bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the 2002 and 2010 version of the TNM classification system regarding the prediction of metastasis-free survival in patients with renal cell carcinoma.
Authors: Hutterer Georg C. , Pichler Martin , Chromecki Thomas F. , Jesche Johanna , Kampel-Kettner Karin , Pummer Karl , Zigeuner Richard 
Published: February 2017

448 Background: A new version of the TNM classification system for renal cell carcinoma (RCC) has been introduced in 2010 by the American Joint Committee on Cancer (AJCC). However, data for it’s ability to predict metastasis-free survival in RCC patients from validation studies of independent cohorts are sparse. Therefore, we decided to compare the predictive ability of the 2010 vs. the 2002 version of the TNM classification system. Methods: Pathological reports of 2595 patients with uni- or bilateral synchronous non-metastatic (pT1-4N0M0) RCCs, treated with radical nephrectomy or nephron sparing surgery between 1984 and 2010 at a single tertiary academic center, were re-evaluated. Metastasis-free survival (MFS) was assessed using the Kaplan-Meier method and pairwise log-rank tests. Results: Mean follow up was 95 (0-322) months and 430 (16.6%) patients were found to develop metastatic disease from RCC. Pairwise comparisons revealed statistically significant differences in MFS between adjacent 2002 primary tumor classifications, including pT1a vs. pT1b (p<0.001), pT1b vs. pT2 (p=0.029), pT3a vs. pT3b (p<0.001), and pT3c vs. pT4 (p=0.007) but excluding, pT2 vs. pT3a (p=0.963) and pT3b vs. pT3c (p=0.968). With the changes to the 2010 primary tumor classification different trends in statistical significance were observed in pairwise comparisons, including pT1a vs. pT1b (p<0.001), pT3a vs. pT3b (p=0.001) but excluding pT1b vs. pT2a (p=0.062), pT2a vs. pT2b (p=0.856), pT2b vs. pT3a (p=0.395), pT3b vs. pT3c (p=0.891) and pT3c vs. pT4 (p=0.933). Conclusions: The 2010 version of the TNM classification system remains a robust predictor of MFS compared to the 2002 version. However, the 2010 version showed less discriminative power in higher pT-stages compared to the 2002 version of the TNM classification system.
Virtual HDR SBRT for localized prostate carcinoma: Efficacy and quality-of-life assessment.
Authors: Fuller Donald B. , Shirazi Reza , Naitoh John , Mardirossian George 
Published: February 2017

45 Background: We designed a CyberKnife (CK) prostate Stereotactic Body Radiotherapy (SBRT) method to recapitulate HDR fractionation and target volume coverage (“Virtual HDR”). We report 4 year efficacy, toxicity and quality of life (QoL) outcomes. Methods: Eligible patients had low- (Gleason < 6, PSA < 10 ng/mL, < T2bN0) or intermediate-risk (Gleason < 6 with PSA 10.01 – 20 ng/mL or Gleason 7 with PSA < 10 ng/mL, < T2bN0) prostate cancer. A dose of 38 Gy/4 fractions was given to > 95% of the PTV; with “HDR-like” bladder, urethral and rectal dose constraints, and “HDR-like” dose escalation in the PTV. Toxicities were assessed using CTCAE3.0 criteria. QoL was assessed using the Expanded Prostate Cancer Index Composite (EPIC). Results: Since July 2006, 59 patients were treated. Two were lost to follow-up and 6 have been followed < 6 months, leaving 51 (32 low- and 19 intermediate-risk) patients for analysis. Median f/u is 42 months (range, 6-60). 4-year actuarial biochemical-disease free survival is 98% (ASTRO, Phoenix). Freedom from local and distant relapse is 100% and 98%. Median baseline PSA of 6.3 ng/mL (range 1.0 – 14.1) decreased to 0.1 ng/mL by 48 months. Acute grade 2 GU and GI toxicity rates were 22% and 4%, respectively (0% Grade 3+). Three (6%) late Grade 3 GU toxicities occurred at 18, 48 and 48 months. No grade 3+ GI toxicity occurred. Late grade 2 GU and GI toxicity rates were 18% and 2%, respectively. Only 2 patients (4%) had ongoing late > grade 2 GU toxicity at last follow-up (0% GI). Mean EPIC urinary and bowel scores decreased at 2 months, with subsequent improvement and stability to 48 months. Mean EPIC sexual scores gradually declined to 48 months. Of patients potent at baseline, 63% were potent at 3 years, including 100% < age 60, 64% age 61-70 and 60% > age 70. Conclusions: To 4 years, HDR-like CK SBRT for low- and intermediate-risk prostate cancer results in a very low PSA nadir and relapse rate, minimal toxicity and a favorable QoL outcome, with an age-dependent potency preservation rate. The occasional occurrence of late grade 3 urethral stricture can likely be reduced by better patient selection (caution re: patients with significant pre-existing uropathy). Acute and late grade 2 GU toxicity usually resolves with conservative management.
Tissue array analysis in patients with renal cancer.
Authors: Areses Manrique Maria C , Anido Urbano , Abdulkader Ihab , Leon Luis 
Published: February 2017

450 Background: Development and progression of kidney cancer is the result of an imbalance in signals promoting and inhibiting cellular proliferation and apoptosis. The aim of this study is to analize the expression of some molecular regulators and correlate them with clinical outcome in renal carcinoma, in order to establish common prognostic biomarkers. Methods: Tissue sample was obtained from nephrectomized patients in our center between 1998 and 2003. Biopsies were taken from 150 patients; a tissue array was done to analyze immunoexpression of proteins related to proliferation, cell cycle control and angiongenesis: p53, Ki 67, VEGF, VEGFR1, VEGFR2, HIF1, HIF2, cyclin D1, cyclin D3, cyclin B1, cyclin A, bcl2, p63, COX2, p16, p27, p21, EGFR, PDGF, PTEN, CAIX, BRAF, Akt and P13K. Subsequently the results were correlated with clinical variables (age, hypertension, smoking), pathological (tumor size, stage, Fuhrman grade) and time to progression and overall survival. Results: 92.3% of patients underwent nephrectomy, 11% associated with lymphadenectomy. Histology: 66.6% clear cell his, 14.1% papillary, chromophobe 6.4% and 15% miscellaneous. Stage I 49.4%; II 17.9%; 14.7% III; IV 14.1%; 3.8% unknown. Of the 150 patients analyzed, 23% had a second tumor. Median time to progression was 90.5 months (95% CI 81.7 to 114.3). The median survival has not yet been reached. Results of tissue array analysis wil be presented in the meeting. Conclusions: Patients in this serie have a good prognosis, since most tumors are stage I and II. We will present data on the expression of factors related to proliferation, cell cycle control and angiogenesis.
Medicines use review in renal cancer: How are we doing? What could we do better?
Authors: MacLeod Nicholas James 
Published: February 2017

458 Background: Following guidance from the National Institute for Clinical Excellence (NICE), sunitinib became available for use in the West of Scotland (WOS) in March 2009 as first line treatment for patients with advanced renal cell carcinoma (RCC) who were suitable for immunotherapy and had a performance status (PS) of 0 or 1. We performed a Medicines Use Review of sunitinib in patients who commenced treatment between March 2009 and February 2010. Data were analysed in April 2011. Methods: Patients were identified from an electronic prescribing database. A mixture of prospective and retrospective data were collected using case notes and electronic patient records. Results: 89 patients commenced treatment during this time. 16 patients were excluded as they were enrolled in clinical trials. 73 patients were included in the study. 54 (74%) were male. At the time of analysis, 31 patients were alive. Mean age at first cycle was 62 years. 22 (30%) patients had non clear cell pathology (NCC). 59 (81%) patients had prior nephrectomy and 31 (42%) had prior drug therapy. Median duration of therapy was 6.9 months. Median survival (MS) was 14.4 months (15.1 months for clear cell patients and 8.1 months for non clear cell patients). The most common toxicities (grade 2 or above) were cutaneous, diarrhoea and fatigue. PS was not documented for 43 patients. Where PS was documented, 13 were PS 0, 13 were PS 1 and 4 were PS 2. 32 patients required at least one dose reduction. Three patients later had their dose re-escalated. Conclusions: Our survival figures are lower than those reported in the pivotal trial 1, but comparable to the expanded access programme 2. This may reflect the high proportion of our patients with NCC and with prior treatment. 1. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cancer. J Clin Oncol 27 (22): 3584-90, 2009. 2. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded access trial. Lan Oncol 10: 757-63, 2009.
Association of hypothyroidism with improved outcomes in first-line treatment of renal cell carcinoma with sunitinib.
Authors: Pinto Flavio Augusto Ismael , Pereira Augusto Akikubo Rodrigues , Formiga Maria Nirvana , Fanelli Marcello Ferretti , Chinen Ludmilla T. D. , Lima Vladmir C. , De Melo Gagliato Debora , Santos Elzabeth Santana , Dettino Aldo A. , Sousa Carlos Eduardo Pires , Rodrigues Newton Augusto Ferreira , Padua Fernando Vidigal , Freitas Paulo Henrique Aires , Alves Marclesson S. , Nicolau Ulisses Ribaldo , Lisboa Joyce , Ribeiro Adriana G. , Jesus Victor Hugo Fonseca , Rinck JosÃƒÂ© A. 
Published: February 2017

466 Background: Sunitinib, a multitarget tyrosine-kinase inhibitor, has become a standard of care for first-line low and intermediate risk metastatic renal cell carcinoma (mRCC). Sunitinib-induced hypothyroidism and hypertension have been correlated with better outcomes in those patients. Methods: Fifty patients with mRCC, treated in the first-line with sunitinib, were retrospective analyzed at one brazilian institution, for overall survival (OS), progression free survival (PFS), overall response rate (ORR) and toxicity. We evaluated clinical and laboratory parameters, such as hypothyroidism (TSH level > 5,5 mIU/L) and hypertension, to identify prognostic factors. Results: The median age of patients was 58 years (range: 37-73 years), 82% were male, 54% were ECOG 0 or 1, and 76% were classified in low or intermediate risk. Nefrectomy was performed in 96% of cases. Lung and bone were the most common sites of metastases. The incidence of hypothyroidism and hypertension during treatment were 40% and 34%, respectively. ORR for the entire population was 40% and it was statistically superior in patients that developed hypothyroidism during treatment (90% vs. 20%; p<0,0001). Median survival and PFS were 21.7 months (10.65-17.70 months, 95% CI) and 14.2 months (15.77-27.58 months, 95% CI), respectively. In univariate analysis, ECOG (p<0,0001), MSKCC criteria (p<0,0001), hypothyroidism (p<00001) and hypertension (p=0,001) were associated with OS. In multivariate analysis, ECOG (p<0,0001), MSKCC criteria (p<0,0001) and hypothyroidism (p<00001) were independent prognostic factors for OS. The most common severe adverse events (G3-4) were asthenia (14%), diarrhoea (6%), neutropenia (14%), thrombocytopenia (10%), hand-foot syndrome (6%) and hypertension (8%). Conclusions: Efficacy in survival and toxicity profile of sunitinib in first-line treatment of mRCC in patients out of clinical trials were comparable to prior studies. Hypothyroidism, MSKCC criteria and ECOG were independent prognostic factors for survival.
MARC-2: An open-label trial to characterize patients with metastatic renal cell carcinoma (mRCC) treated with everolimus after failure of the first VEGFR-TKI therapy.
Authors: Staehler Michael D. , Bergmann Lothar , Grünwald Viktor , Huschke Torsten , Keilholz Ulrich , Ohlmann Carsten Henning , Stöckle Michael , Weigang-Koehler Karin , Hauswald Kirsten , Schaller Felix , Strassl Luise , Junker Kerstin 
Published: February 2017

467 Background: Clinical research in mRCC is leading to increased treatment options. Most patients (pts) are treated with sequenced systemic medications based on the clinical course of the disease. Characterization of pts most likely to benefit from a specific targeted agent has not yet been sufficiently addressed in this area. So far, no reliable biomarkers exist to predict therapy response or resistance in the individual patient. Further investigation is needed to understand drug effects in vivo. In the MARC-2-study, pts treated with everolimus will be characterized by serum and tissue biomarkers in order to identify a pattern possibly suggestive of treatment outcome. Methods: 80 pts are to be enrolled at about 15 study centers in Germany over 2 years. Major inclusion criteria are confirmed predominantly clear cell mRCC, failure of exactly 1 prior VEGFR-TKI therapy, no pretreatment with mTOR inhibitors or bevacizumab. Tumor response is assessed according to RECIST 1.1. Safety assessments include monitoring of adverse events and laboratory parameters. Primary objective is the rate of pts free of disease progression after 6 months of treatment. Secondary objectives are relation of biomarkers to the clinical benefit, progression free survival, overall survival, objective response rate and safety profile. For explorative assessments, blood samples are taken pre-treatment and at prespecified time points during the treatment. Central histopathological classification of tumor samples will be performed. Biomarker projects include: Serum protein profiling by using SELDI-TOF-MS; quantification of Treg cells in blood samples; identification of serum metabolic biomarkers; polymorphisms in genes related to the VEGFR signaling pathway; expression analysis of the mTOR-pathway in tumor samples. Pharmacokinetic consists of everolimus trough levels. Tumor assessments by functional MRI will be performed within a substudy at selected sites. Results: The 1st patient was enrolled in 03/2011. Until 08/2011, 10 sites have been initiated and 9 pts were recruited. Conclusions: The new project MARC-2 was introduced and started successfully in 2011.
Prognostic significance of degree of anemia in renal cell carcinoma.
Authors: Mozayen Mohammad , Tesfaye Anteneh , Katato Khalil 
Published: February 2017

469 Background: Anemia can precede the diagnosis of renal cell carcinoma (RCC). It has been well studied that it has a negative effect on the outcome of RCC. The impact of the severity of anemia on the overall all survival of patients with RCC is not well known. Our study examined the impact of severity of anemia on the overall survival of patients with RCC. Methods: We retrospectively reviewed 204 patients diagnosed with RCC between 1995 and 2008 in a community hospital setting. Patients with additional malignancies, lymphoma of the kidneys, with no follow up data or no preoperative Hemoglobin levels (Hg) measurement were excluded from the study. Demographics, preoperative complete blood count (CBC), pathology, disease stage, operative note, and subsequent follow up data were reviewed. Patients were grouped based on their preoperative Hg. Anemia was defined as Hg <12g/dl for females and <13g/dl for males. Patients were divided based on Hg to Group A (females with Hg<10 g/dl, males with Hg<11g/dl), group B (females with Hg 10-12 g/dl, males with Hg 11-13 g/dl), group C (females with Hg >12 g/dl, males with Hg >13g/dl). Last follow up date was used to calculate the 3 year overall survival for patients. The primary outcome was 3 year overall survival. Results: A total of 204 patients were reviewed, 127 (62.3%) were males, 176 (85.9%) were Caucasians. The median age of the study population was 65 (22-91). Clear Cell was the commonest histology (79%). Anemia was found in 90 (44.1%) patients. The median Hg was 12.8 g/dl (Range: 7.2-18.2). Anemia was present in 41.8% of females and 46.2% of males. The median Hg level for stages I, II, III, IV were (13.05, 12.45, 12.45, 11.45) respectively. The 3 year overall survival for the study population was 67.3% (95% CI: 60.4-73.7). The 3-year overall survival for anemic patients was 51.2% (95% CI: 40-61) compared to 81.6% (95% CI: 72-87) in non anemic (p<0.0001). The 3-year overall survival significantly decreased with Hg levels, as shown by the Groups A (33.3%), B (60.7%), and C (81.6%) (p<0.0001). Conclusions: Our finding was consistent with other studies in portraying anemia as a negative prognostic factor in patients with renal cell carcinoma. Our study also showed that the severity of anemia corresponds to poorer overall patients survival.
Radical salvage prostatectomy for locally recurrent prostate cancer after radiation therapy.
Authors: Heidenreich Axel , Porres-Knoblauch Daniel , Epplen Robin , Piper Charlotte , Pfister David J. K. P. ,   EURO Prostate Center Aachen
Published: February 2017

47 Background: Radical salvage prostatectomy (SRP) is one local treatment option with curative intent in patients failing radiation therapy (RT) for localized prostate cancer (PCA). We compared the surgical, histological and functional outcome of a large cohort of patients who underwent SRP for locally recurrent PCA following LDR – brachytherapy (BRT). Methods: 66 consecutive patients with locally recurrent PCA after BRT underwent retropubic SRP and pelvic lymphadenectomy. Preoperative PSA, PSA doubling time, PSA prior to initial RT, biopsy Gleason score, number of positive biopsies, cT stage, neoadjuvant androgen deprivation were correlated with pathohistological stage, complications and functional outcome by uni- and multivariate analysis. Results: Mean preop. PSA was 5.6 (2-13.5) ng/ml; mean preoperative biopsy Gleason score was y5.6 (4-9). 1 patient (1.5%) experienced a rectal lesion, mean blood loss was 430 (200-900) ml, none of the patients received blood transfusions. Pathohistology demonstrated organ confined prostate cancer pT2a-2c in 38 (57.5%) patients, stage pT3a and stage pT3b was identified in 14 (21.1%) patients and in 14 (21.1%) patients, respectively. Positive surgical margins were diagnosed in 9 (13.6%) patients and 12 (15.1%) patients harboured lymph node metastases. Functional outcome was good with a continence rate of 82%; the mean time until recovery of continence was 8.4 (6-14) months. After a mean follow-up of 22.5 (1-72) months, 28% of the patients experienced a PSA relapse defined as any PSA increase > 0.2 ng/ml validated by 2 consecutive measures. Conclusions: SRP can be performed safely and with a low morbidity in biopsy proven locally recurrent PCA following BRT. However, our data demonstrate an unfavourable histology with locally advanced disease in about 40% of the patients who all were diagnosed with low risk prostate cancer. These data question the quality of the selection process for patients being counselled for BRT and the data raise the possibility of both intrinsic radioresistance of prostate cancer or poorly performed BRT.
Prostate-specific antigen and long-term prediction of prostate cancer incidence and mortality in the general population.
Authors: Orsted David D , Nordestgaard Borge G. , Bojesen Stig E. 
Published: February 2017

5 Background: It is largely unknown whether prostate-specific antigen at first date of testing predicts long-term risk of prostate cancer incidence and mortality in the general population. We tested the hypothesis that baseline prostate-specific antigen levels predict long-term risk of prostate cancer incidence and mortality. Methods: Using a prospective study, we examined 4383 20-94 year old men from the Danish general population followed in the Copenhagen City Heart Study from 1981 through 2009. Prostate-specific antigen was measured in plasma samples obtained in 1981-83. Results: During 28 years of follow-up, 170 men developed prostate cancer and 94 died from prostate cancer. Median follow-up was 18 years (range 0.5-28 years). For prostate cancer incidence, the subhazard ratio was 3.0 (95% confidence interval (CI) 1.9-4.6) for a prostate-specific antigen level of 1.01-2.00 ng/ml, 6.8 (4.2-11) for 2.01-3.00 ng/ml, 6.6 (3.4-13) for 3.01-4.00 ng/ml, 16 (10.4-25) for 4.01-10.00 ng/ml, and 57 (32-104) for >10.00 ng/ml versus 0.01-1.00 ng/ml.. For prostate cancer mortality, corresponding subhazard ratios were 2.2 (1.3-3.9), 5.1 (2.8-9.0), 4.2 (1.8-10), 7.0 (3.8-14), and 14 (6.0-32). For men with prostate-specific antigen levels of 0.01-1.00 ng/ml, absolute 10-year risk of prostate cancer was 0.6% for age <45 years, 0.7% for 45-49 years, 1.1% for 50-54 years, 1.2% for 55-59 years, 1.3% for 60-64 years, 1.1% for 65-69 years, 1.3% for 70-74 years, and 1.5% for age≥75 years; corresponding values for prostate-specific antigen levels >10.00 ng/ml were 35%, 41%, 63%, 71%, 77%, 69%, 75%, and 88%, respectively. Conclusions: Stepwise increases in prostate-specific antigen at first date of testing predicted a 3-57 fold increased risk of prostate cancer, a 2-16 fold increased risk of prostate cancer mortality, and a 35-88% absolute 10-year risk of prostate cancer in those with prostate-specific antigen levels >10.00 ng/ml. Equally important, absolute 10-year risk of prostate cancer in those with levels 0.01-1.00 ng/ml was only 0.6-1.5%.
Multiparametric magnetic resonance imaging in the diagnosis and characterisation of prostate cancer: The PROMIS study.
Authors: Parker Chris , Kaplan Richard S. , Gabe Rhian , Ahmed Hashim Uddin , Rantell Khadija , Emberton Mark ,   on behalf of the PROMIS Trial Management Group
Published: February 2017

62 Background: Over 1 million US men undergo prostate biopsy each year. About two thirds will test negative. This negative status is uncertain as up to a quarter will have prostate cancer on repeat biopsy. Further, a positive result often fails to discriminate clinically significant from insignificant disease. PROMIS will investigate whether multi-parametric MRI (mpMRI) can discriminate between men with no cancer or clinically insignificant cancer versus those with clinically significant cancer, using template prostate mapping (TPM) biopsies as the most accurate and appropriate reference test in men referred for biopsy. Methods: PROMIS is a multicenter, validating paired cohort study designed to include up to 714 men who will have an mpMRI (index test) and, under general anaesthetic, undergo 10-12 core TRUS biopsy (standard test) and TPM with sampling every 5mm throughout the prostate (reference test). All tests will be assessed independently. Clinically significant cancer on TPM is defined as dominant Gleason pattern ≥4 and/or cancer core length of ≥6mm. PROMIS is powered to measure an absolute increase in sensitivity from 48%, on TRUS biopsy, to at least 70%, by mpMRI. Results: The study will report the proportion of men (i) who could safely avoid biopsy and (ii) correctly identified by mpMRI to have clinically significant prostate cancer. mpMRI will be assessed using an ordinal score of 1 to 5 (highly likely benign - highly likely malignant), with a score ≥3 indicating a positive mpMRI for presence of clinically significant cancer. Secondary objectives will include outcomes based on another definition of clinically significant cancer (non-dominant Gleason pattern ≥4 and/or cancer core length ≥4mm), and cost-effectiveness of using mpMRI prior to biopsy. Conclusions: PROMIS will provide level 1 evidence by comparing mpMRI with the current standard, TRUS biopsy, using an accurate reference test that can be applied to all men advised to have a biopsy. If successful, mpMRI could in the future allow between a quarter and a half of US men referred to safely avoid a biopsy and/or improve the detection of clinically significant cancer by 20%.