bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salivary markers in renal cell carcinoma.
Authors: Dudek Alexandra , Appleyard Lauren , O'Brien Tim S. , Chowdhury Simon , Champion Penny , Challacombe Ben , Kooiman Gordon , Carpenter Guy 
Published: February 2017

489 Background: Kidney cancer ranks number 8 among cancer diagnoses in the UK with around 9,600 new diagnoses made each year (Cancer Research UK. Risks and causes of kidney cancer. http://www.cancerresearchuk.org/cancer-help/type/kidney-cancer/about/risks-and-causes-of-kidney-cancer). This study aimed to identify overexpressed proteins in human saliva that could serve as markers for renal cell carcinoma. Methods: Saliva was collected from 144 participants (95 male and 28 female).; 123 RCC patients (85%) and 21 healthy controls (15%), Total salivary protein levels were determined by BCA protein assay. Then 10ug of total saliva protein were evaluated via Western blotting on 4-12% Bis-Tris SDS-PAGE gels. Blots were probed for albumin as well as for three proteins associated with RCC; profilin1, 14-3-3 zeta, and endogenous avidin binding protein (EABP). Additionally, 6 saliva samples were evaluated via quantitative proteomics in a Tandem mass tag (TMT) labelling experiment comparing 4 RCC patients vs. 2 renal cyst patients. Results: Profilin1 levels were determined visually on a scale of 0 to 3 depending on band intensities on Western blots. Cancer patients had a higher percentage of levels 2 and 3 with 62 patients (50.4%). The control group only had 2 patients at level 2 (9.5%) and none at level 3. No difference in profilin1 levels was seen between metastatic vs. non-metastatic disease. Differences were seen in gender and histology, with female and non-CC patients having higher profilin levels. There is a potential link between profilin1 levels and surgical or drug treatment. 14-3-3 zeta could not be detected in saliva with these analyses. Albumin was present across all samples. EABP was found in 40.6% of cancer patients vs. 0% of controls; however no clear trend was seen with respect to disease burden, histology, or gender. Proteomic analysis gave a total of 33 hits showing raised protein levels of up to 20x higher in cancer patients vs. controls. Profilin1 was 2x and 14-3-3 zeta 5x more prevalent. Conclusions: This study has successfully identified profilin1 as a detectable salivary marker for renal cell carcinoma. [Table: see text]
Dysregulation of the beta-catenin complex as an independent predictor of oncological outcomes in patients with ccRCC.
Authors: Krabbe Laura-Maria , Westerman Mary Elizabeth , Bagrodia Aditya , Gayed Bishoy A. , Darwish Oussama M. , Haddad Ahmed Q , Khalil Dina , Kapur Payal , Sagalowsky Arthur I. , Lotan Yair , Margulis Vitaly 
Published: February 2017

493 Background: Epithelial to mesenchymal transition (EMT) is thought to play a crucial role in cancer progression and development of metastasis. Thus, we evaluated dysregulation of beta-catenin as a part of EMT and its clinical implications in patients with clear cell renal cell carcinoma (ccRCC). Methods: Immunohistochemical staining was performed for beta-catenin on tissue microarrays of patients with ccRCC. Membranous and cytoplasmatic beta-catenin expression patterns were assessed separately. Beta-catenin was considered normal if none or only one component was abnormal and was considered dysregulated if both components were abnormal. Differences in pathological characteristics between both groups were investigated. Differences in recurrence-free survival (RFS) and cancer-specific survival (CSS) were assessed with the Kaplan-Meier method. Uni- and multivariate Cox proportional hazard models were used to assess independent predictors of oncological outcomes. Results: 406 patients with a median follow-up of 58 months were included. Overall, 52 (12.8%) and 25 (6.2%) patients recurred and died of ccRCC. Beta-catenin was dysregulated in 70 (17.2%) patients. Dysregulation of beta-catenin was significantly associated with adverse pathologic features, such as higher T-stage, nodal positivity, higher grade, presence of tumor thrombus, sarcomatoid features, necrosis and LVI (all p<0.001). Patients with dysregulated beta-catenin had inferior RFS and CSS (both p<0.001). In multivariate analysis adjusting for tumor stage, nodal status and grade, dysregulation of beta-catenin was an independent predictor of RFS (HR 2.2, 95%CI 1.2-3.9, p=0.008) and CSS (HR 2.4, 95%CI 1.1-5.6, p=0.044). Conclusions: Our results indicate that dysregulation of beta-catenin may be an important phenomenon in ccRCC carcinogenesis. These findings support further study of beta-catenin and systematic assessment of EMT in ccRCC.
U.S. regional practice patterns in metastatic renal cell carcinoma (mRCC) patients: A real-world retrospective analysis.
Authors: Pal Sumanta Kumar , Gorritz Magdaliz , Sherman Steven A. , Liu Zhimei 
Published: February 2017

505 Background: The treatment landscape for metastatic renal cell carcinoma (mRCC) has changed in recent years, with several targeted therapies becoming available for 1st and 2nd line use. The rapidly evolving treatment landscape has left physicians with an abundance of choices for the treatment of mRCC patients. This study aimed to understand whether this has resulted in varying treatment patterns across US regions in 1st and 2nd line targeted therapy for mRCC. Methods: RCC patients who initiated 1st line targeted therapy with a vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFr) or mammalian target of rapamycin (mTOR) inhibitor between January 1, 2004 and June 30, 2011 were identified in the MarketScan database. First-line therapy was defined as the first claim in the database for a targeted therapy. One drug claim was sufficient to establish a line of therapy and a new line was defined as switching to another agent. Treatment patterns in the 1st and 2nd line settings were assessed in patients who initiated 2ndtherapy line after FDA approval of everolimus (Ev) (March 30, 2009) and stratified by geographic region. Results: Of the 6,524 patients included in the study, 1,298 (36%) received a 2nd line targeted therapy after March 30, 2009. Although all possible permutations of treatment sequences were observed, overall, sunitinib (Su) and temsirolimus (Te) combined made up 80% to 83% of the 1st line regimens across regions. The most common sequence was Su->Ev, observed in 18% of patients in the North Central US to 31% in the Northeast; Su->Te was the next most common sequence in all regions. Among patients who received 1st line temsirolimus, the majority initiated 2ndline on either bevacizumab (Be) (7%-12%) or Su (6%-10%) across regions. Conclusions: The most common treatment sequences across all regions were Su->Ev and Su->Te. Although a consistent pattern of sequential therapy emerged across regions, a wide range of on- and off-label strategies was observed outside of the predominant pattern of care. Furthermore, very few patients in this study received additional targeted therapy after 1st line. Further research is needed to identify factors influencing these treatment strategies.
Population-based comparison of surgical margin status for robotic versus open radical prostatectomy.
Authors: Hu Jim C. , Gandaglia Giorgio , Nguyen Paul Linh , Trinh Quoc-Dien , Shih Ya-Chen T. , Abdollah Firas , Chamie Karim , Wright Jonathan L. , Karakiewicz Pierre I. , Sun Maxine 
Published: February 2017

51 Background: Robotic-assisted radical prostatectomy (RARP) remains controversial due to exaggerated marketing claims, higher costs, hidden risks, and few clinically significant benefits, including an absence of improved cancer control compared to open radical prostatectomy (ORP). The purpose of our study is to compare surgical margin status by surgical approach. Methods: We identified 13,434 men with a histologically confirmed, non-metastatic prostate cancer treated with RARP versus ORP during 2004 and 2009 from Surveillance, Epidemiology, and End Results (SEER)–Medicare linked data. Propensity-based analyses were performed to minimize treatment selection biases. Generalized linear regression models were computed for comparison of radical prostatectomy surgical margin status by surgical approach. Results: During the study period, 5,556 and 7,878 men underwent RARP and ORP, respectively. In the propensity-adjusted cohort, the incidence of positive surgical margins was significantly lower among men undergoing RARP versus ORP (13.7% vs. 18.4%, odds ratio [OR]: 0.68, 95% confidence interval [CI]: 0.63–0.73, p<0.001). This reduction in the incidence of positive surgical margins of RARP over ORP was more pronounced among men with more advanced disease—6.6% lower absolute incidence of positive margins among men with intermediate- and high-risk disease (p<0.001, respectively) and 15.4% lower absolute incidence of positive margins among men with extracapsular extension (p<0.001). Moreover, RARP was associated with lower odds of positive surgical margins compared to ORP for pT2 (Odds Ratio [OR] 0.67, 95% Confidence Interval [CI] 0.61–0.74, p<0.001) and pT3a (OR 0.72, 95% CI 0.60–0.85, p<0.001) disease. Additionally, RARP was associated with lower odds of positive surgical margins for intermediate (OR 0.66, 95% CI 0.58–0.74) and high-risk (OR 0.69, 95% CI 0.64–0.75) disease. Conclusions: RARP was associated with improved surgical margin status among men with intermediate and high-risk disease. This has important implications for cancer control, patient quality of life, health care delivery and additional costs of downstream therapies.
Glandular metastasis as a surrogate for long survivors in metastatic renal carcinoma.
Authors: Chanez Brice , Brachet Pierre-Emmanuel , Laguerre Brigitte , Walz Jochen , Joly Florence , Esterni Benjamin , Dermeche Slimane , Salem Naji , Brunelle Serge , Thomassin Jeanne , Gravis Gwenaelle 
Published: February 2017

510 Background: Metastatic renal cell carcinoma (RCC) is still associated with a poor prognosis with an overall survival (OS) of 37 months, although some patients are long survivors despite a disseminated disease. The purpose of this study was to determine whether the presence of at least one glandular metastasis (GM), defined by metastasis in pancreas, thyroid, breast or adrenal contralateral, affect survival outcome in patients with metastatic clear cell RCC (cc-RCC). Methods: In this retrospective analysis, we included patients treated for GM and non GM (NGM) metastatic RCC at the Institut Paoli Calmettes (IPC), Marseille, France between January 2004 and May 2013. Two more centers provided data for GM cc-RCC. GM were authentified using CTscan and/or by histopathological analysis obtained at biopsy or at surgery. Patients were analyzed from the time of metastatic disease to last follow up or death. The purpose of this study was to analyze patients outcomes based on the presence or absence of GM. We analysed survival using a log rank test from the time of the diagnosis of GM to the death or last follow-up visit. Results: Among 180 patients analysed, 59 had GM. Median age 65.2 vs 61.8 years old, male 55% vs 72%, 90% vs 78% prior nephrectomy in GM and NGM group. GM sites were pancreas for 45.5%, adrenal 44.5%, thyroid: 10%, breast10%. GM was the only site of metastasis for 10% of pts. For GM group, 55.5% had histopathology proven RCC metastasis. The median follow up was 72 months and the median survival is 114 months (IC95% [62.9-NR.]) in GM group vs 33.2 months (IC95% [23-41.9]; p<0.0001, HR 2.7 [1.7-4.3]) in non GM group. Conclusions: This retrospective study in a rare metastatic localization finds a longer survival in patients with GM. Despite some obvious limitations, this study questions GM as a surrogate for a better prognosis in RCC. Prospective follow-up and the collection for biological and genomic markers are needed to confirm and extend our present findings.
Late onset of bone metastases as a prognostic parameter in metastatic renal cell cancer (mRCC): A single-center experience in 82 mRCC patients treated with sunitinib.
Authors: Ivanyi Philipp , Koenig Jasper , Trummer Arne , Reuter Christoph W. , Ganser Arnold , Grünwald Viktor 
Published: February 2017

523 Background: Bone metastasis (BM) is considered a negative prognostic marker in metastatic renal cell carcinoma (mRCC). Here, we address the impact of BM onset on overall survival (OS) in mRCC patients during targeted therapy. Methods: Patients with BM who received sunitinib (SU) as 1st targeted treatment at our center between May 2005 and December 2012 were included in this retrospective analyzes. Treatment was performed according to local standard and patients were followed for survival. Spine surgery, fracture or irradiation were considered skeletal related events (SRE). Results: Out of 128 mRCC patients with BM, 82 patients had SU as 1st line targeted agent. 57 (69.5%) patients suffered from BM at initial diagnosis of mRCC (=synchronous BM [sBM]), while 25 (30.5%) patients developed BM during treatment course (=metachronous BM [mBM]). Baseline characteristics showed different histological gradings for sBM compared to mBM patients (p=0.029) and higher frequency of ≥3 metastatic organ sites prior to SU for sBM patients (sBM: n=40 [70.2%] vs. mBM: n=10 [40%], p=0.016). In Kaplan-Meier analysis, sBM patients showed a reduced mean OS from SU start (sBM 23.5 [95%CI:18.6-28.3] vs. mBM 41.3 [95%CI:31.7-50.9] month, p=0.001), whereas PFS during SU treatment was similar (sBM: 8.1 [95%CI:3.9-12.3] vs. mBM: 8.7 [95CI:2.7-14.8] months, p=0.93). Bisphosphonate treatment and SRE revealed no differences between subgroups (p=0.62), while spinal compression occurred in 6 patients with sBM, but none with mBM (p=0.153). 2nd-line targeted agents were less frequently administered in sBM patients (sBM n=17 vs. mBM: n=10). Multivariate Cox-regression confirmed MSKCC score (OR: 2.6 [95%CI:0.99-7.28], p=0.052), liver metastases (OR: 2.66 [95%CI:1.28-5.51], p=0.009], and sBM [OR: 2.45 [95%CI:1.19-5.08], p=0.016) as independent prognostic parameters for reduced OS after SU start. Conclusions: In our cohort, OS in patients with sBM was significantly reduced compared to mBM patients, despite similar PFS with SU and SRE rate. Despite the lower incidence of subsequent therapies in sBM, a more aggressive biology is likely to be the cause of these findings.
The degree of preoperative hydronephrosis to predict pathologic features and oncologic outcomes in high-grade upper tract urothelial carcinoma.
Authors: Darwish Oussama M. , Krabbe Laura-Maria , Chung Paul H. , Westerman Mary Elizabeth , Bagrodia Aditya , Gayed Bishoy A. , Haddad Ahmed Q , Kapur Payal , Sagalowsky Arthur I. , Lotan Yair , Margulis Vitaly 
Published: February 2017

525 Background: There have been multiple reports implicating the role of hydronephrosis (HN) as a predictor of outcome in patients diagnosed with upper tract urothelial carcinoma (UTUC). However, this was done in mixed populations (low-/high-grade) and degree of HN (DOH) was not taken into account. We evaluated the impact of severity of hydronephrosis on systemic and bladder relapse in patients with UTUC. Methods: We retrospectively reviewed the records of 141 patients with localized UTUC that underwent extirpative surgery. Preoperative imaging was used to evaluate ipsilateral DOH. We analyzed the association between DOH (none/mild vs. moderate/severe), pathological findings and oncological outcomes in high-grade vs. low-grade patients. Bladder recurrence was assessed separately from local or systemic (L/S) recurrence. Results: High-grade UTUC was present in 80% of patients, 35% had muscle-invasive disease (≥pT2), and 29% had non-organ-confined disease. At a median follow-up of 34 months (range, 1-149), 35% of patients experienced intravesical recurrence, 20% developed L/S recurrence, and 17% died of UTUC. No difference in outcomes was seen between patients without HN and mild HN. DOH was none/mild in 55% and moderate/severe in 45% of cases. In patients with high-grade UTUC, moderate/severe HN was associated with advanced pathologic stage (p<0.001) and positive lymph node status (p=0.01). On Kaplan-Meier analysis, DOH was a predictor of L/S recurrence-free survival (RFS) (HR 5.5, p=0.019) and cancer-specific survival (CSS) (HR 5.2, p=0.022) but not intravesical recurrence. On multivariable analysis with preoperatively known factors controlling for grade and tumor location, DOH was independently associated with L/S RFS (HR 2.8, p=0.016) and CSS (HR 2.5, p=0.044). Conclusions: Moderate/severe HN was associated with features of advanced disease and predicted worse oncological outcomes in patients with high-grade UTUC. Since preoperative imaging is a routinely available diagnostic tool, this can serve as a surrogate parameter for advanced disease and can help to counsel patients towards preoperative chemotherapy and radical surgery.
Outcomes of patients with metastatic renal cell carcinoma and bone metastases in the targeted-therapy era.
Authors: Kalra Sarathi , Verma Jonathan , Atkinson Bradley J. , Matin Surena F. , Wood Christopher G. , Karam Jose A. , Tamboli Pheroze , Sircar Kanishka , Rao Priya , Corn Paul Gettys , Tannir Nizar M. , Jonasch Eric 
Published: February 2017

528 Background: Bone metastases (BM) occur commonly in patients with metastatic renal cell carcinoma (mRCC). Tyrosine kinase inhibitors (TKIs) have improved outcomes for patients with mRCC. Data on outcomes of mRCC patients with BM treated with TKIs are limited, but suggest a worse outcome compared to non-BM groups. Herein, we describe outcomes of patients with BM treated with TKI therapy, and compare to outcomes in a pre-TKI control group. Methods: Retrospective review of patients with mRCC in the intervals of 2002-2003 and 2006-2007 was performed using the institutional tumor registry. Patient characteristics including demographics, laboratory data, and outcomes were analyzed. Overall survival (OS) was estimated using Kaplan-Meier methods. Predictors of OS were analyzed using Cox regression. Results: 375 patients were reviewed; 187 patients (50%) started treatment with TKIs and 188 patients (50%) started treatment in pre-TKI era. Distribution of patient characteristics was similar. Organ metastases were equally distributed, including BM in 48% of patients in each cohort. Median OS of patient treated with TKI therapy was 22 mo (95% CI: 17-25) compared to 14 mo (95% CI: 10-19; p<0.01) for historical controls. Subset analysis of patients with BM treated with TKI therapy demonstrated a median OS of 24 mo (95% CI: 17-28) compared to 18 mo (95% CI: 10-21; p<0.01), in non TKI treated group. Predictors of shorter OS were higher MSKCC score; liver, lung, and brain metastases; and multiple sites of BM (HR 1.38; 95% CI: 1.02-1.91; p=0.04). Rate of new BM development was the same in the pre-versus-post TKI era. Conclusions: Median survival of patients with BM appears to be slightly longer than the median, irrespective of systemic therapy received. Rate of BM development was the same in the pre-versus post-TKI era. The slightly prolonged OS with BM contradicts published data. The management of bone metastases in mRCC remains a challenge. [Table: see text]
Retrospective study assessing the association of single nucleotide polymorphisms in VEGFR3 and on-target toxicity in patients with advanced renal-cell carcinoma (RCC) treated with sunitinib.
Authors: Rodriguez-Moreno Jf. , Esteban Emilio , Leandro-García Luis Javier , Castellano Daniel E. , Gonzalez del Alba Aranzazu , Climent Miguel Angel , Arranz Jose Angel , Gallardo Enrique , Puente Javier , Bellmunt Joaquim , Mellado Begoña , Martínez Esther , Moreno Fernando , Font Albert , Robledo Mercedes , Polo Susana Hernando , García-Donas Jesús , Rodriguez-Antona Cristina 
Published: February 2017

537 Background: Sunitinib is a tyrosine kinase inhibitor approved as first line therapy of RCC. Some Adverse Events (AEs) of sunitinib are due to its inhibition of VEGFR and could be considered as “on-target” toxicity. They are a class-effects and have been observed even with the most selective antiangiogenic drugs. We aimed to correlate such secondary effects with germline SNPs in VEGFR3. Methods: In order to define “on target ” toxicity we considered any AEs ≥ Grade II (CTCAE 4.0) recorded in more than 10% of the patients included the pivotal studies of axitinib and tivozanib (the most selective tyrosin kinase inhibitors targeting VEGF(R). We assessed associations between polymorphisms in VEGFR3 and on-target toxicity for patients with advanced RCC treated with sunitinib prospectively included in the SUTRENT Study. Results: Polymorphisms in VEGFR3 are associated with less on-target toxicity. Probably these genetic changes confer a reduced susceptibility to the action of sunitinib. This could explain, at least partially, the worse outcome showed in this population. Conclusions: Polymorphisms in VEGFR3 are associated with less on-target toxicity. Probably these genetic changes confer a reduced susceptibility to the action of sunitinib. This could explain, at least partially, the worse outcome showed in this population.
Axitinib: Common questions related to real-world use of a new treatment option in advanced renal cell carcinoma.
Authors: Borst Diane Lorraine , Arruda Lillian Shahied , MacLean Elizabeth A. , Pithavala Yazdi K. , Morgado James E. , Sharma Nikhil 
Published: February 2017

538 Background: Axitinib is a next generation VEGFR inhibitor approved in the US in Jan 2012 for advanced RCC after failure of one prior systemic therapy. Post approval questions may arise in the medical community regarding clinical scenarios which may not have been addressed in the clinical trials. We present the most common inquiries for axitinib submitted to Pfizer US Medical Information (MI) during the first 18 months post FDA approval and review available information that addresses these questions. Methods: MI inquiries were analyzed during the 6-mo period immediately post FDA approval and a second 6-mo period approximately 1 yr later. To gain insight into real-world dosing patterns, de-identified prescription data from Feb 2012-July 2013 obtained from the 21 specialty pharmacies (SP) in the US that distribute axitinib (Inlyta) were analyzed. Algorithms were developed to define dose modifications using dosage strengths dispensed and time between prescription fills over 2 day and 14 day windows. Results: The most frequent inquiries (>5%) common to both time periods included use in patients (pts) who were unable to swallow medication, use in patients with renal impairment (RI), and general dosage and administration questions. A method for preparation of an axitinib oral suspension for NG tube administration was developed for use in pts unable to swallow axitinib tablets. No dose adjustments are recommended for pts with RI; however axitinib should be used with caution in pts with end stage renal disease. The most common dose dispensed, using a 2 day window, was 5 mg bid, comprising 9659 (70%) of all dispensed prescriptions, with 789 (6%) at the 10 mg bid dose. An assessment of the most recent 7 months in the evaluation period shows that 16% and 19% of prescriptions were for doses >5 mg bid or <5 mg bid, respectively. Similar findings were observed using a 14 day window. Conclusions: Axitinib questions in the medical community revolve primarily around use in specific populations and dosing. Analysis of SP data revealed that dose modifications occurred at a lower frequency than observed in clinical trials. Further analysis is needed to understand outcomes associated with the dose modifications made in these patients.