bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new four-tiered grading scheme for postoperative prognostication in renal cell carcinoma with local recurrence.
Authors: Lei Chang , Qu Le , Wang Linhui , Ge Jingping , Zhou Wenquan 
Published: June 2024

e16524 Background: Renal cell carcinoma (RCC) patients suffering from local recurrence (LR) herald variable risk of second progression even after curative surgery for LR. Further risk stratification of these patients will facilitate selection of candidates for adjuvant immunotherapy. Here we evaluate the prognostic significance of tumor grade variation (GV) between the primary tumor (PT) and LR tumor in nonmetastatic RCC in the largest study to date. Methods: We reviewed Research of Multi-institution in East-China on Malignant and Benign Epithelial Renal Tumors (REMEMBER) database to identify ccRCC or pRCC patients who underwent surgery for LR. All pathology slides were centrally reviewed by three independent senior genitourinary pathologists and patients were assigned to groups based on GV as upgrading (WHO/ISUP Ⅰ/Ⅱ for PT grade and Ⅲ/Ⅳ for LR grade), downgrading (WHO/ISUP Ⅲ/Ⅳ for PT grade and Ⅰ/Ⅱ for LR grade), stable low-grade (WHO/ISUP Ⅰ/Ⅱ for both PT and LR grade) and stable high-grade groups (WHO/ISUP Ⅲ/Ⅳ for both PT and LR grade). To evaluate the predictive value of GV, four tumor grade measures (PT grade, LR grade, highest grade for the PT and LR, GV) were separately incorporated for model development. The primary end point was overall survival (OS), defined as the time from LR surgery to death from any cause or last follow-up. A multivariable cox regression analysis was performed to explore associations between timing and survival. Results: 345 patients were identified 114 stable low-grade (33.1%), 56 downgrading (16.2%), 97 upgrading (28.1%), and 78 stable high-grade (22.6%). Median OS were highest among patients with stable low-grade (114 [stable low-grade] vs. 86 [Downgrading] vs. 59 [Upgrading] vs. 33 [Stable high-grade] months). Univariate analysis indicates that PT, LR and GV were significant correlated with poor OS (all P values < 0.05). After separately constructing the PT grade model (#1) via LASSO cox regressions for predicting OS, LR grade model (#2), highest grade model (#3) and GV model (#4) were built by simply replacing the variable of PT grade, it turned out that GV model (#4) achieved the better discriminatory ability (AUC of model (#4) vs. model (#1), 0.812 vs. 0.743; model (#4) vs. model (#2), 0.812 vs. 0.788; model (#4) vs. model (#3), 0.812 vs. 0.762, all p values < 0.05). Conclusions: This is the first study showing that GV is independently associated with clinical outcomes in patients with LR. Routine reporting of LR upgrading or downgrading in relation to the PT and assessment of GV can facilitate more informed treatment decisions by tailoring strategies to an individual patient's risk of progression.
Renal cell carcinoma post-kidney transplant: An analysis of OPTN/UNOS database.
Authors: Savani Saloni , Patel Het , Pawa Arpita , Dhaibar Hemangini , Master Samip R. , Singh Neeraj 
Published: June 2024

e16528 Background: Renal cell carcinoma (RCC) is the most common form of kidney cancer in adults, accounting for 90-95% of primary malignant kidney tumors and representing around 3% of all cancers worldwide.Kidney transplant recipients (KTRs) have a higher incidence of developing RCC compared to the general population but lower compared to ESRD population. In 2018, the incidence of RCC was 1.6/10,000 in the general population and 45-50/10,000 person years in ESRD patients, with an increased incidence in patients with risk factors like old age, African American descent, hypertension, and smoking. With this study, we sought to identify high-risk patients among KTRs who may benefit from surveillance imaging. Methods: The UNOS/OPTN database was used to select kidney transplant recipients between 1/1/2010 to 12/31/2022. Pediatric patients, patients with simultaneous multi-organ transplants, and those with other malignancies were excluded. The study computed the incidence of RCC during the first 5-year and between 5 to 10-year post-transplant periods. Additionally, univariate, and multivariable logistic regression analysis was conducted to identify predictors for the development of RCC. Results: A total of 202,837 patients were included in the study, of them 1042 developed RCC during the follow-up period. The mean time to diagnose RCC was 3.3 (SD:2.7) years. The incidence rate was 11.59 and 11.57 during the first 5 years of follow-up and during the next 5 years per 10,000 person-years respectively. The major risk factors associated with the development of RCC were age 35-49 (OR: 1.88, p<0.001), age 50-64 (OR: 2.79, p<0.001), age >=65 (OR: 2.86, p<0.001), BMI >=30 (OR: 1.27, p=0.004) and race (African American (OR: 1.74, p<0.001) or Caucasian (OR: 1.39, p=0.002)). In addition, underlying hypertension (OR: 1.23, p=0.01), pre-transplant RCC (OR:3.85, p<0.001), and glomerulonephritis (OR: 1.28, p=0.009) causing ESRD were the significant risk factors for the occurrence of RCC during the 10-year follow-up period. The median graft survival and patient survival from the time of diagnosis to graft failure and patient mortality was 466 (109 – 1243) days & 437 (109 – 1058) days respectively. Conclusions: The risk of developing RCC in the first 5 years of kidney transplant increases by 7-fold compared to the general population. Obese, middle-aged, African American, or Caucasian patients with a history of hypertensive nephrosclerosis, pre-transplant RCC, or glomerulonephritis are at a higher risk for developing RCC during the post-transplant period. RCC also increases the risk of early graft failure and death. RCC surveillance for post-kidney transplant patients is not currently recommended due to absence of the studies showing a cost benefit with this approach. Based on this study, further studies are warranted to assess the risks and benefits of initiating RCC surveillance in these select group of patients.
Anlotinib plus everolimus as first-line treatment for advanced non–clear cell renal cell carcinoma: A single-center, single-arm, phase II trial.
Authors: Zhang Hailiang , Ye Dingwei 
Published: June 2024

e16533 Background: For patients (pts) with recurrent or stage IV non-clear cell renal cancer (nccRCC),the medical treatment guidelines recommend the first choice to participate in clinical trials, or use TKI drugs such as sunitinib, and mTOR inhibitors such as everolimus. Anlotinib is a novel multi-target tyrosine kinase inhibitor (TKI). It’s antitumor targets include vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-kit. ALTER-UC-001 is a single-center, single-arm, phase II trial which evaluated the efficacy and tolerability of anlotinib plus everolimus as first-line therapy in pts with nccRCC (NCT05124431). Methods: Patients with advanced nccRCC and no prior systemic drug therapy for advanced disease were eligible for this trial; Eastern Cooperative Oncology Group (ECOG) performance status 0-1. The patients received 12mg anlotinib once daily on days 1-14 every 3 weeks by oral, and 5mg everolimus orally once daily. The primary endpoint was objective response rate (ORR). Secondary endpoints included overall disease control rate (DCR), progression free survival (PFS), and over survival (OS). Adverse events will be monitored throughout the study and graded according to CTCAE V5.0. Results: Between Jan 2022 and Dec 2023, 24 pts were enrolled and received study treatment. The median age was 56 years old (range: 20 to 79 years). Nineteen pts (79.2%; 19/24) had a ECOG PS score of 1, and five pts (20.8%; 5/24) had a ECOG PS score of 0. All pts had not received prior treatment. In addition, 17 (70.8%) had received surgical treatment and 1 (4.2%) had received radiotherapy. The data cutoff was Dec 2023, with a median follow-up of 6.04 (range, 1.34-18.1) months.14 pts had the best overall response (unconfirmed) assessments which inferred the ORR of 57.1%(PR in 8 pts 95% CI, 29.6-81.2)and the DCR of 100% (PR in 8 pts and SD in 6 pts; 95% CI, 73.2-100). The median PFS has not reached. Any grades of adverse events (AEs) were observed in 91.7% (22/24) of pts, the most common of which were mucositis (29.1%), hypertension (25.0%) , creatinine increased(16.7%), proteinuria (16.7%) and glutamic-pyruvic transaminase increased (12.5%).Seven (29.1%) pts experienced grade 3 TRAEs, including hypertension (8.3%), proteinuria (8.3%), mucositis (4.2%), platelet count decreased (4.2%), creatinine increased (4.2%), chronic gastritis (4.2%) and bleeding (4.2%). No treatment-related deaths occurred. Three (12.5%) and two (8.3%) pts had suspension of treatment because of TRAEs caused by everolimus and anlotinib respectively. Conclusions: Anlotinib plus everolimus as first-line therapy is efficacious and safe for pts with advanced nccRCC. We will report more data in the future. Clinical trial information: NCT05124431 .
Impact of cytoreductive nephrectomy (CN) and treatment (trt) sequence on overall survival (OS) in metastatic non-clear cell renal cell cancer (nccRCC).
Authors: Nelson Ariel Ann , Szabo Aniko , Kilari Deepak 
Published: June 2024

e16543 Background: nccRCC accounts for 25% of kidney cancer diagnoses and encompasses a diverse group of kidney tumors with distinct biology for which trt in the metastatic setting is evolving. The role of CN for nccRCC population in the current trt landscape remains unclear. Methods: We retrospectively identified patients (pts) with nccRCC from The National Cancer Database (NCDB) participant user file (PUF) for Kidney and Renal Pelvis Tumors. Pts with de novo metastatic disease diagnosed between 2015 and 2020, received systemic trt with immunotherapy (IO) or non-immunotherapy (NIO) and underwent or could have undergone a CN were selected. Pts classified as having sarcomatoid histology were excluded. Demographic and disease characteristics were summarized using descriptive statistics. The cumulative incidence of CN was estimated using the Nelson-Aalen estimator. The association of demographic and disease characteristics on the cumulative incidence of CN was evaluated using univariate Fine-Gray regression. The effect of CN on survival was visualized via Simon-Makuch plot. P values were based on Mantel-Byar test. Cox regression with a time-dependent predictor was used to estimate the change in the hazard of death after CN. Results: We identified 982 pts, median age 60 (18 – 90) years, 61% male, 69% Caucasian and 28% African American. nccRCC histology included 66.5% papillary (n=653), 10.4% chromophobe (n=102), 9.9% medullary (n=97), 8.8% collecting duct (n=86), 4.4% unclassified (n= 43). 69% of pts received NIO (n= 676), 14% received IO + NIO (n= 134), 18% received IO only (n= 172). 40% had CN (n=390), the majority of CN (86%) occurred within 3 months of diagnosis. 89% had CN followed by systemic trt (n=348), 4.3% underwent initial systemic trt followed by CN (n=42). Median OS was 11 months for the entire group. For those who had CN, mOS was 13.9 vs 10 months for no CN (p=0.002). CN was associated with improved survival; HR 0.79 (95% CI 0.68,0.92; p=0.002). Median OS for pts who received systemic trt followed by CN was 32.6 vs 12.8 months for those who had CN followed by systemic trt vs 10 months for those who had no CN, (p=0.001). Upfront systemic trt followed by CN and CN followed by systemic trt were both associated with improved survival, HR 0.56 (95% CI 0.36, 0.87; p=0.009) and HR 0.83 (95% CI 0.69,0.99; p= 0.034) respectively. Choice of systemic trt was not associated with improved OS (p = 0.139). Unclassified and medullary histology were associated with worse OS, HR 1.60 (95% CI 1.09, 2.34; p=0.015) and HR 2.04 (95% CI 1.46,2.84; p=0.002) respectively. Conclusions: CN is associated with improved outcomes for pts with de novo metastatic nccRCC. Sequencing upfront systemic trt followed by CN may improve survival. Prospective randomized trials in the modern trt era are needed and ongoing (Ie. PROBE trial NCT04510597) to further assess the timing and sequencing of CN in pts with nccRCC.
Baseline geriatric 8 (G8) screening tool to predict overall survival in metastatic urothelial carcinoma treated with immune checkpoint inhibitors.
Authors: Rhee Christopher H , Goyal Subir , Liu Yuan , Martini Dylan J. , Nazha Bassel , Kucuk Omer , Carthon Bradley Curtis , Bilen Mehmet Asim , Brown Jacqueline T 
Published: June 2024

e16575 Background: Checkpoint inhibitors (CPI) blocking PD-1 or PD-L1 are a mainstay in the treatment of metastatic urothelial cell carcinoma (mUC). Due to the high bar for clinical trial participation, older patients are underrepresented in trials resulting in FDA-approved therapies that are not always representative of real-world patients. The G8 questionnaire is an 8-question screening tool designed to assess frailty in older adults and alert to the need for geriatric assessment. We investigated the ability of the G8 score to predict clinical outcomes in patients with mUC treated with CPIs. Methods: We performed a retrospective analysis of patients with mUC treated with CPIs in any line of treatment at Winship Cancer Institute between 2016-2019. We collected demographic data, patient and disease characteristics, and immune-related adverse events (irAE). A baseline G8 score was evaluated using past clinic notes from providers, social workers, and dietitians. The G8 incorporates measures assessing food intake, weight loss, mobility, neuropsychological conditions, BMI, polypharmacy, self-assessed health, and age. A score of ≤ 14 suggests potential geriatric vulnerability. Progression-free survival (PFS) and overall survival (OS) were measured from the start of CPI until death or clinical or radiographic progression, respectively. The survival association with the G8 score was analyzed using univariate (UVA) and multivariable (MVA) analyses by the Cox proportional hazard model and Kaplan-Meier method. irAEs association was handled by logistic regression. Results: A total of 48 patients with a median age of 73.5 years were analyzed with 66.7% male 75% white. 70.8% of patients had a baseline G8 suggesting geriatric vulnerability despite 74.4% of patients being scored as having an ECOG score of 0-1. An impaired G8 score at CPI initiation was associated with an increased risk of death but not progression on both UVA and MVA. The association between lower rates of irAEs in patients with impaired G8 scores approached statistical significance (Table). The median OS in Kaplan-Meier analysis for patients with an impaired G8 score was significantly lower (6.8 vs 14 months, p=0.0110) but median PFS was comparable (2.5 vs 3.4 months, p=0.4237) to those with a normal G8. Conclusions: These results indicate that the G8 screening tool may be a useful prognostic tool in mUC patients when planning treatment with a CPI, however should be validated with larger cohort studies. [Table: see text]
Effect of body mass index (BMI) on efficacy of immune checkpoint inhibitors (ICIs) in patients with metastatic urothelial carcinoma (mUC) in real-world setting.
Authors: Lynn David , Dawsey Scott , Hobeika Charbel , Patgunarajah Ubenthira , Pramod Nikhil , Wei Wei , Nair Monica , Maroli Kimberly , Martin Allison , Ornstein Moshe Chaim , Wee Christopher Eing , Gilligan Timothy D. , Nizam Amanda , Bonham Amanda , Mian Omar Y. , Pavicic Paul G. , Diaz-Montero C. Marcela , Gupta Shilpa 
Published: June 2024

e16577 Background: There is emerging data on the role of BMI and outcomes of ICIs in various solid tumors, with underweight pts having worse outcomes to ICIs. The effect of BMI on efficacy of ICIs in pts with mUC is not clear. Methods: We identified 455 adult pts with mUC at the Cleveland Clinic treated who received >/= 2 cycles of ICI with pembrolizumab (P), atezolizumab (A), or avelumab (Av) between 2015 and 2023. Patient characteristics including age, sex, race, primary site (bladder vs upper tract UC (UTUC)), tumor histology and pre ICI treatment NLR values were collected. BMI was calculated and values were collected and compared to assess impact on overall (OS) and progression free survival (PFS) after ICI start date. BMI was broken down into four categories: underweight (BMI less than 18.5 kg/m2), normal weight (BMI between 18.5 and 24.9 kg/m2), overweight (BMI between 25 and 29.9 kg/m2) and obese (BMI 30 kg/m2 or greater). OS and PFS were estimated by Kaplan Meier method and compared using log rank test. Results: Median age of pts was 73 yrs (35-95) and 341 (75%) pts were males. 269 (59%) received P, 90 (20%) received A, and 96 (21%) received Av. We found that underweight pts had significantly worse OS compared to normal or higher BMI (p=0.001). BMI did not impact PFS (p=0.1) (Table). Conclusions: In our large real-world cohort of mUC pts receiving ICI, we report for the first time the effect of BMI on outcomes with ICI with underweight pts having better outcomes. Further prospective studies are warranted. [Table: see text]
Treatment patterns with intravesical bacillus Calmette-Guérin (BCG) in patients with non-muscle-invasive bladder cancer (NMIBC): A real-world data analysis.
Authors: Sun Ran , Linghu Bolan , Somer Robert A. , Hampras Shalaka , Bhanvadia Sumeet Kaur , Scherer Emily , Greshock Joel , Sweiti Hussein 
Published: June 2024

e16584 Background: Intravesical BCG is the recommended first-line treatment for high-risk NMIBC patients, with a recommended minimum 1-year duration consisting of 6 doses of induction followed by multiple doses of maintenance. However, up to approximately 50% of patients experience BCG failure, often within the first 6 months. Real world treatment patterns with BCG are not well understood. This study aims to characterize real-world BCG treatment patterns and treatment failure in NMIBC patients. Methods: This retrospective cohort study utilized comprehensive claims and electronic health record (EHR) from the US HealthVerity data between Oct 2015 and Dec 2022. This analysis included patients with NMIBC who received first BCG treatment within 90 days of their bladder cancer diagnosis, with a follow-up period of ≥ 3 years post BCG treatment. A descriptive analysis of the number of doses, treatment duration, and treatment discontinuation following the BCG initiation was conducted. Treatment discontinuation was defined as a gap of more than 1 year from the last BCG dose. Initiation of subsequent therapy post BCG was reported and used as a proxy for BCG failure. Results: A total of 13,525 patients met the study criteria and initiated BCG treatment between 2015 and 2022. Of all patients, 3193 (23.6%) received < 5 BCG doses, 3854 (28.5%) received 5-7 doses, and 6478 (47.9%) received > 7 BCG doses. The overall median was 7 doses (interquartile range [IQR]: 5,14). The median duration of BCG treatment was 156 days (IQR: 36, 489). BCG was discontinued in 66.9% patients within 1 year of initiation. A total of 6182 patients (45.7%) experienced treatment failure and received subsequent treatment, with 3550 patients (57.4%) initiating next treatment within 1 year of last BCG dose. Conclusions: In a large US real-world dataset, a majority of NMIBC patients treated with BCG received ≤7 doses and discontinued treatment within < 1 year of treatment initiation. Furthermore, nearly half of patients experienced BCG failure, thereby requiring subsequent therapies. This highlights a significant unmet need for treatments with improved tolerability and efficacy profile for patients with NMIBC.
Retrospective analysis of outcomes of patients with bladder cancer when neoadjuvant chemotherapy is delayed.
Authors: Kanyuka Zakhar , Kassir Sandy , Leong Nelson , Souied Osama 
Published: June 2024

e16588 Background: Bladder (urothelial) cancer is the sixth most common form of cancer in the United States of America and results in significant morbidity and mortality. American Urological Association (AUA) guidelines recommend that muscle-invasive bladder cancer (MIBC) is treated with a course of cisplatin-based multi-agent neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC). The optimal timing of NAC is not well studied. Therefore, we aimed to evaluate the impact of timing NAC treatment to compare clinical outcomes among patients at the Saskatchewan Cancer Agency (SCA). Methods: We conducted a retrospective cohort study of the SCA electronic registry, reviewing the clinical and pathological data of 42 patients diagnosed with MIBC and treated with platinum-based NAC from January 2000 to December 2018. Patients with non-MIBC, metastatic bladder cancer, non-urothelial carcinoma histology, and charts with insufficient data were excluded. Survival analysis using Kaplan-Meier methods and log rank tests were utilized to compare overall survival (OS), disease recurrence, and post-RC surgical pathological staging of patients with respect to pre-specified time intervals between diagnosis, NAC and RC. Results: Patients who received NAC later than 8 weeks after diagnosis were more likely to have reduced OS (HR 1.25, 95% Confidence Interval (CI): 1.09-1.35, p=0.02). They also were more likely to have lymph node involvement (HR 1.63, 95% CI: 1.03-1.77, p=0.006). Patients who received RC more than 6 weeks after NAC completion were more likely to have more advanced primary tumour staging on pathology (HR 1.95, 95% CI: 1.3-2.09, p=0.01), but did not have significantly decreased OS (HR 1.88, 95% CI: 0.48-1.95, p=0.08). Delayed NAC (HR 2.77, 95% CI: 1.44-4.57, p<0.001) and RC (HR 1.50, 95% CI: 1.08-3.10, p<0.001) were associated with increased recurrence. Age, sex, body mass index, NAC regimen, and prior intravesical treatment were not statistically associated with OS upon analysis with univariate cox proportional hazard regression analysis. Conclusions: This review suggests an OS benefit by reducing the time from diagnosis to NAC in MIBC patients. This finding contrasts other studies that do not demonstrate any impact of delayed NAC on OS. These findings align with other works that do not show a survival detriment of delaying RC beyond 6 weeks after NAC completion. However, delaying surgery is associated with more advanced pathologic tumour staging. This study identifies the possibility of an association between delays in treatment delivery and worse clinical outcomes in some cohorts. Accordingly, further investigation of interval timing can better inform treatment planning and resource allocation in the management of patients with MIBC.