bluuebunny/crossref_metadata_2025_split huggingface dataset:
Practice patterns of high-risk non-muscle invasive bladder cancer (HR-NMIBC) in real-world Canadian practice.
Authors: Gotto Geoffrey T. , Alimohamed Nimira S. , Kulkarni Girish S. , Black Peter C. , Kassouf Wassim , Sridhar Srikala S. , Kokorovic Andrea , Eigl Bernhard J. , Blais Normand , Lalani Aly-Khan A. , Osborne Brendan J.W. , Wallis Christopher J.D. 
Published: June 2024

e16594 Background: There is a paucity of evidence pertaining to real-world treatment of localized bladder cancer, particularly in Canada. We sought to investigate real-world treatment patterns in HR-NMIBC patients, treated in Alberta to understand current treatment practices, predictors of BCG utilization and real-world survival outcomes. Methods: We conducted a retrospective, observational cohort study of de novo HR-NMIBC patients diagnosed between 2010-2022 using population-level administrative databases in Alberta. Data sources included Alberta Cancer Registry (ACR), Vital Statistics, Pharmaceutical Information Network (PIN), Health Practitioner Claims, Discharge Abstract Database (DAD) and National Ambulatory Care Report System (NACRS) databases. HR-NMIBC was defined as AJCC stage N0 and M0 with either Tis, T1, or high-grade Ta (HG-Ta). Patients were followed from diagnosis to last known contact with healthcare system, end of 2021, or death. Multivariable logistic regression analysis was used to identify features associated with receipt of BCG. Results: In this cohort, 3874 HR-NMIBC patients were identified: 82% were male and mean age was 71 years. Tumor stage was T1 in 50%, HG-Ta in 33% and Tis in 17%. Following TURBT, 60.8% of the cohort received no intravesical therapy while 35.6% received BCG treatment, 2.9% intravesical gemcitabine, and 0.6% mitomycin C. Patients who received BCG were predominantly male (83.9%), had T1 tumors (52%) and had a CCI of 0-1 (83.5%). Few (<10%) patients underwent cystectomy. In patients who received BCG, 28.3% completed only one dose 56.9% completed five induction doses, and 32% received “adequate” dosing (≥5 induction doses + ≥2 maintenance doses). In multivariable regression analysis, the strongest predictor of receipt of BCG was high-grade disease (OR 1.62; 95% CI: 1.25-2.10; p < 0.001). Other features associated with higher BCG utilization were younger age, fewer comorbidities, and rural residence and being diagnosed closer to 2010. Overall survival was 10.3 years (95% CI: 116-131 years). Conclusions: In this large, population-based retrospective study, we identify relatively poor utilization of BCG among patients with HR-NMIBC with 32% of patients receiving adequate BCG therapy, per FDA definitions. These data, while concordant with other jurisdictions, do not address underlying causes which may relate to BCG supply issues, patient preference, or fitness to receive therapy, or physician beliefs regarding treatment efficacy. Additional research is needed to identify strategies to improve utilization of guideline recommended therapy among HR-NMIBC patients in real-world settings.
Real-world study of urine-based NGS liquid biopsy in organ preservation therapy of muscle-invasive bladder cancer (MIBC).
Authors: Zhang Ruiyun , Jin Di , Zang Jingyu , Xue Wei , Huang Yiran , Zhuang Guanglei , Tang Haoran , Jia Cancan , Xie Feng , Zhang Yue , Jia Shidong , Chen Haige 
Published: June 2024

e16602 Background: Bladder cancer is a common malignancy of the urinary system. For those diagnosed with muscle-invasive bladder cancer (MIBC), radical cystectomy (RC) is the conventional treatment but is associated with a high risk of complications and diminished life expectancy. Consequently, trimodal therapy (TMT)—consisting of maximal transurethral resection of the bladder tumor (TURBT) followed by combined chemotherapy and radiation therapy—has been established as an alternative, bladder-preserving treatment for MIBC patients. Nevertheless, concerns persist regarding disease relapse, and the detection of recurrence at the molecular level poses significant challenges. Methods: In this real-world prospective study, 100 patients with MIBC, either candidates for or having undergone bladder-preserving TMT, were enrolled. Blood and urine samples were collected at each follow-up visit to the cancer center. The study utilized PredicineCARE, a targeted next-generation sequencing (NGS) liquid biopsy assay, to detect somatic changes in urinary tumor DNA (utDNA), including single nucleotide variations (SNVs), gene fusions, and copy number variations (CNVs). These molecular alterations were analyzed to determine the tumor fraction, aiming to identify molecular recurrence among the patients. Results: Within the cohort of 100 patients, 98 underwent urine testing and 94 blood testing, with 92 patients having both. Baseline urine samples revealed TP53 (38%), TERT (30%), FGFR3 (19%), ARID1A (16%), and PIK3CA (14%) as the most common mutant genes. For baseline blood samples, prevalent mutations included TP53 (17%), BRCA2 (13%), ATM (9%), FGFR3 (7%), and ERBB2 (5%). Urine samples showed a significantly higher mutation prevalence associated with MIBC, especially in TP53 (p<0.001), FGFR3 (p=0.004), and PIK3CA (p=0.006), suggesting urine as a more effective medium for mutation profiling in MIBC. The study also monitored disease progression during bladder preservation treatment by tracking tumor fractions in sequential urine and blood samples. Results indicated a ctDNA reduction in tumor fraction levels in urine for 38 patients and in blood for 25 patients, with a consistent overlap in 13 patients, aligning with the observed clinical treatment response. Notably, four patients exhibited no detectable tumor fraction at the latest follow-up, suggesting they may have achieved molecular clearance of MIBC. Conclusions: This study confirms that urine-based NGS liquid biopsy is a promising method for identifying molecular markers in MIBC patients undergoing bladder preservation therapy. Furthermore, the reduction in ctDNA tumor fractions may associate with effective treatment and the possibility of disease eradication.
Non-invasive detection of urothelial carcinoma through ensembled methylation profiles and fragmentomic patterns in urinary cell-free DNA.
Authors: Zhao Huan , Dong Hang , Gan Shuang , Tang Haoran , Zhang Zhihui , Wei Na , Xu Jingjing , Bonora Giancarlo , Dai Chao , Du Pan , Jia Shidong , Xiao Ting , Guo Huiqin 
Published: June 2024

e16604 Background: The detection of epigenetic markers in urinary cell-free DNA (ucfDNA) has shown promise for tumor identification. However, the reliance on changes in methylation patterns presents challenges in the early detection of urothelial carcinoma, particularly when the tumor DNA present in urine is scarce. The incorporation of fragmentomic characteristics could enhance the detection of tumor signals. Methods: This study presents a single-assay approach, PredicineEPIC, which is a genome-wide methylation assay capable of analyzing both methylation and fragmentomic patterns in ucfDNA. Our cohort included 187 subjects: 66 with malignancies, 52 with benign conditions, and 69 healthy controls, divided into training and validation groups at a 2:1 ratio. We used the XGBoost machine learning algorithm for model development, followed by logistic regression to create an ensemble classifier. The training set utilized leave-one-out cross-validation to mitigate sample size constraints and prevent overfitting, with the classifier's performance assessed in the validation set. Results: The classifier's performance was evaluated using beta values of differentially methylated regions, the count of abnormally methylated fragments, and fragmentomic patterns (fragment sizes and transcription factor accessibility), with sensitivities of 0.75, 0.9, and 0.75, and a specificity of 0.86, respectively. The integrated features model showed a notable increase in sensitivity to 0.92 without losing specificity compared to models based on single features. This model also demonstrated precision on par with other methylation-based diagnostics, particularly in detecting early-stage tumors. Conclusions: Our study underscores an approach that differentiates malignant from benign lesions using a combination of omic features, enhancing the potential and precision of non-invasive liquid biopsy methods for early urothelial carcinoma detection.
Correlation of circulating tumor DNA (ctDNA) dynamics with clinical response in patients with muscle-invasive bladder cancer (MIBC) undergoing trimodality therapy (TMT).
Authors: Epstein Ilana B. , Berg Stephanie A. , Mantia Charlene , Mossanen Matthew , Saraf Anurag , Preston Mark A. , Ravi Arvind , Carvalho Filipe Lf , Clinton Timothy , Roberts Daniel Aaron , Peng Luke , McGregor Bradley Alexander , Bellmunt Joaquim , Berchuck Jacob E. , Mouw Kent William 
Published: June 2024

e16606 Background: Trimodality therapy (TMT) is a curative treatment option for patients with muscle-invasive bladder cancer (MIBC). Plasma circulating tumor DNA (ctDNA) is associated with treatment response and clinical outcomes following cystectomy for bladder cancer, but the association of plasma ctDNA with treatment response and clinical outcomes in patients with MIBC treated with TMT is poorly understood. Methods: Select patients with MIBC who received TMT at Dana-Farber/Brigham and Women’s Cancer Center between June 2023 and January 2024 who underwent pre-TMT ctDNA evaluation with the commercially available Signatera assay were included in this analysis. Individual chart review was performed to collect demographic and clinical data including disease stage, histopathology, imaging, and treatment details. Results: Pre-treatment ctDNA results were available for 16 patients. Nine of the 16 patients had at least one post-treatment result available while the remaining 7 patients have not yet completed their first post-TMT ctDNA test. Seven of 16 patients had detectable ctDNA prior to TMT initiation. Of these 7 patients, 4 had at least one post-treatment ctDNA result available (median 11.2 weeks following TMT), and 3 of 4 patients converted to having undetectable ctDNA following TMT and were also free of disease as determined by routine post-TMT surveillance including radiographic, cytologic and cystoscopic assessment. The single patient who had persistent detectable ctDNA following TMT developed radiographic evidence of metastatic disease 3 months following TMT and died from bladder cancer 2 months later. Five patients with undetectable ctDNA prior to TMT had at least one post-TMT ctDNA result available. All five of these patients remained ctDNA-negative following TMT and have had no clinical evidence of recurrence. Conclusions: Plasma ctDNA measured using the Signatera assay can be performed in MIBC patients undergoing TMT and appears to correlate with clinical response to TMT at early time points. Larger cohorts with longer follow-up will be required to define the association between plasma ctDNA status and clinical outcomes following TMT. [Table: see text]
Comparative outcomes of radical nephroureterectomy and kidney-sparing surgery in the treatment of high-grade upper tract urothelial carcinoma.
Authors: Moore Kyle , Gao Helen , Delgado Jennifer , Kulkarni Anirudh , Lichtbroun Benjamin , Chua Kevin J. , Pfail John , Srivastava Arnav , Packiam Vignesh T. , Golombos David , Jang Thomas L , Ghodoussipour Saum 
Published: June 2024

e16609 Background: Patients with upper tract urothelial carcinoma (UTUC) can be managed via radical nephroureterectomy (RNU) or kidney-sparing surgery (KSS) depending on pathology and patient characteristics. Unfortunately, UTUC is a rare disease lacking high-level evidence regarding clinical and oncologic outcomes after management. This study compares outcomes of RNU to KSS for high-grade (HG) UTUC. Methods: We retrospectively reviewed all patients with >1 year follow-up treated for HG UTUC at our institution from 2015-2021. Oncologic and clinical outcomes were recorded. Procedure burden was analyzed as total procedures under anesthesia, anesthesia time, days hospitalized, and estimated cost of care. Results: We identified 17 patients treated with KSS and 46 with RNU. There was no significant difference in 5-year overall survival, 3-year metastasis-free survival, or 3-year recurrence-free survival with KSS compared to RNU (Table). The average change in GFR was 17.9 ± 18.3 mL/min/1.73 m² and 24.8 ± 21.0 mL/min/1.73 m² for patients who underwent KSS and RNU, respectively (p = 0.33). Renal function was preserved (GFR decline <10 mL/min/1.73 m²) 2 years after surgery in 100.0% of patients who had KSS compared to 97.1% of patients who had RNU (p = 0.081). Patients who had KSS experienced a higher total number of procedures but fewer perioperative complications than those who had RNU with 3.4 ± 1.7 procedures vs 2.1 ± 1.7 procedures, respectively (p = 0.016), and 0% vs 41% of patients experiencing complications, respectively (p = 0.0098). Total anesthesia time and days hospitalized for KSS were similar to RNU at 400 ± 218 minutes vs 474 ± 185 minutes (p = 0.26) and 5.5 ± 4.3 days vs 6.8 ± 4.6 days, respectively (p = 0.36). Patients with KSS experienced a lesser in network but similar out of network cost of care to RNU patients at $7881 ± $4438 vs $10799 ± $4539 (p = 0.020) and $22159 ± $12401 vs $24523 ± $11282, respectively (p = 0.46). Conclusions: There were similar oncologic and clinical outcomes in HG UTUC patients treated with KSS or RNU. Patients treated with KSS endured a greater procedural load than patients who had RNU but at a reduced in network cost and with fewer complications. Larger datasets are needed to further evaluate outcomes and treatment burdens of RNU vs KSS as HG UTUC treatment. [Table: see text]
Analysis of the efficacy and tolerance or darolutamide in combination with chemotherapy and ADT in patients with metastatic castration-sensitive prostate cancer (mCSPC) in the Spanish population in a daily clinic.
Authors: Cassinello Espinosa Javier , Garcia Sanchez Lourdes , Gallegos Sancho Isabel , Sanchez-Escribano Morcuende Ricardo , Perezagua Marin Carmen , Sanchez Cendra Alicia , Fiorini Talavera Aldo Bruno 
Published: June 2024

e17069 Background: Darolutamide is an inhibitor of the androgen receptor signaling pathway that increases overall survival both in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and in patients with high-volume mCSPC [Smith et al. N Eng J Med 2022]. Our objective is to analyze the efficacy and tolerance of darolutamide, in combination with chemotherapy and ADT (triplet therapy), in real-life data in several Spanish hospitals. Methods: A multicentric, observational, prospective study was performed in patients with mCSPC which started treatment with triplet therapy including darolutamide between 2022 and 2023 in some Spanish hospitals. A statistical analysis has been carried out with the SPSS v19 platform. Results: Between 2022 and 2023, 11 patients have been included, of which 10 have been analyzed. The mean age was 64 years (57-75 years), most patients with ECOG = 0 (60%) and ECOG = 1 (10%); the mean PSA diagnosis was 1025 ng/ml (12-4735 ng/ml). The majority of patients had a Gleason 9 (70%), 60% with extra regional lymph node metastases (M1a), 70% with bone metastases (M1b) and 60% with visceral metastases (M1c). The median time from diagnosis to statistical analysis was 580 days (366-700 days). The first patient was included in January 2022 and the last one was included in April 2023. Most patients started docetaxel and darolutamide was added a few weeks later. All patients achieved progression-free survival (PFS) with median of 14,5 months. The overall survival (OS) has not been reached. The median response time to 50% PSA was 3 months (2-8 months) and the median response time to 90% was 6 months (2-9 months); 30% of patients achieved complete PSA response. In relation to the objective response evaluation, 70% of the patients achieved a partial response, 30% stable disease and 11% presented disease progression; no complete radiological responses have been observed. Only 2 patients became castration resistant (one in 1 month and another in 11 months). Regarding adverse effects, 5 patients (50%) presented asthenia, 4 patients (40%) hematological toxicity (20% grade 3 neutropenia), 3 patients (30%) hot flashes, 2 patients (20%) elevated transaminases and 1 patient (10%) hyperglycemia; no patient had high blood pressure, weight gain, urinary tract infection or falls. Conclusions: The results of this analysis of real-life data confirm the efficacy of darolutamide within the triplet combination with chemotherapy and ADT in mCSPC patients, similar to the results of the already published phase III trial. Treatment with darolutamide was well tolerated. This analysis is limited by the retrospective nature and the small number of patients included.
Real-world intensification beyond androgen deprivation therapy (ADT) in metastatic hormone sensitive prostate cancer (mHSPC) in the United States 2017-2023: An administrative claims database study.
Authors: Raval Amit D , Lunacsek Orsolya , Korn Matthew J. , Littleton Natasha , Constantinovici Niculae , George Daniel J. 
Published: June 2024

e17082 Background: Severalguidelines recommended the use of androgen receptor pathway inhibitors (ARPIs) and/or docetaxel along with ADT for mHSPC based on improved clinical outcomes demonstrated in clinical trials. Given the evolving treatment landscape since 2016, there is a need to understand the translation of clinical evidence and guidelines into clinical practice. Therefore, we examined the use of, and factors associated with intensification beyond ADT in men with mHSPC. Methods: A retrospective cohort of men treated for mHSPC was selected from private insurance claims of the Komodo Research Dataset (Jan 2017-Sep 2023). Men with mHSPC were identified based on their earliest claim for metastasis on or after prostate cancer diagnosis date without evidence of castration resistance. Index date was the earliest claim of ADT following mHSPC. Continuous insurance coverage for ≥ 12 months pre- (baseline) and ≥ 4 months post-index was required. Intensification beyond ADT was defined as the addition of ARPIs, docetaxel or both within ±4 months of the index date. Multinomial regression was conducted to examine factors associated with ADT intensification. Results: The study cohort comprised of 10,717 men with mHSPC with a median age of 65 years. Most had de novo mHSPC (62%), bone-only metastases (49%), hypertension (68%), diabetes (29%), and received opioids (59%) at baseline. Overall, in addition to ADT, 28% received ARPI (abiraterone: 18%, androgen receptor inhibitors: 10%), 9% docetaxel and 2.5% ARPI + docetaxel. From 2017 to 2023, there has been an increase in the intensification of ADT with ARPI from 13% to 47% and with docetaxel + ARPI from 0.8% to 15%, while the use of ADT + docetaxel declined from 12% to 3% and ADT alone from 74% to 36%. Key factors (age, comorbidity, de novo mHSPC, bone metastases) associated with intensification with either docetaxel or ARPI are listed in Table. Conclusions: There was a linear increase in intensification with ARPI and/or docetaxel in mHSPC between 2017-2023 in the US. Findings highlight a gradual uptake of guideline-recommended treatment for men with mHSPC, while over a third are still receiving ADT alone. [Table: see text]
Triplet therapy in metastatic hormone-sensitive prostate cancer: A real-world Indian multicentre study.
Authors: Mondal Debapriya , Roy Somnath , Bhattacharjee Arnab , Roy Rakesh , Meyur Suman , Biswas Bivas 
Published: June 2024

e17086 Background: The survival benefit of upfront triplet therapy in the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has been demonstrated in two prospective randomised trials using a combination of androgen deprivation therapy (ADT), docetaxel and an androgen receptor signalling inhibitor (ARSi) among abiraterone or darolutamide. This study aimed to evaluate the real-world outcomes of first-line triplet therapy in treating Indian mHSPC patients. Methods: In this multicentre retrospective study, patients with mHSPC started on upfront triplet therapy at three Eastern Indian centres between May 2022 and December 2023 were included. Patients were included if they received at least one cycle of triplet therapy. Descriptive statistics were used for reporting baseline patient and disease characteristics, treatments, and adverse events. Kaplan-Meier and life-table analyses were used for survival estimates. Results: Fifty-eight patients with mHSPC were included in this study. Most of the patients had de novo metastatic disease (93.1%). The mean age was 64 years (range 49-82), and the majority had Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (90%). High-volume disease was present in 94.8%, and 69% of patients had a Gleason score of 8 or higher. Comorbidities were present in 89.7% (2 or more in 37.9%). All the patients received a triplet combination of docetaxel, ADT, and abiraterone. The median number of triplet cycles received was 6. Grade 3 or worse adverse events occurred in 22.4% of patients without any treatment-related deaths. The most common grade ≥3 adverse events were hypertension (6.9%), febrile neutropenia (5.2%), hyperglycemia (5.2%), and urinary tract infection (3.4%). Dose reduction was required in 24.1%. Undetectable PSA (<0.2 ng/mL) as response was achieved in 62%. The 12-month overall survival rate was 98.3%, and the 12-month biochemical progression-free survival rate was 96.6%. Conclusions: First-line triplet therapy in Indian mHSPC patients was effective and tolerable with rare serious adverse events.
Comparing overall survival in patients with metastatic prostate cancer using PSA levels: A multivariate analysis using a national database.
Authors: Albawaliz Anas , Kumar Rohit , Pachika Pranali Santhoshini 
Published: June 2024

e17089 Background: Prostate - specific antigen (PSA) is a useful biomarker for detection of prostate cancer and for risk classification in addition to TNM classification and Gleason score. Data is limited in determining its role in prognostication. The purpose of our study is to learn the impact of PSA value at the time of diagnosis on overall survival in patients with de novo metastatic prostate cancer. Methods: The National Cancer Database (NCDB) 2016-17 was queried to identify all patients diagnosed with de novo metastatic prostate adenocarcinoma. The demographic and clinical characteristics were compared using Pearson’s chi-square test between patients with PSA<98 ng/mL versus >=98 ng/mL. A multivariate cox regression analysis was done to determine the survival difference between the two groups. Results: The NCDB database found a cohort of 18,157 patients with de novo metastatic prostate cancer. A total of 8593 patients had PSA values below 98, while 9564 patients had PSA levels equal to or above 98. Multivariate cox regression analysis was done, and results indicated HR of 1.11 with 95% CI 1.07-1.13 and p value <0.001, indicating 11% worse survival in patients with higher PSA. Patients were further stratified based on age, race, and sites of metastasis. The results were consistent across all groups, with a significant p-value of <0.001. Conclusions: Our study indicates that a higher PSA value at the time of diagnosis is associated with a lower overall survival in patients with de novo metastatic prostate cancer. Further prospective studies with potentially higher PSA thresholds are needed to validate this correlation. Should concordant results be obtained, this may suggest utilizing more aggressive treatment strategies in this subset of patients to improve clinical outcomes. [Table: see text]