IGRT After Prostatectomy: Evaluation of Corrective Shifts and Toxicity Using Online Cone Beam CT vs. Weekly Port Films for Target Localization

Purpose/Objective(s): Image guidance (IG) may permit higher radiotherapy (RT) doses (\u3e65 Gy) after radical prostatectomy (RP) without increased toxicity, with improved accuracy and smaller margins. Conebeam (CBCT) allows IGRT with volumetric images. This study evaluated CBCT shifts and toxicity after conformal IGRT, compared to RT with port films. American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C

Costs of Early Adjuvant Radiation Therapy After Radical Prostatectomy: A Decision Analysis

Purpose/Objective(s): Prospective, randomized trials support adjuvant radiation therapy (RT) for adverse pathologic features after radical prostatectomy (RP). However, adjuvant RT is not universally delivered in this setting. Criticisms of adjuvant RT include toxicity, financial costs, potential overtreatment, and effectiveness of salvage RT. The objective of this study was to construct a decision analytic model to estimate real world cost of RT vs. no RT within the context of the effectiveness of early adjuvant RT for prostate patients based on published clinical results of the Southwest Oncology Group prospective trial of adjuvant RT (SWOG 8794). American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C

A novel role for drebrin in regulating progranulin bioactivity in bladder cancer.

We recently established a critical role for the growth factor progranulin in bladder cancer insofar as progranulin promotes urothelial cancer cell motility and contributes, as an autocrine growth factor, to the transformed phenotype by modulating invasion and anchorage-independent growth. In addition, progranulin expression is upregulated in invasive bladder cancer tissues compared to normal controls. However, the molecular mechanisms of progranulin action in bladder cancer have not been fully elucidated. In this study, we searched for novel progranulin-interacting proteins using pull-down assays with recombinant progranulin and proteomics. We discovered that drebrin, an F-actin binding protein, bound progranulin in urothelial cancer cells. We characterized drebrin function in urothelial cancer cell lines and showed that drebrin is critical for progranulin-dependent activation of the Akt and MAPK pathways and modulates motility, invasion and anchorage-independent growth. In addition, drebrin regulates tumor formation in vivo and its expression is upregulated in bladder cancer tissues compared to normal tissue controls. Our data are translationally relevant as indicate that drebrin exerts an essential functional role in the regulation of progranulin action and may constitute a novel target for therapeutic intervention in bladder tumors. In addition, drebrin may serve as novel biomarker for bladder cancer

PARP-1 regulates DNA repair factor availability.

PARP-1 holds major functions on chromatin, DNA damage repair and transcriptional regulation, both of which are relevant in the context of cancer. Here, unbiased transcriptional profiling revealed the downstream transcriptional profile of PARP-1 enzymatic activity. Further investigation of the PARP-1-regulated transcriptome and secondary strategies for assessing PARP-1 activity in patient tissues revealed that PARP-1 activity was unexpectedly enriched as a function of disease progression and was associated with poor outcome independent of DNA double-strand breaks, suggesting that enhanced PARP-1 activity may promote aggressive phenotypes. Mechanistic investigation revealed that active PARP-1 served to enhance E2F1 transcription factor activity, and specifically promoted E2F1-mediated induction of DNA repair factors involved in homologous recombination (HR). Conversely, PARP-1 inhibition reduced HR factor availability and thus acted to induce or enhance BRCA-ness . These observations bring new understanding of PARP-1 function in cancer and have significant ramifications on predicting PARP-1 inhibitor function in the clinical setting

Preventing Prostate Biopsy Complications: to Augment or to Swab?

Aims for Improvement The aim of this study was to determine the antibiotic prophylaxis associated with the fewest infectious complications following prostate biopsy Determining the safest method allows the Jefferson Department of Urology to modify its biopsy protocol and improve the rate of post-biopsy complication

Awareness of prostate cancer among patients and the general public: results of an international survey

The objective of this study was to assess the level of awareness of prostate cancer (PCa) among the general public and PCa patients in Europe and North America. A survey was undertaken across four European countries (UK, Germany, Italy and Spain), and across the United States and Canada in late 2007. In total, 1008 men with PCa and their partners (the ‘prostate sample'), and 911 men without PCa and their partners (the ‘well sample') participated in the survey, all aged ⩾50 years. Interviews were conducted through telephone, pen and paper, and online. Many people surveyed (53%) thought that breast cancer is more common than PCa. Moreover, 1 in 10 people from the well sample (10%) thought that PCa affects both men and women. When the prostate sample was asked about their perceived level of risk of PCa before diagnosis, 50% believed that they/their husband or partner were previously at low or very low risk, before they were diagnosed. Awareness of the major risk factors for PCa (age and family history) was generally good, but respondents were less clear about the role of other potential factors, such as smoking and drinking alcohol. This international survey, thought to be largest of its type, shows that although patient and public awareness of PCa is generally satisfactory, there is still a considerable lack of clarity about PCa risk factors, and a danger for people to underestimate their own/their partner's perceived risk for PCa. Programmes to responsibly educate and inform men and their partners about risk factors, prevalence and screening tools for PCa are required

Consumer e-health education in HIV/AIDS: a pilot study of a web-based video workshop

BACKGROUND: Members of the HIV/AIDS community are known to use web-based tools to support learning about treatment issues. Initial research indicated components such as message forums or web-based documentation were effectively used by persons with HIV/AIDS. Video has also shown promise as a technology to aid consumer health education. However, no research has been published thus far investigating the impact of web-based environments combining these components in an educational workshop format. METHODS: In this qualitative study HIV/AIDS community members provided feedback on an integrated web-based consumer health education environment. Participants were recruited through organizations that serve the HIV/AIDS community located in Toronto, Canada. Demographics, data on Internet use, including messages exchanged in the study environment were collected. A group interview provided feedback on usability of the study environment, preferences for information formats, use of the message forum, and other sources for learning about treatment information. RESULTS: In this pilot study analysis of the posted messages did not demonstrate use for learning of the workshop content. Participants did not generally find the environment of value for learning about treatment information. However, participants did share how they were meeting these needs. It was indicated that a combination of resources are being used to find and discuss treatment information, including in-person sources. CONCLUSION: More research on the ways in which treatment information needs are being met by HIV/AIDS community members and how technology fits in this process is necessary before investing large amounts of money into web-based interventions. Although this study had a limited number of participants, the findings were unexpected and, therefore, of interest to those who intend to implement online consumer health education initiatives or interventions

A Phase 3 Trial of 2 Years of Androgen Suppression and Radiation Therapy With or Without Adjuvant Chemotherapy for High-Risk Prostate Cancer: Final Results of Radiation Therapy Oncology Group Phase 3 Randomized Trial NRG Oncology RTOG 9902.

PURPOSE: Long-term (LT) androgen suppression (AS) with radiation therapy (RT) is a standard treatment of high-risk, localized prostate cancer (PCa). Radiation Therapy Oncology Group 9902 was a randomized trial testing the hypothesis that adjuvant combination chemotherapy (CT) with paclitaxel, estramustine, and oral etoposide plus LT AS plus RT would improve overall survival (OS). METHODS AND MATERIALS: Patients with high-risk PCa (prostate-specific antigen 20-100 ng/mL and Gleason score [GS] ≥ 7 or clinical stage ≥ T2 and GS ≥ 8) were randomized to RT and AS (AS + RT) alone or with adjuvant CT (AS + RT + CT). CT was given as four 21-day cycles, delivered beginning 28 days after 70.2 Gy of RT. AS was given as luteinizing hormone-releasing hormone for 24 months, beginning 2 months before RT plus an oral antiandrogen for 4 months before and during RT. The study was designed based on a 6% improvement in OS from 79% to 85% at 5 years, with 90% power and a 2-sided alpha of 0.05. RESULTS: A total of 397 patients (380 eligible) were randomized. The patients had high-risk PCa, 68% with GS 8 to 10 and 34% T3 to T4 tumors, and median prostate-specific antigen of 22.6 ng/mL. The median follow-up period was 9.2 years. The trial closed early because of excess thromboembolic toxicity in the CT arm. The 10-year results for all randomized patients revealed no significant difference between the AS + RT and AS + RT + CT arms in OS (65% vs 63%; P=.81), biochemical failure (58% vs 54%; P=.82), local progression (11% vs 7%; P=.09), distant metastases (16% vs 14%; P=.42), or disease-free survival (22% vs 26%; P=.61). CONCLUSIONS: NRG Oncology RTOG 9902 showed no significant differences in OS, biochemical failure, local progression, distant metastases, or disease-free survival with the addition of adjuvant CT to LT AS + RT. The trial results provide valuable data regarding the natural history of high-risk PCa treated with LT AS + RT and have implications for the feasibility of clinical trial accrual and tolerability using CT for PCa

Communication about colorectal cancer screening in Britain:public preferences for an expert recommendation

BACKGROUND: Informed decision-making approaches to cancer screening emphasise the importance of decisions being determined by individuals' own values and preferences. However, advice from a trusted source may also contribute to autonomous decision-making. This study examined preferences regarding a recommendation from the NHS and information provision in the context of colorectal cancer (CRC) screening. METHODS: In face-to-face interviews, a population-based sample of adults across Britain (n=1964; age 50–80 years) indicated their preference between: (1) a strong recommendation to participate in CRC screening, (2) a recommendation alongside advice to make an individual decision, and (3) no recommendation but advice to make an individual decision. Other measures included trust in the NHS and preferences for information on benefits and risks. RESULTS: Most respondents (84%) preferred a recommendation (47% strong recommendation, 37% recommendation plus individual decision-making advice), but the majority also wanted full information on risks (77%) and benefits (78%). Men were more in favour of a recommendation than women (86% vs 81%). Trust in the NHS was high overall, but the minority who expressed low trust were less likely to want a recommendation. CONCLUSION: Most British adults want full information on risks and benefits of screening but they also want a recommendation from an authoritative source. An ‘expert' view may be an important part of autonomous health decision-making