bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic risk assessment for hereditary RCC: Report from the consensus panel meeting.
Authors: Daneshvar Michael , Mendhiratta Neil , Srinivasan Ramaprasad , Jonasch Eric , Ball Mark Wayne , Metwali Adam R , Brugarolas James , Singer Eric A. , Nathanson Katherine , Pierorazio Phillip M. , Boris Ronald S , Finelli Antonio , Pal Sumanta K. , Hakimi A. Ari , Kutikov Alexander , Iliopoulos Othon , Linehan W. Marston , Shuch Brian M. , Bratslavsky Gennady 
Published: February 2020

615 Background: While many genes are now known to be associated with hereditary kidney cancer syndromes, there is a paucity of guidelines or uniform consensus on genetic testing for these patients. An expert panel was organized to assess who, what, when and how patients should be evaluated and what testing should be initiated. Methods: A national, multidisciplinary, panel of experts in urology, medical oncology, clinical geneticists, genetic counselors and patient advocates with background and knowledge in hereditary syndromic kidney cancer convened in person in September 2019. A renal cell carcinoma (RCC) genetic risk assessment questionnaire consisting of 52 questions was compiled prior to the meeting using modified Delphi methodology. The questions were then discussed and reviewed with uniform consensus defined as a minimum of 85% agreement in accordance with the National Comprehensive Cancer Network criteria. Results: The panel consisted of twenty-six attendees represented by urologists (43%), medical oncologist (23%), genetic counselors (13%), clinical geneticists (7%), and patient advocates (3%). The questionnaire consisted of fifty-five statements focusing on who, what, when and how genetic testing should be performed in a patient suspected of hereditary RCC syndrome. A >85% agreement was reached on 30/52 statements with 18/25 (72%) achieving consensus addressing “who”, 2/6 (33%) achieving consensus in “what’ category, 2/7 (29%) in ‘when’ and 4/6 (67%) on how. The questions with least consensus were found in the “what/when?” category with only 4/13 questions with minimum 85% agreement. Specific areas of debate included an age cutoff for prompting a genetic risk assessment as well as need for familial testing in patients with variants of unknown significance. Conclusions: Despite experience of the panel in management of hereditary RCC, the consensus was reached only on 66% of genetic testing. While many issues will need to be discussed further, those statements with consensus may be used to guide physicians and patients on who, what, when and how genetic RCC risk assessment should be performed.
Improving detection of higher-risk or locally advanced disease features in stage I and II renal cell carcinoma.
Authors: Miller Nathan , Derweesh Ithaar , Liu Michael Y. , Bradshaw Aaron , Dutt Raksha , Keiner Cathrine , Meagher Margaret Frances , Ghali Fady , Patel Devin , Wan Fang , Shiehmorteza Masoud 
Published: February 2020

625 Background: Pathologically upstaged T3a renal cell carcinoma (RCC) carries higher oncologic risk than corresponding preoperative clinical stage and presents unique risks from a treatment planning standpoint due to reduced clinician awareness of locally aggressive disease. We sought to identify imaging criteria that predict risk of pathological upstaging of clinical T1 and T2 RCC to T3a and to assess accuracy of CT in detecting T3a RCC. Methods: Single institution retrospective analysis of patients who underwent surgery for RCC. A propensity-score matching process was used to match upstaged patients with non-upstaged (control) patients in a 1:2 fashion. Preoperative CT images were reviewed in a blinded fashion by 2 radiologists for presence of T3a stage imaging criteria. Multivariable analyses assessed risk conferred by imaging features and sensitivity analysis assessed accuracy in detecting T3a RCC. Results: After exclusions, 231 patients were analyzed (mean age 61 years, upstaged 83/control 148, mean tumor size 6.4 cm). In 71/83 (86%) of upstaged tumors, the presence of sinus fat invasion (SFI), perinephric fat invasion (PFI), or venous invasion (VI) was found. The presence of all three was not observed in any non-upstaged tumor. The following features were associated with upstaging: tumor necrosis (OR 2.1, p=0.017), irregular tumor edge (OR 2.9, p<0.001), thickened perirenal fascia (OR 2.6, p=0.001), perinephric stranding (OR 1.8, p=0.043), increased perinephric vascularity (OR 2.02, p=0.021), and perinephric nodules (OR 3.4, p=0.020). The SE/SP for tumor necrosis, irregular tumor edge, thickened perirenal fascia, perinephric stranding, increased perinephric vascularity, and perinephric nodules were 42%/74%, 74%/50%, 48%/74%, 70%/44%, 70%/46%, and 13%/96%, respectively. Conclusions: Upstaged T3a RCC contained several preoperative imaging attributes which were 2-3 times more likely to be present than in non-upstaged tumors. Of these, irregular tumor edge had highest sensitivity, and perinephric nodules had highest specificity. These features should elevate clinical suspicion for T3a disease and may be used to develop a novel risk scoring system. Further investigation is requisite.
An international challenge to use artificial intelligence to define the state-of-the-art in kidney and kidney tumor segmentation in CT imaging.
Authors: Heller Nicholas , McSweeney Sean , Peterson Matthew Thomas , Peterson Sarah , Rickman Jack , Stai Bethany , Tejpaul Resha , Oestreich Makinna , Blake Paul , Rosenberg Joel , Moore Keenan , Walczak Edward , Rengel Zachary , Edgerton Zach , Vasdev Ranveer , Kalapara Arveen , Sathianathen Niranjan J. , Papanikolopoulos Nikolaos , Weight Christopher J. 
Published: February 2020

626 Background: The 2019 Kidney and Kidney Tumor Segmentation challenge (KiTS19) was an international competition held in conjunction with the 2019 International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) and sought to stimulate progress on this automatic segmentation frontier. Growing rates of kidney tumor incidence led to research into the use of artificial inteligence (AI) to radiographically differentiate and objectively characterize these tumors. Automated segmentation using AI objectively quantifies complexity and aggression of renal tumors to better differentiate and describe the tumors for improved treatment decision making. Methods: A training set of over 31,000 CT images from 210 patients with kidney tumors was publicly released with corresponding semantic segmentation masks. 106 teams from five continents used this data to develop automated deep learning systems to predict the true segmentation masks on a test set of an additional 13,500 CT images in 90 patients for which the corresponding ground truth segmentations were kept private. These predictions were scored and ranked according to their average Sørensen-Dice coefficient between kidney and tumor across the 90 test cases. Results: The winning team achieved a Dice of 0.974 for kidney and 0.851 for tumor, approaching the human inter-annotator performance on kidney (0.983) but falling short on tumor (0.923). This challenge has now entered an “open leaderboard” phase where it serves as a challenging benchmark in 3D semantic segmentation. Conclusions: Results of the KiTS19 challenge show deep learning methods are fully capable of reliable segmentation of kidneys and kidney tumors. The KiTS19 challenge attracted a high number of submissions and serves as an important and challenging benchmark in 3D segmentation. The publicly available data will further propel the use of automated 3D segmentation analysis. Fully segmented kidneys and tumors allow for automated calculation of all types of nephrometry, tumor textural variation and discovery of new predictive features important for personalized medicine and accurate prediction of patient relevant outcomes.
Preoperative differentiation of chromophobe renal cell carcinoma from oncocytoma: Aorta-lesion-attenuation difference on multiphasic multidetector computed tomography.
Authors: Hosseiny Melina , Ching Justin , Kooraki Soheil , Raman Steven 
Published: February 2020

627 Background: Differentiation of benign oncocytoma from chromophobe renal cell carcinoma (chRCC) remains a challenge. This study aimed to investigate whether Aorta-lesion-attenuation difference (ALAD) on multiphasic multidetector CT scan (MDCT) can aid to distinguish oncocytoma from chRCC. Methods: This IRB-approved, HIPAA-compliant study consisted MDCT of 111 patients with pathologically proven chRCC (N: 37) or oncocytoma (N: 74). Regions of interest (ROIs) were placed over the renal mass and Aorta on the same axial MDCT slice of un-enhanced (UE), corticomedullary (CM), nephrographic (NP) and excretory (EX) phases. ROIs were devoid of calcification, necrosis and hemorrhage in lesion or atherosclerotic plaque in Aorta. The difference between Aorta and renal mass Hounsfield unit was calculated in all available phases. SPSS v.18 was used to draw receiver-operating characteristic (ROC) curve to calculate accuracy and optimal cutoff values for differentiation of chRCC from oncocytoma. Results: Mean ALAD was significantly higher in chRCC compared to oncocytoma in CM(P: 0.04), NP (P<0.01) and EX (P<0.01) phases. The area under the curves for ALAD in UE, CM, NP and EX phases were 0.47 (95% CI: 0.36- 0.59, p: 0.68), 0.64 (95% CI: 0.51-0.77, p: 0.03), 0.87 (95% CI: 0.79- 0.95, p< 0.01) and 0.80 (0.70-0.90, P<0.001), respectively. ALAD threshold of 19 in nephrographic phase had sensitivity and specificity of 79% and 78%, respectively, for differentiation of chRCC from oncocytoma. Conclusions: ALAD measured in the nephrogenic phase showed the highest accuracy for differentiation of chRCC from oncocytoma on multidetector CT scan. If validated prospectively, ALAD may act as a useful imaging biomarker to distinguish chRCC from oncocytoma.
Is body mass index (BMI) associated with favorable outcomes in metastatic renal cell carcinoma (mRCC) treated with nivolumab? An ancillary study of the NIVOREN-GETUG AFU-26 trial.
Authors: Colomba Emeline , Dalban Cécile , Flechon Aude , Chevreau Christine , Gravis Gwenaelle , Thibault Constance , Laguerre Brigitte , Barthelemy Philippe , Borchiellini Delphine , Gross Goupil Marine , Geoffrois Lionnel , Rolland Frederic , Thiery-Vuillemin Antoine , Joly Florence , Ladoire Sylvain , Tantot Florence , Escudier Bernard , Albiges Laurence 
Published: February 2020

630 Background: Adipose tissue might affect response to immune checkpoint inhibitors (CPI) in cancer patients (pts). Higher BMI is associated with improved outcomes in mRCC under VEGFR TKI but BMI impact under CPI remains unclear. Methods: We analysed BMI in the NIVOREN GETUG AFU 26 study, a prospective study that evaluated the safety and efficacy of nivolumab in mRCC after failure of prior VEGFR inhibitors. We investigated the association between BMI, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). BMI (weight/height 2) was classified according to the World Health Organization (WHO) categories: underweight as BMI < 18.5; normal weight as 18.5 ≤ BMI ≤ 24.9; overweight as 25 ≤ BMI ≤ 29.9 and obesity as BMI ≥ 30. Survival distributions were compared using a Log-Rank test, supported by uni- and multivariate Cox regressions to estimate the Hazard Ratio (HR) and its 95% CIs. Median follow-up (FU) and the 95% CI were calculated using the reverse Kaplan–Meier method. Results: Overall, 708 pts were included in the BMI analysis: 20 pts (2.8%) were underweight, 322(45.5%) had normal weight, 255(36.0%) were overweight and 111(15.7%) obese. Median age was 64 years, 77.3% were male, performance status was ≥ 80% in 81.2%, and IMDC risk group was good, intermediate and poor in respectively 18.2%, 56.4%, 25.4%. Outcomes according to BMI is detailed in table, median FU was 23.9 months (95%CI 23.0-24.5). BMI adjusted to known prognostic factors was not significant in the multivariate analysis. Conclusions: Higher BMI patients seems to have better outcomes with nivolumab in mRCC. Further characterisation is on-going to explore the relation of BMI with established risk factor in pts under CPI in mRCC.[Table: see text]
Effect of obesity on response to checkpoint inhibitors in renal cell cancer.
Authors: Nandagopal Lakshminarayanan , Zakharia Yousef , Yasin Hesham , Nepple Kenneth Gerard , De Shazo Mollie R. , Yang Eddy Shih-Hsin , Garje Rohan , Basu Arnab , Li Peng , Norian Lyse 
Published: February 2020

634 Background: Response to checkpoint inhibitors (CPIs) for renal cell cancer (RCC) remains variable, with markers like PDL1 proving unreliable. Preclinical models suggest that obesity could affect CPI outcomes. We conducted a retrospective study on the effect of obesity on outcomes in RCC patients treated with CPIs. Methods: RCC patients treated with nivolumab +/- Ipilimumab at university of Alabama at Birmingham (UAB) and University of Iowa (UIOWA) from 2015 - 2018 were classified according to WHO standard definition of BMI as non-obese (NOB-<30kg/m2) or obese (OB->30Kg/m2). Overall survival (OS) was defined as the interval from the first CPI dose to date of death or to last follow up date if patients were still alive. Progression free survival (PFS) was defined as the interval from the first dose of CPI to date of progression or date of death and censored at last follow-up date if patients were still alive without progression. Multivariable Cox proportional hazard regression model was used to evaluate the association between OS/PFS and obesity status, controlling for age, sex, race and number of prior therapies. All analyses were performed using SAS 9.4. Results: 84 patients with at least 6 months follow-up received a median of 9 doses of CPI with median follow of 72 weeks. 48 patients were NOB while 36 patients were OB, with 40 patients deceased at time of analysis. The most common response was stable disease in 45%, with CR in 5% and PR in 10% for a disease control rate of 63%. The median OS was 30 months in NOB patients and 20 months in the OB group. The 2 yr survival was 59% in the NOB group vs 28 % in the OB group with a HR of 0.60 (0.32-1.14; p=0.12). Median PFS was 13 months in the NOB group vs 7.3 months in the OB group with 2 yr PFS of 28% in the NOB group vs 5.5% in the OB group (HR 0.58 {0.35-0.98}; p=0.04). Conclusions: In this analysis of RCC patients treated with CPI, BMI < 30 predicts better OS and PFS. Further studies are required to better understand the effect of BMI on CPI outcomes in RCC.[Table: see text]
Trends in PRO reporting in clinical trials leading to GU cancer drug approvals from 2007 to 2018.
Authors: Tamil Monica , Safa Houssein , Semaan Adele , Chahoud Jad 
Published: February 2020

641 Background: Having standardized and high quality reporting of patient reported outcomes (PRO), especially in clinical trials that establish standards of care in oncology is important for patient centered care. This study assessed the status of reporting and quality of analysis of PROs in FDA approved drugs for genitourinary malignancies. Methods: We conducted a systematic review of the FDA archives to identify urological cancer drugs approved between 2007-2018. We retrieved the clinical trials that led to these drug approvals from ClinicalTrials.gov and PubMed. We systematically screened for PROs and reviewed their analytic tools and interpretation methods reported in their published manuscripts and study protocols. A clinical trial was considered to include PROs if they were reported in either the primary or a subsequent manuscript. Results: We identified 22 clinical trials leading to FDA approval of urological cancer drugs between 2007-2018. Only 63% of trials had published PROs. PROs were reported in the primary clinical trial manuscripts for two drugs (9%), and in a secondary PRO manuscript for 12 drugs (54%). The median time between the primary and secondary papers was 12 months (IQR:7.5-26 months). Among the 14 published PRO papers, the hypothesis was broad in 79%, and not reported in 21%. PROs were never included as a primary endpoint of a study. Instead, PROs were reported as secondary endpoints in 5 (36%) and as exploratory endpoints in 7 (50%) studies, while two papers (14%) did not mention PRO reporting in their endpoints. The most common PRO instruments were EQ-5D (64%) and FACT-P (50%). In 92% of PRO papers, statistical analyses were conducted to account for missing data. Control for type I error was needed but not done in 57% of the trials. Conclusions: Delays in publication of PROs occur regularly in trials leading to drug approval in GU malignancies. Our study highlights the need to enhance standardization of the analysis and interpretation of PROs to maximize the value of this data for drug development and approval.
Outcome with immune checkpoint inhibitors in metastatic renal cell carcinoma across different treatment lines.
Authors: Bruchbacher Andreas , Franke Johannes , Alic Zumreta , Nachbargauer Sebastian , Fajkovic Harun , Remzi Mesut , Schmidinger Manuela 
Published: February 2020

651 Background: The introduction of immune checkpoint inhibitors (ICPI) has led to a paradigm change in the management of metastatic Renal Cell Carcinoma (mRCC). Prospective trials focused on ICPI treatment in first- or second-line. The aim of this analysis was to evaluate the benefit of ICPI across different treatment lines. Methods: This is a single center retrospective study from the Medical University of Vienna which included all mRCC patients who received ICPIs in various treatment lines. Overall response rates (ORR), progression free survival (PFS) and overall survival (OS) were evaluated for the entire cohort and by treatment line. Results: Between January 2014 and October 2019, a total of 113 patients received ICPIs. Ninety-four patients were eligible for full evaluation (83% clear cell and 17% non-clear cell). 26.8%, 61.6% and 14.8% were classified good, intermediate and poor IMDC-risk, respectively. 59%, 20% and 21% were treated with ICPI monotherapy, dual ICPI therapy and ICPI + tyrosine kinase inhibitor, respectively. ORR, median PFS and median OS for the entire cohort was 39.4%, 9.67 months (95%CI: 6.9-12.4 months) and 23.6 months (95%CI: 13.3-33.9 months), respectively. The ORR by treatment line was: 33% in first-line (9 patients), 40.4%, in second- (42 patients), 35% in third- (20 patients) and 43.5% in fourth and beyond-fourth-line (23 patients). The median PFS by treatment line was: 8.6 months, 10.3 months, 7.9 months and 7.23 months, respectively. The median OS was not reached (NR) in first-line and 26.2 months, 18.1 months and 20.7 months in second-, third-, and fourth and beyond- ICPI treatment line, respectively. The global OS for the whole patient cohort calculated from diagnosis of metastasis was 80 months (CL 95%: 50.5 – 109.5 months). Conclusions: ICPIs are active in all treatment lines and should also be offered in heavily pre-treated patients, who have not had access in earlier treatment lines.
Patient-reported outcomes on treatment-related side effects in renal cell carcinoma.
Authors: Battle Dena , Rathmell Wendy Kimryn , Jonasch Eric , Msaouel Pavlos , Stern Adam P. , Zhang Tian , George Daniel J. , Staehler Michael D. 
Published: February 2020

654 Background: Effective management of treatment related toxicities is crucial to maximizing patient outcomes and enhancing quality of life in renal cell carcinoma. Little is known about patient perception and reporting of side effects in a real world setting outside clinical trials. We sought to gather independent data from online patient communities to estimate gaps in communication and reporting. Methods: KCCure conducted an anonymous online survey from 07/19 to 09/19 using questions related to side-effect experience and management. Results: 1,136 patients (median age 57 years [range 28-86], 54% male) participated, 411 patients on systemic therapy were asked about side-effects. 47% of patients reported bothersome side effects impacting their daily lives. The most poorly managed side-effect was fatigue (25%), followed by taste alteration (15%) and loss of appetite (15%). Only 50% of patients are confident their medical oncologist will offer help for side effects, and 20% are worried that reporting side effects may result in dose reduction or treatment discontinuation. 6% of patients don’t talk about their side effects. Patients who identified as non-white (Hispanic, African American, Asian/Pacific Islander and Native American) were three times less likely to talk about side effects. 51% indicated the best advice on managing treatment related side effects was provided by their medical oncologist; 40% seek advice from online patient communities and 35% from advocacy organizations. Only 8% used manufacturer support websites. 13% had never had any concomitant medication prescribed to manage side effects. Major unreported side effects are sexual dysfunction, cognitive impairment and vision disturbances. Conclusions: The majority of patients experience treatment related side-effects on a regular basis, but underreporting may be significant due to a variety of factors, including fear of dose-reduction or discontinuation. Sexual side-effects are underreported. Future studies need to explore differences in reporting for minority populations as well as side effect experiences according to the class of agent prescribed, and the setting in which treatment occurs.
Impact of diabetes mellitus on functional and survival outcomes in renal cell carcinoma: An international multicenter study.
Authors: Dutt Raksha , Meagher Margaret Frances , Patil Dattatraya , Saito Kazutaka , Patel Devin , Ghali Fady , Keiner Cathrine , Miller Nathan , Bradshaw Aaron , Wan Fang , Yasuda Yosuke , Fujii Yasuhisa , Master Viraj A. , Derweesh Ithaar 
Published: February 2020

666 Background: Functional decline is an important consideration in the surgical treatment of renal cell carcinoma (RCC). While radical nephrectomy (RN) may be associated with increased risk of functional decline compared to partial nephrectomy (PN), the modifying effect of DM, an independent risk factor of chronic kidney disease (CKD), is not completely understood. We investigated the relationship between DM and decline in kidney function following surgery for RCC, and impact on overall survival (OS) in patients with RCC. Methods: A multicenter dataset of RCC patients undergoing PN and RN was utilized. The cohort was divided based on DM status [DM vs No DM (NDM)]. Multivariable analysis (MVA) elucidated potential variables associated with decline in kidney function [de novo estimated glomerular filtration rate (eGFR) < 45 ml/min/1.73m2 and de novo eGFR < 30 ml/min/1.73m2] and worse all-cause mortality (ACM). Kaplan-Meier analysis (KMA) was used to investigate OS rates in DM and NDM patients undergoing RN and PN. Results: 2928 patients were analyzed (DM = 406, NDM = 2522). On MVA, independent risk factors associated with eGFR < 45 included age (OR = 1.07, p < 0.001), DM (OR = 1.88, p < 0.001), tumor size (OR = 1.03, p = 0.032), and RN (OR = 1.54, p < 0.001). Variables associated with eGFR < 30 included age (OR = 1.05, p < 0.001), African American race (OR = 2.18, p < 0.001), and DM (OR = 2.09, p < 0.001). MVA for ACM revealed age (OR = 1.02, p = 0.002), HTN (OR = 2.47, p < 0.001), tumor size (OR = 1.12, p < 0.001), tumor grade (OR = 1.87, p < 0.001), RN (OR = 1.55, p = 0.011), eGFR < 45 (OR = 1.40, p = 0.03), and eGFR < 30 (OR = 1.87, p = 0.026) to be independently associated. On KMA, 5-year OS stratified by DM status showed that DM is associated with worse OS for RN patients (p = 0.047), but not for PN patients (p = 0.944). Conclusions: Presence of DM is an independent risk factor for renal functional decline and development of worsening CKD is a risk factor for worsening ACM. Furthermore, decreased survival in DM patients was associated with RN recipients but not with PN recipients. Presence of DM may be considered a strong indicator for nephron preservation management strategies when safe and feasible in RCC patients.