bluuebunny/crossref_metadata_2025_split huggingface dataset:
Open versus robotic-assisted radical cystectomies: A risk analysis.
Authors: Simhal Rishabh , Wang Kerith Ruoyao , Shah Yash , Simon Daniel P , Mark James Ryan , Shah Mihir S , Gomella Leonard G. , Chandrasekar Thenappan , Lallas Costas D. 
Published: June 2023

4593 Background: Radical cystectomy (RC) is standard of care for muscle-invasive bladder cancer, but it comes with significant perioperative risk with half of patients experiencing major postoperative complications. Robot-assisted radical cystectomies (RARC) have aimed to decrease patient morbidity and have become increasingly adopted in North America. Currently, both open radical cystectomies (ORC) and RARC are frequently performed. To contribute to the existing literature using newly available data from the American College of Surgeons National Surgical Quality Improvement Project (NSQIP), representing one of the most recent, largest multi-institutional studies, while uniquely accounting for a variety of factors including type of urinary diversion, cancer staging, and neoadjuvant chemotherapy. Methods: RC procedures performed between 2019-2020 were identified in NSQIP and the corresponding Cystectomy Targeted database. Cases in the ORC group were planned open procedures, and cases in the RARC group were robotic with intra- or extracorporeal diversions, including unplanned conversion to open cases for intention-to-treat. Chi-square and t-tests were performed to compare baseline demographics and operative parameters. Multivariate analysis was performed for outcomes including major complications, minor complications, and 30-day mortality, while adjusting for operative approach, medical comorbidities, functional status, age, race, sex, BMI, ASA-classification, preoperative labs, type of urinary diversion, pathological staging, prior pelvic surgery or radiation, need for preoperative transfusion, preoperative sepsis, emergent or elective surgery, and recent chemotherapy. Results: 4,022 RC cases were identified. Of these, 3,146 (78.2%) received planned ORC while 876 (21.8%) received RARC. Baseline demographics of the patients who received ORC versus RARC were largely similar, with no significant difference in age or medical comorbidities. RARC was associated with longer operative times and shorter hospital length of stay compared to ORC. On multivariate analysis, ORC was associated with a higher rate of 30-day mortality [OR 3.1; 95% CI 1.3-7.2; p=0.009], reintubation, cardiac arrest, superficial wound infection, bleeding requiring transfusion [OR 4.7; 95%CI 3.6 - 6.1; p<0.001], prolonged postoperative nasogastric tube use, rectal injury, and ureteral fistula or urine leak compared to RARC. Conclusions: In the NSQIP database, ORC is associated with higher rates of 30- day mortality and operative complications, most notably bleeding, compared to RARC. This study is unique in the size of the cohorts compared, the timeliness of the data (2019-2020), and the ability to control for factors, such as type of urinary diversion, pathological bladder cancer staging, and use of neoadjuvant chemotherapy.
Prognostic impact of PSA nadir (n) ≥0.1 ng/mL within 6 months (m) after completion of radiotherapy (RT) for localized prostate cancer (PCa): An individual patient-data (IPD) analysis of randomized trials from the ICECAP collaborative.
Authors: Ravi Praful , Kwak Lucia , Armstrong John , Beckendorf Veronique , Chin Joseph , D'Amico Anthony Victor , Dearnaley David P. , Denham James William , Di Stasi Savino Mauro , Gillessen Silke , Lukka Himanshu , Mottet Auselo Nicolas , Pommier Pascal , Seiferheld Wendy , Sydes Matthew R. , Tombal Bertrand F. , Zapatero Almudena , Regan Meredith M. , Xie Wanling , Sweeney Christopher 
Published: June 2023

5002 Background: RT + androgen deprivation therapy (ADT) is a standard of care in treatment of intermediate- and high-risk localized PCa. Identification of early surrogate measures for long-term outcome measures such as PCa-specific survival (PCSS), metastasis-free survival (MFS) and overall survival (OS) could expedite development of new systemic therapies added to RT/ADT while potentially identifying patients (pts) for therapy (de)escalation. Methods: IPD from the RT+/-ADT trials in the ICECAP repository with evaluable PSA follow-up were eligible for inclusion. Pts were grouped based on their trial-allocated treatment: RT alone, RT+stADT (short-term ADT: 3-6m), RT+ltADT (long-term ADT: 18-36m). PSAn was defined as the lowest PSA recorded within 6m after RT completion. A 12m landmark analysis for PCSS, MFS and OS was performed to account for guarantee-time bias. Multivariable Cox proportional hazards regression was used to estimate associations of PSAn < or ≥0.1ng/mL with MFS and OS, and a multivariable Fine and Gray distribution used for PCSS to account for competing risk of non-PCa deaths. Models were adjusted for age, ECOG performance status, clinical T stage, Gleason score and PSA at randomization. Results: 10,415 pts from 16 RCTs were included: 2629 (25%) allocated to RT, 6033 (58%) to RT+stADT, and 1753 (17%) to RT+ltADT. Median follow-up was 10.1years (yrs). 2339 (98%), 4756 (84%) and 1258 (77%) of patients allocated to RT, RT+stADT and RT+ltADT respectively achieved a PSAn ≥0.1ng/mL within 6m after RT completion. After adjustment, PSAn ≥0.1ng/mL was associated with poorer PCSS, MFS and OS in pts allocated to RT+stADT (PCSS hazard ratio [HR] = 1.97 [95% CI 1.52-2.92], MFS HR = 1.27 [1.12-1.44], OS HR = 1.26 [1.11-1.44]) and RT+ltADT (PCSS HR = 1.97 [1.11-3.49], MFS HR = 1.58 [1.27-1.96], OS HR = 1.59 [1.27-1.99]). A weaker association was noted in pts allocated to RT (PCSS HR = 1.82 [0.51-6.49], MFS HR = 2.23 [1.20-4.14], OS HR = 1.72 [0.97-3.05]). Table shows 5-yr MFS, 10-yr PCSS and 10-yr OS based on PSAn within 6m after RT completion. Conclusions: PSAn ≥0.1ng/mL within 6 mths after RT completion was strongly prognostic for PCSS, MFS and OS in pts receiving RT+ADT for localized PCa in this IPD analysis of > 10,000 patients. This could be used as an early signal-seeking endpoint in trials evaluating novel systemic therapies with RT + ADT and to help identify pts for therapy (de)escalation trials. [Table: see text]
Presence of somatic/germline homologous recombination repair (HRR) mutations and outcomes in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) receiving first-line (1L) treatment stratified by BRCA status.
Authors: Olmos David , Lorente David , Alameda Daniel , Cattrini Carlo , Romero-Laorden Nuria , Lozano Rebeca , Lopez-Casas Pedro P. , Capone Camille , Vanden Broecke Anne Marie , Trevisan Marco , Van Sanden Suzy , Jürgens Alexandra , Herrera-Imbroda Bernardo , Castro Elena 
Published: June 2023

5003 Background: Understanding of the association between HRR mutations and outcomes in mCRPC pts is limited. This analysis investigated the prevalence and outcomes of pts with/out HRR mutations (somatic and/or germline), stratified as BRCA, non-BRCA, or HRR non-BRCA, who initiated 1L mCRPC treatment with novel hormonal therapy (NHT) or taxane. Methods: Eligible pts from PROREPAIR-B (NCT03075735), PROSENZA (NCT02922218), PROSTAC (NCT02362620), and PROSABI (NCT02787837) studies underwent paired somatic/germline DNA analyses using a custom NGS panel that included ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2, RAD51B, and RAD54L. Those with pathogenic (likely) mutations in ≥1 allele of ≥1 gene were considered deficient (HRR). rPFS, PFS2, and OS were reported for BRCA, non-BRCA, and HRR non-BRCA subgroups; associations between mutations and outcomes were assessed using inverse probability weighted Cox models, which balanced the baseline (BL) characteristics between subgroups. Hazard ratios (HRs) with 95% confidence intervals (CIs) and p values are presented. Results: Of 729 pts, 223 (30.6%) were HRR, including 96 (13.2%) BRCA. 60.4% of pts were treated with NHT and 39.6% with taxane in 1L; 80.7% received at least second-line treatment. Median age at BL was 72.2 years, 63.5% had Gleason >7, 53.1% had ECOG ≥1, and 13.3% presented with visceral metastases. BL characteristics after adjustment were similar (standard mean difference: <0.1 in HRR and maximum 0.11 for all pts). BRCA pts had significantly worse rPFS, PFS2, and OS than non-BRCA pts; BRCA pts also had significantly worse PFS2 and OS than HRR non-BRCA pts. There were no significant differences between the outcomes of somatic and germline BRCA pts. Conclusions: BRCA pts, regardless of somatic/germline origin, had significantly worse rPFS, PFS2, and OS than the total non-BRCA population and significantly worse PFS2 and OS than non-BRCA pts in the HRR subgroup. It is crucial to screen early for HRR mutations, particularly in BRCA1/2, to begin timely, targeted mCRPC treatment and improve prognosis.[Table: see text]
Patient-reported outcomes (PROs) among men receiving talazoparib (TALA) + enzalutamide (ENZA) vs placebo (PBO) + ENZA as first-line (1L) treatment for metastatic castration-resistant prostate cancer (mCRPC): Results from a phase 3 study (TALAPRO-2).
Authors: Agarwal Neeraj , Azad Arun , Matsubara Nobuaki , Saad Fred , De Giorgi Ugo , Joung Jae Young , Fong Peter C.C. , Jones Robert J. , Zschaebitz Stefanie , Oldenburg Jan , Shore Neal D. , Dunshee Curtis , Carles Joan , Fay Andre P. , Cislo Paul , Chang Jane , Healy Cynthia G. , Niyazov Alexander , Fizazi Karim 
Published: June 2023

5013 Background: TALAPRO-2 (NCT03395197) showed statistically significant improvement in radiographic progression free survival with TALA + ENZA (n=402) vs PBO + ENZA (n=403) (HR=0.63 95% CI 0.51-0.78; P<0.001) in men receiving 1L treatment for mCRPC. Here we report PRO endpoints from TALAPRO-2. Methods: PROs were assessed at day 1 (baseline) and at scheduled visits until radiographic progression (every 4 weeks until week 53, and then every 8 weeks) using the EORTC QLQ-C30 and its prostate cancer module, QLQ-PR25. Prespecified PRO analyses included overall mean change from baseline (per longitudinal repeated measures mixed-effects model) and time to definitive clinically meaningful (≥10-point change) deterioration (TTD). Between-arm comparisons of TTD were made using a stratified log-rank test and a Cox proportional hazards model. Results: Of the 805 men randomized and treated, 793 had a baseline score followed by at least 1 post-baseline score; TALA + ENZA (n=395), PBO + ENZA (n=398). Although the treatment effect on global health status (GHS)/quality of life (QoL) significantly favored PBO + ENZA, the predefined threshold of clinical meaningfulness was not met; moreover, no significant differences between the arms were observed in any functioning scales. A significantly longer TTD in GHS/QoL was observed for TALA + ENZA; HR=0.780 (95% CI: 0.62, 0.99), P=0.038; median: 30.8 months vs 25.0 months. A numerical greater delay in TTD in urinary symptoms was longer for TALA + ENZA; HR=0.759 (95% CI: 0.543, 1.061), P=0.105; median not reached vs 35.9 months. Additional PRO results will be presented. Conclusions: Compared with PBO + ENZA, in the TALA + ENZA arm there was 1) a modest deterioration disfavoring GHS/QoL (deterioration was not clinically meaningful based on the predefined threshold), and 2) a maintenance in all functioning scales. TTD in GHS/QoL was significantly longer with TALA + ENZA vs PBO + ENZA, reflecting improved disease control. These results complement the benefit-risk assessment of TALAPRO-2. Clinical trial information: NCT03395197 . [Table: see text]
Association of adaptive immunity/inflammatory genes with survival in prostate cancer.
Authors: Hopper Austin , Krause Harris Benjamin , Elliott Andrew , Farrell Alex Patrick , Sutton Leisa , Tamayo Pablo , Carter Hannah , Shabaik Ahmed , Sharabi Andrew , Kuhn Peter , Heath Elisabeth I. , Antonarakis Emmanuel S. , Nabhan Chadi , Ferrara Napoleone , Asimakopoulos Fotis , Deichaite Ida 
Published: June 2023

5022 Background: Advances in immunotherapy have had little impact in prostate cancer (PCA). We have previously examined the immune microenvironment in both localized and metastatic PCA and found that primary PCA shows local inflammation/adaptive immunity whereas metastatic disease shows a shift towards immune suppression (Deichaite, 2022). Herein, we examine immune remodeling in PCA by evaluating changes in gene expression between localized and metastatic disease with heterogeneous treatment patterns in both primary and metastatic samples. Methods: Tumors from PCA (N = 5,419) were tested at Caris Life Sciences (Phoenix, AZ) with NextGen Sequencing of DNA (592-gene or whole exome) and RNA (whole transcriptome). Samples collected from the prostate gland (N = 3,284) or metastatic sites (N = 2,135) were analyzed. The Mann-Whitney U test was applied as appropriate, with P-values adjusted for multiple comparisons ( q < .05). Real-world overall survival (OS) data was obtained from insurance claims and Kaplan-Meier estimates were calculated for molecularly defined subpopulations. Survival for tumors with high (-H) and low (-L) expression of genes of interest, defined as top and bottom quartile of expression (transcripts per million, TPM) across all tumors, was investigated. Differentially regulated pathways were assessed by gene set enrichment analysis (GSEA). Results: Compared to metastatic PCA, primary samples had increased median expression of pro-inflammatory genes IL-6 (1.2-fold), SELE (1.9-fold), NRK (6.3-fold), CEBPD (1.2-fold), NFKB2 (1.4-fold) and FOXP3 (1.4-fold) (each q < .05). GSEA identified enrichment of E2F target genes in primary samples, while metastatic samples were enriched in inflammatory response, KRAS signaling and IL2/ STAT5 signaling pathways. The expression of inflammatory genes affected OS differently based on site. IL-6, NRK and SELE-H levels in primary samples were associated with increased OS. Within metastatic samples, CEBPD-H was associated with decreased OS and NFKB2-H was associated with an increased OS. FOSB-H was associated with increased OS in both primary and metastatic samples. Conclusions: We identify significant differences in the expression of inflammatory regulators and cytokines between localized and metastatic PCA tumors, which correlate with OS. These changes in the immune microenvironment can be leveraged for rational immunotherapy development and better targeted approaches. [Table: see text]
Prostate cancer public health system database from Brazil: Racial disparities and heterogeneity of treatment interventions to understand evidence-based practice patterns in a large real-world database.
Authors: Herchenhorn Daniel , McKay Rana R. , Sasse Andre Deeke , Monteiro Fernando Sabino Marques , Rose Brent Shane , Carvalhal Gustavo , Maluf Fernando Cotait , Morbeck Igor Alexandre Protzner , Souza Vinicius Carrera , Fernandes Elcio Firminiano , Valverde Douglas Andreas , James Nicholas D. 
Published: June 2023

5025 Background: The Brazilian Public National Health System (SUS) provides an opportunity to understand epidemiologic information, treatments, discrepancies in care, and costs of men with prostate cancer (PCa) using a large real-world dataset. This analysis focuses on racial disparities and heterogeneity of specific interventions to understand evidence-based practice patterns in Brazil. Additionally, the dataset can serve as a model for other low-middle income countries (LMIC). Methods: Patients included in the database were those with a diagnosis of PCa receiving care in the SUS from 01/01/2008 to 08/31/2022. Data were analyzed using a proprietary Healthcare Data Science platform offered by TECHTRIALS and included information regarding stage, demographics, cancer-related information, treatment-related information, and resources utilized. Results: 657,609 PCa pts were diagnosed and treated at SUS during the 14.5-year study period of whom 382,263 (58%) were brown/black (non-white) and 262,820 (42%) white. Median age of the population was 72.6 years, and did not vary with race. 26.16% of the pts were diagnosed with stage IV and this was not impacted by race or localization, including state or type of city (capital or not). Rates of radical prostatectomy and radiation utilization were similar between race categories. Additionally, in patients with stage IV disease, rates of systemic therapy utilization including chemotherapy with docetaxel (7.7%), with a tendency to increase use in the last years, and androgen receptor signaling inhibitors (ARSI) with (0.6%) or enzalutamide (0.08%), were low and similar between race categories. Rates of first-generation anti-androgens and estrogens were higher (56%) The total costs of prostate cancer directed care was R$4.31 billions (US$820 millions) and race did not impact total cost of care and cost by procedure or therapy type options. Conclusions: This is one of the largest studies using public health-system databases for Prostate cancer with Real World Data ever published. Race had no impact in presenting stage, treatment received and even in the costs involved. Underutilization of chemotherapy (docetaxel) in a scenario of limiting resources and without the use of new hormonal therapies is a matter of concern, together with an overuse of agents without proven survival advantage. Our data highlights the need for increased access to life prolonging agents for patients with metastatic PCa in the SUS.
Building a predictive model for outcomes with [177Lu]Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer using VISION data: Preliminary results.
Authors: Herrmann Ken , Gafita Andrei , De Bono Johann S. , Sartor A. Oliver , Chi Kim N. , Krause Bernd J. , Rahbar Kambiz , Tagawa Scott T. , Czernin Johannes , El-Haddad Ghassan , Wong Connie , Zhang Zhaojie , Wilke Celine , Mirante Osvaldo , Morris Michael J. , Fizazi Karim 
Published: June 2023

5028 Background: 177Lu-PSMA-617 is approved in adults with PSMA+ metastatic castration-resistant prostate cancer (mCRPC). This analysis of VISION data sought to build predictive models for clinical outcomes after 177Lu-PSMA-617. Methods: In VISION, adults with PSMA+ mCRPC received 177Lu-PSMA-617 (7.4 GBq every 6 weeks, ≤6 cycles) plus protocol-permitted standard of care (SoC) or SoC alone. In this post hoc analysis, 29 baseline parameters were assessed for prognostic and predictive value on overall survival (OS), radiographic progression-free survival (rPFS) and PSA response (≥50% reduction; PSA50). Parameters associated with outcome regardless of treatment were prognostic, and those associated with outcome after treatment with 177Lu-PSMA-617+SoC vs SoC were predictive. Cox proportional hazards (OS and rPFS) or logistic regression (PSA50) models were used in univariate analyses for parameter selection and to build statistical models. Here, univariate analyses are presented. Multiplicity was corrected by use of q values (ɑ = 0.05). Results: Data from 831 adults were analyzed. In initial univariate analyses, 76%, 69% and 38% of parameters assessed were prognostic for OS, rPFS and PSA50, respectively; fewer were predictive of better outcomes after 177Lu-PSMA-617+SoC vs SoC (subset shown). Conclusions: Baseline prognostic and predictive parameters were identified for OS, as well as for rPFS and PSA50, in adults with mCRPC in VISION receiving 177Lu-PSMA-617+SoC or SoC alone. For clinical application, select parameters will be reassessed categorically, and multivariate predictive models will be developed using identified parameters and parameter shrinkage.[Table: see text]
Effects of ovarian ablation or suppression on breast cancer recurrence and survival: Patient-level meta-analysis of 14,993 pre-menopausal women in 25 randomized trials.
Authors: Gray Richard G. , Bradley Rosie , Braybrooke Jeremy , Clarke Mike , Hills Robert Kerrin , Peto Richard , Bergh Jonas C. S. , Swain Sandra M. , Davidson Nancy E. , Francis Prudence A. , Regan Meredith M. ,   Early Breast Cancer Trialists' Collaborative Group
Published: June 2023

503 Background: Suppressing ovarian function of women with breast cancer may improve outcome by preventing estrogenic stimulation of any residual cancer, particularly for pre-menopausal women with estrogen receptor (ER)-positive tumors. We report a collaborative meta-analysis of individual participant data from randomized trials of ovarian ablation or suppression. Methods: Data were sought from randomized trials that compared ovarian ablation or suppression versus not. Primary analyses included only premenopausal women age < 55 with ER-positive or unknown tumors, stratified into those who received no chemotherapy, or remained premenopausal following chemotherapy, and those whose menopausal status following chemotherapy was not ascertained. Standard log-rank methods estimated ER-weighted annual event rate ratios (RR). Results: Individual patient data were provided for 25 of 27 relevant trials, comprising 14,993 (98.7%) of 15,195 women randomized. Overall, fewer breast cancer recurrences were seen with ovarian ablation/suppression than control (RR = 0·82, 95%CI 0·77–0·88; p < 0·0001). Recurrence reductions were significantly (p = 0.0003) larger among women (n = 7,213) known to be premenopausal prior to ovarian suppression (RR = 0·70, 0·63–0·78; p = 0·0003) than among those (n = 7,786) whose menopausal status was uncertain after chemotherapy (RR = 0·91, 0·83–0·99; p = 0·03). For known premenopausal women, 15-year risk of recurrence was improved by 12·1% (28·9% vs 41·0%; p < 0·0001. 15-year breast cancer and all-cause mortality were improved by 8·0% (20·9% vs 28·9%; RR 0·69, 0·60–0·80; p < 0·0001) and 7.2% (26·0% vs 33·1%; RR = 0·73, 0·64–0·82; p < 0·0001), respectively, with no increase in deaths without recurrence (RR = 0·88, 0·67–1·14; p = 0·33). Recurrence reductions were significantly (p = 0·003) larger among premenopausal women aged under 45 (RR = 0·63, 0·55–0·72; p < 0·0001) than among those aged 45-54 (RR = 0·84, 0·70–1.00; p = 0·045), but did not differ significantly by other recorded patient or tumor characteristics. Conclusions: For pre-menopausal women aged under 45, ovarian ablation or suppression substantially reduces the 15-year risk of recurrence and death from breast cancer without increasing mortality from other causes.