bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prostate-specific membrane antigen expression in endothelial cells of renal tumor-associated neovasculature and risk of recurrence for renal cell carcinoma.
Authors: Kikugawa Tadahiko , Kagimoto Keito , Watanabe Ryuta , Miura Noriyoshi , Saika Takashi 
Published: January 2024

377 Background: PSMA is highly expressed in prostate epithelial cancer cells and used not only for diagnostic but also for therapeutic purposes. Despite its name, PSMA is not specific in prostate cells and is also expressed endothelial cells within the neovasculature of other tumors including renal cell carcinoma. PSMA is particularly the correlation of increased PSMA expression with prostate cancer aggressiveness, but is unknown in renal cell carcinoma patients. Here we estimate whether PSMA expression in endothelial cells of renal tumor-associated neovasculature is associated with pathological venous invasion and prognosis for patients after renal tumor surgery. Methods: A total of 45 patients who underwent radical or partial nephrectomies performed at our institution were included in this study. We investigated pathological venous invasion and PSMA expression in tumor-associated vessels around renal cell carcinoma by immunostaining using removed tumor tissue. The PSMA immunostain was evaluated in tumor-associated vessels according to the staining intensity and divided into three groups: weak, moderate, and strong, respectively. Results: Higher PSMA expression group is increased the percentage of patients with histologically observed venous invasion. The level of PSMA immnostain were detected in 18 cases at weak, 11 at moderate, 16 at strong. Ten patients after surgery had recurrence during the observation period, and the prognosis was worse in the group with strong PSMA expression in tumor-associated vessels around renal cell carcinoma. Conclusions: PSMA expression in endothelial cells of renal tumor-associated neovasculature may be a novel prognostic factor for renal cell carcinoma.
Fluorescence in situ hybridization utility in the care management of renal cell carcinoma (prospective study, 30 cases).
Authors: Ben Tayeb Rafik , Mziyene Mohamed , Tahiri Layla , Bouguenouch Laila , El Fatemi Hinde 
Published: January 2024

378 Background: In Morocco, Kidney cancer is the 18th most common tumour and the 19th lethal cancer in 2020. The average age of diagnosis is 65 years and men are more affected. Molecular studies of renal cell carcinoma (RCC) allowed the detection of several genetic abnormalities in each histological subtype. These aberrations got different diagnostic value depending on their specificity, prognostic implication and for some a therapeutic utility since the development of targeted therapies. The aim of our study is to evaluate the utility of fluorescence in-situ hybridization (FISH) in the diagnostic and the prognostic categorization of patients with renal cell carcinoma. Methods: We included prospectively cases of RCC diagnosed after histological examination and immunohistochemistry analysis for some cases. The methodology consisted in highlighting by FISH molecular abnormalities for each histological subtypes using Zytolight probes. Probes were chosen depending on the histological diagnosis and their corresponding molecular abnormalities. Results: A total of 30 cases of RCC were included. Clear cell carcinoma (ccRCC) represented 56,6%(17 cases) followed by papillary RCC (pRCC) with 20% (6 cases), chromophobe RCC (chRCC) with 10% (3 cases), 2 cases (6,6%) with uncertain diagnosis clear cell carcinoma or papillary carcinoma and one case of renal oncocytoma (RO) (3,3%), tubulo-cystic RCC tcRCC (3,3%). The FISH method supported the morphological diagnosis in all cases except in one biopsy diagnosed histologically as a ccRCC and this method allowed the diagnosis correction to a pRCC by the detection of a polysomy of chromosome 17 described in this histological subtype. The FISH method can also be used in prognostic categorisation of patients by the detection of some genetic aberrations with a prognostic implication like the loss of CDKN2a located in the long arm of chromosome 9 which predict a worse diagnosis. Conclusions: FISH method got an good performance in the diagnostic approach of RCC especially in cases with non-conclusive histology and immunohistochemistry. It can also be used in the prognosis of this tumour in addition to other histo-prognostic factors. This method will lead to more precision in diagnosis and better care management personalisation in RCC.
Criteria and indicators to evaluate quality of care in genitourinary tumor boards.
Authors: Puente Javier , Algaba Arrea Ferran , Buisán Oscar , Castellano Daniel , Duran Ignacio , Fernández Ávila Juan José , Gómez-Iturriaga Alfonso , Parada Blázquez Mariano Jose , Pérez Fentes Daniel , Sancho Gemma , Vallejo Casas Juan Antonio , Gratal Paula , Pardo Maria Teresa , Guillem Vicente 
Published: January 2024

388 Background: Multidisciplinary Tumor Boards are an essential component of patient management, as they integrate input from various healthcare professionals to make comprehensive decisions about patient care. Management of patients with genitourinary (GU) tumors particularly relies on these multidisciplinary Tumor Boards. However, there are no guidelines on how these groups should operate. Methods: A systematic literature review was conducted to identify criteria useful to evaluate quality in GU Tumor Boards (GUTB); publication dates were January 2016 to December 2021. A scientific committee—comprising 12 GU specialists from several disciplines—reviewed the literature findings, proposed a list of criteria, and developed and selected indicators using the Delphi method in a first round. Thirty-nine experts from various disciplines (urology, radiation oncology, radiology, medical oncology, nuclear medicine, hospital pharmacy, and pathology) participated in the second round of the Delphi method to evaluate the indicators. In both rounds the appropriateness and utility of the criteria and/or indicators were scored using a 9-point Likert scale (1, extremely inappropriate or not useful; 9, extremely appropriate or useful). Consensus was defined as at least two-thirds of Delphi respondents selecting a score sub-category (1–3, 4–6, or 7–9) that encompassed the median score of the group. Results: Forty-eight articles were selected from the literature review and were used to develop a list of 67 initial criteria. The scientific committee narrowed these criteria down to 45 to evaluate the quality of GUTB, covering five dimensions: organization (11 criteria), personnel (5 criteria), protocol and registry (21 criteria), resources (6 criteria), and interaction with patients (2 criteria). Then, 33 indicators were developed and evaluated in the first round of Delphi, which led to a selection of 26 indicators. In the second round the group of experts reached consensus on the appropriateness of all 26 indicators and on the utility of 24 of them. Finally, indicators were compiled into a list, including how they should be measured, so that they can be easily used in clinical practice. Conclusions: Criteria and indicators were developed by this working group to evaluate the quality of GUTB, aiming to serve as a guide to improve quality of care and achieve better outcomes in patients with GU.
Management, outcomes and predictors of recurrence in chromophobe renal cell carcinoma: Results from the Canadian Kidney Cancer information system (CKCis).
Authors: Arenovich Erica , Breau Rodney H. , Mallick Ranjeeta , Rendon Ricardo A. , Feifer Andrew , Pouliot Frederic , Tanguay Simon , Lavallee Luke , Lattouf Jean-Baptiste , Nayak Jasmir G. , Bhindi Bimal , Bansal Rahul K. , Finelli Antonio , Mannas Miles , Richard Patrick O. , Lalani Aly-Khan A. , Heng Daniel Yick Chin , Bjarnason Georg A. , Basappa Naveen S. , Wood Lori 
Published: January 2024

389 Background: Chromophobe RCC (chRCC) make up 5% of all RCC however data regarding baseline demographics, management, outcomes, and predictors of recurrence and survival is lacking. Methods: The Canadian Kidney Cancer Information System (CKCis) is a multi-institutional prospective cohort. Patients (pts) with clinically localized chRCC between Jan 2011-Aug 2023 were included. Descriptive statistics were used, time to recurrence and death were estimated using Kaplan-Meier estimates and associations were determined using Cox proportional hazards models. Results: chRCC made up 5.3% of all RCC pts in CKCis and only 2.4% presented with metastatic disease. This study cohort includes 797 pts who presented with localized disease. Median follow up 4.1 yrs, mean age 58.4 yrs and male in 58.5%. Management included: surgery 90.2%, surveillance 5.5%, or other local modalities 3.3%. Recurrence occurred in 59 pts (7.4%): 50 (85%) with metastases, 7 (12%) with local recurrence, and 2 (3.4%) with contralateral tumors. Median time to recurrence was 2 yrs. Management of recurrences included: systemic therapy in 46%, radiation in 29%, metastasectomy in 25%, surveillance in 8%. 5 and 10 year overall survival was 95% and 83% in all pts, 97% and 90% if no recurrence and 75% and 44% if recurrence. In the 90.2% (718 pts) treated with curative surgery, predictors of recurrence on multivariate analysis include: higher T stage, necrosis, and sarcomatoid features. Predictors of worse survival include: sarcomatoid features, larger tumor size, higher T stage, and higher number of comorbidities. Conclusions: In this large Canadian cohort, patients with chRCC usually present with localized disease and have relatively favorable oncologic outcomes, even when they recur. Larger tumors with sarcomatoid features have a worse survival and more intensive follow up may be beneficial. The favorable 5 and 10 year outcomes in chRCC are a reminder that studies must be conducted and reported for individual histologies and not as a large cohort of non clear cell RCC. [Table: see text]
Impact of standard-of-truth method on evaluation of a diagnostic PET radiopharmaceutical: Learnings from the phase 3 SPOTLIGHT study.
Authors: Lowentritt Benjamin H. , Chau Albert , Davis Phillip 
Published: January 2024

39 Background: SPOTLIGHT (NCT04186845) evaluated newly approved diagnostic PET radiopharmaceutical 18F-flotufolastat (18F-rhPSMA-7.3) in patients (pts) with recurrent prostate cancer (PCa). In the absence of the gold standard histopathology, it can be challenging to verify positive findings from a diagnostic agent under investigation, particularly in recurrent PCa where it is neither feasible nor ethical to obtain multiple biopsies from the same patient. Consequently, conventional imaging is often used as a standard of truth (SoT) despite potential for it to be less sensitive than the investigational agent. Here, we explore the impact of SoT methods used in SPOTLIGHT on the study endpoints. Methods: The SPOTLIGHT coprimary endpoints were patient-level verified detection rate (VDR) and combined region-level positive predictive value (crPPV). Patient-level PPV was an exploratory endpoint. Pts with recurrent PCa underwent PET 50–70 min after IV administration of 296 MBq 18F-flotufolastat. For SoT assessment, the protocol required either histopathology or confirmatory imaging (≤60 and ≤90 days post-PET, respectively). Three blinded readers evaluated the scans, with majority read representing agreement between ≥2 readers. A separate Truth Panel established SoT for all pts. Post-study analysis revealed that, likely due to the study occurring during COVID, some pts had neither histopathology nor post-scan confirmatory imaging. These pts had only baseline/historic imaging as SoT. The present analysis stratified endpoint data according to the SoT method the panel used to verify PET-positive lesions. Results: Of 366 evaluable pts, 69 had histopathology and 297 had only confirmatory imaging for SoT. Of those with an imaging SoT, 90 (30%) had baseline/historic imaging only. As the Table shows, for each endpoint the highest value was obtained when using histopathology as SoT. VDR was ~4-fold higher with histopathology vs baseline/historic imaging, crPPV was 2-fold higher and PPV 2.5-fold. Conclusions: These data illustrate the substantial impact SoT methods can have on clinical trial endpoints and highlight a limitation of evaluating SPOTLIGHT endpoints in a cohort with various SoT methods (Table, column 1).1 Notably lower endpoint values are achieved when including pts with baseline/historic imaging SoT vs gold standard histopathology. 1. J Urol. 2023; 210:299-311. Clinical trial information: NCT04186845 . [Table: see text]
Treatment-free survival after first-line therapies for metastatic renal cell carcinoma: An International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) analysis.
Authors: Gupta Mehul , Wells Connor , Regan Meredith M. , Xie Wanling , Navani Vishal , Saliby Renee Maria , Basappa Naveen S. , Donskov Frede , Yuasa Takeshi , Takemura Kosuke null , Kollmannsberger Christian K. , Crumbaker Megan , Lalani Aly-Khan A. , Powles Thomas , Pal Sumanta Kumar , McKay Rana R. , Lee Jae-Lyun , Kanesvaran Ravindran , Choueiri Toni K. , Heng Daniel Yick Chin 
Published: January 2024

390 Background: Patients treated with immune checkpoint blockade (ICB) may experience disease control without need for ongoing systemic therapy, a period not well described by conventional time-to-event endpoints. Treatment-free survival (TFS) represents a novel endpoint to quantify this period. Methods: We identified patients with mRCC from the IMDC dataset initiating first-line systemic therapy with VEGFR monotherapy (sunitinib, pazopanib), combination ICB-VEGFR therapy ([axitinib or envatinib]-pembrolizumab, cabozantinib-nivolumab, axitinib-avelumab), or ICB doublet therapy (ipilimumab-nivolumab) between February 1, 2014, and February 1, 2023. Overall survival from treatment initiation was partitioned into periods including TFS, time on first-line therapy, and survival after subsequent therapy initiation utilizing differences in restricted mean survival time (RMST) over 36-months. TFS was defined as the difference between the 36-month RMST between: (1) time from treatment initiation to discontinuation of first-line therapy, death, or censor at last follow-up and (2) time from treatment initiation to subsequent therapy initiation, death, or censor at last follow-up. Results: 3,758 patients with mRCC initiated first-line VEGFR monotherapy (n=2,635; median age 62 years; 19.1% IMDC favourable risk), ICB-VEGFR regimens (n=354; median age 60 years; 33.3% IMDC favourable risk), or doublet ICB (n=769; median age 62 years; 0% IMDC favourable risk). Patients with favourable IMDC risk initiating VEGFR monotherapy and ICB-VEGFR regimens experienced a TFS duration of 8.5% (3.1 mos 95% CI 1.5 - 4.6) and 10.1% (3.7 mos 95% CI 0.2-7.2) of the 36-month period respectively. Among intermediate/poor risk patients, those treated with VEGFR monotherapy, ICB-VEGFR regimens, and ICB doublet therapy experienced 5.9% (2.1 mos 95% CI 1.4 - 2.8), 10.3% (4.7 mos 95% CI 1.0-6.4), and 14.6% (5.3 mos 95% CI 3.8-6.8) of the 36-month period alive and treatment free respectively. Conclusions: Patients receiving VEGFR monotherapy or ICB-VEGFR combination therapies spent at most 10% of the 36-month period surviving treatment free, while IMDC intermediate/poor risk patients treated with ICB doublet therapy experienced a TFS period of 15% of the 36-month period.[Table: see text]
Ipilimumab/nivolumab (I/N) compared to axitinib/pembrolizumab (A/P) in metastatic renal cell carcinoma (mRCC): Insights from a Canadian population.
Authors: Ohm Hyejee , Ghosh Sunita , Gupta Mehul , Wood Lori , Castonguay Vincent , Graham Jeffrey , Kollmannsberger Christian K. , Bosse Dominick , Soulieres Denis , Heng Daniel Yick Chin , Fallah-Rad Nazanin , Finelli Antonio , Tanguay Simon , Lalani Aly-Khan A. , Bhindi Bimal , Bjarnason Georg A. , Breau Rodney H. , Pouliot Frederic , Basappa Naveen S. 
Published: January 2024

393 Background: First-line treatment for mRCC includes I/N and A/P. These two regimens have not been compared in a randomized clinical trial as both CM-214 and KN-426 used single-agent tyrosine kinase inhibitors (TKIs) as the comparator. Meta-analyses suggest improved efficacy outcomes with A/P, but increased likelihood of complete response with I/N. We compared these treatments in the real-world. Methods: Data of consented mRCC patients with clear cell histology from the Canadian Kidney Cancer information system (CKCis) was obtained from January 2013 to December 2021. Treatment outcomes adjusting for age including overall survival (OS), progression free survival (PFS), and response rate (RR) for all patients and intermediate-poor risk patients were completed. Chi-square tests compared the frequency of side effects. Results: Among 547 patients, 360 received I/N and 187 received A/P. Median follow-up was 30.0 (0.1-112.1) months. Median duration of treatment was 6.9 (0.0-68.4) months for I/N and 20.2 (0.1-72.4) months for A/P. Intermediate-poor risk patients were higher in the I/N compared to A/P cohort (91.9% vs. 66.2%; p<0.0001). Cox regression for OS showed no difference between I/N compared to A/P (aHR 1.1, 95% CI [0.77-1.58], p=0.61). PFS showed no statistical difference but a trend for worse with I/N at 12.1 months compared to 22.3 months for A/P (aHR=1.2, 95% CI [0.95-1.62], p=0.11). RR was 40.9% with I/N compared to 56.0% in A/P (aOR 0.52, 95%CI [0.33-0.83], p=0.005). Subgroup analyses for the intermediate-poor risk mRCC patients showed no differences in OS (aHR 0.95, 95%CI [0.65-1.38], p=0.79) and PFS (aHR 1.21, 95%CI [0.90-1.62], p=0.21) between treatment groups but improved RR (aOR 0.58, 95%CI [0.35-0.96], p=0.06) with A/P. 61.7% of I/N patients compared to 79.1% of A/P suffered adverse events that led to a dose or schedule change (p<0.001). Most common toxicities for both groups include diarrhea, fatigue, transaminitis, rash, and anorexia. Conclusions: There was no difference in OS between mRCC patients treated with I/N compared to A/P. A/P demonstrates improved RR and a trend towards longer PFS at the expense of increased frequency of side effects. Despite a median follow-up of 30 months, the data is limited by a high amount of censoring.[Table: see text]
Treatment patterns and costs among patients with metastatic renal cell carcinoma (mRCC) in the United States: A real-world study using integrated claims and clinical data.
Authors: Geynisman Daniel M. , Hill Nathan , Rosenblatt Lisa , Yin Xin , Haley Valerie , Nguyen Chi , Barron John , Vilanova David , George Saby 
Published: January 2024

398 Background: The treatment landscape for mRCC has evolved in recent years with the use of tyrosine kinase inhibitors (TKI) and immuno-oncology (IO) therapies. This study examined patient characteristics, treatment patterns, costs, and survival for individuals with mRCC who received either IO-IO or IO+TKI as first-line (1L) regimens. Methods: This retrospective cohort study used an administrative claims dataset from a commercial health plan integrated with clinical data from a cancer care quality program (CCQP) and socioeconomic data from national surveys. Eligible patients began treatment for mRCC between 04/01/2018 and 1/31/2023, were aged ≥ 18 years old, and had ≥ 6 months of health plan enrollment prior to and ≥ 1 month after their 1L treatment. Patient characteristics and 1L and second-line (2L) regimens were described. Costs were summarized per patient per month (PPPM) within time intervals. The Kaplan-Meier method was used to estimate treatment-free interval (TFI) and survival times. Results: The study identified 824 eligible mRCC patients; mean age was 60, 77% were male, and 85% White/6% Black race. Patients receiving 1L IO-IO (n = 471; nivolumab plus ipilimumab) or IO+TKI regimens (n = 353; pembrolizumab plus axitinib [63.7%], nivolumab plus cabozantinib [21.8%], pembrolizumab plus lenvantinib [14.4%]) had similar baseline characteristics with the exception of health plan type, body mass index, and risk score (Table 1). As 2L therapy, patients most often received TKI monotherapy (56%) or IO+TKI (26%). Treatment costs were higher for IO-IO in the first 3 months but lower in subsequent time intervals compared with IO+TKI. Medication costs represented 80% of total costs on average. Between IO-IO and IO+TKI arms, median TFI (1.1 and 1.2 months, respectively) and cumulative survival time (75.1% and 78.3% at 12 months, respectively) were similar. Conclusions: The study described treatment patterns for mRCC and found patients receiving 1L IO-IO and IO+TKI regimens were similar demographically, though IO-IO patients started with poorer risk scores. Although IO-IO was associated with higher treatment costs in the first 3 months, the subsequent monthly costs were lower vs IO+TKI. Results also indicated that retreatment with IO in the 2L setting is occurring in real-world practice.[Table: see text]
A meta-analysis of overall survival and response in metastatic adrenocortical carcinoma: A review of 23 prospective trials of 880 patients.
Authors: Hall Angus , Crumbaker Megan , Pham James , Liu Jia (Jenny) , Sim Hao-Wen , Joshua Anthony M. 
Published: January 2024

4 Background: Metastatic adrenocortical carcinoma (mACC) is a rare, aggressive tumour of the adrenal gland, with historically poor survival and limited established treatment modalities. The aim of this study was to systematically search for and analyse all prospective trials for mACC to establish benchmark response and survival outcomes. The study was registered on PROSPERO CRD42023430557. Methods: A systematic review and meta-analysis of five databases was performed between June 2023- July 2023. Key outcomes extracted included patient demographics, overall survival (OS), progression-free survival (PFS) and objective response rates (ORR). ORR was calculated using a random effects model and inverse variance methods. Time-to-event outcomes including PFS and OS, were extracted digitally from available Kaplan- Meier curves using the IPDfromKM tool and individual patient data (IPD) was generated as per Guyot et al. The PFS and OS data from individual studies were then pooled using a multivariate extension of the DerSimonian–Laird method to generate summary survival curves. Results: The final 23 trials (5 Phase 1b, 16 Phase II and 3 Phase 3) encompassed 880 patients were retrieved. Pooled ORR was 9.0% overall (2.9% for targeted therapy, 12.3% for chemotherapy and 15.3% for immunotherapy). Median OS was 9.9 months (7.4 months for targeted therapy, 11.2 months for chemotherapy and 10.6 months for immunotherapy). Median PFS was 2.6 months (2.7 months for targeted therapy, 3.0 months for chemotherapy and 2.1 months for immunotherapy). Kaplan-Meier curves for OS were available for 10 treatment lines (n = 605), with a pooled median OS of 9.9 months (95% CI 7.7-11.9) and 12-month OS of 41.6% (95CI 33.1-51.2). Median OS was 7.4 months for patients receiving targeted therapy (95% CI 4.7–12.0), 11.2 months for patients receiving chemotherapy (95% CI 6.9–14.7) and 10.6 months for patients receiving immunotherapy (95% CI 4.4–13.2]. 12-month OS was 30.4% (95% CI 15.9-58.3) for patients receiving targeted therapy, 45.4% (95% CI 33.7-61.2) for patients receiving chemotherapy and 45.3% (95% CI 36.2-56.6) for patients receiving immunotherapy. Conclusions: This study found that current treatments strategies confer limited survival and response benefit in mACC and highlight the need for research into the pathogenesis and novel strategies in the disease. Immunotherapy and chemotherapy demonstrate modest benefits for patients and future trials should attempt to surpass the survival benchmarks set in this study.