bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular stratification of high-grade unclassified renal cell carcinoma to improve prognostication and management strategy.
Authors: Chen Yingbei , Di Natale Renzo G , Jayakumaran Gowtham , Ghanaat Mazyar , Marcon Julian , Brannon A. Rose , Al-Ahmadie Hikmat , Fine Samson , Gopalan Anuradha , Sirintrapun Sahussapont Joseph , Tickoo Satish , Arcila Maria E. , Motzer Robert J. , Hakimi A. Ari , Reuter Victor E. 
Published: March 2019

640 Background: Unclassified renal cell carcinoma (uRCC) constitutes a large portion of aggressive non-clear cell RCC with limited response to standard therapy. Clinicopathologic parameters or biomarkers to stratify this heterogeneous group of tumors are currently lacking. In a recently reported analysis of 62 high-grade primary uRCC [“discovery cohort (DC)”], we identified distinct molecular subsets. We aimed to validate this molecular schema in an independent clinical cohort and further delineate the clinicopathologic and molecular features that may refine prognostication and management. Methods: All cases was reviewed by experienced GU pathologists based on the current WHO criteria. Primary (n = 54) or metastatic (n = 21) tumor samples from 75 uRCC patients [“validation cohort (VC)”] were analyzed by a CLIA-approved targeted NGS platform for somatic alterations. 37 had germline testing results available. We performed integrative analysis of both VC and DC. Results: Somatic mutations found in VC were NF2 (24%), SETD2 (13%), SMARCB1 (9%), TP53 (9%), TSC1 (9%), FH (8%), TSC2 (5%), MTOR (5%), EP300 (5%), BAP1 (5%), PBRM1 (5%) and PIK3CA (5%), highly consistent with findings in DC. Germline alterations [ FH (11), SDHB (4), and SMARCB1 (1)] were detected in previously unsuspected patients. Integrative analysis supported the presence of NF2-loss (NF2), hyperactive mTOR-driven (MTOR), FH/SDH-deficient (FH/SDH), and chromatin/DNA damage response (Chrom/DDR) molecular subsets. Univariate analysis of combined DC and VC (n = 137, median f/u 26 mos, death 74%) showed a significantly higher risk associated with NF2 subset than the MTOR group (Table). Clonality analysis confirmed NF2 inactivating mutation as a main driver in the NF2 subset. Rare cases with alterations indicating sensitivity or resistance to immunotherapy were also identified. Conclusions: Molecular features of high-grade uRCC improve risk stratification and provide rationale for distinct management strategies. [Table: see text]
Influence of access on survival of renal cancer in a Brazilian center.
Authors: Leite Luciana de Moura , Dettino Aldo A. , Rinck José Augusto , Zequi Stenio Cassio , Loose Simone , Formiga Maria Nirvana Cruz 
Published: March 2019

644 Background: The introduction of tyrosine kinase inhibitors (TKI) and recently immunotherapy has brought major survival benefits for metastatic renal cancer (mRCC) patients (pts). In Brazil, there is no approved 2nd line treatment for mRCC in the Public Health System (PHS). Our center is unique, because it provides care for both PHS and Private System (PrS) population, enabling us to make the comparison of overall survival (OS) of these pts. Methods: We retrospectively reviewed medical records of all mRCC pts treated with 1st line TKI at our service from 2007 to 2018. Categorial variables were compared by Fisher’s exact test and continuous by Mann–Whitney. Survival was estimated by Kaplan-Maier method, prognostic factors adjusted by Cox regression model. Results: 171 pts were eligible, 37 (21.6%) PHS and 134 (78.4%) PrS pts. Between the two groups, there was no differences in age, gender, number and sites of metastasis (mets). PHS pts had worst ECOG (≥2, in 35.1 vs 13.5%, p .007), a trend towards more poor IMDC risk (IMDC favorable 16.2 vs 26.6%, intermediate 51.4 vs 57%, poor 32.4 vs 16.4%, p.09), had less nephrectomies (73 vs 92.5%, p.008) and more non clear cell histology (32.4 vs 12.7%, p.01). Median lines of therapy were 1 for PHS vs 2 for PrS pts (p.03). Sunitinib was the 1st line agent for 91.9 vs 67.2%, and pazopanib 8.1 vs 29.9%, of the PHS and PrS pts, respectively. Median time from diagnosis of mets to treatment start was 2.29 vs 1.79 m (p.59). Median OS was 16.5 vs 26.5 m (p.0002) and progression free survival, 8.4 vs 11 m (p.01), for the PHS vs PrS. On multivariate analysis, after adjusting for factors that were present before the beginning of treatment and were statistically significant for OS in the univariate model, PHS pts still had higher risk of death (HR 1.85, IC 95 1.2-2.9, p.01), probably due to having received fewer lines of therapy (≥2 lines of therapy vs 1, HR 0.51, IC95 0.4-0.7, p .001). Conclusions: Brazilian PHS pts had significant worse OS compared to PrS pts, in part due to less access to drugs. Access to cancer drugs is a challenge worldwide, and in Brazil effort has to be done to change this reality.
Prognostic and predictive role of comprehensive geriatric assessment (CGA) in elderly patients with metastatic renal cell cancer (RCC) treated with sunitinib (SUN) or pazopanib (PAZ): A single center experience.
Authors: Pierantoni Francesco , Basso Umberto , Maruzzo Marco , Brunello Antonella , Anile Giuseppe , Lettiero Annunziata , Tierno Giuseppina , Lamberti Evelina , Zagonel Vittorina 
Published: March 2019

647 Background: Few data are available concerning the prognostic and predictive role of CGA in elderly pts ≥70 years with metastatic RCC treated with either Sun or Paz. Materials and Methods: We retrospectively reviewed the charts of all elderly pts with advanced RCC treated at our Institute with either Sun or Paz, with at least 6 months follow-up after starting treatment. Every pt received at baseline a CGA and was classified as fit, vulnerable or frail according to Balducci’s Criteria. Results: We identified 73 pts who started therapy from January 2006 to March 2018, median age 76 years (range 70-89), 63% males; 42.5% fit and 57.5% unfit pts (38.3% vulnerable, 19.2% frail). Sun to Paz ratio was 40 to 33 pts with a median duration of treatment of 10.8 months; incidence of G1/2 toxicities was 85% vs 93.9% (p = 0.28), G3/4 was 37.5% vs 30.3% (p = 0.63), dose reduction was necessary in 77.5% vs 78.8% of pts (p = 0.9), respectively. Median PFS and OS with Sun or Paz were 13.6 vs 9.4 months (p = 0.152) and 27 vs 22.3 months (p = 0.641), respectively. CGA fit category predicted longer PFS (p = 0.039) and OS (p = 0.001) in the whole cohort. We found no significant differences between fit and unfit pts according to incidence of G1/2 adverse events, incidence of dose reduction or necessity to early suspend treatment due to toxicity, while the incidence of G3/4 events was lower in the fit subgroup (p = 0.026). Out of 67 pts progressing after first line therapy, 27 (40.3%) received a second line consisting in Nivolumab (22.4%), Everolimus (13.4%) and Sorafenib (4.5%), while 40 (59.7%) received only palliative treatments. CGA fit category significantly correlated with a higher chance of receiving a second line treatment (p = 0.004). Conclusions: In our retrospective single-center experience, CGA has a strong prognostic value in terms of OS and has the ability to discriminate pts at higher risk of experiencing G3/4 toxicities with Sun or Paz, with shorter PFS and lower chance of receiving a second line treatment. There were no striking differences in terms of toxicity rates between Sun or Paz, although different in type and possibly biased by patient selection.
Treatment disparities among patients in the National Cancer Database (NCDB) with clinical TIa and TIb renal masses.
Authors: Sterling Joshua , Rivera-Nunez Zorimar , Farber Nicholas , Modi Parth K. , Radadia Kushan Dilip , Kim Sinae , Sharad Goyal , Rahul Parikh , Weiss Robert E. , Kim Isaac , Elsamra Sammy , Jang Thomas , Singer Eric 
Published: March 2019

648 Background: AUA guidelines on the management of renal cell carcinoma (RCC) recommend prioritizing partial nephrectomy (PN) for the treatment of clinical T1a (cT1a) tumors, using PN for clinical T1b (cT1b) tumors when feasible, and performing minimally invasive surgery (MIS) when possible. Since cT1 RCC is a heterogeneous disease, we evaluated patterns of care in this population to examine factors associated with receipt of PN and MIS. Methods: We queried the NCDB from 2010-2014 to identify patients treated surgically for cT1N0M0 RCC. Patient socio-demographics, clinical characteristics, and treatment parameters were compared between cT1a and cT1b patients. Logistic regression models examined factors associated with receiving MIS. Results: Our population included 69,694 patients (44,043 cT1a and 25,651 cT1b). For cT1a tumors, 70% of patients received PN, while 30% received RN; 35% of patients underwent an open procedure and 65% underwent MIS. For cT1b tumors, 32% of patients received PN and 68% received RN; 38% of patients underwent an open operation and 62% underwent MIS. In both cohorts, African Americans and those earning <$62,000 were less likely to have MIS. Distance to treatment was not significant in cT1b patients, but cT1a patients who traveled >31 miles were more likely to undergo MIS. Patients treated at a community hospital were less likely to receive MIS compared to those treated at academic centers (cT1a OR: 0.48, 95% CI: 0.44-0.53 and cT1b OR: 0.63, 95% CI: 0.56-0.7). cT1a patients without private insurance were less likely to receive MIS (OR range: 0.58-0.93). However, only uninsured cT1b patients were less likely to undergo MIS (OR: 0.74, 95% CI: 0.64-0.86). Conclusions: PN occurred more frequently for cT1a (70%) vs. cT1b (32%) tumors. Most cT1 tumors received MIS; 35% of cT1a patients and 38% of cT1b patients underwent an open procedure, presenting an opportunity for improvement. cT1a and cT1b patients with lower household income, without private insurance, and those treated outside academic centers were less likely to receive MIS. Based on these findings additional research on the impact of regionalization of RCC surgery on utilization of PN vs. RN, receipt of MIS, and outcomes is warranted.
Patient perspectives on cytoreductive nephrectomy after CARMENA.
Authors: Battle Dena , George Daniel J. , Bex Axel , Staehler Michael D. 
Published: March 2019

658 Background: Conducted over eight years, enrolling 450 patients at multiple centers in Europe, the CARMENA (Cancer du Rein Metastatique Nephrectomie et Antiangiongeniques) trial demonstrated that systemic therapy using sunitinib alone is not worse than cytoreductive nephrectomy (CN) plus sunitinib in metastatic RCC in an intention to treat analysis (hazard ratio HR): 0.89, 95% confidence interval (CI), 0.71-1.10) (Mejean, NEJM, 2018). We wanted to assess patient views related to CN following the publication of these results. Methods: The Kidney Cancer Research Alliance (KCCure) conducted a survey among kidney cancer patients. The short survey was created via SurveyMonkey and was disseminated in various patient communities using social media and was posted to the KCCure website in June 2018 after the presentation of the CARMENA trial. Patients were asked “The CARMENA trial presented recently at ASCO found that for kidney cancer patients diagnosed with metastatic disease, there is no overall survival benefit of having a nephrectomy prior to starting systemic therapy. Knowing that information, would you still want to have a nephrectomy at diagnosis if you were metastatic?” Patients were also asked whether they had already had a nephrectomy and their stage at diagnosis, whether they were on systemic therapy, gender and age. Results: 186 patients responded with 60.5% being female. Median age 56.5 years (range 26-84). On the question of whether they would want CN. 75.2% of the patients indicated they would still prefer nephrectomy. Of the patients with primary metastatic disease and the tumor in place treated with systemic therapy, 20.1% wanted their kidney tumor to be removed. There was no statistically significant difference between patients who had experience with systemic therapy and those who hadn’t, answers were also consistent regardless of gender and age. Conclusions: Overall survival should not be overestimated as the most important aim in an end-stage patient population. Patients might think differently about benefits, risks and value of surgical procedures then physicians.
Associations of rurality and disease outcomes in urologic malignancies.
Authors: Abello Alejandro , Casilla-Lennon Marianne , Kenney Patrick Aloysius , Leapman Michael 
Published: March 2019

661 Background: Patients residing in rural regions have comparatively worse outcomes for many cancers. However there is less known about treatment and outcome for patients with urologic cancers. The objective of this study is to evaluate differences in treatments and outcomes among patients with urologic malignancies when coming from rural compared to metropolitan communities using national, population-level data. Methods: We queried the Surveillance, Epidemiology and End-Results database to identify patients with urological cancers from 1973 to 2015. We compiled patient clinical, demographic, and outcome data, including rurality at the county level. Rural counties is defined as those with > 50% population living in rural areas. We evaluated the association of rurality with treatment received and cancer-specific death using Cox proportional hazard models. Results: We identified 989,239 patients including those with Kidney (112,477) Bladder (208,230), Prostate (637,005), and Testis cancer (28,527). Among all, 898,050 (90.4%) were male and 64,992 (6.55%) lived in rural counties. Overall, rural patients were older at cancer diagnosis (mean 70 ± 12.1 vs 67.41 ± 12.7) and more frequently of white race (97.1% vs 82.46%) vs urban counterpart. Patients residing in rural counties were less likely to undergo definitive treatment with surgery for stage 1 or stage 2 disease P < 0.001). In multivariable regression, rural status was associated with greater risk of cancer-specific death in kidney cancer (HR: 1.1, 95% CI: 1.02-1.24; P: 0.03) but was not seen in other cancers. Based on % of rurality, adjusted kidney cancer-specific death increased among most rural populations: 15% rurality or more (HR: 1.16, 95% CI: 1.05-1.27; P: 0.03), 40% rurality or more (HR: 1.31, 95% CI: 1.15-1.49; P < 0.001) and 70% or more (HR: 1.32, 95% CI: 1.05-1.67; P: 0.01). Conclusions: There are notable differences in cancer incidence, treatment and outcome for patients residing in rural areas. Rural status was associated with poorer cancer-specific survival for kidney cancer but was not seen in other genitourinary malignancies, independent of stage at diagnosis and treatment received. Further research is warranted to understand the factors underlying these differences in outcome.
Tobacco as a possible prognostic factor in advanced renal cell carcinoma.
Authors: Solis-Hernandez Maria Pilar , Iglesias Clara , Revuelta Alfonso , Gonzalez Mendez Carmen , Juan Rodriguez Lucia , Quiñones Roces Teresa , Gonzalez Lolo Sara , del Río Fernández Jorge , Gómez David , Valcárcel González Sena , Fernandez Arrojo Sara , Alvarez-Fernandez Carlos , Villanueva Noemí , Faez Laura , Uriol Esther , Esteban Emilio 
Published: March 2019

665 Background: It is widely known the causal relationship establised between tobacco use and the development of renal cancer is widely known. Nevertheless, the impact of smoking on the efficacy and safety of anti-angiogenic drugs is unclear. Sunitinib is a tyrosine kinase inhibitor with proven efficacy metastatic renal cell carcinoma (mRCC). Methods: A retrospective analysis was carried out including 194 mRCC patients (pts) who received Sunitinib in a single Institution (Hospital Universitario Central de Asturias) with a high incidence of this disease. The aim of this study is to explore the impact of the smoking habit on treatment response in terms of progression‐free survival (PFS) and overall survival (OS). Results: Most patients presented clear cell histology (92%). Smoking status: 42% (n=82) never‐smoker, and 39% (n=76) former‐smoker and 19% (n=36) current‐smoker. Male predominance 78% (n=145). Median age was 65 (range: 40‐84). Survival analysis favors patients with a history of tobacco use. There was no significant difference in PFS between never‐smoker vs ever-smoker groups: median PFS 8.13 months (95% IC: 4.75‐11.52), vs 12 months (95% IC: 9.97‐14.03) was found respectively (p=0,086). Fewer than 10% developed grade 3 toxicity. A significative improvement in OS in patients ever-smokers: median OS 16.23 months (95% IC: 12.22‐20.25) vs 26.46 months (95% IC: 16.21‐36.73) (p=0.044). The advantage observed in patients with any smoking history became more evident for poor prognosis cases. A median OS 5.03 months (95% IC: 0.84‐9.23) vs 14.03 months (95% IC: 7.81‐20.26). A median PFS 6.4 months (95% IC: 2.53‐10.27) vs 13.33 months (95% IC: 1.14‐26.19) p > 0.05. Conclusions: In this series, tobacco seems to play a role on the efficacy and safety of anti‐angiogenic agents in mRCC. However, additional prospective studies in well‐balanced populations are required to confirm this data.
Effects of sunitinib and pazopanib on patients physical, social, and emotional function: Result of a prospective patients reported outcome tool.
Authors: Das Prantik , Ali Akram , Simmonds Karen , Mckenna Lesley 
Published: March 2019

667 Background: Sunitinib and pazopanib are are effective treatment options for metastatic Renal cell carcinoma (mRCC) and both may impair patient’s quality of life (QOL). There has been no direct comparison between these agents and their effect on these domains. Methods: A prospective study of mRCC patients who had received Sunitinib or Pazopanib as a first line treatment was conducted. A set of questionnaires has been developed in-house, influenced by existing recognised tools, such as EORTC-C 30 and PHQ-9, and is tailored to focus on relevant QoL issues patients face. This questionnaire named as Patient reported outcome tool. They primarily relate to physical, emotional and social functioning in the quality of life of patients. Each category has 4 questions. The questions are quite generic and allow patients to apply them to what’s important in their lives. Answers are on a scale of 0-10. The purpose of the questionnaire is to assess a balance of physical, cognitive and independence related aspects of their life over the course of their treatment. All patients are asked to complete the baseline questionnaire and then in every clinical visit. Results: Data were collected prospectively of metastatic RCC patients who had received Sunitinib or Pazopanib from May 2017 to Aug 2018. Total 45 patients were included, 23 received Pazopanib and 22 were on Sunitinib. There was a higher rate of significant worsening for the physical well-being subscale for Sunitinib versus Pazopanib. Patients on Sunitinib reported worsening tiredness, skin problems and sleep disturbance. Socially, patients on Sunitinib reported more closer to family, better interaction with friends and more motivated to go out. Problem with feeling sad, fear of death and anxiousness were more pronounced on Pazopanib arm. Conclusions: Our study suggested that there are marked differences between Sunitinib vs Pazopanib and their effects on patients physical, emotional and social wellbeing. Physical function was more influenced by sunitnib while pazopanib has more effect emotional wellbeing. Further studies are warranted to confirm these findings.
Sarcopenia is independently associated with decreased overall survival after surgery for inferior vena cava tumor thrombus patients.
Authors: Williams Milton , Nabavizadeh Reza , Khan Amir Ishaq , Patil Dattatraya H , Psutka Sarah P. , Sekhar Aarti , Ogan Kenneth , Bilen Mehmet Asim , Master Viraj A. 
Published: March 2019

674 Background: The presence of sarcopenia, a lean muscle mass deficiency is independently associated with inferior survival following the surgical treatment of localized renal cell carcinoma (RCC). This association has not yet been studied in more advanced disease such as patients with RCC and concomitant IVC thrombus tumors. In this study we retrospectively examined the association between preoperative sarcopenia and overall survival following definitive surgery for IVC tumor thrombus patients. Methods: Baseline lumbar skeletal muscle index (SMI) for patients who underwent surgical treatment for known IVC thrombus tumors between 2006 and 2018 by a single surgeon were quantified at the 3rd lumbar vertebra from preoperative computerized tomography (CT) or magnetic resonance imaging (MRI). The SMI thresholds used to define sarcopenia were developed using ROC analysis of our data and had the most significant relation to overall survival. Overall survival was compared between patients with and without sarcopenia using the Kaplan-Meier method as well as univariate and multivariate cox proportional hazards regression models. Results: The cohort consisted of 194 patients of whom 128 (65%) were male and 146 (75%) were non-Hispanic white. There were 143 (74%) clear cell renal cell carcinoma cases. 110 patients (57%) were sarcopenic. Patients with sarcopenia had significantly decreased overall survival, log-rank p=0.009 (Figure). The presence of sarcopenia was also associated with decreased overall survival in univariate analysis, (hazard ratio (HR)=1.80, 95% CI 1.15-2.83; p=0.010). In multivariable analysis controlled for age, number of comorbidities, and AJCC Stage, sarcopenia maintained significance as a predictor of decreased overall survival (HR= 1.66, 95% CI 1.05-2.61; p=0.030). Conclusions: Preoperative sarcopenia is independently associated with mortality in patients with IVC thrombus tumors.
The genomic landscape of metastatic clear cell renal cell carcinoma (ccRCC) after treatment with systemic therapy.
Authors: Van Der Mijn Johannes , Eng Kenneth , Fernandez Evan , Oromendia Clara , Zhang Tuo , Bareja Rohan , Ramazanoglu Sinan , Vosoughi Aram , Gudas. Lorraine J. , Elemento Olivier , Tagawa Scott T. , Faltas Bishoy Morris , Nanus David M. , Beltran Himisha , Mosquera Juan Miguel , Sboner Andrea , Molina Ana M. 
Published: March 2019

675 Background: The most frequent genomic alterations in patients (pts) with ccRCC have been identified in primary tumors. Here we investigated the genomic landscape of ccRCC in a cohort enriched for metastatic tumors after treatment with systemic therapy. Methods: We prospectively enrolled pts with ccRCC in a clinical study in which Whole-Exome Sequencing (WES) of normal and tumor tissue was performed. Clinical features, treatment outcome and survival were evaluated. Results: Forty-five pts with ccRCC with a median age of 65 years (range 38–86) were enrolled. According to the Heng risk criteria, 15 pts (33.3%) were classified as favorable-risk 23 pts (51.1%) were intermediate-risk and 7 pts (15.6%) were poor-risk. Pts received a median number of 3 lines (range 0–9) of therapy including cytokines (n=7), anti-VEGF (n=36), mTOR inhibitors (n=10) and/or immune checkpoint inhibitors (n=23). The median progression free survival (PFS) after treatment was 3.5 months (0.7-13.1), 11.1 months (1.1–54.2), 2.7 months (0.7-36.2) and 4.9 months (1.4–29.2) after cytokines, VEGF-, mTOR- and immune checkpoint inhibitors, respectively. The median overall survival (OS) from start of treatment to last follow up was 2.2 years (range 0.2–14.9 years). A total of 68 samples were sequenced. These included 9 (12.5%) primary tumors, 38 (55.9%) collected after treatment with anti-VEGF, 16 (23.5%) after mTOR- and 8 (11.8%) after immune checkpoint inhibitor. VHL, KDM5C, SETD2 and PBRM1 were the most frequent somatic mutations detected in this cohort. In two cases with a short and long response to VEGF targeted therapy (PFS 2.8 versus 50.3 months) rapid autopsies were performed which allowed multiregional (n=7, n=4) sampling. The multiregional sequencing in the rapid autopsy case with a prolonged response to VEGF targeted therapy revealed recurrent KDM5C mutations. Conclusions: We present the genomic landscape of metastatic ccRCC after treatment with systemic therapy. We report an increased frequency of KDM5C mutations, previously described to be associated with a favorable response to VEGF-inhibitors.