traditional segmentation in a randomized multicenter clinical trial of recurrent glioblastoma (GBM) patients treated with bevacizumab. Materials and Methods All patients participating in this study signed institutional review board-approved informed consent at their respective institutions prior to enrolling in the multicenter clinical trial. One-hundred sixty patients with recurrent GBM enrolled as part of a HIPAA-compliant, multicenter clinical trial (AVF3708 g, BRAIN trial). Contrast enhancing tumor volumes and change in volumes as a response to therapy were quantified by using either conventional segmentation or CE T1-weighted subtraction maps created by voxel-by-voxel subtraction of intensity-normalized nonenhanced T1-weighted images from CE T1-weighted images. These volumes were then tested as predictors of PFS and OS by using log-rank univariate analysis, the multivariate Cox proportional hazards regression model, and receiver operating characteristic analysis. Results Use of CE T1-weighted subtraction maps qualitatively improved visualization and improved quantification of tumor volume after bevacizumab treatment. Significant trends between the volume of tumor and change in tumor volume after therapy on CE T1-weighted subtraction maps were found for both PFS and OS (pretreatment volume < 15 cm(3), P < .003; posttreatment volume < 7.5 cm(3), P < .05; percentage change in volume > 25%, P = .004 for PFS and P = .053 for OS). CE T1-weighted subtraction maps were significantly better at aiding prediction of 6-month PFS and 12-month OS compared with conventional segmentation by using receiver operating characteristic analysis (P < .05). Conclusion Use of CE T1-weighted subtraction maps improved visualization and aided better prediction of patient survival in recurrent GBM treated with bevacizumab compared with conventional segmentation of CE T1-weighted images. ©RSNA, 2013 Clinical trial registration no. NCT00345163 Online supplemental material is available for this article.Radiology 11/2013; · 6.34 Impact Factor
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ABSTRACT: The association between cancer and thrombosis has been recognized for more than 150 years. Not only are patients with cancer at a substantially increased risk of developing venous thromboembolism (VTE), the link between several coagulation factors and tumor growth, invasion, and the development of metastases has been established. Reported rates of VTE in patients with cancer have increased in recent years likely reflecting, in part, improved diagnosis with sophisticated imaging techniques as well as the impact of more aggressive cancer diagnosis, staging, and treatment. Various therapeutic interventions, such as surgery, chemotherapy, hormonal therapy, targeted therapeutic strategies as well as the frequent use of indwelling catheters and other invasive procedures also place cancer patients at increased risk of VTE. The increasing risk of VTE, the multitude of risk factors, and the greater risk of VTE recurrence and death among patients with cancer represent considerable challenges in modern clinical oncology. The American Society of Clinical Oncology (ASCO) originally developed guidelines for VTE in patients with cancer in 2007. ASCO recently updated clinical practice guidelines on the treatment and prevention of VTE in patients with cancer following an extensive systematic review of the literature. Revised 2013 guidelines have now been presented and will be discussed in this review. Although several new studies were identified and considered, many important questions remain regarding the relationship between thrombosis and cancer and the optimal care of patients at risk for VTE. © 2014 Elsevier Ltd. All rights reserved.Thrombosis Research 05/2014; 133 Suppl 2:S122-7. · 3.13 Impact Factor