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 1,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostate cancer is the most common form of cancer (except skin cancer) in men. Several factors have been associated with an increased risk for prostate cancer, including age, ethnicity, family history, lifestyle, and environmental exposures. Recognition of the importance of the interaction of these factors in prostate cancer has led to an interest in their evaluation as a model both for studying genetic susceptibility patterns and for studying and providing educational tools and preventive interventions. One such model has been developed at Fox Chase Cancer Center. Critical to the implementation of the model has been the establishment of the Prostate Cancer Risk Registry (PCRR) and Prostate Cancer Risk Assessment Program (PRAP). Together, they serve as a unique resource for investigating the interaction between environmental factors and genetic susceptibility patterns; exploring the early, premalignant biological markers of prostate cancer; and prospectively assessing the quality of life (QOL) of men at risk. In addition, PRAP facilitates the evaluation of models for prostate cancer risk counseling and screening in the community. This paper describes this model for early detection and risk reduction, along with preliminary data from its first two study aims. The program is particularly relevant in view of the wealth of genetic information emerging from the Human Genome Project.
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PMID:Prostate cancer risk assessment program. A model for the early detection of prostate cancer. 1020 54

We reviewed our institution's experience treating patients with prostate cancer with 3-dimensional conformal radiation therapy (3DCRT) and short-term adjuvant hormonal therapy to determine biochemical no evidence of disease (bNED) and clinical outcome compared with patients treated with 3DCRT alone. Between 4/1/89 and 11/30/94, 558 patients with clinically localized prostate cancer received treatment at Fox Chase Cancer Center (Philadelphia, Pa.); 484 patients were treated with 3DCRT alone (Group I); 74 patients were treated with 3DCRT and hormones (Group II). Five-year actuarial rates of bNED control, distant metastasis-free survival (DMFS), cause-specific survival (CSS), and overall survival (OS) were calculated for pretreatment PSA, Gleason score, T stage, use of hormones, treatment field size, age, and dose. A matched case/control analysis was performed to further evaluate the effect of hormones on treatment with 3DCRT. Median follow-up was 47 months (range: 2-97 months). The 5-year actuarial rates of bNED control, DMFS, CSS, and OS were 66%, 93%, 98%, and 86%, respectively, for Group I patients and 68%, 93%, 98%, and 89%, respectively, for Group II patients. Multivariate analysis demonstrated that hormone use was an independent predictor of bNED control only. A significant difference in bNED control was observed between Group I and II (43% vs. 71%) using the matched case/control analysis (P = 0.02). A trend towards significance was observed for different rates of DMFS between Group I and II (79% vs. 94%, P = 0.09). Patients with clinically localized prostate cancer with poor prognostic features (pretreatment PSA > or = 10 ng/ml, Gleason score > or = 7, and/or T2c or greater palpation stage) show improved rates of bNED control and a trend towards improved DMFS when treated with 3DCRT and short-term adjuvant hormones compared with 3DCRT alone. Long-term observation will be necessary to see if improvements in bNED control will translate into improvements in overall survival.
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PMID:Is there a role for short-term hormone use in the treatment of nonmetastatic prostate cancer? 1049 66

The purpose of this study was to present patterns and risk of biochemical failure following external beam irradiation of prostate cancer and to make comparisons to a published modern radical prostatectomy series. Between January 1987 and December 1994, 328 men were treated definitively at Fox Chase Cancer Center for localized prostate cancer using conventional or three-dimensional conformal radiotherapy. The median biochemical follow-up was 6.4 years, with all patients having at least 5 years follow-up. Two prognostic patient groups were established on the basis of proportional hazards modeling that considered treatment and presenting tumor characteristics. For each of the two prognostic groups, biochemical failure and hazard functions were estimated using the ASTRO consensus definition of failure and life table methodology. Failure risk comparisons were made to modern published radical prostatectomy series. Multivariate analysis demonstrated the independent predictive power of pretreatment PSA level, palpation stage, Gleason score, and dose. Thus, the favorable prognosis group, Group I, consisted of 83 patients who were treated with a dose level > or = 74 Gy and who presented with PSA levels < 20 ng/ml, T1/T2A tumors, and Gleason score 2-6. Group II consisted of 245 patients with at least one of the following: pretreatment PSA level > or = 20 ng/ml, T2B/T3 tumor, Gleason score 7-10, dose < 74 Gy. The 5- and 8-year bNED estimates were 76% and 76% for Group I, and 51% and 49% for Group II. Only three failures occurred after 5 years, all from Group II, representing 2% of the total failures observed. Hazard function estimates indicate maximum risk of failure at 24 to 36 months, tapering to a low rate at 4 years with no failures observed after 6 years. Differences in patterns of failure by prognostic group show maximum risk of failure at 24 months (median, 31 months) for Group I, and 12 to 36 months (median, 22 months) for Group II. Group II reaches low levels of risk at 6 years, in contrast to 4 years for the patients with a more favorable prognosis. We concluded that patients treated with external beam radiation alone show little risk of failure after 4 to 6 years. This result suggests that the 5-year bNED control rate approximates the eventual cure rate of prostate cancer.
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PMID:Failure pattern implications following external beam irradiation of prostate cancer: long-term follow-up and indications of cure. 1080 36

Earlier studies have demonstrated that hypoxic regions exist in human prostate cancer and the degree of hypoxia correlates with the treatment outcome of radiotherapy. Using the concept of the clinical oxygen enhancement ratio (COER), the linear-quadratic (LQ) model was extended to account for the effect of tumour hypoxia. The clinical data collected at the Fox Chase Cancer Center for prostate cancer were analysed based on the LQ model as well as the tumour control probability (TCP) model. The LQ and TCP parameters (alpha = 0.15 Gy (-1), alpha/beta = 3.1 Gy and the number of clonogens K = 10(6) approximately 10(7) cells) determined in earlier studies were used to derive the COER for prostate cancer: COER = 1.4 with a standard confidence interval (CI) of (1.2, 1.8). The result is consistent with the in vitro OER measurements of human tumour cell lines under chronic hypoxia conditions. This implies that a higher dose is needed to overcome tumour hypoxia. For prostate tumours, the prescription dose required to overcome tumour hypoxia is 165 Gy (CI: 153 approximately 186 Gy) for permanent 125I implants and 88 Gy (CI: 74 approximately 118 Gy) in 2 Gy fractions for external-beam radiotherapy. The impact of LQ parameters on the calculations of COER and dose escalation was discussed. This study provides a preliminary estimate of the dose escalation needed to overcome tumour hypoxia based on clinical data. More clinical data with better statistics and longer follow-up time are required to further tune the radiobiological modelling of hypoxia for prostate cancer.
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PMID:Dose escalation to combat hypoxia in prostate cancer: a radiobiological study on clinical data. 1688 77

As a clinical application of an exciting scientific breakthrough, a compact and cost-efficient proton therapy unit using high-power laser acceleration is being developed at Fox Chase Cancer Center. The significance of this application depends on whether or not it can yield dosimetric superiority over intensity-modulated radiation therapy (IMRT). The goal of this study is to show how laser-accelerated proton beams with broad energy spreads can be optimally used for proton therapy including intensity-modulated proton therapy (IMPT) and achieve dosimetric superiority over IMRT for prostate cancer. Desired energies and spreads with a varying deltaE/E were selected with the particle selection device and used to generate spread-out Bragg peaks (SOBPs). Proton plans were generated on an in-house Monte Carlo-based inverse-planning system. Fifteen prostate IMRT plans previously used for patient treatment have been included for comparison. Identical dose prescriptions, beam arrangement and consistent dose constrains were used for IMRT and IMPT plans to show the dosimetric differences that were caused only by the different physical characteristics of proton and photon beams. Different optimization constrains and beam arrangements were also used to find optimal IMPT. The results show that conventional proton therapy (CPT) plans without intensity modulation were not superior to IMRT, but IMPT can generate better proton plans if appropriate beam setup and optimization are used. Compared to IMRT, IMPT can reduce the target dose heterogeneity ((D5-D95)/D95) by up to 56%. The volume receiving 65 Gy and higher (V65) for the bladder and the rectum can be reduced by up to 45% and 88%, respectively, while the volume receiving 40 Gy and higher (V40) for the bladder and the rectum can be reduced by up to 49% and 68%, respectively. IMPT can also reduce the whole body non-target tissue dose by up to 61% or a factor 2.5. This study has shown that the laser accelerator under development has a potential to generate high-quality proton beams for cancer treatment. Significant improvement in target dose uniformity and normal tissue sparing as well as in reduction of whole body dose can be achieved by IMPT with appropriate optimization and beam setup.
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PMID:Dosimetric advantages of IMPT over IMRT for laser-accelerated proton beams. 1903 41

It is increasingly important for investigators to efficiently and effectively access, interpret, and analyze the data from diverse biological, literature, and annotation sources in a unified way. The heterogeneity of biomedical data and the lack of metadata are the primary sources of the difficulty for integration, presenting major challenges to effective search and retrieval of the information. As a proof of concept, the Prostate Cancer Ontology (PCO) is created for the development of the Prostate Cancer Information System (PCIS). PCIS is applied to demonstrate how the ontology is utilized to solve the semantic heterogeneity problem from the integration of two prostate cancer related database systems at the Fox Chase Cancer Center. As the results of the integration process, the semantic query language SPARQL is applied to perform the integrated queries across the two database systems based on PCO.
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PMID:Integration of prostate cancer clinical data using an ontology. 1949 89

Technical advances have given medicine the opportunity to refine current treatment techniques to improve outcomes. Computed tomography, magnetic resonance imaging and high energy linear accelerators are but a few examples of technology translating into clinical practice. Intensity-modulated radiation therapy is a form of 3D conformal radiation that is being increasingly incorporated into the management of patients with prostate cancer. As with any new technology, the cost of intensity-modulated radiation therapy is considerably greater than standard therapy. Economic models can be useful to compare treatments when this comparison cannot be performed in a clinical trial. A Markov Model was used to compare the use of intensity-modulated radiation with 3D conformal radiation therapy in the treatment of a 70 year old man with a good- and intermediate-risk prostate cancer. Cost data for men with Medicare insurance and prostate cancer treated with intensity-modulated radiation therapy and 3D conformal radiation therapy was obtained from the billing department at the Fox Chase Cancer Center (PA, USA). Utilities were collected from men undergoing intensity-modulated radiation therapy and 3D conformal radiation therapy for prostate cancer. Intensity-modulated radiation therapy was found to be cost effective in the treatment of a 70 year old man with prostate cancer with a incremental cost-effectiveness ratio of USD 16,182/quality-adjusted life year for men with intermediate-risk prostate cancer and USD 17,448/ quality-adjusted life year for men with good-risk prostate cancer. Sensitivity analysis found that a longer time horizon of the analysis and younger age at treatment favorably impact the cost-effectiveness ratio.
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PMID:Cost-effectiveness of intensity-modulated radiation therapy. 1980 69

Rectum and bladder are the crucial organs at risk for curative radiation therapy of localized prostate cancer. We analyzed the incidence, profile and time course of late rectal radiation toxicity. A total of 320 patients with T1-3 prostate cancer were treated with three-dimensional conformal radiation therapy (3D-CRT). The prescription dose was 70 Gy for T1 and T2 patients (n=230) and 74 Gy for patients with locally advanced T3 tumors (n=90). Late rectal toxicity was graded according to the Fox Chase modification of the Radiation Therapy Oncology Group (RTOG) and Late Effects Normal Tissue Task Force (LENT) criteria. The median follow-up time was 6.2 years (range 0.2-10.7 years). At 5 years, the risk for the development of grade 2 and 3 rectal toxicities was 15.6 and 7.0%, respectively. All new cases of grade 2 and 3 rectal toxicities were observed within 5 years after treatment. Prevalence of grade 2 and 3 rectal symptoms showed fluctuation with maximum at 1.5 years and the minor peak at 4.5 years. Toxicity profile changed significantly over time. The proportion of rectal bleeding within grade 2 and 3 toxicity decreased from 85% at 1.5 years to 46% at 4.5 years. Conversely, the proportion of fecal incontinence among grade 2 and 3 rectal symptoms gradually increased (0% at 1.5 years vs 27% at 4.5 years). Late rectal radiation toxicity represents a dynamic process. Rectal bleeding decreases and fecal incontinence increases over time.
Prostate Cancer Prostatic Dis 2010 Jun
PMID:Time course of late rectal toxicity after radiation therapy for prostate cancer. 2003 60

In the current study, we have examined the efficacy of a Src/Abl kinase inhibitor SKI-606 (Bosutinib) for its effect on prostate cancer growth and skeletal metastasis. Treatment of highly invasive human prostate cancer cells PC-3 and DU-145 with different doses of SKI-606 decreased Src activation, cell proliferation, migration, and invasion as determined by Matrigel Boyden chamber invasion assay. For in vivo studies, PC-3 cells were inoculated through s.c. or i.t. route into male BALB/c nu/nu or Fox Chase severe combined immunodeficient mice, respectively. Experimental animals treated with SKI-606 developed tumors of a significantly smaller volume and a significant decrease (50%) in experimental skeletal lesion area. A marked increase (32%) in bone volume to tumor volume ratio was also seen by micro-computed tomography analysis of tibias from control and experimental groups of animals. Western blot analysis showed the ability of SKI-606 to significantly decrease the phosphorylation of signaling molecules (AKT, mitogen-activated protein kinase, focal adhesion kinase) and the expression of tumor progression-associated genes uPAR, MMP-2, MMP-9, N-cadherin, fibronectin, BMP-2 (bone morphogenetic protein 2), BMP-6 (bone morphogenetic protein 6), IL-8 (interleukin 8), and TGF-beta (transforming growth factor beta) in prostate cancer cells. SKI-606 is currently in clinical trials for breast cancer and chronic myelogenous leukemia. Results from these studies provide convincing evidence for evaluating its efficacy in prostate cancer patients.
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PMID:SKI-606 (Bosutinib) blocks prostate cancer invasion, growth, and metastasis in vitro and in vivo through regulation of genes involved in cancer growth and skeletal metastasis. 2042 91

Urokinase plasminogen activator receptor (uPAR) is a multidomain protein that plays important roles in the growth, invasion, and metastasis of a number of cancers. In the present study, we examined the effects of administration of a monoclonal anti-uPAR antibody (ATN-658) on prostate cancer progression in vitro and in vivo. We examined the effect of treatment of ATN-658 on human prostate cancer cell invasion, migration, proliferation, and regulation of intracellular signaling pathways. For in vivo studies, PC-3 cells (1 x 10(6)) were inoculated into the right flank of male Balb C nu/nu mice through subcutaneous or through intratibial route (2 x 10(5)) of male Fox Chase severe combined immunodeficient mice to monitor the effect on tumor growth and skeletal metastasis. Treatment with ATN-658 resulted in a significant dose-dependent decrease in PC-3 cell invasion and migration without affecting cell doubling time. Western blot analysis showed that ATN-658 treatment decreased the phosphorylation of serine/threonine protein kinase B (AKT), mitogen-activated protein kinase (MAPK), and focal adhesion kinase (FAK) without affecting AKT, MAPK, and FAK total protein expression. In in vivo studies, ATN-658 caused a significant decrease in tumor volume and a marked reduction in skeletal lesions as determined by Faxitron x-ray and micro-computed tomography. Immunohistochemical analysis of subcutaneous and tibial tumors showed a marked decrease in the levels of expression of pAKT, pMAPK, and pFAK, consistent with the in vitro observations. Results from these studies provide compelling evidence for the continued development of ATN-658 as a potential therapeutic agent for the treatment of prostate and other cancers expressing uPAR.
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PMID:An anti-urokinase plasminogen activator receptor antibody (ATN-658) blocks prostate cancer invasion, migration, growth, and experimental skeletal metastasis in vitro and in vivo. 2092 16


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