bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carcinomas of the renal medulla: A comprehensive genomic profiling (CGP) study.
Authors: Bratslavsky Gennady , Jacob Joseph M , Shapiro Oleg , Elvin Julia Andrea , Vergilio Jo-Anne , Suh James , Ramkissoon Shakti , Ali Siraj Mahamed , Schrock Alexa Betzig , Miller Vincent A. , Stephens Philip J. , Gay Laurie M. , Bourboulia Dimitra , Mollapour Mehdi , Ross Jeffrey S. 
Published: February 2018

640 Background: Collecting duct carcinoma (CDC) and renal medullary carcinoma (RMC) represent rare tumors that arise in the renal medulla are therapy resistant tumors that progress rapidly. Methods: DNA was extracted from 40 microns of FFPE specimen from refractory CDC (46 cases) and RMC (24 cases). CGPwas performed using a hybrid-capture, adaptor ligation based next generation sequencing assayto a mean coverage depth of > 800X. Tumor mutational burden (TMB) was calculated from a minimum of 1.11 Mb of sequenced DNA as previously described and reported as mutations/Mb. Microsatellite instability status (MSI) was determined on 114 loci. Results: All CDC patients were older and more frequently male (Table). Sickle cell trait was identified in both CDC and RMC, but far more frequently associated with RMC. All (100%) of CDC and RMC were clinically advanced Stage III and IV tumors with the primary tumor used for CGP in 70% of cases and a metastasis biopsy was sequenced in 30%. All (100%) CDC and RMC were intermediate (Grade 3) or high grade (Grade 4). In both tumor types, the GA/tumor was relatively low and there were no (0%) VHL GA. SMARCB1 GA were significantly more frequent in RMC than CDC but common in both tumors. Targeted therapies for kinase ( EGFR, RET) and MTOR ( NF2, TSC2) pathways were more frequent in CDC than RMC. At 1.8 mut/Mb, the median TMB was low for both tumor types with no (0%) of cases showing≥20 mut/Mb. No (0%) of the CDC or RMC cases featured MSI-high status. Conclusions: In addition to their histologic differences, the frequencies and types of GA seen in CDC differ significantly from that seen in RMC. The opportunities for biomarker driven targeted therapies for bothCDCand RMC appear limited with rare opportunities to target GA in TKGFR and MTOR pathways for CDC. Similarly, the relatively low TMB and absence of MSI-High status in CDC and RMCalso predicts that these tumors may be resistant to immunotherapies.[Table: see text]
Patients perspectives on adjuvant therapy in renal cell carcinoma.
Authors: Battle Dena , Jonasch Eric , Hammers Hans J. , Derweesh Ithaar , George Daniel J. , Bex Axel , Ljungberg Borje , Staehler Michael D. 
Published: February 2018

644 Background: At this point in time, there is no approved adjuvant therapy (AT) for renal cell carcinoma (RCC) . The discussion on AT is driven by the pending maturation of overall survival (OS) data for sunitinib in patients at high risk for recurrence. Data on patient´s perception of AT are missing. The purpose of this study was to assess the value of specific adjuvant outcome measures to patients with RCC. Methods: We conducted a survey-monkey survey in n=450 patients with RCC on the perspective on AT. The survey was promoted via kccure.org, facebook and smartpatients.com. Question were not related to specific results of adjuvant trials but asking only about the attitude towards AT as an intervention. Results: Median age was 55.6 years (17-82 years) and 56.4% of the patients were female. 73.6% of the patients underwent nephrectomy as primary therapy, while 22.0% had a partial nephrectomy. 76.4% of the patients had clear cell RCC. 39.1% had recurrence of RCC and 35.3% were receiving systemic therapy for metastatic RCC. 63.1% of patients would use AT if it prolonged OS, followed by 60.1% if AT prolonged disease free survival (DFS), 42.7% if AT demonstrated acceptable toxicity, and 36.7% if guaranteed insurance coverage and efficacy. Experience with systemic therapy was correlated with a wish for a prolonged OS (p<0.0001). Patients with a history of systemic therapy rely on the physician’s recommendation in contrast to patients without a history of systemic therapy (p<0.0001). The recurrence status, age, initial stage and type of surgery had no influence on the patients´ decisions. 28.0% of the patients would need more information prior to their decision, 24.2% would only take AT with a proven OS benefit, 16.9% would use AT if there was moderate toxicity, 13.6% would use AT independent of the associated toxicity level, 8.2% would only use AT without any toxicity. 3.8% of the patients would not use AT. Patients on systemic therapy had a significant higher acceptance of toxicity (p<0.0001). Conclusions: Patients are willing to use AT to achieve OS and DFS benefits, and place lower emphasis on toxicity. These data provide an important perspective on patient perceptions of AT, and emphasize the need for patient education on harms and benefits of AT.
Evaluating neutrophil/lymphocyte ratio as a predictor of 30-day high-grade complications following renal surgery.
Authors: Nasseri Ryan , Bindayi Ahmet , Yim Kendrick , Ryan Stephen , Reddy Madhumitha , Ballon-Landa Eric , Yee Addison , Wan Fang , Proudfoot James , Derweesh Ithaar 
Published: February 2018

659 Background: Radical nephrectomy (RN) and partial nephrectomy (PN) for patients with renal cortical masses may carry significant risk for postoperative complications. We analyzed patient demographics and serum laboratories and morphometric measures to determine predictors of 30-day complications following RN and PN. Methods: Single institution retrospective analysis of RNs and PNs between 7/2008-4/2017. Demographic and clinical characteristics, serum laboratories, and RENAL nephrometry score were recorded. 30-day complications were graded according to the modified Clavien classification system. Primary purpose was to identify predictive factors associated with 30-day complications overall. Secondary purposes included identification of predictive factors high-grade complications (HGC; Clavien ≥3) overall and in the PN group. Factors were screened with logistic regression analysis. Results: 814 patients were analyzed (460 PN, 354 RN). 190 (23%) patients experienced 30-day complications, 107/460 (23%) PN and 83/354 (24%) RN (p = 0.951). Albumin level ≤3.5 mg/dL was predictive of overall complications (OR = 4.803, p = .008), while minimally invasive surgery (MIS) was negatively associated (OR 0.444, p < .001). Overall, 76 (9.3%) HGCs occurred, 52/460 (11%) in PN and 24/354 (6.8%) in RN (p = .028). Preoperative Neutrophil-Lymphocyte Ratio (NLR) of ≥2.78 (OR 3.216, p = .016) was a predictor of HGCs overall. MIS was negatively associated with HGCs (OR 0.444, p > .001). In the PN group only MIS was negatively associated with overall complications (OR 0.323, p < .001) and HGCs (OR 0.259, p < .001). Conclusions: While decreased serum albumin was predictive of overall complications in patients undergoing PN and RN, elevated preoperative NLR is a novel predictor for HGC. Use of serum markers may be incorporated in preoperative risk stratification counseling and nomograms.
A FavorAx study of axitinib in favorable risk patients with metastatic renal cell carcinoma.
Authors: Tsimafeyeu Ilya , Borisov Pavel , Abdelgafur Ahmed , Leonenkov Roman , Novikova Olga , Guseva Irina , Demchenkova Marina , Mikhailova Nadezhda , Semenov Andrey , Yurmazov Zakhar , Sivunova Irina , Ramazanova Madina , Gamayunov Sergey , Kosov Dmitry 
Published: February 2018

666 Background: Targeted therapy with axitinib resulted in a greater objective response rate and prolonged progression-free survival (PFS) compared to sorafenib in patients with previously treated metastatic renal cell carcinoma (mRCC) in AXIS study. 75% of patients had intermediate and poor IMDC prognosis. In this phase 2 study, we assessed the activity of axitinib in mRCC patients with favourable risk and a history of prior VEGFR-directed therapy. Methods: Patients were required to have clear cell mRCC, favourable risk according to IMDC criteria, and to have received first-line treatment with sunitinib or pazopanib. Prior treatment with other agents was not permitted. The primary endpoint of the study was PFS. Additional endpoints included response rate, safety, and overall survival (OS). Results: A total of 21 patients were enrolled, 62% of whom were male. Median age was 59 years. 11 (52%) patients had 2 and more metastatic sites. 67% and 33% of patients received first-line sunitinib or pazopanib with a median PFS of 17 months (95% CI 14-20). After a median follow-up of 16 months, the median PFS and OS was not yet reached. The current study did achieve its primary endpoint based on the 10-month PFS of 71.4%. 3 (14.3%) patients had confirmed partial responses and 14 (66.7%) had stable disease. No grade 3/4 treatment-related adverse events were observed; the most frequent grade 1/2 treatment-related adverse events were hypertension (57.1%), fatigue (57.1%), GI (33%) and skin (19%) toxicity. 7 patients had dose-escalation of axitinib and 1 patient had dose reduction. Conclusions: The encouraging PFS and favorable safety profile observed in FavorAx study support the administration of axitinib in mRCC patients with favourable IMDC risk and a history of prior sunitinib or pazopanib. Clinical trial information: NCT02700568.
Assessing the quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST) in immuno-oncology (I/O): An application to nivolumab vs. everolimus in previously treated advanced renal cell carcinoma (aRCC).
Authors: Shah Ruchit , Botteman Marc , Solem Caitlyn , Luo Linlin , Doan Justin , Cella David , Motzer Robert J. 
Published: February 2018

669 Background: Traditional progression definitions based on the RECIST 1.1 criteria may lead to a premature declaration of progression due to tumor flare or pseudo-progression effects associated with I/O drugs, especially among patients with solid tumors (such as RCC). This analysis compared the Q-TWiST between nivolumab and everolimus, using both traditional and novel I/O-relevant definitions of progression. Methods: Using Checkmate 025 data at ≤45 months (m) of follow up, overall survival (OS) was partitioned into 3 health states: TWiST (time without symptoms of disease progression or toxicity), TOX (time with grade ≥3 toxicity after randomization but before progression), and REL (time after progression). The following REL definitions were considered to declare progression: 1) RECIST 1.1 criteria (i.e., traditional Q-TWiST); 2) increase in tumor burden of ≥25% from nadir; 3) treatment discontinuation; 4) ≥2-point reduction from baseline in Functional Assessment of Cancer Therapy-Kidney Cancer Index-Diseases related Symptoms (FKSI-DRS) score; and 5) any combination of ≥2 out of 3 criteria (traditional progression, treatment discontinuation, FKSI-DRS reduction of ≥2-points from baseline). Mean Q-TWiST was calculated by weighting the restricted mean time spent in each health state by a utility of 1.0 for TWiST and 0.5 for TOX and REL. Relative Q-TWiST gain (Q-TWIST difference divided by mean everolimus OS) was calculated. Results: Compared to everolimus, nivolumab patients had statistically significant improvements in Q-TWiST based on all definitions: 1) traditional Q-TWiST: 3.3 m (relative gain:14.4%); 2) 3.5 m (relative gain: 15.3%); 3) 4.3 m (relative gain: 18.7%), 4) 4.8 m (relative gain: 20.9%); and 5) 4.8 m (relative gain: 20.9%). Conclusions: Regardless of progression definition, nivolumab resulted in a statistically significant and clinically important gain in quality adjusted OS vs. everolimus. These gains were greater when using progression definitions that incorporate more I/O-relevant response definitions and/or treatment discontinuation information. Clinical trial information: NCT01668784.
The impact of prostate cancer diagnosis on the quality of life at 3 years: A case control study.
Authors: Menegaux Florence , Rebillard Xavier , Bouvet Sophie , Castelli Christel , Houede Nadine 
Published: February 2018

67 Background: Prostate cancer (PCa) is the most common cancer in men. Former studies showed a time-dependent worsening of sexual or urinary long term side effects following surgery or radiotherapy that affected patients’ quality of life (QoL). These studies could not discriminate between age-related and treatment-related symptoms, as patients were their own controls. We conducted a case-control study evaluating at 3 years QoL and physical/psychological dysfunctions, whereas patients were on watchful waiting or received a treatment. Methods: We used data from the EPICAP population-based case-control carried out by INSERM and including 1700 participants. Eligible cases were men < 75 years old newly diagnosed with PCa in 2012-2014 living in the Hérault geographic area. Controls were men of the same age recruited in the general population of the same area. Participants answered a QoL questionnaire 3 years after intervention. Primary objective was to compare the impact of diagnosis or/and treatments on QoL as measured by the EORTC QLQ-C30 score. Secondary objective was to compare the impact of diagnosis or/and treatments on urinary dysfunctions (IPSS, ICS), sexual dysfunctions (IEEF-5), anxiety (HADS), and occupational integration. We also assessed these QoL parameters depending on the treatment that was received. Results: Median age was 67.9 years old in the cases and 68.4 years old in the control. At 3 years, 376 cases and 352 controls had sent back their questionnaires. Treatments were: RP (258), RT (90), focal therapy (52), hormone therapy (26) and watchful waiting (61) at the time of the study. The results show no difference between cases and controls for the global QoL score. Other parameters are being assessed and will be presented at the meeting. Conclusions: Though prostate cancer cases and population-based controls showed similar global QoL at 3 years after diagnosis, the large EPICAP study will provide a comprehensive framework to go further in the understanding of PCa sequelae and give some hints on the balance between benefit and risk of PSA testing. This study will be the first to evaluate the different types of sequelae as a function of treatments and the occupational integration for patients < 65 years old.
The role of the blood platelet-lymphocyte ratio, neutrophil–lymphocyte ratio and platelets in prognosis of metastatic renal cell carcinoma (mRCC).
Authors: Huszno Joanna , Kolosza Zofia 
Published: February 2018

670 Background: Renal cell carcinoma (RCC) accounts for 2–3% of all malignant diseases in adults. In some studies, neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR) and PLT have been demonstrated to be closely related to poor prognosis of patients with RCC. The objective of this study was to evaluate the blood platelet-lymphocyte ratio (PLR), neutrophil–lymphocyte ratio (NLR) and platelets (PLT) for its prognostic value in patients with metastatic renal cell cancer (mRCC). Methods: We retrospectively reviewed 141 (49 women and 92 men) patients diagnosed with mRCC previously treated with tyrosine kinase inhibitors from MSC Memorial Cancer and Institute of Oncology, Gliwice Branch in years 2006 - 2016. We assessed the prognostic value (overall survival and progression free survival) of pretreatment PLR, NLR and PLT based on univariate analysis. The cut-off value of NLR was ‘elevated’ as > 3.68 and PLR cut-off value was ‘elevated’ as > 144.4. Results: Median time of overall survival (OS) and progression free survival (PFS) were 34.1 months (from 1 to 109 months) and 8.3 months (from 0.4 to 109 months), respectively. The median PFS was shorter in NLR > 3.68 in comparison to NLR < = 3.68 (11.5 vs. 3.6 months, HR = 2.69; 95%CI, 1.76 to 4.12). Similarly, the median OS was lower in NLR > 3.68 (7.8 vs. 36.1 months, p = 0.00003; HR = 3.39; 95%CI, 2.09 to 5.50). The median PFS was shorter in PLR > 144.4 in comparison to PLR < = 144.4 (5.7 vs. 17.6 months; p = 0.00001; HR = 2.62; 95%CI, 1.76 to 3.90). Similarly, OS was worse for PLR > 144.4 (16.6 vs. 71.2 months; p = 0.00001; HR = 3.31; 95%CI, 1.98 to 5.52). Higher value of PLT ( > 400 G/l) was associated with shorter OS median (7.2 vs. 35.3 months; p = 0.001) than standard level of PLT (150-400G/l). Similarly, patients with higher neutrophil level had shorter OS (8.0 vs. 36.1 months, p = 0.0001) and PFS (3.6 vs. 11.5 months, p = 0.0001). Conclusions: Elevated pre-treatment NLR ( > 3.68) and PLR ( > 144.4) are associated with shorter OS and PFS in patients with mRCC treated with kinase inhibitors independently of other prognostic factors. Higher level of PLT ( > 400 G/l) and higher level of neutrophil ( > 6.0 x 103/ul) were also negative prognostic factors.
Survival following upfront cytoreductive nephrectomy versus targeted therapy for metastatic renal cell carcinoma.
Authors: Bhindi Bimal , Habermann Elizabeth Butzer , Mason Ross , Costello Brian Addis , Pagliaro Lance C. , Thompson Robert Houston , Leibovich Bradley C. , Boorjian Stephen A. 
Published: February 2018

672 Background: The optimal sequence of cytoreductive nephrectomy (CN) and targeted therapy (TT) for patients with metastatic renal cell carcinoma (mRCC) remains to be established. Herein, we compared overall survival (OS) between patients with mRCC receiving initial CN with or without subsequent TT versus initial TT with or without subsequent CN. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed between 2006-2013 with RCC that was metastatic at diagnosis who received CN, TT, or both. Those with other prior cancer history were excluded. The cumulative incidence of receiving TT after CN and CN after TT were evaluated, with death prior to second treatment as a competing risk. To account for treatment selection bias, inverse probability of treatment weighting (IPTW) was performed based on the propensity to receive initial CN or TT. OS from diagnosis was compared using Cox regression. Sensitivity analyses were performed. Results: The cohort included 15,068 patients, of whom 6,731 underwent initial CN and 8,337 underwent initial TT. At 6 months from diagnosis, the probability of receiving TT after CN was 46.2%, with 13.6% of patients having died after initial CN prior to receiving TT. Meanwhile, the probability at 6 months of undergoing CN after initial TT was 4.4%, with 38.3% of this group having died prior to undergoing CN. In the IPTW analysis, baseline characteristics were balanced (standardized difference < 0.1). Initial CN was associated with improved OS compared to initial TT (median 16.5 vs 9.2 months; HR 0.62; 95%CI 0.61-0.64; p < 0.001). Findings were similar in all sensitivity analyses (propensity score matching and adjustment; regression adjustment; 6-month landmark analysis; clear cell mRCC subset; exclusion of patients who had metastasectomy). Conclusions: Although initial CN was associated improved OS versus initial TT in this national dataset, initial CN was associated with delays in, and even death prior to, receipt of TT. As such, while the survival data here support initial CN in appropriate surgical candidates, continued efforts to develop the optimal multimodal approach to these patients are warranted.
Dietary acrylamide intake and risk of renal cell carcinoma in two large prospective cohorts.
Authors: Graff Rebecca E. , Cho Eunyoung , Preston Mark A , Sanchez Alejandro , Mucci Lorelei A. , Wilson Kathryn M. 
Published: February 2018

677 Background: Acrylamide, which has been classified as a probable human carcinogen, is formed during the processing and cooking of many commonly consumed, carbohydrate-rich foods. Accumulating evidence suggests that dietary intake of acrylamide intake is not associated with the risk of most cancers in humans. A meta-analysis of five epidemiological studies, however, found a suggestion of an increased risk of kidney cancer with higher acrylamide intakes. We investigated this association in two large, prospective cohorts. Methods: Acrylamide intake was calculated from food frequency questionnaires completed every four years in the Nurses’ Health Study (NHS; 1980-2014; n = 88,770) and the Health Professionals Follow-up Study (HPFS; 1986-2014; n = 47,802). Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association with renal cell carcinoma (RCC), adjusting for known and suspected risk factors. Results: We documented 569 incident cases of RCC during follow-up, 337 in women and 232 in men. There was no association between cumulative average acrylamide intake and risk of RCC risk in women (HR for top versus bottom quartile of intake: 0.85; 95% CI: 0.62-1.18; p-value for linear trend across quartiles: 0.42) or men (HR: 1.09; 95% CI: 0.77-1.55; p-trend: 0.96). Baseline acrylamide intake was also unassociated with RCC risk. Acrylamide intake was not associated with risk of fatal RCC, risk among never-smokers, or risk of clear cell RCC. Intake of foods and food groups that are the major contributors to acrylamide intake – breads, baked goods, breakfast cereal, potatoes, and coffee – were likewise not associated with risk of total or fatal RCC in women or in men. Conclusions: Dietary acrylamide was not associated with the risk of RCC in two long-term, prospective cohorts of women and men with updated measures of dietary intakes. This analysis of renal cell carcinoma adds to the body of evidence that dietary acrylamide is not an important risk factor for cancer in humans.
Sarcomatoid renal cell carcinoma: Does stage impact survival?
Authors: Blum Kyle A , DiNatale Renzo , Sanchez Alejandro , John Nirmal T , Axler Eden , Ghanaat Mazyar , Kashan Mahyar , Becerra Maria , Russo Paul , Coleman Jonathan , Tickoo Satish , Hakimi A. Ari 
Published: February 2018

693 Background: Sarcomatoid differentiation is associated with poor clinical outcomes and is present in approximately 4% of patients with renal cell carcinoma (sRCC). However, limited studies have evaluated the impact of sarcomatoid differentiation among patients, especially with lower stage pT1−2 disease. Methods: This study evaluated 3,850 patients with RCC who underwent partial or radical nephrectomy between 2000−2017. Patients were divided into four groups for analysis: pT1−2NxMx RCC without sarcomatoid features, pT1−2NxMx sRCC, pT3−4 RCC without sarcomatoid features and pT3−4 sRCC. Clinicopathological outcomes including sex, race, age, primary histology, lymph node involvement and margin status were compared between groups using Chi−squared and T-tests. Overall survival rates were analyzed by constructing Kaplan−Meier curves, p−values were calculated using log−rank tests and fitting Cox proportional hazards models for adjusted analyses. Results: Among 3,850 cases, 168 (4.4%) sRCC patients were identified. Of these, 33 (19.6%) were pT1−2. The mean overall follow up time was 59.9 months. When comparing CSS between groups, survival was poorer in patients with sarcomatoid features regardless of pT stage (p < 0.0001). Of note, CSS was worse in sRCC pT1−2 patients compared to non−sarcomatoid pT3−4 patients. Overall survival (OS) results were similar, with sarcomatoid tumors having worse estimates on survival analysis (p < 0.0001). Conclusions: Patients with pT1−2 sRCC demonstrated worse CSS when compared to pT1-2 and pT3−T4 RCC without sarcomatoid features, regardless of primary histology. Sarcomatoid differentiation in low−stage disease may be a marker of poor oncologic outcomes requiring more vigilant surveillance and possible inclusion in adjuvant therapy trials. Our next step, which is currently ongoing, is to pursue a multi−institutional collaborative effort and establish a larger cohort of sRCC for analysis.