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Horwich A.,Institute of Cancer Research | Hugosson J.,Gothenburg University | Wiegel T.,Klinik For Strahlentherapie Und Radioonkologie Des Universitatsklinikum | Fizazi K.,Institute Gustave Roussy | And 22 more authors.
Annals of Oncology | Year: 2013

The first ESMO Consensus Conference on prostate cancer was held in Zurich, Switzerland, on 17-19 November 2011, with the participation of a multidisciplinary panel of leading professionals including experts in methodological aspects. Before the conference, the expert panel prepared clinically relevant questions about prostate cancer in four areas for discussion as follows: diagnosis and staging, management of early localized disease, management of advanced localized disease and systemic disease. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the Consensus Conference, the panel developed recommendations for each specific question. The recommendations detailed here are based on an expert consensus after careful review of published data. All participants have approved this final update. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. Source

Albers P.,Heinrich Heine University Dusseldorf | Bangma C.,Erasmus Medical Center | Drudge-Coates L.,Kings College | Magnani T.,Prostate Program | And 4 more authors.
European Journal of Cancer | Year: 2011

The widely recognised benefits of a multidisciplinary approach to treating cancer may be particularly important in prostate cancer, where there are so many treatment options to choose from. It offers patients the best chance of receiving high-quality medical procedures administered by a team of specialists in prostate disease, which is able to tailor treatment and observational strategies to their needs, and ensure access to specialist counselling, supportive care and rehabilitation. This article proposes Prostate Cancer Units as the most suitable structures for organising specialist multidisciplinary care for patients at all stages, from newly diagnosed to advanced disease, including preventing and managing the main complications, whether physical, emotional or psychological, arising from the disease and its treatment. Following the German example with prostate cancer, the British example with urological malignancies and the European breast cancer units, this article proposes general recommendations and mandatory requirements for Prostate Cancer Units, with a view to laying the basis for a network of certified units across Europe. Such a network could help improve standards of care throughout the region, providing patients, practitioners and health authorities with a means of identifying high-quality units and providing a system of quality control and audit. The article is intended as a contribution to the debate within the European uro-oncologic community on the best way to organise prostate cancer care. © 2010 Elsevier Ltd. All rights reserved. Source

Folini M.,Fondazione Istituto Nazionale Dei Tumori | Gandellini P.,Fondazione Istituto Nazionale Dei Tumori | Longoni N.,Fondazione Istituto Nazionale Dei Tumori | Profumo V.,Fondazione Istituto Nazionale Dei Tumori | And 9 more authors.
Molecular Cancer | Year: 2010

Background: Aberrant expression of microRNAs, small non-coding RNA molecules that post-transcriptionally repress gene expression, seems to be causatively linked to the pathogenesis of cancer. In this context, miR-21 was found to be overexpressed in different human cancers (e.g. glioblastoma, breast cancer). In addition, it is thought to be endowed with oncogenic properties due to its ability to negatively modulate the expression of tumor-suppressor genes (e.g. PTEN) and to cause the reversion of malignant phenotype when knocked- down in several tumor models. On the basis of these findings, miR-21 has been proposed as a widely exploitable cancer-related target. However, scanty information is available concerning the relevance of miR-21 for prostate cancer. In the present study, we investigated the role of miR-21 and its potential as a therapeutic target in two prostate cancer cell lines, characterized by different miR-21 expression levels and PTEN gene status.Results: We provide evidence that miR-21 knockdown in prostate cancer cells is not sufficient per se i) to affect the proliferative and invasive potential or the chemo- and radiosensitivity profiles or ii) to modulate the expression of the tumor-suppressors PTEN and Pdcd4, which in other tumor types were found to be regulated by miR-21. We also show that miR-21 is not differently expressed in carcinomas and matched normal tissues obtained from 36 untreated prostate cancer patients subjected to radical prostatectomy.Conclusions: Overall, our data suggest that miR-21 is not a central player in the onset of prostate cancer and that its single hitting is not a valuable therapeutic strategy in the disease. This supports the notion that the oncogenic properties of miR-21 could be cell and tissue dependent and that the potential role of a given miRNA as a therapeutic target should be contextualized with respect to the disease. © 2010 Folini et al; licensee BioMed Central Ltd. Source

Rancati T.,Prostate Program | Fiorino C.,San Raffaele Scientific Institute | Fellin G.,Radiotherapy | Vavassori V.,Radiotherapy | And 8 more authors.
Radiotherapy and Oncology | Year: 2011

Background and purpose: To fit an NTCP model including clinical risk factors to late rectal toxicities after radiotherapy for prostate cancer. Methods and materials: Data of 669 patients were considered. The probability of late toxicity within 36 months (bleeding and incontinence) was fitted with the original and a modified Logit-EUD model, including clinical factors by fitting a subset specific TD 50s: the ratio of TD 50s with and without including the clinical variable was the dose-modifying factor (D mod). Results: Abdominal surgery (surg) was a risk factor for G2-G3 bleeding, reflecting in a TD 50 = 82.7 Gy and 88.4 Gy for patients with and without surg (D mod = 0.94; 0.90 for G3 bleeding); acute toxicity was also an important risk factor for G2-G3 bleeding (D mod = 0.93). Concerning incontinence, surg and previous diseases of the colon were the clinical co-factors. D mod(surg) and D mod(colon) were 0.50 and 0.42, respectively for chronic incontinence and 0.73 and 0.64, respectively for mean incontinence score ≥1. Best-fit n values were 0.03-0.05 and 1 for bleeding and incontinence, respectively. The inclusion of clinical factors always improved the predictive value of the models. Conclusions: The inclusion of predisposing clinical factors improves NTCP estimation; the assessment of other clinical and genetic factors will be useful to reduce parameter uncertainties. © 2011 Elsevier Ltd. All rights reserved. Source

Valdagni R.,Prostate Program | Nahum A.E.,Clatterbridge Center for Oncology | Magnani T.,Prostate Program | Italia C.,Radiation Oncology Radiotherapy | And 5 more authors.
Radiotherapy and Oncology | Year: 2011

Background and purpose: To report the long-term biochemical control of a non-randomized trial comparing standard (STD) and hyper-fractionated (HFX) radiation schedules for prostate cancer treatment. Materials and methods: Between 1993 and 2003, 370 patients entered the study; 330/370 (STD: 179; HFX: 151) were evaluable for current analysis. Median doses were 79.2 Gy and 74 Gy for HFX (1.2 Gy/fr, two daily fractions) and STD (2 Gy/fr), respectively; median follow-up was 7.5 yr. The two regimens were compared in terms of biochemical relapse-free survival (according to ASTRO definition, bRFS) by univariate (log-rank test) and multivariate analyses (Cox regression hazard model). Based on published relationships between EQD2 and 5-yr biochemical control, α/β values for each subgroup could be estimated. Results: 7.5 yr bRFS were 53.4% (±4.4%, 95% CI) and 65.4% (±4.0%) for HFX and STD, respectively (p = 0.13); HFX was associated with a poorer outcome in NCCN low + intermediate patients (7.5 yr bRFS: 56.6% vs 73.5%, p = 0.048) while no differences were seen for high-risk patients (7.5 yr bRFS: 44.1% vs 45.3%). Multivariate analysis revealed that NCCN risk grouping (high vs low + intermediate; OR: 0.59, p = 0.009) and age (< vs ≥70 yr; OR: 0.67, p = 0.03) were the main predictors of worse bRFS. In the subgroups of low + intermediate-risk patients <70 yr, the poorer outcome of HFX was more evident (7.5 yr bRFS: 47.1% vs 70.9%, p = 0.078) while no difference was seen for older patients (7.5 yr bRFS: 69.4% vs 72.0%, p = 0.76). Our α/β estimates differ between low + intermediate-risk and high-risk patients. Conclusions: The bRFS long-term results of this non-randomized trial are consistent with different sensitivities to fractionation depending on NCCN risk grouping. The impact of age on the outcome of HFX for younger low + intermediate patients is consistent with an incomplete repair effect in older patients. © 2011 Elsevier Ireland Ltd. All rights reserved. Source

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