bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunohistochemical (IHC) subtypes of metastatic bladder cancer (mBC) using GATA3 and CK5/6.
Authors: Nelson Ariel Ann , Molina Nunez Mariel , Bylow Kathryn A. , Szabo Aniko , Iczkowski Kenneth , Kilari Deepak 
Published: March 2023

557 Background: Genomic analyses have identified that bladder cancers can be divided into distinct molecular subtypes: luminal and basal. IHC markers GATA3 and CK5/6 have demonstrated >80% accuracy in assessing the luminal and basal subtypes of primary bladder tumors and may be easily utilized in clinical practice. Correlation of the primary bladder subtype with that of metastatic sites has not been demonstrated and associations with clinical outcomes are uncertain. Methods: We retrospectively identified patients with mBC who were treated with systemic therapy and had biopsies of either primary bladder or metastatic sites. Patient demographic, metastatic sites, treatment patterns, and clinical outcomes were recorded. Tissue microarrays (TMA) were constructed from primary and/or metastatic tumors. IHC was performed using mouse monoclonal antibodies: GATA-3 (L50-823, Pharmingen, 1:200) and cytokeratin 5/6 (XM26, Thermo Fisher, 1:100). Luminal (GATA3+, CK5/6-), basal (GATA3-, CK5/6+), double positive (GATA3+, CK5/6+) or double negative (GATA3-, CK5/6-) subtyping was applied. Concordance of matched bladder and metastatic pairs was quantified using Cohen’s kappa. Wilcoxon rank-sum tests were used for comparison of continuous and ordinal measures and chi-square tests were performed for comparison of categorical measures. Survival was estimated by Kaplan-Meier method; multivariable Cox analysis was performed. Results: Of 62 specimens, 37 bladder and 16 metastatic sites were interpretable. Four IHC subtype patterns were identified, most were luminal (n=20) followed by double-positive (n=12), basal (n=5), and double-negative (n=5). Of 10 pairs of matched primary tumor and metastatic sites, there was near-perfect subtype concordance between primary and metastatic tumors (κ=0.84; 95% CI:0.58-1.00). No association between sites of metastatic progression and subtype were identified, nor was there any difference in overall survival between the subtypes (p = 0.70). The basal subtype had numerically worse survival compared to the luminal subtype, HR =0.164 (95% CI: 0.02-1.58, p=0.12). Conclusions: IHC subtyping by GATA3 and CK5/6 is feasible in the clinical setting and showed strong correlation between primary and metastatic sites. A larger analysis is planned to further investigate associations with clinical features and outcomes. [Table: see text]
Clinical outcomes after utilization of PSMA PET scans in patients with biochemical recurrent prostate cancer.
Authors: Tsung Irene , Hynes Stephen , Joshi Urvashi Mitbander , Morales Krystal A , Dess Robert Timothy , Jackson William C. , Taylor Jeremy MG , Reichert Zachery R 
Published: March 2023

57 Background: The optimal management of biochemical recurrent prostate cancer (BCR) remains unknown. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scans can visualize micrometastatic disease, thus expanding treatment options for BCR from observation or androgen deprivation therapy (ADT) to potentially include metastasis-directed radiation (XRT) or next-generation hormonal agents (NHA). We aimed to describe how BCR patients were managed after PSMA PET scans and their clinical outcomes. Methods: We performed a retrospective chart review of 262 patients from the University of Michigan’s PSMA PET scan database (825 patients with scans 2017–2021). Patients who received maximal local therapy (defined as XRT alone n=199 or surgery + XRT n=63) are presented. Only patients with BCR and a minimum of 1 year follow-up after scans were included. Baseline patient and tumor characteristics, PSMA PET scan results, first and subsequent therapy delivered after PSMA PET, and prostate-specific antigen (PSA) and standard imaging results post PSMA PET were annotated. Primary endpoint is time from first post-scan therapy (within 6 months of scan) to subsequent therapy. Secondary outcomes include probability of no subsequent therapy in 1 year based on first post-scan therapy and PSMA scan findings and PSMA PET findings and association with Gleason score, PSA at BCR, and time from diagnosis to PSMA scan. Results: Of 262 patients with maximal local therapy, 115 met inclusion criteria. Primary definitive treatment was XRT alone in 58% and surgery + XRT in 42%. Median PSA at time of scan was 4.4 ng/mL, and PSMA PET was positive in 87%. First therapy rendered after PSMA PET included 15% no therapy, 26% XRT only, 28% systemic therapy only (ADT +/- NHA), 27% combination therapy (XRT +/- systemic), and 4% other. Subsequent therapy was given in 26%. The median time from first to subsequent therapy was 41 months in patients who received XRT alone as first therapy and not reached for those with combination XRT + ADT. None of the 33 treated with combination therapy required subsequent therapy in 1 year. Remainder of analyses incomplete due to small sample sizes. Results to be updated by time of symposium. Conclusions: This observational study characterizes longer term clinical outcomes in patients with BCR who undergo various therapies after PSMA PET scans. Data may inform current decision making while prospective clinical trial data is awaited.
Comprehensive gene sequencing to identify progression predictors to muscle-invasive bladder cancer.
Authors: Cyrenne Jocelyne Brianna , Kanjeekal Sindu Mary , Porter Lisa , Cavallo-Medved Dora , Fifield Bre-Anne , Rueda Luis , Atikukke Govindaraja , Alkhateeb Abedalrhman , El-Gohary Yasser 
Published: March 2023

570 Background: Over 8900 Canadians are diagnosed with bladder cancer every year, ranking it the fifth most frequent cancer. It can manifest as either non-muscle invasive bladder cancer (NMIBC) or muscle invasive bladder cancer (MIBC). The majority of patients initially receive a diagnosis of NMIBC, although high-grade NMIBC has a 50–70% recurrence rate and 10–30% chance at progressing to MIBC. The transition from high-grade NMIBC to MIBC is poorly understood, and there are currently no accurate biomarkers that predict disease progression. We propose a comprehensive molecular characterization to pinpoint specific copy number alterations (CNAs) related to either MIBC or NMIBC, and hence define the molecular development. Methods: This study analyzed a public dataset from MSKCC and 30 bladder cancer patient samples from Windsor Regional Hospital, both containing NMIBC and MIBC samples. Comprehensive gene sequencing was performed, and CNAs were obtained in over 500 common tumour gene panels. Results: Preliminary data from this study found MIBC may be predicted with 91% accuracy and 95% precision using CNA values of TP53, DDR2 and MLL2. In particular, MIBC correlates with gain of DDR2 or MLL2. Importantly, it has been demonstrated that high expression of DDR2 is associated with a worse prognosis. A panel of bladder carcinoma cell lines were used to validate the DDR2 findings. DDR2 values were quantified across the panels and corresponded with proliferation and invasiveness of cell lines. DDR2 was examined as a possible therapeutic target. Conclusions: Taken together, these findings provide insight to the pathogenesis of muscle invasion in bladder cancer. The potential to identify "genomic triggers" for the transition was facilitated by creating a genetic profile at these two stages.
Radical nephrectomy in medically underserved patients: Selection bias and disparity in surgical health care delivery.
Authors: Shah Aastha , Ghassemzadeh Saeed , Puri Dhruv , Meagher Margaret , Liu Franklin , Nguyen Mimi , Hakimi Kevin , Dhanji Sohail , Wang Luke , Javier-Desloges Juan , Derweesh Ithaar H 
Published: March 2023

609 Background: Disparities in outcomes of renal cell carcinoma (RCC) exist with respect to survival outcomes between different ethnic, and socioeconomic groups. We sought to evaluate disparities in delivery of surgical care between medically underserved (MU) and non-medically underserved (NMU) patients. Methods: We conducted a single-center retrospective analysis of consecutive patients presenting with localized renal cortical neoplasms who underwent surgical excision [Radical (RN) or Partial Nephrectomy (PN)] at an academic tertiary-care referral center. The cohort was divided into MU and NMU groups and descriptive analyses were conducted for demographics and clinical disease characteristics, type of surgery, time to surgery, estimated blood loss, and 30-day total and major complications (Clavien-Dindo, ≥3). Cochran-Armitage trend analysis was conducted to evaluate for surgical trends, and logistic regression multivariable analyses (MVA) were conducted for type of surgery and major complications. Results: 1418 patients were analyzed (MU n=334/NMU n=1084). Comparing MU vs. NMU, no differences were noted for age (p=0.612), Charlson Comorbidity Index (p=0.803), tumor size (p=0.236), or time to surgery (p=0.482). Significantly greater proportions of white patients were noted in NMU (60.6% vs. MU=45.5%, p<0.001) and higher proportion of RN in MU (47% vs. NMU=40.4%, p=0.028). Subgroup analyses of PN groups revealed no differences with respect to demographics, tumor size (p=0.33), major complications (p=0.66), or blood loss (p=0.583). Subgroup analysis of RN revealed significantly higher proportion of non-white patients (p=0.019) and patients with diabetes (p=0.019). MVA for predictors for receipt of RN were non-white (OR1.4, p=0.002), MU (OR=1.32, p=0.043), age (OR=1.01, p=0.009) and treatment year (OR=0.913, p<0.001). MVA for predictors for 30 day major complications demonstrated RN (OR=0.913 p<0.001). Cochran-Armitage trend analysis indicated that both MU and NMU had significant increases in PN between 2003 and 2021 (p<0.0001). Conclusions: Despite overall similarities with respect to demographics and clinical disease characteristics and time to surgery, MU status was associated with a significantly higher odds of receiving a RN at a tertiary care referral center, which represents a disparity in care and possible selection bias. Nonetheless, RN was also associated with a decreased risk of complications. While trends have demonstrated an increase in proportion of PN for both NMU and MU groups, comparative underutilization of PN in MU patients may be associated with increased downstream risks to health. Further investigation is requisite.
Does body mass index matter in predicting renal mass sizes? Comparison of imaging modalities.
Authors: Son Young , Fink Benjamin , Thomas Brian , DeVincentz Dayna , Dalton Raeann , Mueller Thomas , Brown Gordon Andrew 
Published: March 2023

619 Background: Renal cell carcinoma is most commonly diagnosed as an incidental mass detected on cross sectional imaging. When a renal mass is thought to be cancerous, size on imaging is important for clinical decision-making, as there is a known positive correlation with increasing size prognostic outcomes. Image quality may be adversely impacted by a variety of factors, and we sought to assess the impact of body mass index (BMI) on the ability to obtain accurate renal mass sizes across multiple imaging modalities. Methods: A retrospective multi-institutional chart review was performed for adult patients undergoing partial or radical nephrectomy between January 2018 and December 2021 from three different hospitals and six operating surgeons. BMI groups were assigned by BMI 1: <18.5, BMI 2: 18.5-24.9, BMI 3: 25-29.9, BMI 4: 30-34.9, and BMI 5: >35. Differences between greatest dimensions were compared between pathological measurement and each imaging modality: computerized tomography (CT) with and without contrast, ultrasound (US), and magnetic resonance imaging (MRI). Paired t test was used to analyze the total cohort mean difference testing for a difference between modalities and pathology report. T-tests and Wilcoxon signed-rank tests were used to compare the different BMI groups. Results: A total of 234 patients met inclusion criteria and were identified by age, gender, procedure, and renal mass location. There was a statistically significant difference between the greatest dimension as measured on CT with contrast and MRI compared to pathological measurement in the total cohort. Sub analysis of BMI groups showed the differences in size in BMI group 4 (mean (SD)) (0.46 cm (0.52)) and BMI group 5 (0.4 cm (0.51)) were found to have a significant difference in size estimates compared to BMI 3 for CT with contrast (Table). There was no difference for size estimates by BMI group for any other imaging modality. Conclusions: While CT with contrast and MRI are important modalities for their tissue enhancement abilities, they may not be the strongest choice for strict renal mass size estimation. Specifically, CT with contrast becomes less accurate at estimating mass size for patients with BMI >30. [Table: see text]
Novel retroperitoneal neovascularity scoring system in renal cell carcinoma tumor staging.
Authors: Fateri Cameron , Peta Akhil , Bui Thahn-Lan , Kar Nina , Roth Bradley , Park Sung-Mee , Glavis-Bloom Justin , Houshyar Roozbeh , Landman Jaime 
Published: March 2023

620 Background: Renal cell carcinoma (RCC) is the most common type of kidney cancer worldwide. While radiologists assess enhancement patterns of renal tumors to predict tumor pathology, to our knowledge, no formal scoring system has been created and validated to assess the level of neovascularity in RCC, despite its critical role in cancer metastases. In this study, we characterized and analyzed the level of angiogenesis in tumor-burdened kidneys and their benign counterparts. We then created and validated a scoring scale for neovascularity that can help predict tumor staging for RCC. Methods: After Institutional Review Board approval, the charts of patients who had undergone surgery for RCC between January 13, 2014 and February 4, 2020 were retrospectively reviewed for inclusion in this study. Inclusion criteria were a diagnosis of RCC, simple/radical nephrectomy, pre-operative contrast enhanced computed tomography (CT) scans, and complete pathology reports. Neovascularity was scored on a scale of 0 to 4 where 0= no neovascularity detected, 1= a single vessel <3mm wide, 2= a single vessel >3mm wide, 3=multiple vessels <3mm wide, and 4=multiple vessels >3mm wide Results: A total of 227 patients were included in the study. The majority of tumor pathology was clear cell carcinoma, regardless of tumor staging. The average neovascularity score was 1.07 for pT1x tumors, 2.83 for pT2x tumors, and 3.04 for pT3x tumors. There was a significant difference in neovascularity score between pT1x and pT2x tumors (p = 0.0046), pT1x and pT3x tumors (p < 0.0001), and benign kidneys and kidneys with RCC (p = <0.0001). Furthermore, we sought to address the ability of the Re-VASC score to predict up-staging or down-staging of clinically staged tumors. Only 5 total tumors were upstaged from cT1 to any pathological stage >1, with an average Re-VASC score of 2.33. There were 24 cases that were down-staged to pT1, with an average Re-VASC score of 1.73. Additionally, we specifically looked at cT3a tumors that were down-staged to p1x. The average Re-VASC scores were 0.82 and 2.11 for pT1a and pT1b tumors respectively. Conclusions: Our novel vascular scoring system for renal cell carcinoma demonstrates significant correlation with RCC pathological tumor staging. In future studies, we would like to further explore the ability of the scoring system to predict clinical up-staging and down-staging, as we had a limited sample size to analyze this function. This scoring system may be utilized as part of a comprehensive radiological assessment of renal tumors, potentially improving tumor characterization and clinical decision making.
Predictive accuracy of computer-generated padua nephrometry scores based on continuous variables compared with categorical computer-generated scores and human-generated scores in predicting oncologic and perioperative outcomes.
Authors: Benidir Tarik , Wood Andrew , Abdallah Nour , Remer Erick M. , Campbell Steven , Weight Christopher J. 
Published: March 2023

624 Background: The Preoperative Aspects and Dimensions Used for Anatomical Classification (PADUA) score is a validated predictor of a patient’s perioperative outcomes following partial nephrectomy. The use of a fully automated, unbiased and time sensitive PADUA scoring system is a novel concept that may help circumvent PADUA’s widespread adoptability. We sought to automate the scoring of preoperative computed tomography scans (CT) using a machine-learning-generated PADUA score (P-AI). In doing so, we aimed to compare P-AI’s ability to predict meaningful perioperative and oncologic outcomes as compared to human generated PADUA scores using both categorical (P-H) and continuous variables (P-AI+). Methods: 300 patients with pre-operative CT scans were identified from a cohort of 544 consecutive patients undergoing surgical extirpation for suspected renal cancer at a single institution. A deep neural network approach was used to automatically segment kidneys and tumors and geometric algorithms were developed to estimate each component of PADUA based on the segmented regions (P-AI). Tumors were also manually scored by medical personnel blinded to the P-AI (P-H). The ability of P-AI and P-AI+ to predict meaningful perioperative and oncologic outcomes was compared to P-H using logistic regression and receiver operating characteristics (ROC) curve analyses and areas under the curve (AUC). Results: Median age was 60 years, 40% were female. Median tumor size was 4.2 cm, 91.3% had malignant tumors, including 27% and 37% with high-stage and high-grade, respectively. Both P-AI and P-H were able to predict the need for partial nephrectomy (p < 0.001). From an oncologic standpoint, P-AI and P-H were able to predict meaningful oncologic outcomes including the presence of malignancy, high grade and high stage disease (p < 0.004) although the ROC curves were not different from one another). Interestingly, when each PADUA component was left as a continuous rather than ordinal variables (P-AI+), this automated continuous score was able to predict surgical type (AUC 0.88), presence of malignancy (AUC 0.67), indolent tumors (AUC 0.79) and high grade (AUC 0.77)/high stage disease (AUC 0.82), better than both P-AI and P-H. Conclusions: When viewed along a continuous spectrum, AI generated PADUA scores (P-AI+) yields predictive surgical and oncologic outcomes superior to both categorical AI and human generated PADUA scores. If nephrometry can be calculated automatically, there is no longer a need to simplify the equations and the use of an AI generated PADUA scoring system, provides a reliable estimate of meaningful outcomes in a manner that is time sensitive and superior to human expert evaluation. Further prospective work and reproducibility from other centers is encouraged.
Local and systemic therapies for renal cell carcinoma with brain metastases: A single-institution series.
Authors: Ganta Teja , Miller Eric James , Anker Jonathan Forrest , Galsky Matt D. , Tsao Kai 
Published: March 2023

627 Background: Current practice guidelines for the management of renal cell carcinoma (RCC) with brain metastases (BM) recommend a multimodal approach with systemic therapy, radiation, and/or surgery. The purpose of this study is to assess treatment patterns and identify prognostic factors for survival in this population. Methods: This retrospective, single-center study evaluated patients with RCC who were diagnosed with metastatic disease between 2015-2020 and were identified to have BM at any point in their care. Fisher's exact test and Mann-Whitney test were used to compare differences among groups. Kaplan-Meier curves were used to estimate time to events from the date of BM diagnosis. Univariate Cox proportional hazards model was used to estimate the effect of factors on survival. Results: 29 patients are included. Median follow-up was 25 months (range: 0.5-73). 16 (55%) patients presented with BM at the time of diagnosis of metastatic disease. 17 (58%) were treated with radiation. 8 (28%) were treated with surgery of which 7 also received radiation. Median overall survival was 10 months (95% CI: 7-not reached). Patients received a median of one (range 0-4) system therapy regimen after diagnosis of BM. 19 (66%) patients were exposed to at least one class of medication therapy for management of BM while 10 (34%) were exposed to two or more classes. 10 patients experienced long term survival (defined as survival ≥12 months). Patients with long term survival were more likely to have received radiation (90% vs 42%; P=0.02). However, use of radiation was not associated with survival (HR 0.47, 95% CI 0.1-1.3). Conclusions: The study is limited by sample size but suggests there is a population of patients with RCC with BM who can experience long term survival. Optimal selection for patients with BM that can be feasibly treated within radiation fields appears favorable. Most patients are not exposed to more than one systemic medication class during their care. Additional research is needed to compare efficacy in BM to guide first line systemic therapy selection. [Table: see text]
Real world outcomes of patients with non-clear cell renal cell carcinoma: A single Asian centre experience.
Authors: Chan Johan W.K. , Peh Daniel , Tan Wei Chong , Tan Hui Shan , Ng Quan Sing , Rajasekaran Tanujaa , Teh Yi Lin , Saw Stephanie , Tan Wan Ling , Lai Gillianne , Jain Amit , Kanesvaran Ravindran 
Published: March 2023

632 Background: Non-clear cell RCC (nccRCC) represents a heterogenous group of tumors which is less well studied than clear cell RCC. Clinical data supporting the treatment of nccRCC are still based on phase 2 studies and clinical trials conducted in ccRCC. Little is known about this group of patients in Asia. In this study, we aim to report the real world outcomes of nccRCC patients in a cancer centre in Singapore. Methods: We conducted a retrospective analysis on 81 non-clear cell RCC patients treated at the National Cancer Centre Singapore from 2007-2022. Data on patient demographics, disease characteristics, treatment outcomes and adverse events were collected retrospectively up till March 2022. Overall survival (OS) and progression free survival (PFS) were estimated using the Kaplan-Meier method. Responses to treatment were recorded based on RECIST v1.1 and analyzed using logistic regression. Results: 81 patients were included in this analysis, with a median age at diagnosis of 57 years old. Papillary RCC accounted for 32% (n=26) of the cases, chromophobe RCC was 2% (n=2), unclassified RCC was 28% (n=23), and other subtypes was 20% (n=24). Sarcomatoid features were present in 8% (n=10). Median follow-up time was 24 months. Among this cohort, 73 patients (90%) received tyrosine kinase inhibitors (TKI) alone, 8 patients (9%) had immunotherapy with VEGF TKI while 4 patients (4%) underwent dual checkpoint inhibitors. Median OS for the cohort was 19.4 months, while median PFS was 16 months. Overall disease control rate rate (CR/PR/SD) for first-line treatment was 60%. Comparison of outcomes shown below. Conclusions: This real-world Asian study provides important data regarding clinical outcomes in this rare and heterogeneous group of non-clear cell RCC patients. OS in nccRCC remains inferior to ccRCC and is comparable to data reported in Western populations [Table: see text]