bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-institution analysis of ablations versus partial nephrectomies for small renal masses.
Authors: Sun Fionna , Dreyer Zachary , Moudgil Pranav , Studzinksi Diane , Vartanian Stephen 
Published: May 2020

e17074 Background: Renal cell carcinoma (RCC) has the highest mortality rate of the genitourinary cancers with detection rising annually for small ( < 4cm) renal masses (SRM). Nephron-sparing partial nephrectomy (PN) is recommended over other approaches such as ablations (Abl). This study aims to evaluate the outcomes and costs associated with treating patients with SRM RCC that undergo PN, laparoscopic cryoablation (lcryo), or various percutaneous ablations-cryoablation (pcryo), microwave (pmv), and radiofrequency (prf). Methods: A retrospective chart review of 295 patients that had either a PN or Abl from 2010-2019 at Beaumont Hospital- Royal Oak was performed. 189 patients with SRM were analyzed. Data collected included demographics, comorbidities, pathology, 30-day ED readmission, recurrence rate, and hospital-billed costs and charges. Data was analyzed using Mann-Whitney, chi-square, unpaired t-tests, Kruskal Wallis post-test, and Dunn’s multiple comparison test. Results: 133 patients with an index Abl (6 lcryo, 73 pcryo, 44 pmv, and 10 prf) and 56 patients with an index PN were analyzed. Mean tumor size for Abl (2.34cm; 90% biopsy-confirmed RCC) and PN (2.48cm; 87% histology confirmed RCC) was comparable. The populations undergoing PN or Abl were similar for both demographics and comorbidities except for age at index procedure (PN 58, Abl 71, p < 0.01). Length of stay (LOS) following index procedure differed with an avg PN LOS = 2.74 days and Abl LOS 0.52 (p < 0.01). 55% of PN patients presented to the ED within 30 days (38% readmitted) whereas only 8% of Abl patients did (42% readmitted)(p < 0.01). The recurrence rate for PN compared to Abl was 23% to 14%, respectively (p = 0.14), with an average follow-up time of 4.95 years for PN and 2.78 years for Abl (p < 0.01). Total hospital charge analysis showed PN being 1.57 the charge of all Abl types (p < 0.01) while cost analysis demonstrated PN being more costly than Abl as a whole by 2.79x (p < 0.01). When evaluating ablation subtypes, trends were noted lcryo being comparable to PN in both charge and cost while percutaneous interventions pmv, pcryo, and prf displayed lower charge and cost when compared to both PN and lcryo. Conclusions: With treatment decisions for SRM RCC are multifactorial, this single-site study demonstrated similar populations with comparable pathologies undergo both PN and Abl procedures. Complication and readmission rates differ between PN and Abl and consideration should be made for these variables as well as the costs associated with each procedure type when managing SRM RCC.
Data to decisions: The impact of online education on immunotherapy in advanced renal cell carcinoma.
Authors: Parikh Kinjal , Lucero Katie , Warren Charlotte , Van Laar Emily Sherene , Carothers Ann , Kadkhoda Haleh , Rini Brian I. 
Published: May 2020

e17076 Background: Cytokine therapy was initially the only immunotherapy for patients with advanced renal cell carcinoma (RCC). The advent of targeted therapies ushered in a new area of precision medicine in the treatment paradigm. Recently, immunotherapy in the form of immune checkpoint inhibitors has shown improved outcomes as compared to targeted therapies and has become a mainstay in treatment. As immunotherapy use moves into earlier stages of disease and combination therapies are explored, education remains essential to optimize patient outcomes. Through the partnership between Medscape Oncology and the Society for Immunotherapy of Cancer, educational activities were designed to increase the knowledge and competence among oncologists surrounding the role of immunotherapy in patients with advanced RCC and uncover remaining educational needs. Methods: The 2 educational activities included a 30-minute online, video discussion with 2 faculty presenters and synchronized slides and a text-based online activity with 2 patient cases and interactive questions. Educational effectiveness was assessed with repeated paired pre/post assessment where learners served as their own controls. The first activity launched September 19, 2018, the second activity launched December 19, 2018, and the data were collected and are reported through December 27, 2019. Results: A total of 9474 learners participated from September 2018-December 2019 including 1029 oncologists. Participation in education resulted in significant improvements for oncologist who answered all pre/post questions for an activity during the study period (n = 302). Improvements in knowledge and competency were observed in the following areas: Knowledge regarding the latest clinical trial data on the use of cancer immunotherapies for the treatment of RCC (49% vs. 74%, p < .001). Knowledge regarding the immune checkpoint inhibitor regimens on the care of patients with RCC (49% vs. 70%, p < .001). Competence related to choosing the most appropriate regimen for patients with mRCC across the continuum of care (54% vs. 76%, p < .001). Conclusions: Participation in online, video- and case-based CME-certified educational activities resulted in statistically significant gains in oncologist knowledge and competency surrounding the use of immunotherapy in advanced RCC. These results demonstrate the value and benefit of multi-modal and sequential activities on improving knowledge and competence outcomes for oncologists caring for patients with advanced renal cell carcinoma.
TCGA Kidney Cell Atlas: A differential gene expression database for the dissection of tumor-specific gene modules.
Authors: Alimohamed Saif , Geller James I. , Aronow Bruce 
Published: May 2020

e17078 Background: The Cancer Genome Atlas project has become a leading source for data that has allowed the identification of a broad range of human cancer tumor types and subtypes and has revealed deep complexity with respect to the differentiation, or lack thereof, among human cancers. In particular, differential gene expression analyses have revealed a wealth of active oncogenic pathways, underlying gene mutation drivers, discriminative markers, and candidate therapeutic targets. Despite its rich composition, several factors have led to it not attaining the utility it would seem to offer. Methods: To study this, we dissected molecular subtypes in the TCGA and used the Pan-Kidney (n = 1022 samples) Portion within it to determine where obstacles seem to limit its utility. We re-clustered the renal carcinomas to create more appropriate histology annotations for these samples. The molecular subtypes were then found through K-means using differentially expressed known developmental regulators per histological annotation. After deriving these new annotations, the histology and molecular subtypes were compared to one another via T-test to generate gene modules that characterize these classes/subclasses. Results: We identified a number of factors that include inconsistent metadata attributes, apparent misclassification of histological subtypes, and molecular subtypes that do not match with that obtained by focused approaches to rederive principle subclasses. Our gene modules showed a molecular subtype of clear cell renal carcinoma that was enriched for vascular development and nephron development. In general, the clear cell renal carcinoma and papillary renal cell carcinoma cohorts both showed significant co-expression with atlases that were enriched for genes involved in kidney development. Conclusions: Our atlas highlights the limitations of the current TCGA atlas and provides another tool to capture the rich insights from the TCGA repository through the efforts explained above, highlighted by its use in kidney carcinoma.
A non-interventional retrospective study to describe early clinical experience with cabozantinib in patients with advanced renal cell carcinoma (aRCC) in the United Kingdom.
Authors: Pillai Manon , Powles Thomas , Szabados Bernadett , Savage Philip , Fife Kate , Klair Bhupinder , Perrot Valérie , Michael Agnieszka , Venugopal Balaji 
Published: May 2020

e17089 Background: Cabozantinib is approved in the UK in treatment-naïve adults with intermediate or poor risk aRCC or following prior VEGF-targeted therapy. Here we describe treatment pathways and clinical outcomes of patients with aRCC who received cabozantinib early and later in the UK managed access program (MAP) as disease severity may differ in these patient populations. Methods: A non-interventional retrospective chart review study was carried out in six specialist centres in the UK to describe early clinical experience with cabozantinib in patients with aRCC (CERES, NCT03696407). Progression-free survival (PFS) and overall survival (OS) were calculated from cabozantinib initiation using the Kaplan-Meier method. Patients were grouped into those who initiated cabozantinib early (Aug 2016-Feb 2017) or late (Mar-Aug 2017) in the MAP. Results: Overall 100 patients were eligible; median (95%CI) PFS was 6.01 (5.16; 7.85) months and median OS was 10.84 (7.92; 16.85) months. Patients in the early MAP group received a mean (SD) of 2.2 (1.4) lines of prior therapy, most commonly sunitinib (n = 32, 56.1%) and pazopanib (n = 30, 52.6%). Patients in the late MAP group received a mean of 1.9 (SD 1.2) lines of prior therapy, most commonly pazopanib (n = 23, 53.5%) and sunitinib (n = 19, 44.2%). At least one post-cabozantinib therapy was prescribed in 44.6% (25/57) and 27.9% (12/43) of patients in the early and late groups, respectively, most commonly nivolumab (both groups). See table for characteristics and outcomes by MAP group. Conclusions: Cabozantinib was effective in this small, real-world study of patients receiving treatment as part of a MAP. The results are supportive of the data seen in the registrational study, METEOR. Patients enrolled early in the MAP were possibly more heavily pre-treated but overall outcomes were similar to those who enrolled later. [Table: see text]
Response to checkpoint inhibitors (CPI) in sarcomatoid renal cell carcinoma (sRCC).
Authors: Sheng Iris Yeong- Fung , Wei Wei , Desai Kunal , Allman Kimberly D. , Martin Allison , Wood Laura S. , Nehez Sarah , Taylor Susan , Gupta Shilpa , Gilligan Timothy D. , Ornstein Moshe Chaim 
Published: May 2020

e17095 Background: sRCC have a generally poor prognosis though recent clinical trial data suggest improved outcomes with CPI. We present a real-world experience of metastatic sRCC patients (pts) treated with a variety of CPI. Methods: Pts with sRCC treated with CPI Cleveland Clinic from 1/1/2015 to 12/31/2019 were identified. Overall survival (OS) was estimated using Kaplan-Meier and compared by log rank test. Results: Of 28 eligible pts identified with sRCC, median age 58, 82% Caucasian, all KPS score > 80%, 86% had IMDC intermediate/poor risk disease, 75% were clear cell, and 71% had prior nephrectomy. 46.4% had prior non-CPI systemic therapy. CPI therapy in this cohort included: 46% nivolumab monotherapy, 18% axitinib/pembrolizumab, 21% ipilimumab/nivolumab, 4% atezolizumab/bevacizumab, 7% atezolizumab, 4% carboplatin/pemetrexed/pembrolizumab. At a median follow up of 13.6 months (range 6.5-31.4), ORR was 36% (4% CR, 32% PR) and median OS was 13.8 months (95% CI: 9.23-NA). Median time to response was 3.2 months (range 2.4-13.1) and median duration of response was 8.1 months (range 0-25.5). Ten of the 13 patients started subsequent therapy due to progression. At the time of analysis, 39% were still alive and 25% of patients were still on initial I/O therapy (7+ -30+ months). There were no clear correlations between specific disease-related factors (including IMDC risk, time-to treatment of > or < 1 year, or prior systemic therapy) and response (all were p > 0.05). Conclusions: ORR and CR rates were lower in this real-world population of metastatic sRCC pts compared to clinical trial data, which should be a result of various CPI treatments and lines of treatment. However, these data highlight the heterogeneity of sRCC in general and need for additional investigations into impact of percentage of sarcomatoid features, genomic analyses, line of therapy, and CPI choice to optimize outcomes in sRCC pts.
Understanding the treatment effect modification of mono- or combination PD-1/PD-L1 inhibitor therapies on survival outcomes in patients with metastatic renal cell carcinoma: What does the literature say?
Authors: Sati Neha , Boyne Devon J , Brenner Darren , Arora Paul 
Published: May 2020

e17097 Background: PD-1/PD-L1 inhibitors are immune checkpoint inhibitors widely used in the treatment of metastatic renal cell carcinoma (mRCC) and other cancers. There is a lack of understanding regarding which factors predict response to these therapies. To address this gap, a systematic literature review and meta-analyses were conducted. The objectives of this study were to a) conduct a systematic literature review of studies examining factors that modify the clinical efficacy of PD-1 or PD-L1 inhibitors among patients diagnosed with mRCC and b) quantitatively synthesize the magnitude to which each predictive factor modifies the effect of PD-1/PD-L1 inhibitors. Methods: Electronic databases MEDLINE and COCHRANE were searched for studies published in English from 2006 onwards. We included all phase II/III randomized trials that provided subgroup analyses of any baseline characteristics regarding the effect of PD-1/PD-L1 inhibitors, alone or as part of a combination therapy, with respect to overall or progression-free survival among patients with mRCC. We developed a novel quantitative approach to synthesize subgroup findings across trials. The ratio of the subgroup-specific hazard ratios (HRs) from each study were pooled using a random effects meta-analysis whereby ratios of 1.00 would indicate that the subgroup-specific HRs were equal in magnitude. Results: From an initial 662 studies, five trials were judged to be eligible for inclusion. Meta-analyses suggested the treatment effect of PD-1/PD-L1 inhibitors in mRCC patients was modified by age (overall survival: ratio of HRage > 75 vs. HRage < 65= 1.51; 95% CI:1.01-2.26; I2= 0%, p= 0.04), PD-L1 expression (progression-free survival: ratio of HRPD-L1 > 10% vs. HRPD-L1 < 1%= 2.21; 95% CI:1.14-4.27; I2= 2.26%; p= 0.01), and sarcomatoid tumor presence (progression-free survival: HRno sarcomatoid differentiation vs. HRsarcomatoid differentiation= 1.54; 95% CI:1.07-2.21; I2= 0%; p= 0.02). Conclusions: Evidence suggests that older age, lower levels of PD-L1 expression, and absence of sarcomatoid tumour differentiation diminish the clinical efficacy of anti-PD-1/PD-L1 immunotherapies among mRCC patients.
Gender impact on renal cell carcinoma survival: A population-based analysis.
Authors: Baidoun Firas , Ruhban Inas A. , Saad Anas M , Gad Mohamed , Al-Husseini Muneer J. , Ornstein Moshe Chaim , Gupta Shilpa , Rini Brian I. 
Published: May 2020

e17099 Background: Prior evidence has suggested that females diagnosed with renal cell carcinoma (RCC) present at an earlier stage compared to males, but a survival difference between males and females has been controversial. We aimed to evaluate the impact of gender on RCC survival in the US. Methods: Data of RCC patients diagnosed between 1973 and 2015 in the US was obtained using Surveillance Epidemiology and End Results (SEER) database. We studied the overall and cancer-specific survival of patients diagnosed with RCC in the US according to gender using multivariable covariate-adjusted Cox models and Kaplan-Meier test. Results: We reviewed 155,430 RCC patients, of which 96,656 were males, and 58,774 were females. The median overall survival of female patients was 122 months and was significantly higher than male patients (98 months). Cancer-specific survival showed similar trends with females having significantly higher survival (p-value < 0.001). Adjusted for age, race, stage and grade of cancer, undergoing cancer-targeted surgery, and marital status, female sex was associated with improved overall and cancer-specific survival outcomes; HR = 0.829 (p-value < 0.001), and HR = 0.923 (p-value < 0.001), respectively. Conclusions: Females have a significantly better overall and cancer specific survival compared to males diagnosed with renal cell carcinoma. In previous studies this disparity was attributed to the lower grade and earlier stage of RCC presentation in females, but gender-based disparity persisted in this analysis after adjusting for patient baseline and tumor characteristics. This raises the question of the hormonal effects on the progression of RCC.
Circulating tumor DNA sequencing analysis of patients with metastatic renal cell carcinoma (mRCC).
Authors: Zengin Zeynep Busra , Dizman Nazli , Salgia Nicholas , Jones Jeremy , Zhang Jingbo , Liu Yunchao , Xu Bing , Li Fuwei , Wang Yan , Li Mengjian , Du Rong , Zhou Ye , Hsu Joann , Salgia Meghan , Yang Lixin , Pal Sumanta K. 
Published: May 2020

e17100 Background: Despite extensive work to characterize genomic alterations (GAs) in metastatic renal cell carcinoma (mRCC), GAs are not currently used for treatment sequencing or selection. Circulating tumor DNA (ctDNA) in both blood and urine may elucidate potential mRCC biomarkers through a minimally invasive approach. We aimed to validate previous blood-based ctDNA studies (Pal et al Eur Urol 2017) and compare detection rates of clinically relevant GAs in plasma and urine. Methods: From a single institution, patients (pts) with mRCC were recruited to provide a plasma and urine specimen. ctDNA next-generation sequencing was performed using an investigational 120-gene panel, and we limited our assessment to 7 GAs with biological relevance in RCC ( VHL, MTOR, PIK3CA, TSC2, MET, AKT1, TSC1). Further, only pathogenic alterations previously recognized in RCC and cited in the Catalogue of Somatic Mutations in Cancer (COSMIC) database were considered. Clinicopathologic variables, treatment type and response to therapy were collected from an institutional mRCC patient database. Concordance analysis was performed at the gene level between blood and urine using previously published approaches (Chae et al Oncotarget 2016). Results: 50 pts (40M:10F) were enrolled with a median age of 65. 40 pts (80%) had clear cell histology, while the remainder were papillary (12%), chromophobe (4%) or other (4%). Pts received a median of 1 line of therapy (range, 0-7). GAs were identified in 45 pts (90%) in blood and in 45 pts (90%) in urine . Applying the above criteria, the most frequently observed GAs in blood specimens were TSC2 (9%), MTOR (4%), and VHL (2%). The most frequently observed GAs in urine were VHL (4%) and MTOR (2%). The rate of concordance between blood- and urine-detected GAs was 93%. Of pts bearing mTOR pathway alterations in blood or urine, 3 received everolimus-based therapy. All 3 pts remain on therapy at 10.4, 13.8 and 14.0 months, respectively. Conclusions: Biologically relevant GAs can be detected in pts with mRCC using blood and urine. Our methodology showed high concordance between both platforms. Consistent with prior reports, ctDNA assessment of pts with pretreated mRCC shows a higher frequency of TOR pathway alterations and a lower frequency of VHL mutation.
Percutaneous microwave ablation of stage T1b renal cell carcinoma: Assessment of technical feasibility, clinical outcomes, and safety.
Authors: Arellano Ronald , Guo Jianhai 
Published: May 2020

e17104 Background: The use of percutaneous microwave ablation (MWA) for T1b (4.1-7.0 cm) renal cell carcinoma (RCC) has not yet been widely adopted. Methods: This single-center retrospective study investigated consecutive patients who underwent CT-guided percutaneous MWA for T1b RCC from December 2015 to May 2019. Patient baseline characteristics, tumor biological features, technical parameters, clinical outcomes, and complications were recorded and evaluated. Local progression-free and overall survival (OS) rates were estimated using the Kaplan-Meier method. Results: This study included 23 patients (18 men [mean age ± standard deviation, 74.6 y ± 10.2; range, 58–89 y] and 5 women [mean age, 71.6 y ±10.1; range, 62–86 y]; overall mean age, 74.0 y ± 10.0; range, 58-89 y) with 23 T1b tumors. Technical success was achieved in all of tumors. Local progression-free survival was 94.7%, 86.1%, and 86.1% at 1-, 2-, and 3-year respectively. OS was 95.2%, 85.7%, and 71.4% at 1-, 2-, and 3-year respectively. Of the 2 (8.7%) complications, both were classified as Clavien-Dindo grade I complication. Conclusions: CT-guided percutaneous MWA was associated with high rates of technical success, excellent local progression-free survival and OS, and a low complication rate for stage T1b RCC.
Integrated single-cell spatial multi-omics of intratumor heterogeneity in renal cell carcinoma.
Authors: Hsieh James J , Miheecheva Natalia , Ramachandran Akshaya , Lyu Yang , Galkin Ilia , Svekolkin Viktor , Postovalova Ekaterina , Bagaev Alexander , Lozinsky Yaroslav , Zyrin Vladimir , Zaitsev Aleksandr , Nuzhdina Katerina , Nomie Krystle , Ogloblina Anna , Frenkel Felix , Ataullakhanov Ravshan 
Published: May 2020

e17106 Background: Clear cell renal cell carcinoma (ccRCC) exhibits conspicuous intratumor heterogeneity (ITH) - a driver of tumor evolution and metastasis. ITH in RCC has been studied extensively with bulk tumor DNA sequencing, which lacks the ability to integrate single cell resolution data, spatial architecture, and microenvironment composition. Therefore, we analyzed primary ccRCC tumors at multiple biopsy sites with CyTOF, multiplex immunofluorescence (MxIF), whole exome sequencing (WES), RNA sequencing (RNA-seq), single nuclei RNA-seq (snRNA-seq), and whole genome bisulfite sequencing (WGBS). Methods: Primary ccRCC tumors collected from 6 patients (pts) were biopsied at multiple locations and subjected to CyTOF (n = 21 sites, 6 pts), MxIF (20 markers, n = 8 sites, 3 pts), WES (n = 8 sites, 3 pts), RNA-seq (n = 8 sites, 3 pts), snRNA-seq (n = 8 sites, 3 pts), and WGBS (n = 8 sites, 3 pts), enabling integrated multi-omics analysis. MxIF, CyTOF, and genomic/transcriptomic analyses were performed by BostonGene. Results: Genomic intratumor (IT) evolution of ccRCC cells was tracked with WES, and subclonal distribution of SETD2, STAG2, TSC2 and PBRM1 mutations was observed in different IT regions. Different regions of the same tumor were similar, whereas individual patient tumors were distinct according to tumor microenvironment cellular composition measured by CyTOF or deconvoluted from RNA-seq. The cellular deconvolution of the ccRCC tumors reconstructed from RNA-seq correlated with CyTOF, snRNA-seq and WGBS, showing high concordance among the methods. The promoter CpG island methylation levels, averaged across all genes, positively correlated with ccRCC grade. MxIF revealed spatial IT heterogeneity in the distribution of immune infiltrate components. Macrophages and T cells dispersed among malignant cells; whereas, T cells formed clusters at unique tumor margins. Conclusions: The utilization of multi-omics methods produced a high-resolution portrait of the ccRCC tumor composition and identified differential ITH among regions within the primary tumors or among individual primary tumors. This study demonstrated strong concordance among the different technologies, suggesting that tumor deconvolution by bulk RNA-seq might be clinically applicable for ccRCC tumors. MxIF analysis enabled a fine elucidation of the spatial relationships among the tumor and the immune and stromal cells, missed by common omic platforms. Integrated single cell multi-omics could render specific pathobiological and therapeutic insights that impact treatment decisions.