bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-line therapy for metastatic renal cell carcinoma with pancreatic metastases: Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).
Authors: Roussel Eduard , Kinget Lisa , Beuselinck Benoit , Albersen Maarten , Wells Connor , Ernst Matthew Scott , Donskov Frede , Schmidt Andrew Lachlan , Szabados Bernadett , Pal Sumanta K. , Meza Luis A , Agarwal Neeraj , Weickhardt Andrew James , Davis Ian D. , Alva Ajjai Shivaram , Wood Lori , Porta Camillo , Choueiri Toni K. , Heng Daniel Yick Chin , Navani Vishal 
Published: February 2022

317 Background: Metastatic renal cell carcinoma (mRCC) with pancreatic metastases (PM) is characterised by heightened angiogenesis, which is associated with improved outcomes with vascular endothelial growth factor (VEGF) inhibitors. We aimed to compare the efficacy of first-line (1L) ipilimumab/nivolumab (IOIO) vs. anti-PD(L)1/anti-VEGF (IOVE) vs. VEGF monotherapy (VE) in mRCC patients with and without PM. Methods: We performed a retrospective analysis of patients with and without PM, using the IMDC. Sites of metastases were captured at initiation of 1L. Patients with PM could also have metastases at other sites. We studied overall survival (OS) from start of 1L therapy using Cox regression, adjusted for IMDC risk groups. Kaplan Meier survival curves were generated. Results: 543/7,634 (7%) patients had PM. Patients with PM in the overall population had improved OS compared to those without, 56 vs 25.6 months respectively (HR 0.63, 95% CI 0.55-0.73, p<0.0001). When examining the effect of PM within 1L options, those treated with IOVE exhibited a longer OS if PM were present vs absent, median not reached vs 45 months respectively (HR 0.41, 95% CI 0.18-0.93 p=0.03). This association was also seen in patients with treated with 1L VE, in those with PM vs absent, median 53.1 vs 25.1 months respectively (HR 0.65, 95% CI 0.55-0.76, p <0.0001). Contrastingly there was no difference in median OS of patients with or without PM in patients receiving IOIO, 41.4 vs 44.4 months respectively (HR 0.86, 95% CI 0.48-1.56, p=0.62). Comparing the outcomes between 1L therapies in patients with PM the median OS of IOVE vs VE was not reached vs 53.1 months respectively (HR 0.37, 95% CI 0.16-0.83 p=0.02). Conversely, upfront VE and IOIO had a similar median OS of 53.1 vs 41.4 months respectively (HR 0.81, 95% CI 0.45-1.47 p=0.49). We were unable to find any difference in OS between those treated with IOVE vs IOIO, median not reached vs 41.4 months respectively (HR 0.52 95%, CI 0.19-1.45, p=0.21), but the low event rate limited this interpretation. Conclusions: We found that the presence of PM leads to an indolent biological behavior and was associated with improved outcomes when 1L therapy included a VE component. PM patients had comparable OS outcomes on 1L VE and 1L IOIO therapy, but improved OS when treated with 1L IOVE. Anti-angiogenic therapy may be necessary to optimize outcomes in PM and this warrants prospective evaluation. [Table: see text]
Tivozanib (T) as first-line (1L) treatment of metastatic renal cell carcinoma (mRCC): A real-world outcome review in North-West of England (NWE), UK.
Authors: Heseltine Jonathan , Allison Jennifer , Wong Sam , Prasad Kellati , Wong Helen , Oong Zhu , Charnley Natalie , Law Andrea , Parikh Omi , Pillai Manon Rhys , Waddell Tom , Griffiths Richard , Chow Shien 
Published: February 2022

335 Background: The TIVO-1 study demonstrated improved PFS in mRCC patients (pts) undergoing 1L treatment with T compared with sorafenib. We previously presented outcomes of our experience of T in 4 cancer centres in NWE. Here we present updated outcomes with longer follow-up (FU). Methods: mRCC pts commencing 1L T March 2017- May 2019 were identified. Outcomes of interest included overall response rate (ORR), survival (OS, PFS) and toxicity. Data cut off for this update was 30/11/2020. Results: 113 pts were identified with characteristics as in the table. Median FU was 25.9 mo (18.3-44.7mo), 18% pts remain on treatment at data cut-off. 88.5% commenced T at full dose, of which 67% maintained dose intensity. 11.5% commenced T with dose reduction due to prior TKI toxicities or comorbidities. Median number of cycles was 7 (1-33). In terms of efficacy, ORR was 29% (CR 0%, PR29%, SD39%, PD26%, NE 6%) and median PFS was 9.0 months (95% C.I. 6.0-12.1mo). Median PFS by IMDC risk group was: F= 23.0 months (95% C.I. 7.6-38.4mo); I= 10.0 months (95% C.I. 6.3-13.7mo); P= 3.0 months (95% C.I. 1.5.- 4.5mo), p value<0.0001. Median OS was 25.0 months (95% C.I. 15.4-34.6mo). Median OS by IMDC risk group was: F= NR with 72% alive at data cut-off; I= 26.0 months (95% C.I. 17.9-34.1mo); P= 7.0 months (95% C.I. 4.4-9.6mo), p value<0.0001. Adverse events (AEs) of any grade occurred in 77% (≥G3 13%) including fatigue 42% (≥G3 0%), diarrhoea 19% (≥G3 < 1%), mucositis 24% ( ≥G3 2%), anorexia 12% (≥G3 < 1%); and hypertension 7% (≥G3 2%). Notable ≥G3 events included abnormal liver function 3%; vascular events 2% and seizure < 1%. 18% of patients discontinued treatment due to toxicity with no treatment-related deaths. Conclusions: Our real world experience of 1L T suggests comparable activity with randomized data and other TKIs, particularly in F and I IMDC risk groups. The low incidence of serious AEs makes it an attractive option if unsuitable for combination therapies. [Table: see text]
The impact of baseline peripheral cytokines on survival in metastatic clear cell renal cell carcinoma (RCC) treated with nivolumab: NIVOREN GETUG-AFU 26 Translational study.
Authors: Carril Lucia , Naigeon Marie , Dalban Cécile , Desnoyer Aude , Rioux-Leclercq Nathalie , Sautes-Fridman Catherine , Meylan Maxime , Vano Yann-Alexandre , Beusenlick Benoit , Chouaib Salem , de Oliveira Caroline , Tantot Florence , Escudier Bernard , Albiges Laurence , Chaput Nathalie 
Published: February 2022

379 Background: The NIVOREN GETUG-AFU 26 study reported safety and efficacy of nivolumab in patients with RCC in a “real world setting”. A translational research program was launched to quantify baseline cytokine levels and correlate them with outcomes to nivolumab. Methods: Extreme responder patients (pts) treated with nivolumab as part of the phase II NIVOREN GETUG-AFU 26 were included in this TRAINING cohort. A panel of 14 different plasma cytokines and proteins (VEGF, VCAM-1, IL-6, IL-7, IL-8, IL-10, APRIL, BAFF, 4-1BB, BCA, SDF-1, MDC, IFN-gamma and TNF-alpha) were quantified for each plasma sample using the Elisa-based Meso Scale Discovery electrochemiluminescence assay. The association between baseline cytokine levels and objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) was evaluated. Results: Overall, 80 pts, 40 responders and 40 progressors, were included for cytokine analysis. Baseline characteristics were similar to the overall trial population. The IMDC risk score breakdown was 11.3% good, 56.3% intermediate and 32.5% poor. With a median follow-up of 21.2 months, mOS data was immature at data cut-off. Overall survival rate was 67.3% at 12 months and median PFS was 3.8 months. Increased levels of IL-6 (75th percentile=P75), IL-7 (P75), IL-8 (P50) and VEGF (P50) were significantly negatively associated with survival (IL-6: HR=2.44, p=0.0112; IL-7: HR=2.38, p=0.0123; IL-8: HR=2.80, p=0.0045, and VEGF: HR=2.43, p=0.0133). 4-1BB (P50) was associated with improved OS (HR=0.39, p=0.0375). Higher levels of IL-8 (P50) and VEGF (P50) were associated with worse PFS (IL-8: HR=2.50, p=0.0133, and VEGF: HR=1.96, p=0.0132) and worse ORR (IL-8: p=0.013, and VEGF: p=0.044). Except for IL-8 and VEGF, no other associations with response were observed. Conclusions: Higher baseline plasma levels of IL-6, IL-7, IL-8 and VEGF were significantly associated with worse survival outcomes in mRCC pts treated with nivolumab within TRAINING cohort of the NIVOREN trial. In contrast, 4-1BB was significantly associated with improved OS. IL-8 and VEGF were also associated with worse PFS and ORR. VALIDATION cohort within the entire NIVOREN study is ongoing.
Racial, ethnic, and geographical differences in testicular cancer mortality trends in the United States.
Authors: Ghosh Anushka , Goldberg Saveli , Chino Fumiko , Efstathiou Jason A. , Kamran Sophia C. 
Published: February 2022

409 Background: Incidence rates of Testicular cancer (TC) have been slowly increasing in the United States in recent decades. Prior research has identified racial disparities in mortality; however, these trends have not been extensively evaluated. Given that TC has a diverse presentation, this study was undertaken to establish racial, ethnic, geographical differences in longitudinal mortality trends. Methods: Age-adjusted cancer mortality rates for TC were obtained for men in the United States from the CDC Wide-ranging Online Data for Epidemiologic Research database. Testicular cancer-specific mortality (TCSM) rates from 1999-2019 were calculated using linear regression. Trends in mortality by race (White versus Black), ethnicity (Hispanic versus non-Hispanic), urbanization, and census region were analyzed using SAS 9.4. TCSM rates were compared by F-test. A two-sided hypothesis test was performed for p-values, where values < 0.05 were considered statistically significant. Results: From 1999-2019, overall age-adjusted TCSM has been slowly, but not significantly, increasing per year (Table). There was worsening TCSM rates for Hispanics (+)0.0019 per 100,000 compared to non-Hispanics (-)0.003; p=0.010. Black men had slightly improved TCSM rates/year (-0.0007) compared to white men (+0.0006); p=0.049. Significant geographical differences in mortality rates were observed, with a decreasing TCSM rate of (-)0.00092 the Northeast and an increasing rate of (+)0.00086 in the West (p = 0.032 for difference between slopes). Among urbanization categories, TCSM rates in Large Central Metros regions (central counties in metro areas with population > 1 million) and Small Metro regions (counties with population 50,000-249,999) were significantly different [(-)0.0004 and (+)0.0022 respectively; p =0.048]. All other comparisons were not significant. Conclusions: Using comprehensive, contemporary data on TCSM over 2 decades, we found significant differences in TCSM rates. Mortality rates from TC have been increasing, particularly among Hispanics. Understanding racial, ethnic, and geographical trends in TCSM rates is important in treating men with the disease and, ultimately, reducing deaths caused by TC.[Table: see text]
Early changes in peripheral blood neutrophil-lymphocyte ratio (NLR) to predict outcomes with immune checkpoint inhibitors (ICIs) for metastatic urothelial carcinoma (mUC).
Authors: Thomas Jonathan , Riaz Irbaz Bin , Freeman Dory , Adib Elio , Nuzzo Pier Vitale , El Zarif Talal , Davidsohn Matthew , McClure Heather , Curran Catherine , Ravi Praful , Yadav Ritu , Kalluri Uttam , Zeineddine Jana , Matar Ayah , McGregor Bradley Alexander , Mantia Charlene , Sonpavde Guru P. 
Published: February 2022

449 Background: ICIs have provided advances in the therapy of mUC. However, the objective determination of benefit from ICIs determined by radiographic imaging may take months and may be confounded by pseudoprogression. Peripheral blood cells appear to reflect tumor microenvironment immune infiltrating cells. Given the known prognostic impact of baseline peripheral blood NLR, we aimed to investigate dynamic early changes in NLR as a biomarker of benefit in patients (pts) with mUC. Methods: Deidentified data from mUC pts who were treated with ICIs at Dana Farber Cancer Institute from 2015 to 2020 were reviewed retrospectively. Demographic data (age, gender), setting (untreated vs. post-platinum), sites of metastasis, performance status (PS), platelet count, and NLR at baseline and 3-4 weeks after initiating the ICI were collected. We assessed the association of NLR at baseline and 3-4 weeks after starting the ICI with any regression of tumor (ART) and overall survival (OS). A multivariable logistic regression model and Cox proportional-hazards model was employed to identify the association of NLR changes with ART and OS, respectively, using backward selection. Results: A total of 144 pts were included. The median age was 76 years and 100 (69.3%) were male. Overall, 54.8% (n=79) had ART and the median OS was 15.2 (12.2-23.5) months. 37.5% (n=54) were platinum naive and the remaining received post-platinum ICI therapy. In the multivariable models (Table), an increase in NLR, defined as an increase in NLR by ≥1.0 from baseline at 3-4 weeks was significantly associated with lower odds of ART (Odds Ratio (OR)= 0.80; 95% CI = 0.70-0.90; p = 0.0004) and worse OS (HR = 1.08; 95% CI = 1.05-1.11; p < 0.0001). The presence of liver metastasis was associated with lower odds of ART (OR = 0.30; 95% CI = 0.13-0.70; p = 0.006) and OS (HR 2.73; 95% CI 1.71 - 4.36; p<0.0001). Conclusions: Change in NLR in the first 4 weeks after initiating ICI for mUC was associated with tumor regression and survival in pts with mUC. Change in NLR may assist in early identification of benefit as well as identification of pts who may have progression of disease. Further validation is warranted to facilitate the early discrimination of benefit from ICIs in pts with mUC.[Table: see text]
Comprehensive genomic profiling of urine DNA for urothelial carcinoma detection and risk prediction.
Authors: Salari Keyan , Lee Jason J. , Bicocca Vincent T. , Caruso Vincent , Mazzarella Brian C. , Phillips Kevin G. , Levin Trevor G. , Feldman Adam S. 
Published: February 2022

450 Background: Clinical diagnosis and risk stratification of patients with urothelial carcinoma (UC) remains a challenge, with high rates of recurrence and disease progression following treatment. Urinary comprehensive genomic profiling (uCGP) has significant potential to aid in both diagnosis and prognostication of non-muscle-invasive and muscle-invasive disease. Methods: uCGP was performed on urine specimens collected at 9 centers across the US from 577 subjects prior to cystoscopy. 152 subjects were UC tumor positive (de novo and recurrence), 191 had a history of UC but negative by surveillance cystoscopy at time of collection, and 234 were urology control subjects undergoing cystoscopy without evidence of UC. Urine DNA was sequenced and comprehensively profiled across 60 genes for 6 classes of mutations using the CLIA-validated UroAmplitude test. Disease detection and molecular grade (high grade vs. low grade) algorithms were trained (n=345) and validated (n=232) in independent cohorts. Results: Among UC tumor positives, grade distribution was 53% high grade, 41% low grade, and 6% unknown. Stage distribution was Tis (5%), Ta (57%), T1 (16%), ≥T2 (15%), Tx (7%). 99% of tumor positive patients had one or more mutation identified. Interestingly, 69% of UC surveillance negative and 49% of urology controls also had at least one high impact mutation. The prevalence of mutations among controls necessitates machine learning algorithms to classify disease status. In validation, de novo tumor diagnosis demonstrated sensitivity of 93.8% and specificity of 89.4% and a NPV of 98.8% in urology controls. Recurrent tumors were detected with a PPV of 73.5%, sensitivity of 62.5% and specificity of 89.0% in patients with a history of UC. Molecular grading predicted high-grade with a PPV of 90.9% and a specificity of 96.7% compared to pathology. Urinary TP53 mutations were enriched in ≥T2 tumors relative to Ta (OR=14.8 [95%CI 4.6-47.5], P=0.00001). Copy number alterations were also associated with increased risk of muscle invasion, metastasis, and enriched for CIS relative to Ta tumors (≥T2: OR=6.4 [95%CI 1.8-22.9], P=0.019; CIS: OR=10.5 [95%CI 1.9-58.9], P=0.04). Conclusions: We developed and validated a uCGP test that provides robust noninvasive detection of UC across a diverse group of patients and clinical contexts, including non-muscle-invasive and muscle-invasive UC. Mutations with actionable or prognostic value are found in most subjects. These data suggest that uCGP classifies tumor presence with better performance than traditional urinary biomarkers. Importantly, uCGP identifies genomic markers of muscle invasion, metastasis, and CIS. With longer term follow-up, uCGP mutational profiles may reveal important prognostic information regarding risk of disease recurrence and progression. Additional studies are underway to further support the generalizability of these findings.
Impact of selection bias on outcomes in veterans with muscle-invasive bladder cancer receiving bladder preserving trimodality therapy.
Authors: Kumar Abhishek , Kotha Nikhil V. , Nelson Tyler J. , Cherry Daniel R. , Stewart Tyler F. , McKay Rana R. , Rose Brent S. 
Published: February 2022

462 Background: Retrospective studies using large registries comparing outcomes between radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC) to trimodality therapy (TMT), which includes transurethral resection of bladder tumor followed by chemoradiation, often cannot distinguish whether patients receiving TMT were eligible for cystectomy but declined or simply ineligible for cystectomy. The objective of this study was to compare survival outcomes of patients with MIBC receiving TMT stratified by whether they were cystectomy-eligible to patients receiving RC +/- NAC. Methods: We used the national Veterans Affairs’ (VA) database to identify patients diagnosed between 2000-2017 with urothelial histology, MIBC (T2-4a/N0-3/M0) who underwent RC or TMT. Overall survival (OS) was evaluated with multivariable Cox proportional hazards model. Bladder cancer-specific mortality (BCSM) was evaluated with multivariable Fine-Gray regression. We conducted a chart review of clinical notes to ascertain if patients were eligible for cystectomy. Results: Overall 2306 Veterans with MIBC were included: 1472 (64%) with RC without NAC, 506 (22%) with RC-NAC, 107 (4.6%) with TMT eligible for RC, and 221 (9.4%) with TMT ineligible for RC. Median follow up time was 4.7 years. Patients receiving RC were on average 10 years younger, had higher creatinine clearance, and fewer comorbidities than those receiving TMT. Cystectomy-eligible TMT patients had higher creatinine clearance and fewer comorbidities than those ineligible for cystectomy. On multivariable analysis, compared to RC-NAC, TMT in cystectomy-eligible patients was associated with similar OS (hazard ratio [HR] 0.99; 95% confidence interval [CI] 0.76 - 1.28; p = 0.93) and BCSM (HR 1.02; 95% CI 0.71-1.47; p = 0.91). Compared to RC-NAC, TMT in cystectomy-ineligible patients was associated with inferior OS (HR 1.39; 95% CI 1.13 - 1.71; p = 0.002) and BCSM (HR 1.61; 95% CI 1.23 - 2.10; p < 0.001). Conclusions: There is a significant selection bias among patients with MIBC receiving TMT. Cystectomy-eligible patients receiving TMT likely have similar survival outcomes as those receiving RC. Comparisons between RC and TMT in large registry data that lack information regarding eligibility for cystectomy in the TMT arm may be unreliable.
Management, surveillance patterns, and costs associated with low-grade papillary (Ta) nonmuscle-invasive bladder cancer.
Authors: Bree Kelly K. , Shan Yong , Hensley Patrick J. , Lobo Niyati , Hu Chengrui , Tyler Douglas S. , Chamie Karim , Kamat Ashish M. , Williams Stephen B. ,   IBCG Center for Bladder Cancer Population Health and Health Services Research
Published: February 2022

464 Background: Low-risk non-muscle invasive bladder cancer (NMIBC) is associated with extremely low rates of progression and cancer-specific mortality, however, these patients may often receive non-guideline recommended and potentially costly surveillance and treatment(s). We sought to describe current surveillance and treatment practices, oncologic outcomes, and cost of care for low-grade papillary (LG Ta) NMIBC and identify predictors of increased cost of care. Methods: This population-based cohort study identified 13,054 patients diagnosed with LG Ta tumors in the Surveillance, Epidemiology and End Results-Medicare linked database from January 1, 2004 through December 31, 2013. The primary outcome was to characterize trends in population-level surveillance and treatment practice patterns over time among LG Ta patients. The secondary outcomes were recurrence, progression, and costs of care. Results: Of the 13,054 patients who met inclusion criteria, 9,596 (73.5%) were male and 3,485 (26.5%) were female, with a median age of 76 (Interquartile Range (IQR): 71–81) years. Rates of surveillance cystoscopy increased over the study period (79.3% to 81.5%, p = 0.007) with patients undergoing a median of three cystoscopies per year (IQR: 2–4). Rates of upper tract imaging utilization also increased, namely the use of computed tomography (CT) or magnetic resonance imaging (MRI) (30.4% to 47%, p < 0.001), with most patients undergoing a median of two imaging tests per year. Similarly, the use of urine cytology or other urine biomarkers also increased (44.8% to 54.9%, p < 0.001). Rates of compliance with current guidelines decreased over time suggesting overutilization of all surveillance testing modalities. A total of 17.2% of patients received intravesical bacillus-Calmette Guerin (BCG) and 6.1% received intravesical chemotherapy (excluding single perioperative dose). Among all LG Ta patients, 1.7% and 0.4% experienced disease recurrence and progression, respectively. Total annual median costs of LG Ta surveillance and care increased 1.6-fold from $34,792 to $53,986 over the study period, with increased expenditures noted among those with disease recurrence ($53,909 and $76,669). Conclusions: Despite low rates of disease recurrence or progression, rates of surveillance testing increased during the study period. Annual cost of care increased over time, particularly among patients with recurrent disease. Efforts to improve adherence to current practice guidelines, with the focus on limiting overutilization of surveillance testing and overtreatment, may mitigate associated rising costs of care.