El-Khoueiry A.B.,University of Southern California |
Rankin C.,Statistical Center |
Siegel A.B.,Columbia University |
Iqbal S.,University of Southern California |
And 5 more authors.
British Journal of Cancer | Year: 2014
Background:Gallbladder cancers and cholangiocarcinomas make up a heterogenous group of tumours with a poor prognosis in advanced stages. On the basis of evidence of dysregulation of the epidermal growth factor receptor, vascular endothelial growth factor and mitogen-activated protein kinase pathways in biliary cancers, we performed a phase 2 trial of sorafenib and erlotinib in patients with advanced biliary cancers.Methods:Eligible patients were previously untreated in the advanced setting with adequate hepatic and bone marrow function. Sorafenib and erlotinib were administered continuously at 400 mg BID and 100 mg daily, respectively.Results:Thirty-four eligible patients were recruited. The study was terminated after the first stage of accrual owing to failure to meet the predetermined number of patients who were alive and progression free at 4 months. There were two unconfirmed partial responses (6%, 95% CI: 1-20%), with a median progression-free survival of 2 months (95% CI: 2-3), and median overall survival of 6 months (95% CI: 3-8 months). Grade 3 and 4 adverse events included hypertension, AST/ALT increase, bilirubin increase, diarrhoea, hypokalaemia, hypophosphatemia and rash.Conclusions:Despite compelling preclinical rationale, the combination of sorafenib and erlotinib does not have promising clinical activity in an unselected population of patients with biliary cancers. Improved patient selection based on tumour biology and molecular markers is critical for future evaluation of targeted therapies in this disease. © 2014 Cancer Research UK.
Nanda A.,Anderson Cancer Center Orlando |
Chen M.-H.,University of Connecticut |
Moran B.J.,Prostate Cancer Foundation of Chicago |
Braccioforte M.H.,Prostate Cancer Foundation of Chicago |
D'Amico A.V.,Dana-Farber Cancer Institute
International Journal of Radiation Oncology Biology Physics | Year: 2013
Purpose: To assess the impact of coronary artery disease (CAD) risk factors and sequelae on the risk of all-cause mortality (ACM) in men treated for prostate cancer (PC). Methods and Materials: The study cohort comprised 5077 men with PC consecutively treated with curative intent between 1997 and 2006 at the Chicago Prostate Cancer Center. Cox and Fine and Gray's competing risks regression multivariable analyses were performed, assessing whether cardiovascular comorbidity impacted the risk of ACM and PC-specific mortality, respectively, adjusting for CAD risk factors (diabetes mellitus, hypercholesterolemia, or hypertension) and sequelae (congestive heart failure or myocardial infarction), age, year and type of treatment, and known PC prognostic factors. Results: When compared with men with no comorbidity there was a significantly increased risk of ACM in men with congestive heart failure or myocardial infarction (adjusted hazard ratio [AHR] 1.96, P<.001) and in men with diabetes mellitus (AHR 1.60, P=.03) and hypertension (AHR 1.25, P=.04). In contrast, men with hypercholesterolemia had a similar risk of ACM (AHR 0.68, P=.17) when compared with men with no comorbidity. Other factors associated with a significantly increased risk of ACM included age (AHR 1.09, P<.001), prostate-specific antigen level (AHR 1.25, P=.008), and Gleason score 8-10 disease (AHR 1.71, P=.003). Cardiovascular comorbidity did not impact the risk of PC-specific mortality. Conclusions: In addition to age and unfavorable PC prognostic factors, select CAD risk factors and sequelae are associated with an increased risk of ACM in men treated for PC. These comorbidity prognostic factors predict time courses of mortality from competing causes, which may be factored into the decision-making process when considering management options for PC in a given individual. © 2013 Elsevier Inc.
Beilan J.A.,Urologic |
Beilan J.A.,University of Central Florida |
Lawton A.,Orlando Health Anderson Cancer Center Orlando |
Hajdenberg J.,Anderson Cancer Center Orlando |
And 2 more authors.
BMC Urology | Year: 2013
Background: Pheochromocytoma (paraganglioma) of the urinary bladder is a rare tumor. Herein we sought to review the contemporary literature on pheochromocytomas of the urinary bladder in order to further illustrate the presentation, treatment options and outcomes of patients diagnosed with these tumors. Methods. A comprehensive review of the current literature was conducted according to the PRISMA guidelines by accessing the NCBI PubMed database and using the search terms "paraganglioma, pheochromocytoma, bladder." This search resulted in the identification of 186 articles published between January 1980 and April 2012 of which 80 articles were ultimately included in our analysis. Results: Pheochromocytomas usually occurred in young adult Caucasians (mean age, 43.3 years; range,11-84 years). According to the literature, the most common symptoms and signs of pheochromocytomas of the urinary bladder were hypertension, headache, and hematuria. Of the 77 cases that commented on catecholamine production, 65 patients had biochemically functional tumors. Approximately 20% of patients were treated by transurethral resection alone, 70% by partial cystectomy and 10% by radical cystectomy. The 75 patients with follow-up information had a mean follow-up of 35 months. At the time of last follow-up, 15 (14.2%) had disease recurrence, 10 (9.4%) had metastasis, and 65 (61.3%) were alive. Conclusions: Pheochromocytomas of the urinary bladder tend to be functional and occur mostly in young adult Caucasians. Patients with localized tumors have an extremely favorable prognosis and may be managed by less aggressive modalities, whereas patients with metastatic disease have a significant reduction in survival rates despite aggressive treatment. © 2013 Beilan et al.; licensee BioMed Central Ltd.
The dosimetric effect of intrafraction prostate motion on step-and-shoot intensity-modulated radiation therapy plans: Magnitude, correlation with motion parameters, and comparison with helical tomotherapy plans
Langen K.M.,Anderson Cancer Center Orlando |
Chauhan B.,Anderson Cancer Center Orlando |
Siebers J.V.,Virginia Commonwealth University |
Moore J.,Virginia Commonwealth University |
Kupelian P.A.,University of California at Los Angeles
International Journal of Radiation Oncology Biology Physics | Year: 2012
Purpose: To determine the daily and cumulative dosimetric effects of intrafraction prostate motion on step-and-shoot (SNS) intensity-modulated radiation therapy (IMRT) plans, to evaluate the correlation of dosimetric effect with motion-based metrics, and to compare on a fraction-by-fraction basis the dosimetric effect induced in SNS and helical tomotherapy plans. Methods and Materials: Intrafraction prostate motion data from 486 fractions and 15 patients were available. A motion-encoded dose calculation technique was used to determine the variation of the clinical target volume (CTV) D95% values with respect to the static plan for SNS plans. The motion data were analyzed separately, and the correlation coefficients between various motion-based metrics and the dosimetric effect were determined. The dosimetric impact was compared with that incurred during another IMRT technique to assess correlation across different delivery techniques. Results: The mean (±1 standard deviation [SD]) change in D95% in the CTV over all 486 fractions was 0.2 ± 0.5%. After the delivery of five and 12 fractions, the mean (±1 SD) changes over the 15 patients in CTV D95% were 0.0 ± 0.2% and 0.1 ± 0.2%, respectively. The correlation coefficients between the CTV D95% changes and the evaluated motion metrics were, in general, poor and ranged from r = -0.2 to r = -0.39. Dosimetric effects introduced by identical motion in SNS and helical tomotherapy IMRT techniques were poorly correlated with a correlation coefficient of r = 0.32 for the CTV. Conclusions: The dosimetric impact of intrafraction prostate motion on the CTV is, in general, small. In only 4% of all fractions did the dosimetric consequence exceed 1% in the CTV. As expected, the cumulative effect was further reduced with fractionation. The poor correlations between the calculated motion parameters and the subsequent dosimetric effect implies that motion-based thresholds are of limited value in predicting the dosimetric impact of intrafraction motion. The dosimetric effects between the two evaluated delivery techniques were poorly correlated. © 2012 Elsevier Inc. All rights reserved.
Waghorn B.J.,Anderson Cancer Center Orlando
Journal of applied clinical medical physics / American College of Medical Physics | Year: 2013
Intrafraction motion during intensity-modulated radiation therapy can cause differences between the planned and delivered patient dose. The magnitude of these differences is dependent on a number of variables, including the treatment modality. This study was designed to compare the relative susceptibility of plans generated with three different treatment modalities to intrafraction motion. The dosimetric effects of motion were calculated using computational algorithms for seven lung tumor patients. Three delivery techniques - MLC-based step-and-shoot (SNS), beam attenuating compensators, and helical tomotherapy (HT) - were investigated. In total 840 motion-encoded dose-volume histograms (DVHs) were calculated for various combinations of CTV margins and sinusoidal CTV motion including CTV offsets. DVH-based metrics (e.g., D95% and D05%) were used to score plan degradations. For all three modalities, dosimetric degradations were typically smaller than 3% if the CTV displacement was smaller than the CTV margin. For larger displacements, technique and direction-specific sensitivities existed. While the HT plans show similar D95% degradations for motion in the SI and AP directions, SNS and compensator plans showed larger D95% degradations for motion in the SI direction than for motion in the AP direction. When averaged over all motion/margin combinations, compensator plans resulted in 0.9% and 0.6% smaller D95% reductions compared to SNS and HT plans, respectively. These differences were statistically significant. No statistically significant differences in D95% degradations were found between SNS and HT for data averaged over all margin and motion track combinations. For CTV motion that is larger than the CTV margin, the dosimetric impact on the CTV varies with treatment technique and the motion direction. For the cases presented here, the effect of motion on CTV dosimetry was statistically smaller for compensator deliveries than SNS and HT, likely due to the absence of the interplay effect which is present for the more dynamic treatment deliveries. The differences between modalities were, however, small and might not be clinically significant. As expected, margins that envelop the CTV motion provide dosimetric protection against motion for all three modalities.
Shah A.P.,Anderson Cancer Center Orlando
Journal of applied clinical medical physics / American College of Medical Physics | Year: 2011
In the past 10 years, techniques to improve radiotherapy delivery, such as intensity-modulated radiation therapy (IMRT), image-guided radiation therapy (IGRT) for both inter- and intrafraction tumor localization, and hypofractionated delivery techniques such as stereotactic body radiation therapy (SBRT), have evolved tremendously. This review article focuses on only one part of that evolution, electromagnetic tracking in radiation therapy. Electromagnetic tracking is still a growing technology in radiation oncology and, as such, the clinical applications are limited, the expense is high, and the reimbursement is insufficient to cover these costs. At the same time, current experience with electromagnetic tracking applied to various clinical tumor sites indicates that the potential benefits of electromagnetic tracking could be significant for patients receiving radiation therapy. Daily use of these tracking systems is minimally invasive and delivers no additional ionizing radiation to the patient, and these systems can provide explicit tumor motion data. Although there are a number of technical and fiscal issues that need to be addressed, electromagnetic tracking systems are expected to play a continued role in improving the precision of radiation delivery.
Bakhru A.,University of Michigan |
Bakhru A.,Anderson Cancer Center Orlando
Journal of Gynecologic Oncology | Year: 2012
Objective: Deep venous thrombosis and pulmonary embolism are common in patients with epithelial ovarian cancer, resulting in high costs associated with diagnosis and treatment. I aimed to identify subtypes of epithelial ovarian cancer that pose greater and lesser venous thromboembolism (VTE) risk. Methods: I assessed the outcomes of 641 patients with epithelial ovarian, fallopian tube, and primary peritoneal cancer over a ten-year period. All inpatient, outpatient, and pathology records were reviewed. The rates at which people were evaluated for and diagnosed with venous thromboembolism were assessed. Results: Of the 641 cases, 30.0% underwent an imaging test to evaluate for deep venous thrombosis (DVT) and 21.7% underwent testing for pulmonary embolism (PE). A 10.8% of all subjects were diagnosed with DVT and 7.2% were diagnosed with PE. Borderline tumors and mucinous showed a strikingly low rate of both DVT and PE. Clear cell and high-grade undifferentiated adenocarcinomas were the most likely to result in VTE. In a multivariate model, pathologic subtype was not only a significant predictor of VTE, but was the single best predictor of VTE. Conclusion: Clear cell and undifferentiated pathology in epithelial ovarian carcinomas is associated with a higher VTE risk. The underlying reason for this may related to differences in tumor biology. By identifying low and high risk groups, I may both better conserve medical resources and design more effective thromboprophylaxis for my patients. © 2013. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.
Daurkin I.,University of Florida |
Eruslanov E.,University of Florida |
Stoffs T.,University of Florida |
Perrin G.Q.,University of Florida |
And 6 more authors.
Cancer Research | Year: 2011
Renal cell carcinoma (RCC), the most common human kidney cancer, is frequently infiltrated with tumor-associated macrophages (TAM) that can promote malignant progression. Here, we show that TAMs isolated from human RCC produce substantial amounts of the proinflammatory chemokine CCL2 and immunosuppressive cytokine IL-10, in addition to enhanced eicosanoid production via an activated 15-lipoxygenase-2 (15-LOX2) pathway. TAMs isolated from RCC tumors had a high 15-LOX2 expression and secreted substantial amounts of 15(S)- hydroxyeicosatetraenoic acid, its major bioactive lipid product. Inhibition of lipoxygenase activity significantly reduced production of CCL2 and IL-10 by RCC TAMs. In addition, TAMs isolated from RCC were capable of inducing in T lymphocytes, the pivotal T regulatory cell transcription factor forkhead box P3 (FOXP3), and the inhibitory cytotoxic T-lymphocyte antigen 4 (CTLA-4) coreceptor. However, this TAM-mediated induction of FOXP3 and CTLA-4 in T cells was independent of lipoxygenase and could not be reversed by inhibiting lipoxygenase activity. Collectively, our results show that TAMs, often present in RCCs, display enhanced 15-LOX2 activity that contributes to RCC-related inflammation, immunosuppression, and malignant progression. Furthermore, we show that TAMs mediate the development of immune tolerance through both 15-LOX2-dependent and 15-LOX2-independent pathways. We propose that manipulating LOX-dependent arachidonic acid metabolism in the tumor microenvironment could offer new strategies to block cancer-related inflammation and immune escape in patients with RCC. ©2011 AACR.
Huh W.W.,University of Houston |
Holsinger F.C.,University of Houston |
Levy A.,Anderson Cancer Center Orlando |
Palla F.S.L.,University of Houston |
Anderson P.M.,University of Houston
Head and Neck | Year: 2012
Background. Pediatric jaw osteosarcoma is uncommon, and data are scarce regarding clinical presentation, prognostic factors, and outcome. Methods. A single-institution medical record review from 1983 to 2008 for 12 patients age ≤21 years was undertaken for this study. Results. Median diagnosis age was 16.3 years (range, 6.3-21.9). Nine patients had mandible tumors. Osteoblastic subtype was most common (4 patients). Most tumors were large (ie, T2; n = 8) and high-grade (n = 8). Treatment characteristics were varied. Median follow-up was 27.1 months (range, 8-252 months). Five patients had tumor necrosis <80% after chemotherapy. No deaths were observed. Conclusion. Jaw osteosarcoma outcome is better compared to extremity osteosarcoma, but further study is required regarding clinical prognostic factors. © 2011 Wiley Periodicals, Inc.
Shah A.P.,Anderson Cancer Center Orlando |
Kupelian P.A.,Anderson Cancer Center Orlando |
Waghorn B.J.,Anderson Cancer Center Orlando |
Willoughby T.R.,Anderson Cancer Center Orlando |
And 4 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2013
This article describes the first-ever use of the Calypso system to acquire real-time motion tracks in lung cancer patients. This experience demonstrates that transponder implantation is possible, upon visual inspection transponders are stable once implanted, and electromagnetic tracking is achievable within the lung. Although improvements to the commercially available tracking system are necessary and cannot be used for clinical use, this article describes a technique for acquisition of lung tumor motion documentation. Purpose: To describe the first use of the commercially available Calypso 4D Localization System in the lung. Methods and Materials: Under an institutional review board-approved protocol and an investigational device exemption from the US Food and Drug Administration, the Calypso system was used with nonclinical methods to acquire real-time 4-dimensional lung tumor tracks for 7 lung cancer patients. The aims of the study were to investigate (1) the potential for bronchoscopic implantation; (2) the stability of smooth-surface beacon transponders (transponders) after implantation; and (3) the ability to acquire tracking information within the lung. Electromagnetic tracking was not used for any clinical decision making and could only be performed before any radiation delivery in a research setting. All motion tracks for each patient were reviewed, and values of the average displacement, amplitude of motion, period, and associated correlation to a sinusoidal model (R2) were tabulated for all 42 tracks. Results: For all 7 patients at least 1 transponder was successfully implanted. To assist in securing the transponder at the tumor site, it was necessary to implant a secondary fiducial for most transponders owing to the transponder's smooth surface. For 3 patients, insertion into the lung proved difficult, with only 1 transponder remaining fixed during implantation. One patient developed a pneumothorax after implantation of the secondary fiducial. Once implanted, 13 of 14 transponders remained stable within the lung and were successfully tracked with the tracking system. Conclusions: Our initial experience with electromagnetic guidance within the lung demonstrates that transponder implantation and tracking is achievable though not clinically available. This research investigation proved that lung tumor motion exhibits large variations from fraction to fraction within a single patient and that improvements to both transponder and tracking system are still necessary to create a clinical daily-use system to assist with actual lung radiation therapy. © 2013 Elsevier Inc.