bluuebunny/crossref_metadata_2025_split huggingface dataset:
The comparison of cytoreductive nephrectomy (CN) with tyrosine kinase inhibitor therapy alone in patients with primary metastatic renal cell carcinoma (mRCC).
Authors: Hatakeyama Shingo , Naito Sei , Numakura Kazuyuki , Kato Renpei , Koguchi Tomoyuki , Kojima Takahiro , Kawasaki Yoshihide , Kandori Kandori , Tsushima Eiki , Nishiyama Hiroyuki , Ito Akihiro , Kojima Yoshiyuki , Habuchi Tomonori , Obara Wataru , Tsuchiya Norihiko , Ohyama Chikara 
Published: March 2021

304 Background: We aimed to compare overall survival (OS) between patients with metastatic renal cell carcinoma (mRCC) treated by cytoreductive nephrectomy (CN) and those not treated by CN. Methods: We retrospectively evaluated 278 patients with mRCC treated with first-line tyrosine kinase inhibitors (TKIs) between January 2008 and November 2019. Patients were divided into two groups, CN group (immediate or deferred CN) and systemic TKI therapies alone without CN (Ctrl group). The OS was compared in all patients between the Ctrl and CN groups, between the Ctrl and immediate CN groups, between the Ctrl and deferred CN groups, and between the deferred CN and immediate CN groups. Analyses were weighted using the propensity score–based inverse probability of treatment weighting (IPTW) method to adjust for group imbalances. Results: The median age of the patients was 65 (range 59–73) years. Of the 278 patients, 132 and 146 were in the Ctrl and CN (immediate: 107 and deferred: 39) groups, respectively. A significant difference was noted between the Ctrl and CN groups in age, clinical stage, IMDC risk factors, and the number of metastatic sites. An IPTW-adjusted Cox regression analysis revealed a significant difference in OS between the Ctrl and CN groups and between the Ctrl and immediate or deferred CN groups. However, there was no significant difference in OS between immediate and deferred CN groups. Conclusions: The OS in CN group was significantly longer than that in Ctrl group even after the adjustment of potential selection biases.
A framework for living evidence synthesis in cancer: Living, interactive network meta-analysis for first-line treatment of metastatic renal cell carcinoma (mRCC).
Authors: Riaz Irbaz Bin , He Huan , Ryu Alexander J. , Siddiqi Rabbia , Naqvi Syed Arsalan Ahmed , Yao Yuan , Husnain Muhammad , Maheswari Deepa , Sipra Qurat Ul Ain Riaz , Montori Victor , Joseph Richard Wayne , Liu Hongfang , Wang Zhen , Herasevich Vitaly , Singh Parminder , Ho Thai Huu , Bryce Alan Haruo , Pagliaro Lance C. , Murad M. Hassan , Costello Brian Addis 
Published: March 2021

335 Background: Systematic reviews are outdated quickly when the evidence is rapidly evolving as the process is laborious and there is little incentive for primary author team of an index SRMA to update the evidence. Consequently, there is an epidemic of redundant SRMAs performed by different teams—sometimes with conflicted results—for treatment of first line mRCC. Methods: We have created a living, interactive systematic review (LISR)and network meta-analysis(LINMA) for the treatment of first line mRCC using an Artificial intelligence (AI) assisted framework for evidence synthesis (Living, Interactive evidence synthesis framework) (LIvE) . The framework is implemented in five-layered architecture (application layer, shared module layer, core service layer, middleware layer, and storage layer) which work together to automate the identification of new studies and analysis and semi-automate the screening and data extraction. Dynamic features such as interactive tables, figures and evidence maps are enabled using Python and JavaScript programming languages. Results: We have maintained a living, interactive evidence profile for the first line treatment mRCC since September 2019 ( LIVING WEBSITE) . Living search strategy identifies new studies as they become available. As of October 13, 2020 LISR, includes data 14 clinical trials ( PRISMA ). Baseline characteristics are summarized in an interactive table ( TABLE) . Cabozantinib& Nivolumab (Cabo-Nivo) is the highest ranked drug for improving Overall Response (OR), Progression Free Survival (PFS) and Overall Survival (OS) whereas Ipilimumab in combination with Nivolumab (Ipi-Nivo) is highest ranked drug for achieving complete response (CR). Ipi-Nivo and Atezolizumab & Bevacizumab (Ate-Bev) ranked highest and Cabo-Nivo ranked lowest for treatment related Adverse events (TRAEs). Results of network meta-analysis are summarized as interactive tables and plots ( NMA ), summary of findings tables ( MULTIPLE COMAPRISONS ) and evidence maps ( MAP ). Conclusions: LISRs can potentially reduce redundancy, increase transparency, reproducibility, enable shared-decision making (at a guideline level, or in a patient-clinician dyad) and support living guidelines.
Association of the neutrophil to eosinophil ratio with response to immunotherapy-based combinations in metastatic renal cell carcinoma.
Authors: Tucker Matthew D , Beckermann Katy , Ancell Kristin Kathleen , Schaffer Kerry , McAlister Renee , Wallace Deborah , Kaiser Elizabeth , Davis Nancy B. , Rathmell W. Kimryn , Rini Brian I. 
Published: March 2021

341 Background: Neutrophilia is known to be associated with worse prognosis in metastatic renal cell carcinoma (mRCC); however, less is known about the role of eosinophils in the response to immunotherapy (IO). We investigated the association of the baseline neutrophil to eosinophil ratio (NER) with outcomes to IO-based combination treatment in mRCC. Methods: Patients with mRCC treated with ipilimumab plus nivolumab, pembrolizumab plus axitinib, or avelumab plus axitinib at the Vanderbilt-Ingram Cancer Center were retrospectively identified. Patients on >10mg prednisone and patients with prior IO were excluded. Baseline NER (at time of first IO) and association with progression free survival (PFS), overall survival (OS), and objective response rate (ORR) were investigated. Data cutoff was 9/1/2020. Analysis for PFS and OS was performed using the log-rank test and Mantel-Haenszel method, and analysis of the odds ratio for ORR was performed using Fischer’s exact test. Results: Sixty-one patients were identified: 89% clear cell histology, 74% prior nephrectomy, 69% IMDC intermediate risk, and 72% treatment-naïve. Patients with baseline NER < median (N=31) had improved clinical outcomes compared to patients with baseline NER > median (N=30) (Table). Improvement in PFS by NER was maintained when stratified by anti-PD-1/CTLA-4 and anti-PD(L)-1/VEGF (p= 0.0062 and p= 0.049); however, differences in OS and ORR were no longer significant. The median baseline NER among patients with partial response (PR) was significantly lower at 22.7 (95% CI 18.9-31.1) vs. 51.6 (95% CI 39.5-93.1) among those with progressive disease (PD) (p= 0.0054). For comparison, the median neutrophil to lymphocyte ratio was not significantly different between PR (2.60) and PD (3.84, p= 0.056). Conclusions: Patients with a low baseline NER treated with IO-based combinations had improved clinical outcomes compared to patients with a high baseline NER. Additional investigation of this parameter in larger cohorts is warranted. [Table: see text]
Absolute eosinophil count as predictive biomarker of irAEs in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICIs).
Authors: Giorgione Roberta , Pillozzi Serena , Mela Marinella Micol , Giommoni Elisa , Paderi Agnese , Doni Laura , Pellegrini Elisa , Di Costanzo Alessandro , Antonuzzo Lorenzo 
Published: March 2021

345 Background: Nivolumab and ipilimumab are associated with immune-related adverse events (irAEs) and, to date, few biomarkers predictive of ICIs toxicity are reported in mRCC. Methods: We conducted a single-center, observational, retrospective study at Clinical Oncology Unit, Careggi University Hospital, Florence, Italy. We evaluated 43 patients (pts) with mRCC treated with ICIs from April 2013 to May 2020. Absolute Eosinophil Counts (AEC, N°/μL) were registered at baseline and at time of occurrence of irAEs. This study aims to evaluate whether the AEC could be a predictive biomarker of irAEs in patients with mRCC treated with ICIs. Results: Median age was 65 years and males were 81.4%. 10 pts received Nivolumab+Ipilimumab, while 33 pts received Nivolumab single agent. 74.4% pts (32/43) developed at least 1 irAE, 11.6% with G3-G4 irAEs. The most frequent first irAE was endocrine event (40.6% pts; 37.5% with hypo-/hyper-thyroidism). The baseline mean AEC was 163.1/μL in our cohort, in particular 132.2/μL in pts who did not develop irAEs and 176.7/μL in pts who developed irAEs (p=0.134). Among the pts who developed irAEs, the mean AEC was lower in pts with G1-G2 (153.1/μL) than in those with G3-G4 (330/μL; p=0.0013) irAEs. At the time of onset of the first irAE, the mean AEC increased to 247/μL (Δ 140.1%). Analyzing the trend of AEC from baseline to time of occurrence of irAE for the 32 pts who had developed at least one irAE, 53.1% (17 pts) showed an increasing trend; among these pts, the most frequent irAEs were endocrine occurring in 4/17 pts (23.6%). An increasing trend was also observed in the majority of pts who developed G1-2 (14/27, 51.9%) and G3-4 (3/5, 60.0%) irAEs. Additional analyzes are ongoing to identify appropriate cut-offs of AEC to better stratify patients. Conclusions: There is little evidence in the literature about the potential role of absolute eosinophil counts as a predictive biomarker of irAEs in patients with solid tumors treated with ICIs, and most refer to patients with melanoma. In this study we observed that the baseline AEC values in patients that will develop irAEs are higher than in those without irAEs and, among the former, the values are lower for patients with toxicity G1-G2 vs G3-G4. We also found an increase of the mean AEC from baseline to the onset of the first irAE. Of the patients who experience toxicity, most have an upward trend in AEC at the onset of the first irAE. Compatibly with all the limitations of a retrospective analysis, our is the first experience exploring the role of the eosinophil count in the development of irAEs in mRCC patients treated with ICIs, and a prospective study is ongoing in our Unit to confirm the role of the eosinophil count in patients treated with ICIs.
Insights on oncologist and urologist gaps in bladder (UC) and kidney (RCC) cancer education.
Authors: Parikh Kinjal , Chen Pan 
Published: March 2021

358 Background: Treatment paradigms for bladder (UC) and kidney (RCC) cancers is evolving with the advent of novel treatment approaches, personalized medicine, and combinatorial strategies. As the medical literature in the space evolves, identifying oncologists’ (oncs) and urologists’ (uros) educational gaps is important to inform continuing medical education (CME) needs and, ultimately, to improve patient outcomes. Methods: Medscape Oncology conducted a 16 question, online, incentivized survey in June 2020 targeting genitourinary (GU) cancer physicians. Respondents’ confidentiality was maintained and responses were de-identified and aggregated for analysis. Results: Results are reported for 100 respondents (50 oncs & 50 uros): In UC: Learners identified CME as mostly/very important for: Managing treatment related adverse events (trAEs) – 84% Clinical trial outcomes – 77% Timely/appropriate biomarker testing – 68% Understanding mechanism of action (MOA) and rationale of novel agents – 66% Treatment planning CME was considered mostly/very important for: All stages: non-muscle invasive (NMIBC), muscle-invasive (MIBC), and first line (1L) metastatic – 72%, 85%, 92% respectively Determining the optimal role for immunotherapy (IO) – 82% Sequencing therapies – 72% In subgroup analyses More oncs vs. uros identified biomarker testing and treatment selection as mostly/very important (p < .01) More general oncs vs. GU oncs identified education on clinical trial outcomes and sequencing of therapies as mostly/very important (p < .05) More uros vs. oncs identified NMIBC treatment education as mostly/very important (p < .01) More low vs. high volume treaters identified education on sequencing and MIBC as mostly/very important (p < .01) Rating % very experienced: Counseling on trAEs – 41% but mitigating AEs of FGFR therapies, ADCs, or IO was only: 16%, 19%, and 26% respectively In RCC: Learners identified CME as mostly/very important for: Selecting optimal 1L therapy – 80% Clinical trial outcomes – 77% Sequencing therapies – 69% Managing trAEs – 64% Understanding MOA and rationale of novel agents – 62% In subgroup analyses More general oncs vs. GU oncs identified importance of education on clinical trial outcomes and 1L treatment selection (p < .05) More low vs. high volume treaters identified importance of education on 1L treatment selection and clinical trial outcomes (p < .05) Rating % very experienced: Counseling on trAEs – 30% but mitigating AEs of targeted therapy or IO was only: 22% and 23% respectively Determining risk score – 22% Selecting 1L therapy – 28%. Conclusions: Medscape Oncology surveys provide valuable information to guide education for oncs and uros and individualize education unique to their treatment setting, patient volume, and practice coverage.
Sarcopenia prior to and following chemotherapy to predict morbidity in patients undergoing post-chemotherapy retroperitoneal lymphadenectomy (PC-RPLND).
Authors: Baky Fady , Woldu Solomon L. , Margulis Vitaly , Bagrodia Aditya 
Published: March 2021

381 Background: Patients undergoing post-chemotherapy retroperitoneal lymphadenectomy (PC-RPLND) are subject to variable but substantial risks. Unlike those patients undergoing other extirpative GU surgeries, patients undergoing PC-RPLND are usually younger and possess fewer co-morbidities. Despite this, the burden of metastatic disease and the effects of pre-operative chemotherapy may leave patients poorly conditioned prior to undergoing surgery. Sarcopenia has previously been demonstrated to predict adverse clinical outcomes in a variety of abdominal surgeries. We hypothesized that sarcopenia would be similarly predictive of morbidity and mortality in patients undergoing PC-RPLND. Methods: The records of all patients undergoing post-chemotherapy retroperitoneal lymphadenectomy for the treatment of metastatic germ cell tumors at both a public safety net hospital and an academic tertiary medical center were reviewed. Sarcopenia was assessed by measuring cross sectional area of the psoas muscle at the middle of the third lumbar vertebral body on pre-chemotherapy and preoperative computerized tomography. Psoas Muscle Index (PMI) was calculated by adjusting total psoas area for patient height (cm2/m2). Univariate and multivariate analysis was performed to assess the predictive value of sarcopenia for morbidity and mortality following PC-RPLND. Results: 90 patients underwent PC-RPLND from the year 2006-2019, of whom 81 patients had both pre-chemo and preoperative cross sectional imaging available. Prior to chemotherapy the mean PMI for this cohort was 7.32 cm2/m2, and this did not significantly change following chemotherapy mean PMI = 7.06 cm2/m2 (p = 0.44). Lower PMI both prior to (p = 0.05) and following chemotherapy (p = 0.03) were predictive of a higher risk of post-operative complication. There was a trend towards longer hospital length of stay in patients with more significant sarcopenia, however this was not clinically significant (p = 0.09). Conclusions: Sarcopenia was predictive of morbidity in patients undergoing PC-RPLND. Although sarcopenia did worsen following chemotherapy this was not statistically significant. Further assessment of sarcopenia and pre-operative nutritional status in this population may provide opportunities to reduce morbidity following PC-RPLND.
Pre-orchiectomy serum tumor markers as a predictor of recurrence in stage I germ cell tumors.
Authors: Badia Rohit R , Ghandour Rashed , Howard Jeffrey , Cheaib Joseph G , Saoud Ragheed , Eggener Scott E. , Singla Nirmish , Pierorazio Phillip M. , Bagrodia Aditya 
Published: March 2021

389 Background: Organ confined (stage IA/IB) testicular cancer has a high cure rate regardless of initial treatment modality, making it important to weigh the toxicities of treatment against potential benefits. While many clinicians routinely obtain serum tumor markers (STMs) prior to radical orchiectomy, their role in predicting recurrence in stage IA and IB testicular cancer has not been studied. Methods: A multi-institutional database of stage I testicular cancer patients diagnosed between 2006 and 2018 was created. Univariate and multivariate regression models were created to understand which factors predict recurrence. Recurrence analyses using Kaplan-Meier curves for elevated and normal pre-orchiectomy STMs were also generated. Results: 150 patients met the study criteria, of whom 16 (11%) relapsed (Table). 9 (56%) patients with recurrence had elevated pre-orchiectomy STMs, and 7 (44%) had normal pre-orchiectomy STMs. Similarly, 75 patients (56%) without relapse had elevated pre-orchiectomy STMs. Of 9 patients with elevated pre-orchiectomy STMs, 6 (67%) had normal STMs at recurrence; of 7 with normal pre-orchiectomy STMs, 4 patients (57%) had elevated STMs at recurrence. On Kaplan-Meier analysis, no association between level of pre-orchiectomy STMs and recurrence free survival was observed. Conclusions: Pre-orchiectomy STMs were not independently associated with recurrence in stage I testis cancer. Interestingly, there was also no association between positivity of pre-orchiectomy STMs and whether or not STMs were elevated at recurrence. These findings support the continued use of standard-of-care imaging and STMs in surveillance of stage IA/IB testicular cancer patients regardless of pre-orchiectomy STMs. [Table: see text]
Severe-COVID-19 and mortality among patients (pts) with prostate cancer (PCa) receiving androgen deprivation therapy (ADT).
Authors: Tucker Matthew D , Schmidt Andrew Lachlan , Hsu Chih-Yuan , Shyr Yu , Armstrong Andrew J. , Bakouny Ziad , Chapman Christina Hunter , Dawsey Scott , Gartrell Benjamin Adam , Halabi Susan , Joshi Monika , Khaki Ali Raza , Menon Harry , Puc Matthew , Sharifi Nima , Shaya Justin , Wulff-Burchfield Elizabeth Marie , Zhang Tian , Gupta Shilpa , McKay Rana R. ,   CCC19 Prostate Cancer Working Group
Published: March 2021

39 Background: The presence of progressing cancer, male sex and advanced age have been shown to increase the severity of coronavirus disease 2019 (COVID-19). Given that the androgen regulated gene TMPRSS2 has been implicated in SARS-CoV-2 viral entry, we hypothesized that ADT may improve COVID-19 outcomes. This analysis evaluated clinical outcomes of pts with PCa with concurrent SARS-CoV-2 infection and investigated the impact of ADT on occurrence of severe-COVID-19 and mortality. Methods: Data was obtained via the COVID-19 and Cancer Consortium (CCC19), a multicenter registry including >120 cancer centers with de-identified data from pts with COVID-19 and cancer. Men with confirmed SARS-CoV-2 infection and a primary diagnosis of prostate cancer were included: data cutoff of July 31, 2020. The primary endpoint was the development of severe-COVID-19 (death, ICU admission, or mechanical ventilation) among pts on ADT vs. those not on ADT at time of COVID-19 infection. Secondary endpoints included 30-day mortality based on ADT use. Mortality and development of severe-COVID-19 were assessed in Pts grouped by therapy: 1st generation androgen receptor inhibitor (ARI-1), 2nd generation ARI (darolutamide, enzalutamide, apalutamide, ARI-2), abiraterone/prednisone, and chemotherapy. Propensity score matching was utilized. Logistic regression was utilized to adjust for age, ECOG PS, comorbidities, and race. Results: 589 pts were included; median follow-up was 42 days (IQR 25-90) and 62% (363/589) were hospitalized. Severe-COVID-19 developed in 28% of pts and the all-cause 30-day mortality rate was 19%. There was no significant difference in the development of severe-COVID-19 or 30-day mortality between Pts on ADT vs not on ADT, whether using descriptive statistics with the entire population or using the propensity score matched population (Table). Among the descriptive population, the numerical rates of severe-COVID-19 and mortality were lowest in Pts receiving ARI-2, but sample size was low. Conclusions: The overall 30-day mortality rate and percentage developing severe-COVID-19 were high. There was no statistical difference in the development of severe-COVID-19 or mortality based on receipt of ADT; however, this analysis is limited by the retrospective nature and small N after propensity-matching. [Table: see text]
First results from the phase 3 CheckMate 274 trial of adjuvant nivolumab vs placebo in patients who underwent radical surgery for high-risk muscle-invasive urothelial carcinoma (MIUC).
Authors: Bajorin Dean F. , Witjes Johannes Alfred , Gschwend Jürgen , Schenker Michael , Valderrama Begoña P. , Tomita Yoshihiko , Bamias Aristotelis , Lebret Thierry , Shariat Shahrokh , Park Se Hoon , Ye Dingwei , Agerbaek Mads , Collette Sandra , Unsal-Kacmaz Keziban , Zardavas Dimitrios , Koon Henry B. , Galsky Matt D. 
Published: March 2021

391 Background: The standard of care (SOC) for patients (pts) with MIUC is radical surgery ± cisplatin-based neoadjuvant chemotherapy (chemo), but many pts are cisplatin-ineligible. There is no conclusive evidence supporting adjuvant chemo in pts who did not receive neoadjuvant chemo and in those with residual disease after neoadjuvant cisplatin. This phase 3 trial of adjuvant nivolumab (NIVO) vs placebo (PBO) in pts with MIUC after radical surgery ± neoadjuvant cisplatin (CheckMate 274) aims to address an unmet need in these pts. We report the initial results. Methods: This is a phase 3, randomized, double-blind, multicenter trial of NIVO vs PBO in pts with high-risk MIUC (bladder, ureter, or renal pelvis) after radical surgery. Pts were randomized 1:1 to NIVO 240 mg Q2W or PBO for ≤ 1 year of adjuvant treatment. Pts had radical surgery within 120 days ± neoadjuvant cisplatin or were ineligible/declined cisplatin-based chemo, evidence of UC at high risk of recurrence per pathologic staging, were disease-free by imaging, and ECOG PS ≤ 1. Primary endpoints: disease-free survival (DFS) in all randomized pts (ITT population) and in pts with tumor PD-L1 expression ≥ 1%. DFS was stratified by nodal status, prior neoadjuvant cisplatin, and PD-L1 status. Non–urothelial tract recurrence-free survival (NUTRFS) in ITT pts and in pts with PD-L ≥ 1% is a secondary endpoint. Safety is an exploratory endpoint. Results: In total, 353 pts were randomized to NIVO (PD-L1 ≥ 1%, n = 140) and 356 pts to PBO (PD-L1 ≥ 1%, n = 142). The primary endpoint of DFS was met in ITT pts (median follow-up, 20.9 mo for NIVO; 19.5 mo for PBO) and in pts with PD-L1 ≥ 1%. DFS and NUTRFS were improved with NIVO vs PBO in both populations (Table). DFS improvement with NIVO was generally consistent across subgroups. Grade 3–4 treatment-related adverse events (TRAEs) occurred in 17.9% and 7.2% of pts in the NIVO and PBO arms, respectively. Conclusions: NIVO demonstrated a statistically significant and clinically meaningful improvement in DFS vs PBO for MIUC after radical surgery, both in ITT pts and pts with PD-L1 ≥ 1%. AEs were manageable and consistent with previous reports. These results support adjuvant NIVO as a new SOC for pts with MIUC with high risk for recurrence despite neoadjuvant chemo or those ineligible for and/or declining cisplatin-based chemo. Clinical trial information: NCT02632409 . Research Sponsor: Bristol Myers Squibb[Table: see text]