bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of patients (pts) with poor risk metastatic renal cell carcinoma (mRCC): Results from a pooled clinical trials database.
Authors: Hamieh Lana , McKay Rana R. , Lin Xun , Simantov Ronit , Choueiri Toni K. 
Published: March 2017

515 Background: Survival outcomes are heterogeneous across different subsets of mRCC pts. Poor risk pts have grim outcomes and are less likely to be enrolled in clinical trials, hence the lack of prospective data characterizing this pt population. We provide a comprehensive analysis of poor risk pts, as defined by three widely used prognostic models, in the era of targeted therapy. Methods: We conducted a pooled retrospective analysis of 4,736 mRCC pts treated on phase II and III clinical trials. Pts were defined as poor risk according to the Memorial Sloan Kettering Cancer Center (MSKCC), International Metastatic Database Consortium (IMDC), and Hudes prognostic risk models. We evaluated overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) in poor risk pts in each of the risk models in the total cohort and in a subset of pts who remained on treatment for >12 months (mos). The models’ concordance (c-) index was used to assess their prognostic performance. Results: We identified 1145 (24.2%), 904 (19.1%), and 1901 (40.1%) poor risk pts by IMDC, MSKCC, and Hudes models, respectively. The majority were <65 years of age (70-73%) with clear-cell histology (85-88%), prior nephrectomy (62-66%), and no prior systemic therapy (80-86%). The efficacy and toxicity outcomes as well as the c-indexes for each of the models are reported in the table below. Additionally, 9-14% of poor risk pts remained on therapy for >12 mos and had higher OS (29.8-35.2 mos) and ORR (42-53%). Conclusions: In this large database of poor risk mRCC pts, we highlight that the models have similar predictive accuracy in the targeted therapy era. We also demonstrate that poor risk pts continue to have dismal outcomes and should be considered for trials of novel agents and combinations. A subset of these pts appears to derive prolonged clinical benefit and should be further explored.[Table: see text]
Use of liquid biopsy for detection of renal cell carcinoma.
Authors: Laganosky Dean , Lorentz Charles , Al-Qassab Usama , Ogan Kenneth , Master Viraj A. , Issa Muta , Pattaras John , Roberts David , Bergquist Sharon , Rossi Michael R. , Arnold Rebecca , Goecks Jeremy , Petros John 
Published: March 2017

521 Background: Circulating tumor DNA (ctDNA) displays characteristics of an ideal serum biomarker. We sought to develop whole-exome sequencing of ctDNA to interrogate commonly mutated genes in renal cell carcinoma (RCC) for early tumor detection through a single blood sample. Methods: Patients with solid renal tumors and healthy controls provided 40 mL blood from which purified plasma cell-free DNA was prepared. A multiplex bar-coded polymerase chain reaction amplification using the Fluidigm Access Array was performed to prepare sequencing libraries for the Illumina HiSeq platform. Galaxy workflow was then utilized to identify mutations within the plasma cell-free DNA samples and results were compared to buffy coat sequencing containing control DNA for each individual’s sample. The following genes were queried: VHL, PBRM1, SETD2, BAP1, KDM5C, KIT, NFE2L2, MET, TP53, CDKN2A, FGFR3, PIK3CA, BRAF, and MUC4. Criteria for calling mutations included adequate frequency by overall count and percentage of reads, identification in all overlapping sequences and presence of buffy coat-derived control DNA for comparison with <0.5% containing the mutation. Results: Of the preoperative RCC patients, 20/30 (67%) had detectable somatic mutations compared to 2/48 (4.2%) controls. These included nonsynonymous, frameshift, stop-gain, and splice site mutations. Mutations were detected in RCC patients with both early and advanced stage disease, including a patient with a 1.1 x 0.7 x 0.5 cm tumor. Mutations were seen in all genes assayed. Conclusions: The majority of RCC patients of various stages and histology had ctDNA detected in a single preoperative blood sample. Comparatively, only two of the control patients sampled were ctDNA positive. Controls will be followed to identify the possible sources of ctDNA. Developing such non-invasive methods for RCC detection has the potential to enhance both diagnosis and surveillance of renal malignancy, even in the setting of small renal masses.
CLOVIZ: Clinical outcomes visualization of IMDC criteria in metastatic renal cell carcinoma for patient-centered decision making.
Authors: Odisho Anobel Y. , Pal Sumanta K. , Shapiro Michael , Dixon Ashley , Wells Connor , Ruiz Morales Jose Manuel , Choueiri Toni K. , Heng Daniel Yick Chin , Gore John L. 
Published: March 2017

527 Background: The International Metastatic Renal Cell Carcinoma Database (IMDC) Criteria (Heng Criteria) is a validated risk prediction tool for patients with metastatic renal cell carcinoma (mRCC). It provides valuable prognostic data but clinical application can be challenging due to limited available tools. We created an interactive visualization to facilitate clinical application of IMDC Criteria. Methods: A multi-institutional cohort of 436 patients with mRCC was used to create an interactive visualization depicting IMDC Criteria at the patient level. Usability testing was performed with non-medical lay-users and medical oncology fellows. Subjects used the tool to calculate median survival times based on IMDC Criteria in six increasingly complex clinical scenarios. Confidence using the tool was surveyed and measured along a 5-point Likert scale. Results: The interactive visualization is available at http://faculty.washington.edu/odisho . 400 lay-users and 15 medical oncology fellows completed clinical scenarios and surveys. Overall, lay-users were able to obtain the exact correct answer in 48% of scenarios, compared to 60% of medical oncology fellows. The proportion of exact correct answers decreased with increasing task complexity, but the proportion of answers within 25% of the expected answer remained stable at 68-78% for lay-users and 73-93% for medical oncology fellows. When surveying usability, 65% of lay-users felt it was easy to use, compared to 80% of fellows, and 83%-87% felt it became intuitive with increasing use. Among lay-users, 69-77% were confident selecting lab values and drugs, compared to 87-93% of medical oncology fellows. 75% of lay-users felt it helped them better understand survival in mRCC. 68% of lay-users wanted to use a similar tool with their doctor, while 87% of medical oncologists wanted to use this with patients, and 93% wanted to incorporate it into their clinical practice in some way. Conclusions: A graphical method of interacting with a validated nomogram for mRCC outcomes provides real-time individual level data that can be used by untrained nonmedical users and medical oncologists, with potential for use in the clinic setting.
Biomarker study of early death in patients with intermediate and favorable risk metastatic renal cell carcinoma.
Authors: Harris Wayne , Zhang Chao , Liu Yuan , Kucuk Omer , Carthon Bradley Curtis , Master Viraj A. 
Published: March 2017

530 Background: The primary objective of this study was to determine whether severe systemic inflammation (SSI) could serve as a biomarker for terminal disease progression and early death in patients with intermediate and favorable risk metastatic renal cell carcinoma (mRCC). Methods: Retrospective chart reviews of patients treated with targeted therapy for mRCC were conducted at the Winship Cancer Institute of Emory University (WCIEU) and the Atlanta Veterans Administration Medical Center (AVAMC) after obtaining institutional authorizations. The modified Glasgow Prognostic Score (mGPS) was used to quantify intensity of systemic inflammation (ISI) at baseline and at least two additional time points that were at least 10 days apart. Early death was defined as death within two years of Day 0, the first day ISI was quantified. Descriptive statistics were employed along with Kaplan-Meier survival analysis. Results: ISI was quantified 2,428 times in 135 patients at the WCIEU with a median of 16 per patient and a range of 3 to 51 versus 758 times in 46 patients at the AVAMC with a median of 12 per patient and a range of 3 to 48. Baseline risk stratification was as follows: favorable (mGPS=0), intermediate (mGPS=1) and poor (mGPS=2) with 96 (51%), 36 (19%), and 53 patients (29%) in the respective risk groups of the combined cohort (n=181). Sixty eight of the 90 patients who died in the time frame of the study did so within 2 years of Day 0. Of these early deaths, only 34 (50%) were among patients with poor risk at baseline versus 18 (26%) and 16 (24%) of the intermediate and favorable risk patients, respectively. Furthermore, 90% of these early deaths were associated with SSI as a terminal event as were 87% of all deaths in spite of the fact that 64% of poor risk patients had died as of Year 2 versus only 27% of patients in the combined group of intermediate and favorable baseline risk. Conclusions: Severe acquired systemic inflammation is a promising biomarker for terminal disease progression and early death in patients with intermediate and favorable risk mRCC. Prospective confirmatory studies are required.
Additive prognostic impact of elevated De Ritis ratio and renal score in predication of survival outcomes in localized renal cell carcinoma.
Authors: Hamilton Zachary , Bloch Aaron , Field Charles , Fero Katherine Elaine , Berquist Sean , Hassan Abd−elrahma , Han Daniel , Proudfoot James , Derweesh Ithaar 
Published: March 2017

532 Background: Renal Cell Carcinoma (RCC) is a metabolically driven neoplasm. Inflammatory markers and morphometric measures have been suggested to be predictive for prognosis. We investigated the impact of a novel combination of preoperative tumor morphology (RENAL score) and a laboratory based inflammatory marker (DeRitis Ratio, AST/ALT) on survival outcomes in localized RCC. Methods: Single center, retrospective analysis of 264 patients with RCC (112 PN, 152 RN, mean follow-up 45 months) from 2003−2015. A priori, we assigned a positive marker score of “1” if RENAL >8 or DeRitis >1.5. Patients were stratified by increasing positive markers (“0”=RENAL ≤8 and DeRitis ≤1.5, “1”=RENAL >8 or DeRitis >1.5, “2”=RENAL >8 and DeRitis>1.5). Primary outcome was overall survival (OS). Cox models and Kaplan−Meier curves were utilized. Results: 264 patients, 61.7% male, mean age 64.5 ± 12.8 years, mean BMI 28.5 ± 5.6, mean AST/ALT 1.1 ± 0.4. With regards to tumor characteristics, mean clinical tumor size 4.7 ± 3.2cm and median RENAL score 9 (IQR 7−10). For clinical staging, 75.7% were cT1, 17.4% were cT2, and 6.9% were >cT2. 32.6% had 0 positive markers, 60.2% had 1 marker, and 7.2% had 2 markers. Kaplan−Meier analysis for “0”, “1”, and “2”demonstrated significantly worsened OS (log−rank p=0.03). On Cox model for OS, RENAL >8 (HR 2.13, p=0.01) or AST/ALT >1.5 (HR 2.25, p=0.028) were significantly associated with worsened survival, as was combined RENAL >8 and DeRitis > 1.5 (HR 5.1, p<0.001). Conclusions: Novel combination of a morphological score (RENAL) and an inflammatory marker (DeRitis ratio) was associated with worsened OS in localized RCC. Our findings point toward development and validation of a prognostic index to assist in risk stratification for localized RCC.
Comparison of multiparametric MRI to PSA kinetics as an indication of prostate cancer progression in men on active surveillance.
Authors: Maruf Mahir , Kongnyuy Michael , George Arvin Koruthu , Siddiqui Mohummad Minhaj , Sidana Abhinav , Jain Amit L , Calio Brian P. , Sugano Dordaneh , Chelluri Raju , Valayil Subin , Muthigi Akhil , Frye Thomas P , Choyke Peter L. , Turkbey Baris , Wood Bradford J. , Pinto Peter A. 
Published: March 2017

59 Background: Pathologic progression is identified in > 25% of prostate cancer (CaP) patients on active surveillance (AS). Yet, identifying patients at risk for progression is limited to PSA based biomarkers with variable utility. Multiparametric MRI (mpMRI) with fusion-guided prostate biopsy (FBx) has shown utility in risk stratification for patients considering AS. We compared mpMRI characteristics with PSA kinetics for the prediction of pathologic progression in AS patients. Methods: A review of men on AS with serial mpMRI and 2 or more FBx sessions was performed. FBx sessions consisted of targeted biopsies and a 12 core systematic biopsy. Men who met NIH Expanded AS criteria included those with low and intermediate risk CaP, Gleason score ≤ 3+4 = 7 with no restriction on percent core involvement or number of cores positive. Progression was defined by patients with initial Gleason 3+3 = 6 to any Gleason 4, and Gleason 3+4 = 7 to a primary Gleason 4 or higher. MRI progression was defined as increase in suspicion score, size, or new lesion on follow-up. PSA velocity (PSAV) > 0.75ng/ml/yr, PSA doubling time (PSAdt) < 3 yrs, and imaging characteristics were examined for association with pathologic progression at surveillance biopsy. Results: A total of 164 men, median age of 63 yrs [58-67], were included. Median length of follow up was 19.4 months [IQR 14.3-30.0]. Median PSA, and prostate volume of our cohort were 4.9ng/ml [3.3-7.3] and 47.0ml [36.5-59.8]. The sensitivity and specificity of predicting pathologic progression by mpMRI, PSAV and PSAdt were 45% and 65%, 30% and 76%, and 17% and 86% respectively. A combination of MRI, and PSAV or PSAdt yielded a sensitivity and specificity of 61% and 49% or 54% and 56% respectively. Using a decision curve analysis, mpMRI offers minimal benefit for predicting pathologic progression of CaP. Conclusions: MpMRI alone marginally outperforms PSA kinetics for predicting pathologic progression in men on AS for CaP. The combination of mpMRI along with PSA parameters increase the sensitivity of prostate imaging in identifying progression in AS patients. Research in combinations of imaging with other biomarkers will be needed to more accurately risk stratify AS patients.
Quality of life evaluation of the effect of decapeptyl compared with zoladex preradiotherapy: Final results of randomised controlled trial.
Authors: Bahl Amit , Challapalli Amarnath , Greenwood Rosemary , Hurley Katrina , Persad Rajendra 
Published: March 2017

62 Background: Hormone therapy in combination with radiotherapy is a curative treatment option for prostate cancer (CaP). There is paucity of data regarding quality of life (QoL) evaluation of neoadjuvant Decapeptyl. We reported on the equivalence of cytoreductive efficacy of neoadjuvant Decapeptyl and Zoladex previously. Here we present the final QoL evaluation of the effect of Decapeptyl compared with Zoladex preradiotherapy. Methods: Seventy-one patients with localised CaP who have chosen radical radiotherapy had been randomised by stratified block design, toreceive either Decapeptyl (D: n = 37) or Zoladex (Z: n = 34) with bicalutamide cover. All the patients had subsequent radical radiotherapy and followed up as per departmental protocol. The effect of Decapeptyl and Zoladex on QoL was assessed using EQ5D, QLQ-PR25, QLQ-C30 questionnaires, which were completed at baseline, 6, 10 & 14 weeks after start of therapy. QoL scores were analysed as mean scores over the 4 treatment time points for all domains, controlling for baseline scores using Analysis of Covariance. Results: There was no clinically significant difference or trend towards worsening QoL with either Z or D in the global (EQ5D) and cancer-specific (QLQ-C30) domains. The cancer-specific (QLQ-C30) symptom score also showed no trend towards worsening QoL with either Z or D. Symptom scores in the QLQ-PR25 questionnaire did not show a significant difference between Z and D arms with the exception of hormone symptoms. The hormone symptoms showed an increasing trend over the 4 treatment time points, with those in the Z arm significantly (p = 0.02) more affected (3 points higher on average) than patients in the D arm, despite equivalence in cytoreductive effect and achieving castrate levels of testosterone. Conclusions: There were no clinically significant differences in QoL domains between Zoladex and Decapeptyl, apart from hormones symptoms which were worse with Zoladex. Further validation is required with affect on hormone symptoms as the primary outcome measure. To our knowledge this is the first reported prospective randomised data demonstrating the effect of Zoladex and Decapeptyl, on QoL in the neoadjuvant setting. Clinical trial information: EduraCT: 2008-007028-25.
Impact of comorbidity and PSA doubling time on the risk of death in men experiencing PSA failure following radiation therapy with or without androgen deprivation therapy for unfavorable-risk prostate cancer.
Authors: Patel Sagar Anil , Chen Ming-Hui , Loffredo Marian , Renshaw Andrew A. , Kantoff Philip W. , D'Amico Anthony Victor 
Published: March 2017

68 Background: The optimal management of men with PSA failure following initial prostate cancer therapy based on comorbidity is unknown. We investigated the impact that PSA doubling time (DT) and comorbidity had on the risk of all cause (AC), prostate cancer-specific (PCS) and other cause mortality (OCM) following PSA failure. Methods: Between 1995 and 2001, 206 men with unfavorable-risk PC were randomized to receive radiation therapy alone or in combination with 6 months of androgen deprivation therapy (ADT). After a median follow up of 16.2 years, 108 men experienced PSA failure (85, no or minimal; 23, moderate to severe comorbidity) and formed the study cohort. Cox and Fine-Gray regression analysis was used to determine whether PSA DT was associated with the risk of ACM and PCSM/OCM respectively, stratified by ACE-27 comorbidity score. Results: After a median follow up of 13.71 years following PSA failure, 81 of the 108 men (75%) died. Longer PSA DT was associated with a decreased risk of PCSM in men with no/minimal (AHR 0.33, 95% CI 0.17-0.65, p= 0.001) and moderate/severe comorbidity (AHR 0.014, 95% CI 0.002-0.129, p= 0.0002) with a trend toward an increased risk of OCM in men with no/minimal (AHR 1.42, 95% CI 0.94-2.16, p= 0.10) and moderate/severe comorbidity (AHR 1.68, 95% CI 0.85-3.35, p= 0.14). However, increasing PSA DT was only associated with a decreased risk of ACM in men with no/minimal (AHR 0.69, 95% CI 0.50-0.96, p = 0.03) but not moderate/severe comorbidity (AHR 0.95, 95% CI 0.51-1.78, p= 0.87). Conclusions: The extent and natural history of comorbidity as well as PSA DT should be taken into consideration when deciding on appropriate management and/or clinical trial eligibility at the time of PSA failure. Specifically, randomized studies are needed to determine whether survival is prolonged in men with life-shortening comorbidity with salvage ADT at the time of PSA failure versus surveillance and reserving ADT use for symptomatic progression. For all other men, trials comparing ADT with or without novel agents shown to prolong survival in men with metastatic castrate resistant PC is warranted.
Twitter mentions and academic citations in the urologic oncology literature.
Authors: Hayon Solomon , Stormont Ian , Dunne Meagan M , Siddiqui Mohummad Minhaj 
Published: March 2017

70 Background: Social media use has dramatically increased in academic medicine with over 70% of journals now using twitter accounts. This calls into question if there is a measurable association between academic impact and Twitter use. We sought to quantify the relationship between the number of Twitter mentions and the number of academic citations a urologic oncology publication receives. Methods: 210 papers from 7 prominent urology journals were examined 18 months after publication from December 2014-January 2015. Articles were evaluated with 2 citation based “bibliometrics” (Scopus, Google Scholar) and 1 social media based metric (Altmetric). Altmetric software allowed for individual tweets regarding an article to be examined. Scores and Twitter mentions for oncology and non-oncology publications were compared using ANOVA and contingency analysis. Results: 79 articles were oncology related while 131 pertained to other topics. The mean number of Twitter mentions for oncology articles was 4.1, compared to 2.4 for non-oncology articles (p=0.004). Articles with at least one twitter mention had 2.0 fold more Scopus citations (p<0.01), 2.1 fold more Google Scholar citations (p<0.01), and 27.8 fold higher Altmetric scores (p<0.001). Oncology authors tended to be more active on Twitter, with 13.9% of oncology authors self-tweeting their own articles versus 5.3% of non-oncology authors (p=0.04). Authors self-tweeting oncology articles was associated with an increased number of citations, with a 10.3 and 7.9 mean citation increase in Google Scholar and Scopus scores (p=0.04 and p=0.01) compared to non-self-tweeted oncology articles. (See table.) Conclusions: Social media appears to be more prominent in the urologic oncology community. The number of citations a urologic oncology publication receives is associated with the number of mentions it has on Twitter. Authors self-tweeting articles may be a factor that increases paper visibility and academic impact. [Table: see text]
Prediction of pathological outcome at radical prostatectomy for MRI-ultrasound fusion prostate biopsy versus standard transrectal ultrasound guided prostate biopsy.
Authors: Arora Hans , Nyame Yaw A. , El-Shafei Ahmed , Kara Onder , Purysko Andrei , Stephenson Andrew J. , Jones J. Stephen , Klein Eric A. 
Published: March 2017

73 Background: Magnetic resonance imaging (MRI)-ultrasound (US) fusion prostate biopsy has been shown to be able to detect prostate cancer, with the goal of targeting specific lesions. Our objective was to evaluate the ability of this technique to accurately determine the final pathological outcome at the time of radical prostatectomy as compared to standard template 12-core transrectal ultrasound (TRUS) guided prostate biopsy. Methods: We performed a retrospective analysis of patients who underwent both prostate biopsy and prostatectomy at the Cleveland Clinic. Patients who underwent standard template 12-core TRUS biopsies between January 2005 through December 2013, and MRI-US fusion biopsies from January 2014 through June 2015 were included. Patients who had more than 12 cores taken during TRUS biopsy were excluded. Relevant covariates included patient demographics as well as pre-biopsy PSA and prostate size, which were collected from the electronic medical record. Continuous variables were compared using Wilcoxon rank-sum tests and categorical variables were assessed with χ2 test. Results: In total 543 patients were included. Of these, 491 underwent 12-core standard template TRUS biopsy whereas 54 underwent MRI-US fusion biopsy. Between the two groups there were no significant differences in age (median 62 years versus 63 years, p = 0.21), race (17.5% versus 12.3 % African American, p = 0.32), family history (31.5% versus 29.3% positive, p = 0.74), prostate size (47.75g, IQR 39.5-59 versus 42.7g, IQR 37-56, p = 0.08), pre-biopsy PSA (5.2 ng/mL, IQR 4.1-7.6 versus 4.97, IQR 3.24-6.95, p = 0.14). Of the fusion biopsy patients, 14 of 54 (25.9%) were upgraded from biopsy to prostatectomy, whereas 214 of 491 (43.6%) of TRUS biopsy patients were upgraded (p = 0.02). Conclusions: Of men undergoing transrectal biopsy for the diagnosis of prostate cancer, MRI-US fusion techniques have a lower rate of upgrading at final pathology at prostatectomy as compared to standard 12-core TRUS-guided biopsy.