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Background African Americans (AAs) experience a disproportionally high rate of bladder cancer (BLCA) deaths even though their incidence rates are lower than those of other patient groups. Using a metabolomics approach, this study investigated how AA BLCA may differ molecularly from European Americans (EAs) BLCA, and it examined serum samples from patients with BLCA with the aim of identifying druggable metabolic pathways in AA patients. Methods Targeted metabolomics was applied to measure more than 300 metabolites in serum samples from 2 independent cohorts of EA and AA patients with BLCA and healthy EA and AA controls via liquid chromatography-mass spectrometry, and this was followed by the identification of altered metabolic pathways with a focus on AA BLCA. A subset of the differential metabolites was validated via absolute quantification with the Biocrates AbsoluteIDQ p180 kit. The clinical significance of the findings was further examined in The Cancer Genomic Atlas BLCA data set. Results Fifty-three metabolites, mainly related to amino acid, lipid, and nucleotide metabolism, were identified that showed significant differences in abundance between AA and EA BLCA. For example, the levels of taurine, glutamine, glutamate, aspartate, and serine were elevated in serum samples from AA patients versus EA patients. By mapping these metabolites to genes, this study identified significant relations with regulators of metabolism such as malic enzyme 3, prolyl 3-hydroxylase 2, and lysine demethylase 2A that predicted patient survival exclusively in AA patients with BLCA. Conclusions This metabolic profile of serum samples might be used to assess risk progression in AA BLCA. These first-in-field findings describe metabolic alterations in AA BLCA and emphasize a potential biological basis for BLCA health disparities.

BACKGROUND The current study compared the incidence of vascular thromboembolic events (VTEs) in patients with metastatic or unresectable urothelial carcinoma (UC) who were treated with gemcitabine and carboplatin (GCb); gemcitabine, carboplatin, and bevacizumab (GCbBev); or gemcitabine and cisplatin (GCis). METHODS Patients with UC who were treated with GCbBev on protocol were analyzed prospectively and 2 contemporary control cohorts receiving GCb or GCis were evaluated retrospectively. VTE was defined as either venous or arterial (myocardial infarctions or cerebral vascular accidents) thrombosis. VTEs were considered to be related to treatment if they occurred during treatment or within 4 weeks of the completion of treatment. Associations with chemotherapy regimen were tested using either the Fisher exact test or Kruskal-Wallis test. Clinical factors associated with VTEs were analyzed using conditional logistic regression stratified by treatment regimen. RESULTS Among 198 patients, VTEs occurred in 13 of 51 patients treated with GCbBev (26%), 22 of 92 patients treated with GCb (24%), and 8 of 55 patients treated with GCis (15%). Patient characteristics were significantly different between the treatment cohorts in terms of age, prior cystectomy, tumor location near pelvic vessels, Khorana risk group, and receipt of antiplatelet therapy. The incidence of VTE and type of VTE (arterial vs venous) did not differ by type of chemotherapy. Prior cystectomy was associated with an increased risk of VTE (odds ratio, 2.2; 95% confidence interval, 1.0-4.9 [P = .047]). CONCLUSIONS The incidence of VTE in Cis-treated patients was similar to prior reports. However, the VTE rate in Cb-treated patients was > 20%, a figure not previously defined in patients with UC and higher than expected. This high incidence of both Cis-related and Cb-related VTEs warrants greater awareness by treating physicians and deserves further study. Cancer 2015. © 2015 American Cancer Society.

Objective TRC105 is a chimeric immunoglobulin G1 monoclonal antibody that binds endoglin (CD105). This phase I open-label study evaluated the safety, pharmacokinetics and pharmacodynamics of TRC105 in patients with metastatic castration-resistant prostate cancer (mCRPC). Patients and Methods Patients with mCRPC received escalating doses of i.v. TRC105 until unacceptable toxicity or disease progression, up to a predetermined dose level, using a standard 3 + 3 phase I design. Results A total of 20 patients were treated. The top dose level studied, 20 mg/kg every 2 weeks, was the maximum tolerated dose. Common adverse effects included infusion-related reaction (90%), low grade headache (67%), anaemia (48%), epistaxis (43%) and fever (43%). Ten patients had stable disease on study and eight patients had declines in prostate specific antigen (PSA). Significant plasma CD105 reduction was observed at the higher dose levels. In an exploratory analysis, vascular endothelial growth factor (VEGF) was increased after treatment with TRC105 and VEGF levels were associated with CD105 reduction. Conclusion TRC105 was tolerated at 20 mg/kg every other week with a safety profile distinct from that of VEGF inhibitors. A significant induction of plasma VEGF was associated with CD105 reduction, suggesting anti-angiogenic activity of TRC105. An exploratory analysis showed a tentative correlation between the reduction of CD105 and a decrease in PSA velocity, suggestive of potential activity of TRC105 in the patients with mCRPC. The data from this exploratory analysis suggest that rising VEGF level is a possible compensatory mechanism for TRC105-induced anti-angiogenic activity.

Purpose: Clinical use of 18F-Sodium Fluoride (NaF) PET/CT in metastatic settings often lacks technology to quantitatively measure full disease dynamics due to high tumor burden. This study assesses radiomics-based extraction of NaF PET/CT measures, including global metrics of overall burden and local metrics of disease heterogeneity, in metastatic prostate cancer for correlation to clinical outcomes. Methods: Fifty-six metastatic Castrate-Resistant Prostate Cancer (mCRPC) patients had NaF PET/CT scans performed at baseline and three cycles into chemotherapy (N=16) or androgen-receptor (AR) inhibitors (N=39). A novel technology, Quantitative Total Bone Imaging (QTBI), was used for analysis. Employing hybrid PET/CT segmentation and articulated skeletal-registration, QTBI allows for response assessment of individual lesions. Various SUV metrics were extracted from each lesion (iSUV). Global metrics were extracted from composite lesion-level statistics for each patient (pSUV). Proportion of detected lesions and those with significant response (%-increase or %-decrease) was calculated for each patient based on test-retest limits for iSUV metrics. Cox proportional hazard regression analyses were conducted between imaging metrics and progression-free survival (PFS). Results: Functional burden (pSUVtotal) assessed mid-treatment was the strongest univariate predictor of PFS (HR=2.03; p