bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pazopanib with low fat meal (PALM) in advanced renal cell carcinoma (RCC).
Authors: Reimers Melissa Andrea , Daignault Stephanie , Shango Maryann , Dedinsky Rachel , Riddle Liam , Wen Bo , Redman Bruce G. , Alva Ajjai Shivaram 
Published: February 2018

683 Background: Pazopanib, a highly lipophilic standard first-line therapy for metastatic RCC, is conventionally taken in a fasting state but has significant gastrointestinal toxicities and 96% of ingested drug is fecally excreted, with major financial implications. Single dose studies with fat meals suggested bioavailability is increased two-fold. We sought to evaluate toxicity/safety, bioavailability and anti-tumor efficacy of daily pazopanib taken with a low fat meal over 12 weeks. Methods: Enrolled pts had unresectable locally advanced or metastatic RCC with clear cell component, RECIST 1.1 measurable disease, ECOG PS ≤2, adequate organ function, and up to 3 prior therapies including VEGF(R) and checkpoint inhibitors. Subjects took pazopanib, starting dose of 400 mg, once daily with low-fat meal ( < 400 cal with < 20% fat/10 g of fat) in 2 wk cycles with MD discretion to dose-escalate q2wks up to 800 mg or irreversibly dose-reduce as low as 200 mg based on tolerance/toxicity for 12 wks. Baseline and end of study echocardiograms, and triplicate ECGs at each cycle start were monitored. Home pill diaries were collected. PK was analyzed in the first 3 cycles. Results: Sixteen pts were accrued: median age 60 (range: 47 – 75),75% men,11 were ECOG PS 0. Most (12/16) subjects with no prior therapy, 13/16 had intermittent Heng risk criteria, 3 favorable; 5 sarcomatoid component. Diet compliance by pill diary was outstanding, except for 1 pt for 1 cycle. Calculated mean daily dose was 535 mg (153-750 mg). Therapy was well tolerated; 5 Grade 3 AEs (1 HTN, 1 chest pain, 2 AST/ALT elevations, 1 Abd pain) occurred. LVEF declined by > 15% in 3 pts but none to < 50%. QTc prolongation > 450 ms did not occur. All but 3 pts completed protocol (off d/t toxicity-HTN, LFTs, chest pain). ORR was PR 5 (31%); SD 7 (44%). PK data and pharmacogenomics CYP3A4 polymorphism data correlated with toxicity. Conclusions: Pazopanib taken with a low fat meal appears to be better tolerated compared to published data on empty stomach administration, especially with fewer GI toxicities, including diarrhea. It also resulted in comparable efficacy with fewer cumulative pills over the 12-week period, with substantial cost implications. Larger trials of pazopanib with low fat meal are warranted. Clinical trial information: NCT02729194.
Adjuvant antiangiogenic agents in post-nephrectomy renal cell carcinoma (RCC): A systematic review and meta-analysis.
Authors: Sonbol Mohamad Bassam , Hilal Talal , Firwana Belal , Ho Thai Huu , Wang Zhen , Joseph Richard Wayne 
Published: February 2018

689 Background: The role of antiangiogenic agents in advanced RCC is well established. However, it is still not clear whether this benefit can be extrapolated to the adjuvant setting. In this meta-analysis of 3 randomized control trials (RCTs), we sought to determine the efficacy of these agents in RCC patients who underwent nephrectomy with high risk of relapse. Methods: We searched three databases, including Pubmed, Embase, and Cochrane Central Register of Controlled Trials to identify RCTs comparing antiangiogenic agents to placebo in post-nephrectomy RCC patients. We evaluated: 1) the effect of antiangiogenics in highest risk groups as defined by individual studies; 2) the role of each agent separately; and 3) the effect in clear-cell RCC population. Outcomes of interest included overall survival (OS) and disease-free survival (DFS). The overall effect was pooled using the DerSimonian and Laird random effects models Results: Three RCTs (N = 3693 patients) were identified. All studies were comparing placebo to antiangiogenics: sunitinib, sorafenib, and pazopanib. Overall, antiangiogenics did not improve DFS (HR 0.92, 95% CI 0.78 to 1.07) or OS (HR 0.99, 95% CI 0.79 to 1.25). These results persisted when restricting the analysis to patients with clear cell carcinoma and patients with highest risk of relapse. Similarly, sunitinib did not show any improvement in the entire studied group for either DFS (HR 0.89, 95% CI 0.67 to 1.19) or OS (HR 1.11, 95% CI 0.90 to 1.37). In addition, when restricting the analysis to the high risk group, sunitinib did not show any advantage in terms of DFS (HR 0.85, 95% CI 0.67 to 1.07) and OS (HR 1.04, 95% CI 0.83 to 1.31). Conclusions: Based on the available evidence, antiangiogenics do not seem to add an advantage over placebo in terms of OS and DFS in high risk RCC patients after nephrectomy. Further studies are needed to identify the patient population which might derive a benefit from antiangiogenics in the adjuvant setting.
Can health-related quality of life (HRQoL) predict conditional survival (CS) in metastatic renal cell carcinoma? Results from a large phase 3 trial.
Authors: Doan Justin , Malcolm Bill , Valaitis Eduardas , Hoover Kristopher , George Saby 
Published: February 2018

691 Background: In the absence of mature overall survival (OS) endpoints, interim clinical trial data can be used to predict long-term survival in patients (pts) with advanced malignancies and inform trial continuation, treatment preference, and reimbursement decisions. Research shows that HRQoL assessments can be associated with OS, offering potential utility for validated HRQoL scales. We describe a predictive model used to determine the extent to which HRQoL data could predict CS (survival conditional on progression at either 6 or 12 months). Methods: Using pt-level data from a large phase III trial of nivolumab vs everolimus, a simulation approach with a survival random forest algorithm identified factors statistically important in predicting CS from a large number of covariates measured at baseline. Stepwise Cox proportional hazard survival models were fitted using covariates identified as important. Baseline scores and change over time were tested to determine the influence on the predictive power of the HRQoL data. Results: For both nivolumab and everolimus, baseline FKSI values were significant predictors of CS; median survival times roughly doubled for pts with baseline FKSI scores ≥30 vs pts with scores < 30 (nivolumab, 31.3-16.6; everolimus, 26.6-11). Baseline FKSI scores were the most important predictor vs the other baseline covariates from the survival random forest simulation, and a statistically significant covariate when fitting a stepwise Cox proportional hazard survival model. Change in scores over time influenced CS for pts with high baseline scores, and pts who demonstrated improvement in scores vs baseline had significantly higher CS vs pts with low baseline and no improvement in scores vs baseline. However, when examining change in HRQoL score over time, the statistical importance of the covariate begins to diminish due to high correlations with factors such as adverse events and weight change. Conclusions: We found that HRQoL data, specifically the FKSI, could be useful in predicting CS, especially at the onset of a trial. The importance of the FKSI score in predicting CS could be a powerful complement to existing clinical prognostic factors.
Evaluation of serial measurements of C-reactive protein: Albumin ratio in patients with clear cell renal cell carcinoma.
Authors: Patil Dattatraya H , Anastasiades Ella N , Torlak Mersiha , Lay Aaron , Alemozaffar Mehrdad , Pattaras John , Kucuk Omer , Carthon Bradley Curtis , Bilen Mehmet Asim , Ogan Kenneth , Master Viraj A. 
Published: February 2018

695 Background: Sequential measurements of prognostic markers is an important protocol for accurate prediction of clinical outcomes in clear cell RCC. We propose that change in value of C-Reactive Protein to albumin ratio before and after surgery would be a good prognostic indicator for assessment of overall survival and risk stratification in clear cell RCC. Methods: Patients that underwent nephrectomy for clear cell RCC between 2007 and 2016 were followed up with CRP-Albumin measurements for 3 post-op visits (1, 3, 6 months). All measurements between post-op day 1 to 21 were excluded from analysis owing to possible confounding effect due to surgical stress. We assessed if change in CRP-Albumin ratio from pre-operative level is associated with any patient and tumor characteristics by fitting linear regression generalized estimating equations models to account for correlation in repeated measures. Average change in level for each post-op visit was used to stratify for an eventual end of follow-up outcome. Results: 302 clear cell RCC patients were treated with nephrectomy with mean age at surgery was 59.9±11 years, and mean BMI of 30.1± 6.6. 103 patients had at least 2 time-points available after surgery. Table 1 depicts mean CRP-Albumin ratio with 95% CI for each visit stratified with vital status. A linear GEE model fitted for baseline factors affecting change in ratio , identified t-stage, Fuhrman nuclear grade, gender, and BMI as significantly associated (p < 0.05). Conclusions: Serial measurement of CRP/Albumin ratio is useful factor for personalized risk-stratification for prognosticating overall survival as well as recurrence in patients with clear cell RCC. Significant effect of T-stage, tumor grade, and BMI depicts close relationship of CA-ratio and established risk predictors. [Table: see text]
Perioperative outcomes of aspirin use in partial nephrectomy.
Authors: Ingham Matthew D. , Krasnow Ross Erik , Mossanen Matthew , Wang Ye , Althaus Adam B. , Chang Steven Lee 
Published: February 2018

698 Background: Increasing cardiovascular disease has led to increases in the patient population on anti-platelet therapy who require urologic surgery. We sought to study perioperative outcomes for those undergoing partial nephrectomy (PN) while taking or not taking perioperative aspirin (pASA). Methods: A retrospective review of those undergoing PN was performed on the Premier Hospital Database from 2003 to 2015, with survey projection weighting resulting in a cohort of 10,807 patients. Two groups were formed – those continued on pASA (group 1, n = 774) and those with no pASA (group 2, n = 10,033). In-hospital complication rates were studied: major bleeding, overall transfusion, day-of-surgery transfusion, prolonged ( > 4 days) length of stay (LOS), and prolonged ( > 285 minutes) operative time. We also assessed 90-day rates of: cardiovascular catastrophe, readmission, major complication, and DVT/PE. Unadjusted rates were calculated for all PN patients and further subdivided into open and minimally invasive PN. Adjusted odds ratios (OR) were then calculated between groups 1 and 2. Results: Group 1 was older (58% vs 38% ≥65 years, p < 0.0001), largely male (73.1% vs 58.7%, p = 0.001), and less healthy (34.8% vs 18.4% with a CCI score ≥2, p = 0.003) than to group 2. For in-hospital outcomes, no significant differences were noted. Stratifying by surgical approach, those in group 1 undergoing minimally invasive PN were slightly less likely to require a day-of-surgery transfusion (OR 0.29, CI [0.05-0.99], p < 0.05). For 90-day outcomes, group 1 were far more likely to suffer a cardiovascular catastrophe (OR 7.56, CI [3.38-16.92], p < 0.001) regardless of surgical approach. Conversely, group 1 was slightly less likely to experience readmission (OR 0.48, CI [0.24-0.94], p < 0.05) and was likely driven by those undergoing minimally invasive PN. Conclusions: This large review of academic and community hospitals provides insight into the impact perioperative ASA has on PN outcomes. As noted, in-hospital outcomes were largely equivalent between groups while 90-day cardiovascular catastrophe rates were much higher in the ASA group. Despite this, this study lends support to the belief that pASA should not be considered an absolute contraindication to PN.
TCEB1-mutated renal cell carcinoma in relation to renal cell carcinoma with smooth muscle stroma in tuberous sclerosis complex.
Authors: Parilla Megan , Alikhan Mir , Segal Jeremy , Kadri Sabah , Fitzpatrick Carrie M , Antic Tatjana 
Published: February 2018

699 Background: TCEB1-mutated renal cell carcinomas (RCC) are a subtype of RCC which are distinct from both clear cell and clear cell papillary RCCs. These tumors are well-circumscribed, have predominantly tubular and papillary architecture, and have thick intersecting fibromuscular bands imparting a renal angiomyoadenomatous tumor (RAT)-like morphology. Tuberous sclerosis (TSC) patients have an increased risk of developing a number of tumors, including RCC. The histomorphology of RCCs in TSC have been well documented with 30-52% demonstrating “RCC with smooth muscle stroma” morphology, referred to as “TSC-associated papillary RCC (PRCC).” Interestingly the histologic features of TSC-associated PRCC are identical to that of the RAT-like TCEB1-mutated tumors. Methods: A total of 5 patients were found in our archives with histology that matched TSC-associated PRCC /RAT-like morphology. All 5 cases were retrieved and the formalin-fixed, paraffin-embedded blocks were reviewed with a representative block sent for molecular analysis on the UCMC-OncoPlus panel, a 1,213 gene targeted hybrid capture NGS panel. Variant and copy number calling was performed using custom-designed computational pipelines. A subset of cases had additional immunohistochemical stains preformed. Results: These 5 cases all revealed mutations in either TSC1, TSC2 or TCEB1 genes. Conclusions: The TCEB1 gene encodes the protein elonginC, a protein which complexes with VHL. A loss of elonginC results in a VHL complex which is unable to ubiquitinate HIF1-alpha. Non-degraded HIF1-alpha ultimately activates the transcription of a number of genes which lead to tumorgenesis. Interestingly, TSC1 and TSC2 protein products are also responsible for inactivating HIF1-alpha through RHEB/mTORC1/4E-BP1. This intimate molecular relationship with linked pathways of tumorgenesis, coupled identical histomorphology, suggests that TSC-associated PRCC and RAT-like RCC with TCEB1 mutation are the same tumor type.
U-SMART: (UCSD-small mass alt renal score tumor diameter) a novel scoring system of preoperative predictors to stratify oncologic risk of small renal mass.
Authors: Yim Kendrick , Bindayi Ahmet , Ryan Stephen , Reddy Madhumitha , Nasseri Ryan , Wan Fang , Long Christopher , Hamilton Zachary , Derweesh Ithaar 
Published: February 2018

700 Background: Small renal masses (SRMs, < 4 cm in diameter) are heterogeneous, with significant proportions of benign as well as high-grade malignancy. We developed a scoring system incorporating patient factors, serum markers, and morphometric characteristics to elucidate benign and high grade pathology and guide decision making. Methods: Single institution retrospective analysis of surgically treated SRMs from 2003-2017. Demographic and clinical factors, including RENAL score, were analyzed. Patients were categorized into 3 groups: benign (BNGN), low grade (LG), or high grade (HG) disease and uni- and multivariable logistic regression were used to screen for association between potential parameters and the 3 groups. Each significant variable was analyzed by risk group and broken into quartiles. The 75th percentile of the HG group was assigned a value of 3. Below the 75th percentile of the BNGN group was assigned a value of 1; values that fell between these cutoffs were assigned 2 points. Tumor diameter was weighted twice that of other factors. Receiver-operating-characteristic (ROC) analysis was used to assess for predictive capability. Results: 312 patients were analyzed (65 BNGN, 204 LG, 43 HG). Factors associated with increased risk of HG were male sex (OR 1.868, p = 0.045), higher ALT (OR 1.036, p = 0.022), higher RENAL score (OR 1.318, p = 0.002), and larger tumor diameter (OR 2.415, p < 0.001). Patients with low (5-8), intermediate (9-11) and high (12-14) scores had 32.8%, 5.2%, and 0% frequency of BNGN pathology. Patients with low, intermediate, and high scores had 7.7%, 18.6%, and 34.9% frequency of HG pathology. ROC analysis revealed AUC of 0.767. Conclusions: Preoperative clinical parameters were incorporated into a model that significantly predicts benign and aggressive pathology for SRMs. This risk stratification may provide a non-invasive method to aid in clinical decision making. External validation is requisite.[Table: see text]
Comparing cabozantinib (C) treatment for a cohort of patients with metastatic clear cell (ccRCC) and variant histology renal cell carcinoma (vhRCC): A retrospective study.
Authors: Lemke Emily , Shah Amishi Yogesh , Msaouel Pavlos , Bilen Mehmet Asim , Jonasch Eric , Venkatesan Aradhana M. , Chandramohan Anuradha , Duran Cihan , Tannir Nizar M. , Campbell Matthew T. 
Published: February 2018

702 Background: Both the randomized METEOR and CABOSUN studies in ccRCC found substantial benefit for patients receiving (C). We have previously reported (C) to have significant activity in vhRCC. To date no comparative data exists in evaluating the utility of (C) in ccRCC and vhRCC. Methods: This is a retrospective study of patients with ccRCC and vhRCC who received (C) at a single center from 1/2014-9/2017. Data tabulated included baseline characteristics, toxicity, dose reductions, time on (C) and survival data. A blinded radiologist assessed the radiographic response using RECIST v1.1. Cox regression analysis of time to treatment failure (TTF) in ccRCC and vhRCC was performed, adjusting for age, gender, IMDC score, neutrophil to lymphocyte ratio (NLR), prior TKI treatment, and number of metastatic sites. Statistical analysis were performed using SPSS 23.0. Results:Time to treatment failure was significantly longer in vhRCC compared with ccRCC (16.1 vs 7.64 months, HR 0.42, 95%CI 0.22-0.79, p = 0.007). This difference persisted in the adjusted Cox regression model (HR 0.36, 95% CI 0.15-0.85, p = 0.02). Conclusions: In this retrospective comparative analysis of C treated vhRCC and ccRCC patients, C was found to have substantial activity in both cohorts of patients. The IMDC score was important to predict outcome. Both heavily pretreated patients with ccRCC and those with vhRCC appeared to have substantial benefit.[Table: see text]
Validation of a genomic classifier to predict adverse pathology in men diagnosed with low risk prostate cancer.
Authors: Kim Hyung Lae , Li Ping , Huang Huei-Chung , Deheshi Samineh , Knudsen Beatrice , Abou-Ouf Hatem , Lam Lucia L.C. , Margrave Jennifer , Du Plessis Marguerite , Davicioni Elai , Tosoian Jeffrey J. , Ross Ashley , Davis John W. , Hyndman M. Eric , Klein Eric A. , Bismar Tarek A. 
Published: February 2018

71 Background: The Decipher 22-feature genomic classifier (GC) has been validated to predict metastasis and prostate cancer specific mortality in needle biopsy (Bx) tissue of men with intermediate and high-risk prostate cancer. We validate GC in diagnostic Bx specimens for the prediction of high-grade/stage (HGS) disease at radical prostatectomy (RP) in men with low and favorable-intermediate (fav-int) NCCN risk group disease. Methods: We identified 176 men diagnosed with low or fav-int NCCN risk group disease who had available Bx GC scores and pathological information after RP from Cedars-Sinai, University of Calgary, Cleveland Clinic, MD Anderson, and Johns Hopkins. The GC score was calculated based on a locked random forest model. Scores range from 0-1 with cut points for GC low, intermediate and high risk groups as <0.45, 0.45-0.6, and >0.6, respectively. The primary endpoint was HGS (Gleason group 3-5 or pT3b or lymph node invasion (LNI)). Univariable (UVA) and multivariable (MVA) logistic regression models were used to evaluate GC and CAPRA. Results: Median age of the cohort was 62 years, 87% and 13% had Bx grade group (GG) 1 or 2 disease. 76% and 24% were NCCN low and fav-int risk, respectively. CAPRA classified 70% as low (0-2) and 30% as average risk (3-5). GC classified 80% low, 16% intermediate and 4% high genomic risk. After RP, 41% had RP GG 1, 46% GG 2 and 13% had GG 3-5 disease. pT3b or positive lymph nodes were observed in 7 men (4%), overall 27 (15%) of men had HGS at RP. In the UVA and MVA, GC was the only significant predictor of HGS with odds ratio (OR) of 1.38 and 1.34 per 10% unit increase, before and after adjusting for CAPRA (p=0.011, 0.027). A low risk score (GC<0.45) had a negative predictive value (NPV) of 92% to identify men who do not have HGS at RP. In exploratory analysis, a very low risk cut-point (GC<0.2) was found which had a sensitivity of 96% and an NPV of 99%. 26% of men had GC<0.2. Conclusions: We validated GC in a multi-institutional study to predict HGS at RP among men with NCCN low and fav-int risk disease with high sensitivity and NPV. Future studies will aim to validate the very low risk genomic cut-point to guide decision-making and follow-up biopsy protocols for men considering or in active surveillance.
Impact of genomic risk scores on treatment decisions following radical prostatectomy in a prospective Medicare registry.
Authors: Gore John L. , Dai Darlene , Den Robert Benjamin , Yousefi Kasra , Le Tiffany , Du Plessis Marguerite , Padre Roanna , Sosu-Sedzorme Worlanyo , Davicioni Elai , Nguyen Paul L. , Ross Ashley 
Published: February 2018

72 Background: Prostate cancer patients and providers confront uncertainty as they consider adjuvant or salvage radiation therapy (ART, SRT) after radical prostatectomy (RP). We prospectively evaluated the impact of the Decipher RP test, which predicts metastasis risk after RP, on decision-making for postoperative radiation therapy. Methods: Between October 2016 and May 2017, 1,319 patients treated with RP and considering ART or SRT were enrolled into a Medicare Certification and Training Registry (CTR). Providers submitted a management recommendation based on initial clinical and pathology findings prior to obtaining the Decipher RP test and again upon receiving test results. Only Medicare patients that met the Local Coverage Determination inclusion criteria (i.e., non-organ confined prostate cancer or positive margins or rising PSA) and whose provider was certified in the CTR registry were included in the analysis. Results: Based on clinical variables alone, treatment was recommended for 26% of adjuvant and 19% of salvage patients. Obtaining a Decipher score, changed treatment recommendations in 34% (95% CI 30-39%) and 28% (95% CI 19-38%) of men considering adjuvant or salvage therapy respectively. Among men considering ART, 9% of Decipher low risk patients and 45% of Decipher high-risk patients were recommended treatment. Multivariable logistic regression demonstrated that – independent of pathology risk factors, a high-risk Decipher score was associated with an odds ratio of 7.3 (95% CI 3.9-14.2 p < 0.001) in the adjuvant and 5.5 (95% CI, 1.3-27.8, p = 0.026) in the salvage setting. Conclusions: A prospective CTR demonstrated that use of Decipher resulted in significant changes in treatment decisions for Medicare beneficiaries with PCa considering adjuvant and salvage therapies. Ongoing prospective studies aim at determining how increased use of therapy in men with high Decipher risk impacts oncologic outcomes and whether decreased use in Decipher low risk individuals improves health related quality of life without harming patient survival.