bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of intraoperative tranexamic acid use on overall survival and cancer specific survival in patients undergoing radical cystectomy.
Authors: Ahmed Mohamed E. , Andrews Jack R. , Mahmoud Ahmed M. , Thapa Prabin , Khanna Abhinav , Shah Paras , Sharma Vidit , Thompson R. Houston , Tollefson Matthew K. , Frank Igor , Karnes R. Jeffrey 
Published: January 2024

642 Background: Perioperative blood transfusion has been reported in up to 60% of patients undergoing RC. Unfortunately, perioperative blood transfusion in patient undergoing RC has been associated with poor oncological outcomes. Tranexamic acid (TXA) use has been proposed to decrease the need for perioperative blood transfusion. Here we seek to investigate the impact of intraoperative TXA on survival outcomes in patients undergoing radical cystectomy (RC) for bladder cancer. Methods: We queried the prospectively maintained Mayo Clinic Radical Cystectomy registry and identified all RC performed for bladder cancer between 1990-2021. Primary outcomes were patient’s overall survival and cancer specific survival among patients who received TXA versus patients who did not receive TXA. Results: Among 2929 patients who underwent RC in our institution between 1990-2021, 468 received TXA (IV) intraoperatively (Group A) and were propensity score matched 1:1 for age, neoadjuvant chemotherapy, adjuvant chemotherapy, pT stage, pN stage, and preoperative hemoglobin with a group who did not receive TXA (Group B, n= 468). At 8 years followup, 61% of patients who received TXA were alive versus 46% of patients who did not receive TXA. In univariable and multivariable analyses of factors associated with CSS (Table1), node positive disease, pT2-T4, peri-operative blood transfusion were associated with poor survival outcomes. While use of TXA was associated with improved CSS outcomes. Conclusions: In our study, TXA use in patients undergoing radical cystectomy was associated with decreased risk or peri-operative transfusion, improved patient’s overall survival, and cancer specific survival. We can’t explain the biological rational for improved survival however these findings warrant further prospective investigation. [Table: see text]
Impact of squamous histology on outcomes with enfortumab vedotin in patients with advanced urothelial carcinoma: Analysis of the UNITE study.
Authors: Jindal Tanya , Alhalabi Omar , Nguyen Charles B , Bakaloudi Dimitra Rafailia , Nizam Amanda , Bilen Mehmet Asim , Basu Arnab , Zakharia Yousef , Milowsky Matthew I. , Brown Jason R , Kilari Deepak , Shah Sumit , Emamekhoo Hamid , Grivas Petros , Hoimes Christopher J. , Gupta Shilpa , Bellmunt Joaquim , Campbell Matthew T , Alva Ajjai Shivaram , Koshkin Vadim S 
Published: January 2024

651 Background: Squamous histology (SH) is the most common variant of Urothelial Carcinoma (UC) and is associated with lower response rates to chemotherapy. The impact of SH on outcomes with enfortumab vedotin (EV) is less defined. We hypothesized that increased SH component would correlate with inferior outcomes with EV treatment. Methods: UNITE is a multi-institutional retrospective study in pts advanced UC (aUC) treated with targeted agents. In this analysis, we compared EV monotherapy outcomes in pts with pure UC (pUC) and pts with urothelial predominant histology (UCP) [<50% SH], SH-predominant [50-99% SH] and pure SH (pSH) [100% SH] respectively. We also compared pSH to UCP and SHP. Observed Response Rate (ORR) was compared in evaluable pts with scans after ≥1 cycle of EV using Chi-squared test. Progression-free survival (PFS) and overall survival (OS) from EV start were assessed and compared using the KM method and Cox proportional hazard test. Results: This analysis included 460 pts from 17 US sites treated with EV monotherapy. 366 pts had pUC and 94 pts had SH component (including pSH). In the overall cohort, median age was 70, 73% men, 88% Caucasian, 73% ECOG PS 0-1, 67% lower tract tumor, 30% liver mets, 38% bone mets, 65% had ≥ 2 prior therapy lines. There were no significant differences in baseline clinical characteristics between pts with pUC vs SH component except for higher incidence of liver mets in pts with pUC (32% vs 20%; p = 0.02). Among all 460 pts, median follow up was 20.7 mos from EV start, ORR was 51%, mPFS and mOS were 5.8 mos (95% CI: 5.3-6.4) and 12.7 mos (95% CI: 11.5-14.3). Among 94 pts with SH component, 70 were UCP, 17 SHP and 7 pSH. Inferior outcomes were noted in pts with pSH relative to pts with pUC and pts with UCP (Table). No differences in outcomes were seen across other cross-group comparisons. Conclusions: These hypothesis-generating findings suggest that SH component may impact outcomes with EV treatment in pts with aUC. A subset of pts with SH-predominant histology can have robust responses and outcomes with EV treatment, but larger studies and further biomarker data are needed to determine pts most likely to benefit. Patients with pSH are shown to have worse outcomes with EV, but further studies with a larger sample size are needed to validate our findings and define the role of EV for this rare and biologically distinct entity. [Table: see text]
Single-center analysis on a real-world cohort of patients with metastatic urothelial carcinoma studied by NGS: Molecular landscape and efficacy of targeted therapies.
Authors: Gutiérrez Pérez César , Rodríguez Ledesma Inmaculada , Pumares González María , Vela Domínguez Miriam , Espinosa Cabria Noelia , Cabrera Pinos María Liliana , Calvo Otero Laura , Valencia Cárdenas Lina Marcela , Viña Gopar Laura , Blanco Abad Carmen , Folgueira Hernández Benjamín , García Muñoz María , García Girón Carlos , García Toro Enrique , Lastra Aras Enrique , López Peraita Sandra , Ramos Reguera Irene , Saiz López Patricia , de la Torre Lázaro Sofía , Crespo Herrero Guillermo 
Published: January 2024

661 Background: the median overall survival (OS) in metastatic urothelial carcinoma (mUC) treated with multiagent therapy is approximately 13 months (mo). Around 69% of these tumors harbor potential therapeutic targets. Real-world evidence on using Next Generation Sequencing (NGS) in mUC management is limited. Methods: we conducted a single-center analysis on a real-world cohort of patients (pts) with mUC. The study population included pts aged >18 years with diagnosis of mUC studied by NGS at the moment of starting immunotherapy (enrollment period: 09/04/2019 – 03/25/2022). Median OS and median progression-free survival (PFS) were determined using Kaplan-Meier curves. Results: we included 43 pts. Median age at mUC diagnosis was 67 years; 38 (88.4%) pts were men; 38 (88.4%) pts were ECOG 0-1 at mUC diagnosis; one or more adverse prognostic factors (Bellmunt Risk Score) were identified in 33 (76.7%) pts; primary tumor site was lower tract in 36 (83.7%) pts. All pts were treated with platinum-based combinations (neoadyuvant, adyuvant or first line) and immunotherapy. Pathogenic alterations were found in 25 (58.1%) pts. In the group of 25 pts with pathogenic alterations, 17 pts progressed to immunotherapy and 7 pts of them received targeted therapies; 10 pts could not receive targeted therapies due to poor prognosis. In the group of 18 pts without pathogenic alterations, 11 pts progressed to immunotherapy and 8 pts of them received other chemotherapy options; 3 pts could not receive other chemotherapy options due to poor prognosis. The median OS (time since mUC diagnosis) among 25 pts with pathogenic alterations was 30.2 (CI 95%: 18.9-41.5) mo compared to 22.9 (CI 95%: 12-33.9) mo among 18 pts without pathogenic alterations, (p = 0.557). Focusing on the subgroup of 7 pts treated with targeted therapies (Table), we found an objective response rate (ORR) of 42.9%; the median PFS was 7.3 (CI 95%: 6.7-7.9) mo and the median OS (time since beginning targeted therapies) was 10.9 (CI 95%: 2.4-19.5) mo. Conclusions: We recommend that all pts with mUC undergo NGS at the time of diagnosis, given the high percent (58.1%) of pathogenic alterations in our real-world cohort and the efficacy in terms of ORR, PFS and OS in pts treated with targeted therapies. [Table: see text]
The impact and mechanisms of gut microbiota on the efficacy of neoadjuvant therapy in patients with MIBC.
Authors: Li Tao , Qi Tianyu , Wu Kaijie 
Published: January 2024

669 Background: Platinum-based neoadjuvant chemotherapy, such as gemcitabine/cisplatin (GC) or dose-dense methotrexate/vinblastine/doxorubicin/cisplatin (ddMVAC), followed by radical cystectomy (RC), represents the current standard of care for T2-T4aN0M0 muscle-invasive bladder cancer (MIBC). Regrettably, only 40% of patients who received neoadjuvant chemotherapy achieved a pathological complete response (pCR). Recently, several trials showed a promising efficacy of immune checkpoint inhibitors (ICIs) plus neoadjuvant chemotherapy. BGB-A317-2002 study indicated that the addition of tislelizumab to GC can increase the pCR rate to 54.5%, with a pathological downstaging rate of 77.3%. Nevertheless, a subset of patients failed to derive benefits from ICIs plus neoadjuvant chemotherapy. Methods: This study aimed to explore the impact and mechanisms of gut microbiota on the efficacy of neoadjuvant therapy through the analysis of fecal samples obtained from MIBC patients who received GC or GC plus ICIs. Here, we reported the impact of gut microbiota on treatment outcomes in patients who received GC. Results: A total of 54 patients who received neoadjuvant GC chemotherapy were enrolled. Among them, 23 (42.59%) exhibited a pathological response (responsive group), and 31 (57.41%) showed no response (non-responsive group; no imaging changes or disease progression). Metagenomic sequencing on fecal samples from patients before and after therapy showed that the Shannon index in species level (1.182 vs. 0.954, p=0.016) and abundance of Ruminococcus gnavus were significantly greater in the responsive group than non-responsive group. It suggested that responsive patients displayed higher species richness of gut microbiota. Conclusions: The efficacy of neoadjuvant GC chemotherapy in MIBC patients may be potentially influenced by the number of gut microbiota populations. Additionally, the potential application value of Ruminococcus gnavus in improving the efficacy of non-responsive patients is noteworthy. A larger-scale study is needed to determine the above findings.
Effect of prednisone dosing on mineralocorticoid-related side effects with abiraterone in prostate cancer.
Authors: Goryachok Maksym , Nicklawsky Andrew , Ahmad Hiba , Flaig Thomas W. 
Published: January 2024

67 Background: Abiraterone, a 17a hydroxylase inhibitor, is used for prostate cancer and can lead to mineralocorticoid excess syndrome (e.g. hypertension and hypokalemia). Concurrent prednisone mitigates these effects; however, the optimal prednisone dosage is unclear. This study examines the occurrence of mineralocorticoid side effects from Abiraterone with 5 mg of prednisone daily versus 5 mg twice daily. Methods: Data for 1410 patients treated with abiraterone from 2011 to 2022 were identified from a large academic/community hospital system (Health Data Compass Data Warehouse project). Laboratory measures, clinical parameters, and ICD10 codes were collected from 6 months prior to abiraterone initiation through treatment duration. 348 patients were excluded for missing medication data, discordant prednisone initiation, and use of a second steroid; 1062 patients remained (5 mg daily, N = 555, 10 mg daily, N = 507). Prednisone dose was treated as a time-varying covariate due to dose-switching (N = 122). Hypokalemia and hypertension incidence over 24 weeks after abiraterone initiation was analyzed via time to event frailty cox-proportional hazard models using both CTCAE v5.0 grade and ICD 10 code outcomes. Results: Patients on 5 mg of prednisone twice daily had approximately a 96% longer average time to first event for a combined-endpoint of hypertension and hypokalemia via ICD10 code methodology at any point during the 24 weeks following abiraterone initiation (HR 0.51, CI 0.43 - 0.62, P < 0.001). This trend was durable with individual ICD10 analysis in hypertension (HR 0.52, CI 0.43 - 0.62, P < 0.001) and hypokalemia (HR 0.45, CI 0.30 - 0.66, P = <0.001). Assessing direct clinical measurements via incidentally recorded blood pressure and potassium lab values, the analysis for grade 2/3 hypertension (HR 0.81, CI 0.7-0.93, P = 0.004) and grade 3 hypokalemia (HR 0.46, CI 0.26-0.82, P = 0.008) also showed a corresponding increase in average time to first measure favoring the 5 mg twice daily cohort during the 24-week period. Conclusions: This study shows a significant delay in the development of hypertension and hypokalemia from abiraterone with 5 mg twice daily compared to 5 mg of prednisone daily. This was observed both with ICD10 coding and direct clinical measurements of these events within the EMR. Assessments of other physiologic parameters and survival are ongoing. These findings highlight the impact of prednisone dosing with abiraterone, which may merit additional consideration in specific at-risk patient populations including those with baseline hypertension or cardiovascular risk factors.
Differential mutation profiles between benign and cancerous urothelium in patients with non-muscle invasive bladder cancer (NMIBC).
Authors: Miyagi Hiroko , Linscott Joshua , Gould Billie , Murthy Prithvi , Du Pan , Jia Shidong , Li Roger 
Published: January 2024

675 Background: Differentiating passenger and driver mutations of oncogenesis is essential in understanding disease biology and developing biomarkers that use genomic mutations for diagnosis or prognostication. Accumulating research shows normal urothelium harbors many mutations commonly reported in molecular profiling of urothelial carcinoma. This is especially true of NMIBC. Here, genetic profiling of the mutational landscape of pathologic NMIBC tumors (pNMIBC) was performed and compared to matched pathologically benign urothelial tissue (pBT) to determine the frequency of passenger mutations. Methods: From a prospective observational cohort, 9 patients with high-risk NMIBC and pBT on repeat TURBT were identified. Somatic mutational profiles of the index tumor (pNMIBC) and subsequent pBT of each patient was performed via PredicineWES+ whole exome sequencing. Somatic variants were identified using the Predicine DeepSea in-house algorithm as previously described. Briefly, non-synonymous variants are captured and probabilistically annotated as germline vs. somatic in comparison with matched germline PBMC WES+ sequencing. NS somatic mutations observed in pBT were compared to those in pNMIBC to evaluate for putative passenger versus driver mutations. Results: A median of 236 mutations (IQR:100-732) were detected for pNMIBC compared to 37 (IQR: 5-80) in the pBT group (p=0.018). The number of genes with likely somatic mutations in pNMIBC only, both samples, and pBT only, were 2239, 500, and 1, respectively. The most frequently mutated genes in pNMIBC tissue samples were ARID1, TERT, CREBBP, LMTK3 and NCOR1. Notably, both pBT and pNMIBC tissue shared mutations in commonly reported bladder cancer genes such as ARID1A, ERBB2, ATM, ERCC2 and CKDN2A. Somatic mutations in FGFR3, LMTK3, NCOR1, AKAP9, COL11A2, CRYBG3, KMT2A, MCM3AP, PHF3, VPS13A and ZNF28 were present solely in pNMIBC tissue, whereas OVGP1 mutation was exclusive to pBT. Analysis of the functional impact of mutations in genes that are mutated in both benign tissue and pNMIBC offers a deeper understanding of the evolution of bladder cancer via field cancerization. Conclusions: Analysis of the mutational profile of pBT and pNMIBC revealed differential patterns of somatic mutations. Many expected gene mutations were detected in pNMIBC, but surprisingly 18% of all mutated genes were shared between tumor and pathologically benign samples. The fact that only one somatically mutated gene was exclusive to pBT signifies excellent censoring of variants by the DeepSea algorithm. In summary, these preliminary findings suggest that common gene mutations in NMIBC are frequently observed as passenger mutations. This underscores the potential significance of tissue-informed biomarkers tailored to an individual's mutational profile, which may outperform panel assays.
Clinical and molecular characterization of urothelial (UC) vs. small cell carcinoma (SCC) of the urinary tract.
Authors: Chawla Neal Shiv , Mercier Benjamin D. , Govindarajan Ameish , Li Xiaochen , Castro Daniela V. , Ebrahimi Hedyeh , Barragan-Carrillo Regina , Zang Peter D. , LeVee Alexis Ann , Dizman Nazli , Hsu Joann , Meza Luis A , Zengin Zeynep Busra , Salgia Nicholas , Chehrazi-Raffle Alex , Dorff Tanya B. , Pal Sumanta Kumar , Tripathi Abhishek 
Published: January 2024

682 Background: SCC is an uncommon variant of bladder cancer with sparse data pertaining to its genomic landscape. Utilizing Tempus Lens, a real world clinical and genomic dataset, we investigated the clinical and genomic characteristics of SCC compared to UC. Methods: The de-identified Tempus Lens dataset was queried for patients diagnosed with UC or SCC of the bladder or ureter, of any stage. Baseline demographic, pathologic features, and results from blood or tissue-based genomic sequencing were catalogued. Clinical and pathological variables were summarized using descriptive statistics to compare the UC and SCC groups, using a Chi-square or Fisher’s exact test for a significance threshold of P<0.05. The prevalence of genomic alterations in the two groups were compared using a two proportions Z-test with a significance level of 0.00167, calculated using the Bonferroni correction for multiple comparisons. Results: A total of 4,569 pts (UC: 4429; SCC: 140) were included in the analysis. Gender, race, the proportion of patients ≥65 years, stage, and tumor grade were similar between the two groups. Use of blood based genomic sequencing was relatively similar (29.8% and 27.1%) between UC and SCC patients, respectively. Compared to UC, the SCC cohort had a significantly higher prevalence of TP53 (93.6% vs 60.8%; P<0.001), RB1 (73.6% vs 21.5%; P<0.001), and PTEN (13.6% vs 5.1%; P<0.001) alterations, and a lower frequency of CDKN2A (7.1% vs 29.5%; P<0.001), MTAP (2.9% vs 18%; P <0.001) and FGFR3 (6.4% vs 15.6%; P=0.003) mutations. Actionable alterations in SCC cohort included PIK3CA (21.4%), ERBB2 (13.6%), ATR (13.6%), ATM (9.3%), BRCA2 (8.6%), MSH6 (5.7%), TSC1/2 (4.9%), and PMS2 (4.3%). Conclusions: This is the largest study characterizing the genomic features of SCC. Our findings are consistent with prior studies suggesting a distinct genomic profile of SCC, with actionable alterations in a significant subset of patients. The impact of these alterations on outcomes and therapeutic strategies targeting these mutations warrant further investigation.
Identification of patients with metastatic urothelial cancer not able to receive maintenance avelumab.
Authors: Jackson-Spence Francesca , Chauhan Vishwani , Silva Diaz Sofia , Gurung Ayushma , Young Matthew Nicholas , Nally Elizabeth , Wells Connor , Szabados Bernadett , Powles Thomas 
Published: January 2024

702 Background: Maintenance avelumab following frontline platinum-based chemotherapy for metastatic urothelial cancer (mUC) is associated with survival benefit. Eligibility to receive avelumab maintenance requires receiving 4-6 cycles chemotherapy without disease progression. Not all patients complete 6 cycles of chemotherapy or meet eligibility to receive avelumab and these patients may need to have alternative therapies. Here we present real world data to assess whether baseline characteristics can be used to identify patients unable to complete 6 cycles of chemotherapy and whom may not be eligible for maintenance avelumab. Methods: This retrospective audit was performed at Barts Cancer Centre for consecutive patients from January 2010 until August 2023. Patients who received frontline gemcitabine and cisplatin/carboplatin chemotherapy for advanced mUC were included. Eligibility for avelumab is defined as completing 4-6 cycles of chemotherapy without disease progression (PD). Characteristics of patients completing 6 cycles of chemotherapy, versus those who do not were described. Chi-squared tests were conducted to compare characteristic between the two groups, using SPSS v28. Results: 265 patients receiving frontline systemic therapy were identified over a 13-year period. 242 (91%) received Gem/Cis or Gem/Carbo chemotherapy. 151 (63%) patients were eligible to receive maintenance avelumab. 91 (38%) patients were not eligible due to receiving less than 4 cycles chemotherapy (68%) or due to PD (75%), or both. 91 (38%) patients completed 6 cycles of chemotherapy. Having a low baseline Hb <100g/dl was the only baseline characteristic associated with receiving less than 6 cycles chemotherapy (p=0.002). 33% of patients who completed less than 6 cycles chemotherapy had a Hb <100g/dl, compared to 10% of the patients who completed chemotherapy (p=0.002). Any dose delays was associated with a lower likelihood of being eligible to receive avelumab (32% and 18% dose delays in avelumab eligible vs ineligible cohorts, respectively (p<0.001). Patients with any dose delays had more frequently received carboplatin (65% vs 39%, p=0.012) and had visceral metastases including liver metastases (63% vs 39%, p=0.014), compared to those without dose delays. Conclusions: Specific baseline factors predispose to an inability to deliver 6 cycles of chemotherapy without complications or progression. These patients are less likely to receive maintenance avelumab. These data help the optimise number of cycles offered to patients in mUC.