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      Bone metastases in patients with metastatic renal cell carcinoma: are they always associated with poor prognosis?

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      , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
      Journal of Experimental & Clinical Cancer Research : CR
      BioMed Central
      Bone metastasis, Prognostic factors, Renal cell carcinoma, Time to distant metastasis

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          Abstract

          Purpose

          Aim of this study was to investigate for the presence of existing prognostic factors in patients with bone metastases (BMs) from RCC since bone represents an unfavorable site of metastasis for renal cell carcinoma (mRCC).

          Materials and methods

          Data of patients with BMs from RCC were retrospectively collected. Age, sex, ECOG-Performance Status (PS), MSKCC group, tumor histology, presence of concomitant metastases to other sites, time from nephrectomy to bone metastases (TTBM, classified into three groups: <1 year, between 1 and 5 years and >5 years) and time from BMs to skeletal-related event (SRE) were included in the Cox analysis to investigate their prognostic relevance.

          Results

          470 patients were enrolled in this analysis. In 19 patients (4%),bone was the only metastatic site; 277 patients had concomitant metastases in other sites. Median time to BMs was 16 months (range 0 − 44y) with Median OS of 17 months. Number of metastatic sites (including bone, p = 0.01), concomitant metastases, high Fuhrman grade (p < 0.001) and non-clear cell histology ( p = 0.013) were significantly associated with poor prognosis. Patients with TTBM >5 years had longer OS (22 months) compared to patients with TTBM <1 year (13 months) or between 1 and 5 years (19 months) from nephrectomy (p < 0.001), no difference was found between these two last groups (p = 0.18). At multivariate analysis, ECOG-PS, MSKCC group and concomitant lung or lymph node metastases were independent predictors of OS in patients with BMs.

          Conclusions

          Our study suggest that age, ECOG-PS, histology, MSKCC score, TTBM and the presence of concomitant metastases should be considered in order to optimize the management of RCC patients with BMs.

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          Most cited references25

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          Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study.

          There are no robust data on prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (RCC) treated with vascular endothelial growth factor (VEGF) -targeted therapy. Baseline characteristics and outcomes on 645 patients with anti-VEGF therapy-naïve metastatic RCC were collected from three US and four Canadian cancer centers. Cox proportional hazards regression, followed by bootstrap validation, was used to identify independent prognostic factors for OS. The median OS for the whole cohort was 22 months (95% CI, 20.2 to 26.5 months), and the median follow-up was 24.5 months. Overall, 396, 200, and 49 patients were treated with sunitinib, sorafenib, and bevacizumab, respectively. Four of the five adverse prognostic factors according to the Memorial Sloan-Kettering Cancer Center (MSKCC) were independent predictors of short survival: hemoglobin less than the lower limit of normal (P < .0001), corrected calcium greater than the upper limit of normal (ULN; P = .0006), Karnofsky performance status less than 80% (P < .0001), and time from diagnosis to treatment of less than 1 year (P = .01). In addition, neutrophils greater than the ULN (P < .0001) and platelets greater than the ULN (P = .01) were independent adverse prognostic factors. Patients were segregated into three risk categories: the favorable-risk group (no prognostic factors; n = 133), in which median OS (mOS) was not reached and 2-year OS (2y OS) was 75%; the intermediate-risk group (one or two prognostic factors; n = 301), in which mOS was 27 months and 2y OS was 53%; and the poor-risk group (three to six prognostic factors; n = 152), in which mOS was 8.8 months and 2y OS was 7% (log-rank P < .0001). The C-index was 0.73. This model validates components of the MSKCC model with the addition of platelet and neutrophil counts and can be incorporated into patient care and into clinical trials that use VEGF-targeted agents.
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            Interval estimation for the difference between independent proportions: comparison of eleven methods

            Several existing unconditional methods for setting confidence intervals for the difference between binomial proportions are evaluated. Computationally simpler methods are prone to a variety of aberrations and poor coverage properties. The closely interrelated methods of Mee and Miettinen and Nurminen perform well but require a computer program. Two new approaches which also avoid aberrations are developed and evaluated. A tail area profile likelihood based method produces the best coverage properties, but is difficult to calculate for large denominators. A method combining Wilson score intervals for the two proportions to be compared also performs well, and is readily implemented irrespective of sample size.
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              Prognostic factors for survival in previously treated patients with metastatic renal cell carcinoma.

              To describe survival in previously treated patients with metastatic renal cell carcinoma (RCC) who are candidates for clinical trials of new agents as second-line therapy. The relationship between pretreatment clinical features and survival was studied in 251 patients with advanced RCC treated during 29 consecutive clinical trials between 1975 and 2002. Clinical features were first examined in univariate analyses, and then a stepwise modeling approach based on Cox regression was used to form a multivariate model. Median survival for the 251 patients was 10.2 months and differed according to year of treatment, with patients treated after 1990 showing longer survival. In this group, the median overall survival time was 12.7 months. Because the purpose of this analysis was to establish prognostic factors for present-day clinical trial design, prognostic factor analysis was performed on these patients. Pretreatment features associated with a shorter survival in the multivariate analysis were low Karnofsky performance status, low hemoglobin level, and high corrected serum calcium. These were used as risk factors to categorize patients into three different groups. The median time to death in patients with zero risk factors was 22 months. The median survival in patients with one of these prognostic factors was 11.9 months. Patients with two or three risk factors had a median survival of 5.4 months. Treatment with novel agents during a clinical trial is indicated for patients with metastatic RCC after progression to cytokine treatment. Three prognostic factors for predicting survival were used to categorize patients into risk groups. These risk categories can be used in clinical trial design and interpretation.
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                Author and article information

                Contributors
                mattymo@alice.it
                alessandro.conti@hotmail.com
                giuseppe.procopio@istitutotumori.mi.it
                c.porta@smatteo.pv.it
                t.ibrahim@irst.emr.it
                sandro.barni@ospedale.treviglio.bg.it
                f.guida@unicampus.it
                an.fontana@ao-pisa.toscana.it
                alfredo.berruti@gmail.com
                r.berardi@univpm.it
                fmassari79@gmail.com
                b.vincenzi@unicampus.it
                cortega@ircc.mauriziano.it
                davide.ottaviani@gradenigo.it
                cartenigiacomo@gmail.com
                g_lanzetta58@hotmail.com
                d.delisi@unicampus.it
                silvestrisnicola@libero.it
                mariaantonietta.satolli@unito.it
                elena.collova@ao-legnano.it
                antonio.russo@usa.net
                giuseppe.badalamenti@unipa.it
                s.luzifedeli@ospedalesansalvatore.it
                fmtanca@mail.com
                adamovi@libero.it
                e.maiello@operapadrepio.it
                sabbatini@unimore.it
                alefelici01@gmail.com
                saverio.cinieri@ieo.it
                r.montironi@univpm.it
                sergio.bracarda@usl8.toscana.it
                g.tonini@unicampus.it
                s.cascinu@univpm.it
                d.santini@unicampus.it
                Journal
                J Exp Clin Cancer Res
                J. Exp. Clin. Cancer Res
                Journal of Experimental & Clinical Cancer Research : CR
                BioMed Central (London )
                0392-9078
                1756-9966
                5 February 2015
                5 February 2015
                2015
                : 34
                : 1
                : 10
                Affiliations
                [ ]Department of Medical Oncology, AOU Ospedali Riuniti, Università Politecnica delle, Marche, Ancona Italy
                [ ]Department of Clinical and Specialist Sciences, Urology, Università Politecnica delle Marche, Ancona, Italy
                [ ]Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
                [ ]Division of Medical Oncology, I.R.C.C.S. San Matteo University Hospital Foundation, Pavia, Italy
                [ ]Osteoncology and Rare Tumors Center, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Meldola, FC Italy
                [ ]Medical Oncology Department, Azienda Ospedaliera Treviglio-Caravaggio, Treviglio, Italy
                [ ]Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, Italy
                [ ]Unit of Medical Oncology 2, Istituto Toscano Tumori, Azienda-Ospedaliero-Universitaria Pisana, Pisa, Italy
                [ ]Dipartimento di Specialità Medico-Chirurgiche, Medical Oncology, Scienze Radiologiche e Sanità Pubblica, Università degli Studi di Brescia, Azienda Ospedaliera Spedali Civili, Brescia, Italy
                [ ]Department of Medical Oncology, “G.B. Rossi” Academic Hospital, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy
                [ ]Department of Medical Oncology, Institute for Cancer Research & Treatment (IRCC), Candiolo, Torino Italy
                [ ]Department of Medical Oncology, Presidio Sanitario Gradenigo, Turin, Italy
                [ ]Department of Medical Oncology, Cardarelli Hospital, Naples, Italy
                [ ]Department of Neurological Sciences, Neuromed Institute, IRCSS, Pozzilli, IS Italy
                [ ]Istituto Neurotraumatologico Italiano, Unità Funzionale di Oncologia, Grottaferrata, Italy
                [ ]Medical Oncology Unit, National Cancer Research Centre “Giovanni Paolo II”, Bari, Italy
                [ ]Department of Oncology, University of Turin, Medical Oncology 1, AOU Città della Salute e della Scienza, Turin, Italy
                [ ]Division of Medical Oncology, Hospital of Legnano, Milan, Italy
                [ ]Department of Surgery and Oncology, Section of Medical Oncology, University of Palermo, Palermo, Italy
                [ ]Department of Medical Oncology, AOU Ospedali Riuniti, Università Politecnica delle Marche, Presidio San Salvatore, Pesaro, Italy
                [ ]Department of Medical Oncology, University of Cagliari, Cagliari, Italy
                [ ]Department of Human Pathology, Medical Oncology Unit AOOR Papardo-Piemonte, University of Messina, Messina, Italy
                [ ]Oncology Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG Italy
                [ ]Dipartimento Integrato di Oncologia ed Ematologia, Medical Oncology Division, Università degli Studi di Modena e Reggio Emilia, Modena, Italy
                [ ]Department of Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy
                [ ]Medical Oncology Department & Breast Unit - Hospital of Brindisi and Medical Oncology Department - European Institute of Oncology, Milan, Italy
                [ ]Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy
                [ ]Department of Oncology, USL-8, Ospedale San Donato, Arezzo, Italy
                Article
                122
                10.1186/s13046-015-0122-0
                4328067
                25651794
                9ca80fea-54c2-4617-bedf-16dac72d46a3
                © Santoni et al.; licensee BioMed Central. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 8 November 2014
                : 3 January 2015
                Categories
                Research
                Custom metadata
                © The Author(s) 2015

                Oncology & Radiotherapy
                bone metastasis,prognostic factors,renal cell carcinoma,time to distant metastasis

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