bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of second targeted therapy in metastatic renal carcinoma: A retrospective chart review in the EU.
Authors: Heng Daniel Yick Chin , Park Jinhee , Signorovitch James E. , Yang Hongbo , Song Jinlin , Patel Dony , Lin Chinjune , Powles Thomas 
Published: February 2017

558 Background: This study describes the real-world outcomes of metastatic renal cell carcinoma (mRCC) patients treated with everolimus (EVE), sorafenib (SOR), and axitinib (AXI) as 2nd targeted therapy in the UK, Germany, and France. Methods: A retrospective chart review was conducted among oncologists and urologists in the UK, Germany and France. Charts were reviewed for adult mRCC patients satisfying the following eligibility criteria: 1) experienced disease progression on 1st targeted therapy with sunitinib or pazopanib; 2) initiated 2nd targeted therapy with EVE, AXI, or SOR between 10/2012 and 6/2013. Kaplan-Meier analysis was used to estimate overall survival (OS) after initiation of 2nd targeted therapy among all patients and stratified by type of 2nd targeted therapy. Results: A total of 281 charts were reviewed, with 99, 91, and 91 mRCC patients receiving EVE, AXI, and SOR as 2nd targeted therapy, respectively. Mean age was 60.6 years old at initial mRCC diagnosis and 65.5% were male. The majority of patients used sunitinib (79.4%), with the rest using pazopanib (20.6%) as 1st targeted therapy. Median duration of 1st targeted therapy was 9.7 months. At the initiation of 2nd targeted therapy, 91.8% of patients had an ECOG score ≤ 2. The most common sites of metastases were lung (71.2%), bone (53.0%), and lymph nodes (47.0%). Median OS from the initiation of 2nd targeted therapy among all patients was 21.8 months (95% CI: 16.5-26.2). The median OS was 23.0, 23.5, and 18.7 for EVE, AXI, and SOR respectively. The majority of patients (87.5%) initiated 2nd targeted therapy on the recommended dose. Patients receiving AXI had a higher rate of dose increase (13.2%), compared to EVE (1.0%) and SOR (0.0%), while patients on EVE had a higher rate of dose decrease (12.1%), compared to AXI (5.5%) and SOR (8.8%). Conclusions: In this retrospective chart review study of several EU countries, the observed median OS was numerically comparable for EVE and AXI, but rates of dose adjustment differed by treatments. Retrospective chart reviews may be subject to selection bias and errors in data entry, and further analysis is underway to address confounding effects of unobserved patient characteristics.
A novel preoperative inflammatory marker prognostic score in patients with clear cell renal cell carcinoma.
Authors: Sekar Rishi Robert , Patil Dattatraya , Pearl Jeff , Baum Yoram , Kucuk Omer , Harris Wayne B. , Carthon Bradley Curtis , Alemozaffar Mehrdad , Filson Christopher Paul , Ogan Kenneth , Master Viraj A. 
Published: February 2017

566 Background: Several inflammatory markers have been singularly studied as potential biomarkers in clear cell renal cell carcinoma (RCC), however few reports have analyzed their prognostic value in aggregate. We hypothesize that a combination of preoperative C-Reactive Protein (CRP), albumin, Erythrocyte Sedimentation Rate (ESR), corrected calcium, and AST/ALT ratio into a RCC Inflammatory Score (RISC) could serve as a rigorous prognostic indicator in patients with clear cell RCC. Methods: Patients that underwent nephrectomy for localized clear cell RCC were queried from our nephrectomy database. The optimal threshold for individual biomarkers was determined using grid search methodology, receiver operating characteristic (ROC) analysis, and sensitivity-specificity trade-off analysis. The final score, RISC, was the sum of all points accrued from each biomarker (Table). ROC and chi-square analysis was performed to compare the prognostic ability of RISC to SSIGN and UISS. Impact on overall survival was analyzed with multivariate logistic regression analysis. Results: 280 patients were included in the study. Area under the curve (AUC) for RISC, SSIGN and UISS was 0.77, 0.78, and 0.81, respectively. Chi-square analysis of AUCs revealed no statistically significant difference between RISC, SSIGN, and UISS (p= 0.975 and p =0.299, respectively). On multivariate analysis, after adjusting for confounding variables, each unit increase in RISC was associated with a 31% increase in mortality (HR=1.31, 95%CI 1.13-1.50, p<0.001). Conclusions: RISC is an independent and significant predictor of overall survival in clear cell RCC with accuracy at least as good as other established prognostic tools. Notably, RISC is composed of standardized laboratory markers easily and cost-effectively obtained preoperatively, allowing crucial prognostic information to be integrated into medical decision making prior to surgery. [Table: see text]
Axitinib treatment among patients with mRCC in a U.S. community oncology setting: A retrospective study of 135 patients.
Authors: Hutson Thomas , Jiao Xiaolong , Wilson Thomas , Cisar Laura A. , MacLean Elizabeth A. 
Published: February 2017

569 Background: We have previously reported differences in a variety of outcome measures between clinical trial and real world use of several therapies for advanced renal cell carcinoma (RCC) (Vogelzang NJ, et al. Clin Genitourin Cancer, 2015, Hutson TE et al. Lancet Oncol, 2013, Motzer RJ, et al. NEJM, 2013). In an attempt to better understand the real-world use of axitinib in patients (pts) with metastatic RCC (mRCC) after one prior systemic therapy, a retrospective study was conducted using the US Oncology’s (USON) iKnowMed electronic health records database and medical record review data. Methods: Eligibility criteria were: pts with mRCC ≥ 18 years of age at first diagnosis, treated with VEGFR-TKIs or immunotherapy including IL-2 and IFN as first line of therapy (LOT), received second or third line axitinib between 1/1/2012 and 10/31/2014, with ≥ 2 visits within the USON. LOT was defined based on treatment sequence. Dosing analysis included duration of therapy, dose change, and reasons for discontinuation. Results: 135 pts met eligibility criteria. The most common prior therapies were sunitinib (48.5%) and pazopanib (48.5%) for pts with axitinib as 2nd LOT (n=68), and everolimus (55.2%), temsirolimus (19.4%), and pazopanib (14.9%) for pts with axitinib as 3rdLOT (n=67). 80.7% (109) of pts started axitinib at 5mg BID, and 68.9% remained at this dose. 17.8% had a dose increase mainly due to physician’s choice and 13.3% a dose decrease mainly due to toxicity. The median duration of therapy was 4.57 months (mean 6.32, SD 5.91, range 0.03-35.49). Axitinib was discontinued in 91 (67.4%) pts, and the most common reasons for discontinuation were disease progression (39.3%) and toxicity (17.0%). Conclusions: In the community oncology setting, axitinib was commonly used in the 2nd and 3rd line setting for pts with mRCC. The usage pattern appears to be consistent with published NCCN guideline recommendations. Surprisingly and in contrast to our experience with other agents for RCC, dose changes were less common and duration of therapy was consistent with the pivotal clinical trial results. These findings suggest ease of use among community oncologists and patient tolerance are key features of axitinib.
Patient disability and treatment variation among older adults with kidney cancer.
Authors: Tan Hung-Jui , Chamie Karim , Litwin Mark S. , Hu Jim 
Published: February 2017

573 Background: Beyond age and comorbidity, functional status shapes the long-term survival potential of patients with cancer. Accordingly, we explored the relationship between preexisting disability and surgery among older adults with kidney cancer. Methods: Using SEER-Medicare data from 2000–2009, we sampled 28,326 patients ≥66 years old diagnosed with primary kidney cancer. Disability was quantified using function-related indicators (FRI)—claims indicative of patient dysfunction (e.g., mobility-assist devices, falls). We used competing risk regression to assess the relationship between FRI score and non-cancer-related mortality and generalized estimating equations to estimate the probability of surgery according to FRI score, adjusting for patient and tumor stage. Results: We identified 13,619 (48.1%) adults with ≥1 FRI. Disability was associated with older age, greater comorbidity, female gender, unmarried status, lower socioeconomic status, and higher cancer stage (p<0.001). Patients with a FRI score of 1 (SHR 1.10, 95% CI 1.04–1.16) and ≥2 (SHR 1.52, 95% CI 1.44–1.60) had higher likelihoods of non-cancer-related death compared with those with a FRI score of 0. Predicted 10-year incidence of non-cancer-related death was 35, 38, and 48% while the incidence of kidney cancer-related death was 26, 28, and 29% for patients with FRI score of 0, 1, and ≥2, respectively. Patients with FRI of ≥2 received surgical treatment less often than those without disability (OR 0.61, 95% 0.56–0.66), though treatment probabilities remained high for patients with loco-regional disease and low for adults with metastatic cancer (Table). Conclusions: Among older adults with kidney cancer, functional status stands as a significant predictor of long-term survival. Although preexisting disability modulates treatment use to some degree, receipt of cancer-directed surgery appears largely determined by cancer stage. Patient functionality should be considered more heavily when deciding treatment for kidney cancer. [Table: see text]
Phase II study of axitinib for downstaging cT2a to cT1 renal tumors for allowing partial nephrectomy (AXIPAN).
Authors: Patard Jean-Jacques , Bernard Jean-Christophe , Bensalah Karim , Baumert Herve , Lang Herve , Jacqmin Didier , Duclos Brigitte , Ravaud Alain , Laguerre Brigitte , Albiges Laurence , Arnoux Armelle , Escudier Bernard 
Published: February 2017

575 Background: Laparoscopic Radical nephrectomy (RN) is the current standard of care for large organ confined renal tumors while partial nephrectomy (PN) is recommended for tumor sizes up to 7 cm. PN preserves long term renal function with possible effect on overall survival. Axitinib, a potent VEGFR TKI can reduce the size of primary tumor in metastatic setting. Our primary objective was to test the ability of axitinib to reduce the size of large tumors for shifting from a RN to a PN indication. Methods: Patients with localized (cT2N0M0) RCCs were enrolled in a prospective phase II trial assessing the effect of neoadjuvant axitinib prior to surgery (PN or RN). Main inclusion criteria were: age ≥ 18, histologically proven clear cell RCC, MDRD creatinine clearance ≥ 60 ml/min, cT2a N0NxM0 tumors ( Ø> 7cm; ≤ 10 cm). Medical treatment consisted in axitinib 5 mg up to 10 mg tw/d during 2 to 6 months prior surgery according to radiological response. Results: A total of 18 patients including 11 men (61%) and 7 women (39%) with a median age of 60 yrs were enrolled. Median baseline tumor size, R.E.N.A.L. score, serum creatinine and MDRD estimated GFR were: 7.5 cm, 11, 0.8 mg/dl and 96.5 ml/min respectively. Duration of treatment was 2, 4 and 6 months in 12 (66%), 3 (17%) and 3 cases (17%), respectively. After neoadjuvant treatment median tumor size and RENAL score decreased to 5.9 cm and 10. 93 % of patients presented a decrease in maximum tumor diameter, with median size reduction of 21.7%. Out of the 17 patients who were operated, 16 (94%) underwent a PN (9 robotic and 7 open), including 84% of the cases which were performed for tumors ≤ 7cm. At 1 month from surgery, median serum creatinine and MDRD estimated GFR were 0.88 mg/dl and 88 ml/min, respectively. Medical and surgical complications rate was 11% including 1 embolization for severe bleeding and 1 Clavien V complication at 1 month after surgery due to massive myocardial infarction. Conclusions: Neoadjuvant axitinib in cT2renal tumors allowed cT1 downstaging and nephron sparing surgery in more than 80% of the cases. However, PN procedures remained high complexity cases requiring adequate surgeon expertise and information of the patients for possible morbidity of these procedures. Clinical trial information: RECF2256.
Cost-effectiveness analysis of initial management strategies for low-risk prostate cancer.
Authors: Thong Alan E. , Lee Justin K. , Carlsson Sigrid V. , Ehdaie Behfar 
Published: February 2017

58 Background: A proportion of men with low-risk prostate cancer managed expectantly with active surveillance (AS) go on to definitive treatment in part due to initial understaging during transrectal ultrasound (TRUS) guided biopsy. Newer diagnostic tools including genomic tumor profiling, magnetic resonance (MR) imaging, and MR-ultrasound fusion biopsy have been advocated as effective strategies to risk-stratify men prior to entry into AS. We developed a decision analytic model to determine the cost-effectiveness of various initial management options for low-risk prostate cancer. Methods: A decision tree was constructed with repeat TRUS guided biopsy, MR imaging, genomic tumor profiling, and radical prostatectomy as initial management options with downstream Markov nodes to model annual recurring risks of continued AS, definitive treatment, and death from other causes. Value was optimized from the societal perspective over a lifetime horizon. We evaluated model heterogeneity and assumptions on the probability of understaging and test performance characteristics using Monte Carlo microsimulation and probabilistic sensitivity analysis. Results: At a willingness-to-pay (WTP) threshold of $100,000 per quality adjusted life year (QALY), immediate radical prostatectomy and genomic tumor profiling were dominated strategies with higher costs and lower effectiveness. MR imaging with MR-ultrasound fusion biopsy when targetable lesions are identified was the optimal strategy across 93% of simulations with an incremental cost-effectiveness ratio of $1,096 per QALY. Eliminating uncertainty in our model would lead to cost savings and increased effectiveness. This expected value of perfect information was $516 per patient. Conclusions: With multiple initial management options for low-risk prostate cancer, clinical decision-making can be challenging. Cost-effectiveness analysis demonstrates that image-guided biopsy techniques deliver optimal value from both a patient and societal perspective. However, given the prevalence of low-risk prostate cancer, there is value to be obtained from additional research to optimize management strategies.
STAT-3 and Β-catenin expression in metastatic clear cell renal cell carcinoma (mRCC).
Authors: Fares Aline Fusco , Cunha Isabela , Araujo Daniel Vilarim , Boente Leonardo de Azevedo , Garcia Daniel , Rinck Jose A. , Formiga Maria Nirvana Cruz 
Published: February 2017

583 Background: In mRCC, there are no prospectively validated biomarkers to guide the treatment and therapy decision is based on prognostic scores and histology. STAT-3 and Wnt/b-cateninare cell proliferation pathways and have already been related to prognostic in renal cell carcinoma. Objective: to evaluate the role of STAT-3 and b-catenin expression as prognostic biomarkers in clear cell mRCC. Methods: 684 medical records of renal cell carcinoma patients treated at AC Camargo Cancer Center from 2007 to 2015 were reviewed. 86 out of 684 patients fulfilled the study criteria: metastatic clear cell carcinoma, no sarcomatoid features, previous systemic therapy, previous nephrectomy and available tumor specimens from metastatic site. Pathological samples were arranged in a TMA. The number of positive stainings cells for each antibody in each core was categorized as low positive or negative versus highly positive expression. Results: We had available tissue blocks from 47 tumors. 32/45 patients (71,1%) had highly positive membrane b-catenin and none of the patients was positive for nuclear b-catenin. 27 /45 (60%) were categorized as low positive or negative STAT-3. There was no statistically significant association between STAT-3 and b-catenin expression with clinical prognostic criteria (MSKCC and Heng criteria). In the multivariate analysis, KPS < 80% (p = 0.02; HR: 2.7), time from nephrectomy to metastasis < 1 year (p = 0.04; HR: 2.1), no hypothyroidism (p = 0.05; HR: 2.4) and MSKCC criteria (p = 0.02; HR: 2.5) were confirmed as negative prognostic factors. Associative analysis showed that none of the patients with negative membrane b-catenin had response to systemic therapy (p=0.02). OS was 35.5 months (IC 22.2-48.8) and PFS was 12.5 months (IC 10.0-14.0). Conclusions: in our cohort, STAT-3 and B-catenin expression are not associated with the prognostic criteria (MSKCC and Heng). The loss of B-catenin expression is associated to a worse response rate to antiangiogenic therapy in metastatic clear cell renal cancer. [Table: see text]
External validation of preoperative AST/ALT (De-Ritis) ratio as a prognostic indicator in localized and metastatic renal cell carcinoma.
Authors: Patil Dattatraya H , Sekar Rishi Robert , Pearl Jeff , Baum Yoram , Alemozaffar Mehrdad , Filson Christopher Paul , Ogan Kenneth , Master Viraj A. 
Published: February 2017

589 Background: Recently, the De-Ritis ratio, defined as the ratio of preoperative aspartate aminotransferase (AST) to alanine aminotransferase (ALT), was shown to be an independent predictor of overall and recurrence-free survival in a European cohort with localized renal cell carcinoma (RCC). In this study, we perform an external validation of the De-Ritis ratio as a prognostic indicator in a distinct cohort of patients with localized and metastatic RCC. Methods: Patients that underwent nephrectomy for localized and metastatic RCC between 2001 and 2014 with available laboratory values within one week of surgery were queried from the Emory Nephrectomy Database. De-Ritis ratio of 1.2 was used to divide subjects into high and low subgroups. Using clinical follow-up data, prognostic value of the De-Ritis ratio was analyzed using the Kaplan-Meier method and Cox proportional regression models. Results: In a cohort of 451 patients, an elevated De-Ritis ratio (AST/ALT ≥ 1.2) was associated with significantly decreased overall survival (log-rank, p=0.0023) and recurrence-free survival (Log-rank, p=0.0395). On multivariate analysis, De-Ritis ratio was shown to be an independent and significant predictor of overall survival (HR=0.52, p=0.002) and recurrence-free survival (HR=0.47, p=0.014) as seen in Table. Conclusions: Elevated De-Ritis ratio (AST/ALT ≥ 1.2) is an independent and significant predictor of overall and recurrence-free survival and is capable of differentiating high-risk disease in patients with localized and metastatic RCC. These findings are consistent with a previous study investigating the prognostic value of the De-Ritis ratio in a European cohort, and further validates its prognostic ability in a geographically distinct cohort including patients who presented with metastatic disease [Table: see text]
The role of ZNF395 in renal cell carcinoma proliferation, migration, and invasion.
Authors: Zhao Chen , Wood Christopher G. , Karam Jose A. , Maity Tapati , Wang Lei 
Published: February 2017

592 Background: Zinc finger protein 395 (ZNF395) is frequently altered in several tumor types. However, the role of ZNF395 remains poorly studied in patients with clear cell renal cell carcinoma (RCC). In this study, we investigated the in vitro and in vivo role of ZNF395 in ccRCC. Methods: cBioPortal For Cancer Genomics was used to correlate the expression of ZNF395 with RCC patient clinical, pathological and molecular profiles. ZNF395 protein and mRNA levels were studied in several RCC cell lines in vitro. Subsequently, ZNF395 knockdown was performed in 786-O and UMRC3 RCC cells and overexpression was done in Caki-1 and 769-P RCC cells. We then evaluated ZNF395 modulation in these cell lines by in vitro MTT, migration and invasion assays. Finally, we studied the effect of ZNF395 knockout and overexpression in vivo using SCID xenograft models. Results: Patients with higher expression of ZNF395 experienced longer disease-free survival and overall survival. Using in vitro models, we confirmed that knockdown of ZNF395 decreased ZNF395 expression, and increased proliferation, migration and invasiveness of 786-O and UMRC3, while overexpression of ZNF395 increased ZNF395 expression, and reduced proliferation, migration and invasiveness of Caki-1 and 769-P. Using in vivo mouse models, knockdown of ZNF395 expression in 786-O promoted tumor growth while its overexpression in Caki-1 resulted in tumor growth inhibition. We are currently performing experiments to understand the process by which ZNF395 regulates ccRCC pathogenesis. Conclusions: Our data support the role of ZNF395 as an important tumor suppressor gene in the pathogenesis of RCC.
Sorafenib versus sunitinib as first-line treatment in metastatic renal cell carcinoma: Largest multicenter retrospective analysis.
Authors: Sheng Xinan , Zhang Hailiang , Li Xuesong , Chi Zhihong , He Zhisong , Ye Dingwei , Guo Jun 
Published: February 2017

594 Background: For the mRCC patients, selecting the first-line regimen for a particular patient has become a hard decision for clinicians. However, there was few clinical studies directly comparing the efficacy of first-line treatment with sorafenib and sunitinib. Methods: Reviewing medical records at the Peking University Cancer Hospital, Fudan University Cancer Hospital and Peking University First Hopital from May 2005 to March 2015 revealed 483 patients receiving sorafenib (400 mg orally BID continuously in a 4-week cycle) and 362 patients receiving sunitinib (50 mg orally daily in a 6-week cycle; 4/2 schedule) as the first-line targeted therapy. Results: Median follow-up was 23.0 months (95% CI: 2.5-25.4 months).There was significant differences in progression-free survival (PFS) between the sorafenib and sunitinib groups (11.1 months [95% CI: 8.00-13.00] vs 10.0 months [95% CI: 9.00-14.00], respectively; P = 0.028) .No significant differences was seen in overall survival (24.0 months [95% CI: 20.00-29.00] vs 24.0 months [95% CI: 18.00-31.00], respectively; P = 0.298). A subgroup analysis based on Karnofsky performance status (KPS), pathological type, Memorial Sloan Kettering Cancer Center score, metastases, and tumor load was also conducted. Clinical benefit rate was higher in sorafenib-treated patients (94.67%) than sunitinib-treated patients (84.33%). Multivariate analysis revealed that sorafenib had superior efficacy in patients with a KPS of < 90 and significantly better PFS (hazard ratio: 0.460 [95% CI: 0.222-0.954]). Conclusions: To our knowledge, this is largest mutli-center retrospective study determined the efficacy of sorafenib versus sunitinib as first-line therapy for mRCC patients. Our study results support administration of sorafenib as an effective first-line treatment agent in Chinese patients with mRCC.