bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical utility of a custom next-generation sequencing panel in the diagnosis of needle biopsies from renal masses.
Authors: Gowrishankar Banumathy , Janakiraman Manickam , Padmanabhan Raghavendra , Thodima Venkata Jaganmohan , Spaliviero Massimiliano , Stratton Kelly Lynn , Soni Rekha , Durack Jeremy C. , Chaganti Raju S.K. , Solomon Stephen Barnett , Coleman Jonathan A. , Kamalakaran Sitharthan , Houldsworth Jane 
Published: February 2017

528 Background: Image-guided core-needle biopsies are increasingly being utilized to assist in the management of patients with renal masses, where only limited material is available for analysis. In this study, the performance of a custom next-generation sequencing (NGS) panel was evaluated for diagnostic and prognostic utility in this setting. Methods: DNA was available for NGS from 41 of 48 core-needle biopsies from renal masses previously submitted to array-CGH (aCGH) in this IRB-approved study. The targeted NGS panel comprised genes mutated in renal cancer, prognostic SNPs, and a 3Mbp SNP backbone. After library preparation from as little as 25ng DNA, sequencing was performed (MiSeq, Illumina), variants identified using CLCbio, and genomic gain/loss estimated by CNVKit (Talevich E, et al, manuscript in preparation). A classification algorithm based on 15 copy number alterations (CNAs) was applied to aCGH and NGS CNA profiles (PMID: 25498568). Histology of the biopsy or resected specimen (if available) served as the gold standard. Results: By histology, the 41 profiled biopsies comprised: 13 clear cell RCC (ccRCC), 9 papillary RCC (pRCC), 2 chromophobe RCC (chrRCC), 12 benign neoplasms, 2 unclassified, 2 high grade/poorly differentiated RCC, and 1 non-diagnostic. Among ccRCC, aCGH correctly subtyped 8/13. No CNAs were detected in the remaining 5, but for which NGS detected CNAs in 3/5 and TET2 mutations in 1. Mutations in PBRM1 and BAP1 with reported prognostic significance in ccRCC were found in 3 and 1 specimens respectively. Apart from 1 without any detectable mutations or CNAs, aCGH and NGS correctly subtyped 8/9 pRCCs based on CNAs. Also, activating MET mutations were seen in 2 pRCC specimens. aCGH and NGS accurately diagnosed the 2 chrRCC and detected pRCC-related CNAs in 2/13 benign neoplasms. In the two unclassified specimens, both methods identified ccRCC-related CNAs. Notably, NGS identified CNAs and mutations in the biopsy non-diagnostic by histology. Conclusions: Overall, targeted NGS can robustly detect genomic alterations requiring only limited DNA, that together with histology, contributes important diagnostic and prognostic information in the management of renal mass patients.
Nephrectomy status, race, and overall survival in patients with metastatic renal cell carcinoma.
Authors: Robertson Dale Kesley , Zhang Chao , Liu Yuan , Gillespie Theresa Wicklin , Kucuk Omer , Carthon Bradley Curtis , Master Viraj A. , Issa Muta , Petros John , Harris Wayne B. 
Published: February 2017

529 Background: In most settings median overall survival (OS) is longer for non-Hispanic whites relative to non-Hispanic blacks with metastatic renal cell carcinoma (mRCC). However, absence of nephrectomy has been a predictor of shorter OS for both groups. The primary objectives of this study were to define the reasons why patients with mRCC do not undergo nephrectomy and to correlate absolute contraindications to surgery with race and OS. Methods: Retrospective chart reviews of patients treated with targeted therapy for mRCC were conducted at the Winship Cancer Institute of Emory University and the AVAMC after obtaining institutional authorizations. Reasons for not undergoing nephrectomy were categorized as absolute, relative or no contraindication to nephrectomy. Descriptive statistics were employed along with Kaplan-Meier survival analysis. Results: See Table. The median OS (months) by nephrectomy status was 15.9 (6.8 – 24.7) vs. 41.8 (25.6 – 49.4), p value 0.0003, for patients at Emory with no nephrectomy vs. nephrectomy, respectively. The corresponding AVAMC values were 15.5 (8.5 – 29.5) vs. 45.2 (30.3 – 100.9), p value 0.0002. Conclusions: The number of patients with absolute contraindications to nephrectomy varied widely by race and institution, yet absence of nephrectomy was the predominant predictor of shorter OS in both settings. [Table: see text]
Socioeconomic disparities in the receipt of radiation for node-positive prostate cancer.
Authors: Muralidhar Vinayak , Mahal Brandon Arvin Virgil , Chen Yu-Wei , Nezolosky Michelle Daniel , Nguyen Paul L. 
Published: February 2017

53 Background: Radiation therapy in the setting of node-positive prostate cancer has been controversial, although some recent data suggests a survival benefit to radiation in this setting. We evaluated socioeconomic disparities in the receipt of radiation for node-positive prostate cancer to identify groups that may be less likely to receive this potentially life-saving treatment. Methods: We identified 3,283 patients with N1M0 prostate cancer diagnosed 1982-2011 using the Surveillance, Epidemiology, and End Results database who were treated with radiation or no local therapy. We conducted multivariable logistic regression to determine socioeconomic predictors of not receiving radiation treatment. Results: Several patient and demographic factors were associated with a reduced likelihood of receiving radiation: African American (AA) vs non-AA race (31.7% vs. 37.7%, adjusted odds ratio [AOR] 0.74, p = 0.012); unmarried vs married status (31.9% vs 38.6%, AOR 0.72, p < 0.001); bottom third vs top third in income level (33.7% vs. 39.8%, AOR 0.72, p < 0.001); age over 65 versus < = 65 years (34.6% vs 39.8%, AOR 0.81, p = 0.005); diagnosis before 2000 versus starting in 2000 (31.6% vs 43.5%, AOR 0.56, p < 0.001). In a separate analysis, patients under the age of 65 who had Medicaid or no insurance were less likely than patients with other insurance to receive radiation (43.5% vs 55.9%, OR 0.61, p = 0.041), although on multivariable analysis, no significant association persisted (p = 0.512). Conclusions: African American race, unmarried status, lower income level, older age, and insurance status were all associated with significantly reduced odds of receiving radiation therapy for node-positive prostate cancer compared with no local therapy. Given the accumulating data suggesting that radiation therapy can improve survival in node-positive patients, it is increasingly important to understand the reasons for these treatment disparities so that they can be reduced.
Comparison of sunitinib (su) versus temsirolimus (tem) in patients (pts) with poor-risk metastatic renal cell carcinoma (prmRCC).
Authors: Keizman Daniel , Neiman Victoria , Sella Avishay , Rosenbaum Eli , Gottfried Maya , Sarid David , Gez Eliahu , Maimon Natalie , Carducci Michael Anthony , Hammers Hans J. , Eisenberger Mario A. , Sinibaldi Victoria J. , Peer Avivit , Neumann Avivit , Kovel Svetlana , Mermershtain Wilmosh , Rouvinov Keren , Feldhamer Ilan , Berger Raanan , Hammerman Ariel 
Published: February 2017

539 Background: Based on a single phase 3 study, the mTOR inhibitor tem was approved as 1st line therapy for prmRCC. However, in daily practice, prmRCC pts are often treated with the VEGFR and PDGFR inhibitor su. We aimed to compare the clinical effectiveness of su vs tem in prmRCC pts. Methods: We performed an international multicenter retrospective study of pts with prmRCC (HENG criteria), who were treated in 8 centers across 2 different countries. 31 pts were treated with 1st line tem. Each tem treated pt was individually matched with a 1st line su treated pt, by clinicopathologic factors. The effect of tx type (tem vs su) on clinical benefit, progression free survival (PFS) and overall survival (OS), was tested using a chi-square test and partial likelihood test from cox model. Furthermore, univariate and multivariate analyses of association between clinicopathologic factors and tx type (tem vs su), and outcome were performed using the entire pt cohort (n=62). Results: The groups were matched by age (median 65), gender (male 68%), prior nephrectomy (58%), renal cell carcinoma histology (clear cell 81%), smoking status (active in 35%), use of angiotensin system inhibitors (42%), and pre-tx neutrophil to lymphocyte ratio >3 (58%). In tem vs su treated pts, clinical benefit (partial response + stable disease) was 61% (n=19) (partial response 6%, n=2) vs 71% (n=22) (partial response 29%, n=9) (p=0.62). Median PFS was 5 vs 8 mos (p=0.08), and median OS 9 vs 17 mos (p=0.03). In multivariate analyses of the entire pt cohort (n=62), su tx was independently associated with OS (HR 0.6, p=0.001). Conclusions: In prmRCC patient, the VEGFR inhibitor su may be associated with an improved outcome vs the mTOR inhibitor tem.
Prospective assessment of the adherent perinephric fat in partial nephrectomies: Predictors and impact on peri-operative outcomes.
Authors: Dariane Charles , Badoual Cecile , Tordjman Joan , Clement Karine , Le Guilchet Thomas , Hurel Sophie , Mejean Arnaud , Timsit Marc Olivier 
Published: February 2017

543 Background: The surgical complexity of partial nephrectomy (PN) can be partly anticipated using renal morphometric scores that do not consider patient related issues such as obesity or perirenal fat. Our primary objective was to prospectively assess the predictive factors for adherent perinephric fat (APF) and its impact on the onset of complications. The secondary objective was to correlate the surgical appraising with the histological reality of APF. Methods: Fifty consecutive patients undergoing robotic or open PN were prospectively included from November 2014 to March 2015. The previously published Mayo adhesive probability score (MAP score) was calculated and compared to the per-operative surgical assessment of APF using a 0 to 3 scale (APF being defined by a score ≥ 2). Fat was analyzed histologically for fibrosis (HES staining and picrosirius red) and inflammatory infiltrate of macrophages (immunohistochemistry using anti-CD68 antibody). Results: APF was present in 18 patients (36%), with no impact on surgical approach (31.3% vs 38.9 robotic way, without surgical conversion). APF was associated with longer operating time (169 min vs. 146 min, p = 0.036) and increased blood loss (469 mL vs 179 mL, p = 0.014). Duration of clamping, rate of positive margins, blood transfusion and the Clavien-Dindo score were not different (Table 1). In multivariate analysis, only male gender (p = 0.044), age (p = 0.014) and MAP score (p = 0.00057) were significant predictors of APF. Histologically, APF was characterized by a marked fibrosis but no macrophage infiltrate. Conclusions: APF can be accurately predicted using radio-clinical data as the MAP score, combined with age and gender. APF is associated with increased operative time and blood loss without impacting the rate of complications. Histological analysis of APF demonstrates significant fibrosis without inflammatory infiltrate. [Table: see text]
First-line sunitinib versus pazopanib in metastatic renal cell carcinoma (mRCC): Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).
Authors: Ruiz Morales Jose Manuel , Wells J Connor , Donskov Frede , Bjarnason Georg A. , Lee Jae-Lyun , Knox Jennifer J. , Beuselinck Benoit , Vaishampayan Ulka N. , Brugarolas James , Broom Reuben James , Bamias Aristotelis , Yuasa Takeshi , Srinivas Sandhya , Ernst D. Scott , Pezaro Carmel Jo , Wood Lori , Kollmannsberger Christian K. , Rini Brian I. , Choueiri Toni K. , Heng Daniel Yick Chin 
Published: February 2017

544 Background: Sunitinib (SU) and Pazopanib (PZ) have been compared head-to-head in the first-line phase III COMPARZ study in metastatic renal cell carcinoma (mRCC). We compared SU versus PZ, to confirm outcomes and subsequent second-line therapy efficacy in a population-based setting. Methods: We used the IMDC to assess overall survival (OS), progression-free survival (PFS), response rate (RR) and performed proportional hazard regression adjusting for IMDC prognostic groups. Second-line OS2 and PFS2 were also evaluated. Results: We obtained data from 3,606 patients with mRCC treated with either first line SU (n=3226) or PZ (n=380) with an overall median follow-up of 43.5 months (m) (CI95% 41.4 – 46.4). IMDC risk group distribution for favorable prognosis was 440 (17.3%) for SU vs 72 (25%) for PZ, intermediate prognosis 1414 (55.6%) for SU vs 153 (53%) for PZ, poor prognosis 689 (27.1%) for SU vs 62 (22%) for PZ, p= 0.0027. We found no difference between SU vs. PZ for OS (20.1 [CI95% 18.76-21.42] vs. 23.68 m [CI95% 19.54 - 28.81] p=0.19), PFS (7.22 [CI95% 6.76 - 7.78] vs. 6.83 m [CI95% 5.58 - 8.27] p=0.49). The RR was similar in both groups (Table 1). Adjusted HR for OS and PFS were 0.952 (CI95% 0.788 – 1.150 p=0.61) and 1.052 (CI95% 0.908 – 1.220 p = 0.49), respectively. We also found no difference in any second-line treatment between either post-SU vs. post-PZ groups for OS2 (12.88 [CI95% 11.89 – 14.19] vs. 12.91 m [CI95% 10.3 – 19.1] p=0.47) and PFS2 (3.67 [CI95% 3.38 – 3.87] vs. 4.53 m [CI95% 3.08 – 5.35] p=0.4). There was no statistical difference in OS2 and PFS2 if everolimus was used after SU or PZ (p = 0.33 and p = 0.41, respectively) or if axitinib was used after SU or PZ (p = 0.73 and p = 0.72, respectively). Conclusions: We confirmed in real world practice, that SU and PZ have similar efficacy in the first-line setting for mRCC and do not affect outcomes with subsequent second-line treatment. [Table: see text]
Assessing the frequency of somatic mutations in high-risk clear cell renal cell carcinoma to provide new perspectives.
Authors: Manley Brandon , Tennenbaum Daniel , Casuscelli Jozefina , Hsieh James 
Published: February 2017

548 Background: Previous large collaborative studies have been conducted to characterize the genetic mutations found in Clear Cell Renal Cell Carcinoma (ccRCC). However, these studies have covered all stages of disease. We examine the genetic frequency of mutations in recurrently mutated genes found in ccRCC among patients with advanced localized ccRCC, defined as T3 disease and no known metastasis at presentation. Methods: Reviewing data from The Cancer Genome Atlas (TCGA), The International Cancer Genome Consortium (ICGC), The Cancer Genomics Project Tokyo, Japan and our prospectively collected intuitional database we identified 76 patients with ccRCC and T3 disease. We calculated the frequency of several previously reported recurrently mutated genes including VHL, PBRM1, SETD2, BAP1, KDM5C, TERT (including promoter), TP53, MTOR, and PTEN. .We also reviewed and reported corresponding clinical information for this cohort. Results: Table provides the frequency of somatic mutations as well as demographic information of our cohort. Mutual exclusivity was found between mutations of BAP1 and TERT in all patients studied. Additionally, KDM5Cmutations were found in 20% of our patients. Conclusions: These results describe the frequency of several recurrently mutated genes present in high-risk ccRCC. The mutual exclusivity between BAP1 and TERT, both having been associated with aggressive disease, suggests a possible interesting relationship between the two. Focusing our investigation on a more precise cohort of patients’ staged disease allows for new perspectives on the genetics present. Further investigation into how these mutation burdens differ from lower-risk disease deserves further investigation. [Table: see text]
Phosphodiesterase type 5 inhibitors (PDE5i) and prostate cancer recurrence.
Authors: Loeb Stacy , Folkvaljon Yasin , Robinson David , Schlomm Thorsten , Garmo Hans , Stattin Pär 
Published: February 2017

55 Background: Phosphodiesterase type 5 inhibitors are commonly used for management of erectile dysfunction after prostate cancer (CaP) treatment. Single-institution studies have reported conflicting data on PDE5i use and recurrence after radical prostatectomy (RP). We re-evaluated the association between PDE5i use after RP and RT with biochemical recurrence in a nationwide, population-based registry. Methods: We performed a nested case-control study using data from the National Prostate Cancer Register of Sweden (including >98% prostate cancer cases nationwide), linked to the national Prescribed Drug Register. Among men with localized CaP who underwent primary RT or RP from 2006-2007 with 5 years of follow-up, we identified those with biochemical recurrence (n=293 cases). For each case, we identified 20 controls who were recurrence-free at the event date of the index case, using incidence density sampling stratified by age and treatment (n=5,767 controls). Multivariable conditional logistic regression was used to examine the relationship between overall PDE5i use and cumulative pill number with biochemical recurrence. Results: Among men treated by RT, PDE5i were not associated with BCR (OR 0.97, 95% CI 0.48-1.94), adjusting for marital status, education, income, PSA, clinical stage, Gleason score, and proportion of positive biopsies. As shown in the table, PDE5i were not associated with biochemical recurrence after RP adjusting for clinical features (OR 0.79, 95% CI 0.60-1.05), or with additional adjustment for surgical pathology (OR 0.83, 95% CI 0.62-1.10). Men whose cumulative number of PDE5i pills was above the median had a slightly lower risk of biochemical recurrence in the clinical model, and no difference in risk of biochemical recurrence after adjustment for RP features. Conclusions: Our results from a population-based setting suggest against an increased risk of biochemical recurrence among men using PDE5i after CaP treatment. [Table: see text]
Prognostic utility of a multi-gene signature (the cell cycle proliferation score) in patients with renal cell carcinoma (RCC) after radical nephrectomy.
Authors: Morgan Todd Matthew , Mehra Rohit , Wolf J. Stuart , Gangnang Fosso Placede , Orr Brian , Wu Shulin , Sangale Zaina , Stone Steven , Wu Chin-Lee , Feldman Adam S. 
Published: February 2017

555 Background: There are currently no RCC biomarkers being routinely used in the clinic, and prognostic nomograms rely almost entirely on tumor size, stage and age. There is a critical need for improved prognostic discrimination given the increasing awareness that some patients may be managed with active surveillance, while others with higher risk disease might benefit from adjuvant therapy following surgery. We hypothesized that a previously developed multi-gene proliferation signature would predict long-term oncologic outcomes in surgically resected RCC. Methods: The cell cycle proliferation (CCP) score was derived after radical nephrectomy in 305 patients who were treated at a single center from 2000 to 2007 for clear cell, papillary or chromophobe RCC with localized disease (N0M0). Sixty-four percent of the cohort had stage I disease. Outcomes were either disease recurrence (local or metastatic), or disease specific mortality (DSM). Association with outcomes was evaluated by CoxPH survival analysis and likelihood ratio tests. Hazard ratios (HR) are given for one-unit increase in CCP score (equivalent to a doubling of gene expression). Results: Patient data were censored at 5-years of follow-up, by which time 32 patients (10%) recurred and 16 (5%) died of disease. The median CCP score was 0.095 (IQR -0.50 to 0.60). In univariable analysis, CCP score was a significant prognostic variable for both recurrence (p < 10-4) and DSM (p < 10-5). After adjusting for clinical variables including tumor size, stage, and grade, the CCP score HR for recurrence was 1.74 (95% CI (1.14, 2.65)), and for DSM was 2.59 (95% CI (1.43, 4.67)). There was no interaction between CCP and any clinical variable. A prognostic model combining clinical and molecular information will be presented along with external validation in a second cohort (N~400). Conclusions: The CCP score appears to be a significant and independent predictor of key long-term oncologic outcomes in patients who have undergone nephrectomy for RCC, providing prognostic information beyond what is available from clinical parameters. Once validated, the CCP score may have utility in the clinical management of patients with RCC.
External validation of a prediction model of survival after cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC).
Authors: Bex Axel , van Werkhoven Erik D. , Noe Allard , Karam Jose A. , Matin Surena F. , Margulis Vitaly , Stewart Grant , Staehler Michael D. , Wood Christopher G. 
Published: February 2017

556 Background: In 2013 a model to predict cancer-specific survival (CSS) after CN was published (Eur Urol 63:947-52, 2013), consisting of a preoperative nomogram to predict 6-month (mo) probability of death (PoD) based on serum albumin and serum lactate dehydrogenase and a postoperative nomogram (12-mo PoD) to which were added pathologic primary tumour stage, nodal stage and intraoperative blood transfusion. We externally validated the model with a contemporary European dataset of patients treated in the VEGF-targeted therapy era. Methods: After having received the original calibration indices, data from 205 mRCC patients who underwent CN between 2006 and 2013 at 3 European centres in Amsterdam, Edinburgh and Munich were used for external validation. Next to the variables for the nomogram, age, MSKCC, IMDC, number and metastatic sites and subtype were collected. Both nomograms were used to obtain predictions for the subjects. Based on the quantiles of the distribution of predictions subjects were grouped into 4 categories and Kaplan-Meier estimates calculated as were calibration plots of observed versus predicted PoD. Since all subjects had follow-up for > 1.25 years CSS at 6 and 12 mo as a dichotomous outcome and the ROC curves were plotted. Results: With a median follow-up of 29 mo and a median OS of 15 (95% CI 12-22) mo for the entire cohort, 32 and 82 patients died from RCC at 6 and 12 mo after CN respectively. For the pre- and postoperative nomogram the respective ROC curve had an AUC of 0.667 and 0.712. In the preoperative calibration plot the observed PoD at 6 mo was higher than the predicted, resulting in a lower discrimination when compared to the original validation (0.76 and 0.74 for pre- and postoperative nomograms respectively). Conclusions: In external validation the pre- and postoperative nomograms perform well in patients with primary mRCC. Their discrimination is in the reported range of MSKCC and IMDC risk scores, which were not developed to address the decision of CN (concordance index 0.657 and 0.71, Lancet Oncol 14:141-8, 2013). Although discrimination of the preoperative nomogram was lower in external validation, it retains ability to predict early death after CN.