bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world clinical and toxicity outcomes in older Veterans with metastatic renal cell carcinoma (mRCC) treated with front-line systemic therapy.
Authors: Aly Ragia , Yang Ziyi , Schmitt Jordan Marie , King Jennifer 
Published: June 2024

e16525 Background: The United States veteran population represents a unique group of patients with distinct health care challenges, particularly for older veterans. Here, we describe a real-world cohort of veterans with mRCC treated with systemic therapy and assess if outcomes and toxicities with front-line systemic therapy differ for older adult veterans. Methods: Veterans diagnosed with mRCC between 2010- 2023 at the Richard L. Roudebush VA in Indianapolis and treated with front-line systemic therapy were identified. Patients were classified as £65yo and >65yo. Comparisons between groups were done using Chi-square tests for categorical variables or Wilcoxon test for continuous variables. Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS), with Cox model used to adjust for confounders. Results: A total of 73 patients with mRCC were identified. Median age was 67.4. 31 patients (42%) were £65yo and 42 (58%) were >65. 99% of patients were male. 69% of patients had clear cell histology, 11% papillary, 11% poorly differentiated, 5% unclassified, 2% chromophobe, 2% sarcomatoid, and 2% other. 52% of patients ≤65yo had IMDC int/poor risk disease vs. 85% of patients >65 (p=0.016). There was no statistically significant difference in disease grade, stage, or presence of sarcomatoid/rhabdoid features between groups. The table lists and compares therapies received and toxicity outcomes. The median PFS was 18.7 months in pts ≤65yo vs. 7.1 months in pts >65 (p=0.24). The median OS was 58.1 months in pts ≤65 vs. 12.6 months in pts >65. (p=0.048). When using the Cox model to adjust for IMDC risk, the OS difference was not maintained, with a hazard ratio of 1.16 (CI 0.59, 2.27; p=0.664). Conclusions: In this cohort of veteran patients with mRCC, older veterans had higher rates of IMDC int/poor risk disease, likely leading to decreased survival outcomes. Front-line systemic therapies used were similar to younger veterans without an apparent difference in toxicity. This material is the result of work supported with resources and the use of facilities at the Richard L. Roudebush VA in Indianapolis. [Table: see text]
Impact of β-adrenergic blockade on efficacy of immunotherapy in patients with metastatic clear cell renal cell carcinoma.
Authors: Semaan Karl , Eid Marc , Saad Eddy , Issa Wadih , Saliby Renee Maria , Paul Morgan , Zhong Caiwei , Gunenc Damla , Phillips Noa , Nawfal Rashad , Machaalani Marc , El Hajj Chehade Razane , Yekeduz Emre , Labaki Chris , El Zarif Talal , Baca Sylvan C. , Xie Wanling , McGregor Bradley Alexander , Zhang Tian , CHOUEIRI Toni K. 
Published: June 2024

e16529 Background: Immunotherapy (IO) has become a cornerstone in the standard of care of patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC). Recent studies suggest concomitant beta-blockers (BB) use may improve the effectiveness of IO in melanoma by increasing CD8+ T cells tumor infiltration through β-adrenergic blockade. Herein, we assess the impact of BB on the clinical outcomes of pts with mccRCC treated with IO-based regimens in first-line (1L) settings. Methods: Real-world data from Dana-Farber Cancer Institute and the University of Texas Southwestern Medical Center were collected retrospectively. Pts with mccRCC who received 1L standard of care IO-based regimens, including dual-IO or IO in combination with vascular endothelial growth factor-targeted therapies (IO+VEGF-TT) were included. Pts receiving BB at the 1L initiation were classified as BB-treated pts, while pts who were not on BB at 1L initiation were labeled as BB-untreated pts. Time to treatment failure (TTF) and overall survival (OS) were compared between groups using a multivariable Cox regression adjusting for age at 1L start, body mass index (BMI), and IMDC risk group. Objective response rate (ORR; responders vs. non-responders/not evaluable) per RECIST 1.1 criteria was compared between groups using a Chi-Squared test. Results: Our cohort included 171 pts with mccRCC, 134 (78.4%) were male, and the median (Q1-Q3) age was 62 (56-68) years. A total of 55 deaths were observed. The median follow-up of pts was 28.1 months. At 1L treatment initiation, 52 (30.4%) pts were receiving BB. BB-treated pts (vs. those not) were older (65.1 vs 60.8; p=0.003) and had higher BMI (31.1 vs. 29; p=0.004) at 1L initiation. BB-treated pts (vs. those not) had comparable TTF (adjusted HR (aHR) = 1.0; 95% confidence interval (CI): 0.7-1.5; p=0.88) and comparable OS (aHR=1.1; 95%CI: 0.6-2.0; p=0.67). BB-treated pts (vs. those not) had a numerically increased ORR, but this difference was not statistically significant (31/52, 59.6% vs. 59/119, 49.6%; p=0.29). A sensitivity analysis within each of dual-IO (n=83, 48.5%) and IO+VEGF-TT (n=88, 51.5%) subgroups showed similar results (Table). Conclusions: This is the first effort to investigate the impact of β-adrenergic blockade on IO activity in pts with mccRCC. While previous data suggest concomitant BB use may enhance IO efficacy in pts with melanoma, our results show that the use of BB was not associated with better IO effectiveness in pts with mccRCC. Limitations of the study arise from its retrospective design. [Table: see text]
Cabozantinib outcomes for metastatic renal cell carcinoma at a tertiary NHS hospital in the United Kingdom (UK).
Authors: Arumugam Shanmugasundaram Guhan , Holden Emily , Al-Husban Hadeel , Kazmi Farasat , Maskell David , Kapur Gaurav 
Published: June 2024

e16538 Background: Kidney cancer remains the seventh most common solid organ cancer in the UK, USA and Europe, with renal cell carcinoma forming most of these cases [1]. In the UK, kidney cancer accounts for 3% of all new cancer diagnoses of which 25–31% present with metastatic RCC (mRCC) at initial diagnosis. [2] Methods: The METEOR trial was used as the comparator for response rates and progression-free survival to evaluate our outcomes. In the METEOR trial, treatment with Cabozantinib was associated with significantly better overall survival (OS) (21.4 months (m) with Cabozantinib vs 16.5m Everolimus), progression-free survival (PFS) (7.4m vs 3.9m), objective response rates (ORR) (17% vs 3%), and an equivalent safety profile when compared to Everolimus, a second-line treatment for patients with advanced renal cell carcinoma. [3] We present the results of Cabozantinib outcomes in the first to third line setting for mRCC at an NHS tertiary hospital. A direct comparison of OS is not feasible, as the METEOR data was for Cabozantinib in the second line. In contrast, Cabozantinib was used in first, second and subsequent line settings according to the NHS funding in our hospital trust. Results: From 16 April 2018 to 13 November 2023, 43 patients with mRCC received Cabozantinib at our NHS trust. Compared to the METEOR study, the median follow-up for our NHS tertiary centre patients was 7.5 m, as opposed to 18.7 m. Comparing the real-world data from our NHS centre with the METEOR trial, the ORR (partial response according to RECIST criteria) was 25% compared to 17%, whilst the PFS was 10.6m vs 7.4m. Interestingly, we observed that patients who had received immunotherapy before Cabozantinib had significantly better PFS (12m OS = 22% vs 0%; Log Rank = 0.03). Grade 3 and above toxicities was 32.5% vs 71% (NHS hospital vs METEOR trial). Conclusions: Overall, Cabozantinib showed better than expected response rates, and the toxicities in our NHS tertiary hospital were less severe than in the METEOR trial. Significantly, we observed that individuals who had received immunotherapy before Cabozantinib had higher survival outcomes. References: 1. U.S. Cancer Statistics Working Group. U.S. Cancer Statistics Data Visualizations Tool, based on 2022 submission data (1999-2020): U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute; https://www.cdc.gov/cancer/dataviz , released in November 2023; 2. Cancer Research UK [Internet]. Kidney cancer statistics. Available from: http://www.cancerresearchuk.org/healthprofessional/cancer-statistics/statistics-by-cancer-type/kidney-cancer. [Cited: 2019 Jan 15]; 3. Choueiri, Toni K., et al. "Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial." The Lancet Oncology 17.7 (2016): 917-927.
Clinical features, genomic alterations, and survival outcomes for variant histology urothelial carcinoma.
Authors: Sevgi Mert , Hassoun Rebecca , Althouse Sandra K. , Tran Mya , Fausel Christopher A. , Schneider Bryan P. , Salous Tareq , Adra Nabil , King Jennifer 
Published: June 2024

e16549 Background: Twenty-five percent of urothelial tumors exhibit variant histology. Each variant exhibits unique genomic composition and has a distinct clinical course. While there is emerging work describing the clinical and genomic features of variant histology, the integration of both with their impact on clinical outcomes remains less studied. Here, we describe the clinical features, genomic alterations, and outcomes of a real-world cohort of variant urothelial histology. Methods: This was a retrospective review of patients with variant histology urothelial carcinoma who underwent genomic sequencing and were treated at our institution between 2016-2023. Genomic data was derived from standard of care CLIA-next generation sequencing. Demographics and outcomes were derived from chart review. Kaplan-Meier method was used for progression free survival (PFS) and overall survival (OS). Results: 78 patients (pts) were included. Median age was 68.6 (33.7-90.7). 69.2% were male. Variant histology included 15 pts with squamous cell component, 14 pts with plasmacytoid component, 13 pts with micropapillary component, 8 pts with adenocarcinoma. The remaining variant histologies are listed in table 1. 10 pts (12.8%) had more than one variant histology present. 60 pts (76.9%) had metastatic disease; 24 (40%) of them with de novo metastatic disease. Metastatic sites were distant lymph nodes (LN) in 37 pts, lung in 25 pts, bone in 22 pts, and liver in 14 pts. The table lists genomic findings by variant histology. Overall, 2-yr PFS was 29% and 2-yr OS was 69.4%. Median PFS was 0.3 yrs for plasmacytoid vs. 0.4 for adenocarcinoma vs. 0.7 for micropapillary vs. 0.8 for squamous. Median OS was 1.5 yrs for plasmacytoid vs. 2.9 for adenocarcinoma vs. 3 for micropapillary vs. not evaluable for squamous. Conclusions: In this cohort of patients with variant urothelial histology, the most common genomic alterations were TERT and TP53 mutations. Several targetable alterations including KRAS, PIK3CA, and TSC1 were detected across various histology subtypes and suggest a potential avenue for further therapeutic research. Though not statistically significant, PFS and OS were shorter for patients with plasmacytoid and adenocarcinoma variants. [Table: see text]
Characterizing genomic alterations in patients with metastatic urothelial carcinoma (mUC) treated with enfortumab-vedotin (EV) with a focus on 1q23.3.
Authors: Saliby Renee Maria , Semaan Karl , Epstein Ilana B. , Liria Sonsoles , Dall Christopher , Saad Eddy , Eid Marc , Canniff John , Kwak Lucia , Berg Stephanie A. , Mantia Charlene , McGregor Bradley Alexander , Braun David A. , CHOUEIRI Toni K. , Bellmunt Joaquim 
Published: June 2024

e16570 Background: EV has improved outcomes for patients with mUC whether used as monotherapy or in combination. Limited studies have explored EV's efficacy and toxicity using combined genomic data from multiple platforms. We explored the association of genomic alterations with clinical outcomes in patients with mUC receiving EV treated at a single institution. Methods: Clinical and genomic data from patients with mUC treated with EV at the Dana-Farber Cancer Institute was analyzed. Genomic data was obtained using the targeted Oncopanel platform. Overall survival (OS), progression-free survival (PFS), and toxicity-free survival (TFS) as well as objective response rate (ORR) and progressive disease (PD) as best response according to RECIST 1.1 criteria were studied. Patients were categorized based on genomic alterations employing log-rank tests and univariate Cox regression for OS, PFS, and TFS, and Fisher’s exact test for ORR and PD. Results: We identified 286 patients treated for advanced UC since the approval of EV in 2021, of whom 65 received EV monotherapy, had available genomic data and were included in our analysis. Two genomic regions, 1q23.3 and 9p21.3 were found of interest. 17% (N=11) exhibited gain or amplification at the 1q23.3 cytoband ( PVRL4 cytoband) while 35% (N=23) had a two-copy deletion or loss at 9p21.3 ( MTAP, CDKN2A/B cytoband). While none of the results were statistically significant, gain or amplification of 1q23.3 was associated with a trend towards worse OS (Table). ORR was 29% compared to 60% in those without, but this difference was not statistically significant (p.value = 0.62). Two-copy deletion or loss at 9p21.3 was associated with numerically longer OS (Table) ORR was 57% in patients with the alteration versus 50% in those without, and 9% versus 17% for PD, respectively. These differences also did not reach statistical significance (p.value = 0.46). Conclusions: Our study did not find significant correlations between specific somatic alterations and clinical outcomes in patients with metastatic UC treated with EV though limited by small sample size. The observed trends in alterations of 1q23.3 and 9p21.3 warrant further investigation in larger cohorts. [Table: see text]
First-line (1L) systemic therapy in locally advanced/metastatic urothelial cancer (Ia/mUC): A living interactive systematic review and network meta-analysis.
Authors: Saxena Akshat , Riaz Irbaz Bin , Naqvi Syed Arsalan Ahmed , Bibi Arifa , Channar Aneeta , Tripathi Nikita , Khan Muhammad Ali , Raina Ammad , Khakwani Kaneez Zahra Rubab , Childs Daniel S , Bryce Alan Haruo , Singh Parminder 
Published: June 2024

e16579 Background: Recent results from EV 302 and CheckMate 901 have transformed the treatment landscape of untreated locally advanced/metastatic urothelial cancer (Ia/mUC). Here, we present the most up-to-date evidence of comparative efficacy and safety of first line (1L) treatment options in Ia/mUC with emphasis on Enfortumab vedotin (EV)-pembrolizumab (P) and gemcitabine (Gem)-cisplatin (Cis)-nivolumab (N). Methods: This living systematic review used the living interactive evidence (LIvE) synthesis framework. Full-text and abstract publications of phase II/III randomized clinical trials comparing 1L immunotherapy combined with chemotherapy (IO+C) or immunotherapy alone (IO) regimens with platinum-based chemotherapy (Plat) in Ia/mUC were included. Outcomes of interest included overall survival (OS), progression-free survival (PFS) and treatment-related grade 3 or greater adverse events (≥G3 TRAE). Mixed treatment comparisons were made using network meta-analysis. P-scores were computed to assess relative treatment rankings. Results: A total of 5 trials (8 references) with 4,749 patients and 9 unique treatments were included. EV-P and Gem-Cis-N were ranked first and second in terms of OS and PFS improvement. EV-P improved OS compared to Gem-Cis-N (HR: 0.60; 0.45-0.81), Gem-Plat-atezolizumab(A) (0.55; 0.42-0.72), durvalumab(D)- tremelimumab(T) (0.55; 0.42-0.72), Gem-Plat-P (0.55; 0.42-0.72), P (0.51; 0.39-0.68), D (0.47; 0.36-0.63), A (0.48; 0.36-0.63) and Gem-Plat (0.47; 0.38-0.58). EV-P also improved PFS compared to Gem-Cis-N (0.63; 0.48-0.82), Gem-Plat-A (0.55; 0.43-0.69), D-T (0.42; 0.33-0.53), Gem-Plat-P (0.58; 0.45-0.74), P (0.34; 0.26-0.44), D (0.35; 0.27-0.44) and Gem-Plat (0.45; 0.38- 0.54). For ≥G3 TRAE, A was ranked first with the lowest adverse events compared to others. EV-P (rank 5) had significantly fewer events compared to Gem-Plat, Gem-Plat-A, Gem-Cis-N and Gem-Plat-P. Gem-Cis-N was ranked last with significantly greater events compared to A, P, D, D-T, Gem-Plat, EV-P, and Gem-Plat-A (Table with ranks [p-scores]). Conclusions: Current evidence suggests that patients with untreated la/mUC experience improved survival and slower disease progression with EV-P when compared to other contemporary options. Gem-Cis-N may be a reasonable alternative in patients who are cisplatin-eligible. Cost and access to these treatments are crucial and should be considered to facilitate shared decision making. [Table: see text]
In-hospital outcomes of acute pulmonary embolism admissions in individuals with genitourinary cancers: Insights from a national population study in the United States.
Authors: Benjamin David Joseph , Rezazadeh Arash , Shafi Irfan , Yazdanpanah Omid 
Published: June 2024

e16581 Background: Management of acute pulmonary embolism (PE) in patients with genitourinary (GU) malignancies is usually challenging. It is usually associated with adverse outcomes and can significantly contribute to morbidity and mortality and detrimentally impacts quality of life among cancer patients. There has been scarce previous national population study on patients with PE and GU malignancies. Here, we studied the rate of readmissions and mortality for patients admitted for PE with GU cancers in the U.S. and its burden on health care system. Methods: Utilizing the Nationwide Readmissions Database (NRD), we conducted a retrospective cohort study on patients admitted with PE and segregated the individuals with GU cancers (GUC) including renal cell carcinoma (RCC), urothelial Carcinoma (UC), prostate cancer (PCa), testicular cancer (TC), and penile cancer (Pen Ca) between 2016 and 2019 across the United States. We used multivariable logistic regression to determine the predictors of unplanned readmissions within 30 days and mortality. Results: A total of 402,054 patients hospitalized with PE and 44,373 (11%) were readmitted within the next 30 days. Mean length of stay was 4.64 days (95% CI 4.62-4.65). Total charge for index hospitalization was $51,409 (95% CI 51,174-51,643). A total of 8,998 patients were found to have GU cancers. Following baseline comorbidities were associated with highest risk of readmission: Atrial fibrillation, proximal and caval deep vein thrombosis, obesity, hypertension, smoking, and diabetes mellites ( P <0.001). Among GUC, rate of readmission was highest for UC (P<0.01; OR 2.49, 95% CI 1.76 - 3.5) as shown in the table. Risk of in hospital mortality was also highest for UC (P<0.01; OR 2.40, 95% CI 1.39-4.14) followed by RCC (P<0.01; OR 2.06, 95% CI 1.62-2.5). Conclusions: There was higher risk of readmission and mortality for patients with GU malignancies who were hospitalized for PE. UC was the leading GU cancer for rate of readmission and mortality. These readmissions were lengthy and costly for the health care system. This study suggests that more aggressive intervention might be needed in this population to prevent readmission and mortality. [Table: see text]
Efficacy and safety of neoadjuvant therapy with disitamab vedotin plus toripalimab in treating muscle invasive urothelial bladder cancer followed by selective bladder-preserving or radical cystectomy.
Authors: Ou ZHENYU , Hu Jiao , Chen Minfeng , Li Yangle , Zu Xiongbing 
Published: June 2024

e16590 Background: Neoadjuvant cisplatin-based chemotherapy remains the standard systemic therapy for cisplatin-eligible patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). However, its application is constrained due to suboptimal efficacy and considerable safety concerns. The combination of immunotherapy with antibody-drug conjugates is being actively explored as an innovative approach to neoadjuvant therapy for MIBC. Disitamab vedotin (DV) has demonstrated encouraging outcomes in HER2-positive locally advanced or metastatic urothelial carcinoma. Thereby our study aimed to assess the effectiveness and safety of DV combined with toripalimab (PD-1 inhibitor) as neoadjuvant therapy in patients with HER2-expressing MIBC followed by either selective bladder preservation or RC. Methods: This retrospective, single-arm study included patients with histopathologically diagnosed MIBC (T2-4N0-1M0). The regimens comprised DV at a dose of 2.0 mg/kg and toripalimab at 3.0 mg/kg, both delivered intravenously biweekly. Following the neoadjuvant therapy, patients achieving a complete response (CR) or downstaged to non-MIBC were given the choice of either RC or opting for bladder-sparing. Patients not meeting the criteria underwent RC. The primary endpoint was the complete clinical response (cCR) rate. Secondary endpoints included bladder intact disease-free survival (BI-DFS), pathological downstaging (pDS) rate, and safety. Furthermore, we investigated the correlation between cCR and HER2 expression levels. Results: This study enrolled 47 patients between June27, 2022, and October 20, 2023. The median age was 66.0 years, with male representation at 85.1%. Baseline molecular profiling revealed varying levels of HER2 expression: HER2 IHC 3+ (17.0%), HER2 IHC 2+ (48.9%), and HER2 IHC 1+ (34.0%). The median number of treatment cycles administered was 4 ( 3.0-9.0). Remarkably, out of 47 patients, 29 achieved cCR (61.7%). This cCR rate positively correlated with the levels of HER2 expression. Additionally, 37 of the 47 patients achieved pDS (78.7%). Post neoadjuvant therapy, 30 patients opted for bladder-preserving and the rest underwent RC. Over a median follow-up period of 8.0 months (3.0-14.0), the median BI-DFS was not reached, with a 1-year BI-DFS rate of 100%. The most common TRAEs of any grade included anorexia (68.1%), peripheral sensory neuropathy (66.0%), and fatigue (61.7%). Grade 3 or worse TRAEs occurred in 25% of patients, primarily involving anemia, elevated ALT, and fatigue. Conclusions: The combination of DV and Toripalimab as neoadjuvant therapy demonstrated notable efficacy and a manageable safety profile in patients with HER2-expressing MIBC followed by either selective bladder preservation or RC.