bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical efficacy of lurbinectedin in metastatic neuroendocrine carcinomas of the genitourinary tract: Multi-institutional real-world experience.
Authors: Moussa Mohammad Jad , Naqvi Syed Arsalan Ahmed , Khandelwal Jaanki , Campbell Matthew T , Aparicio Ana , Siddiqui Bilal Ahmed , Bryce Alan Haruo , Singh Parminder , Alhalabi Omar 
Published: January 2024

601 Background: Neuroendocrine carcinomas (NEC) of the genitourinary (GU) tract, including small cell (SC) NEC and large cell (LC) NEC, are rare aggressive malignancies. Although highly sensitive to cisplatin-based chemotherapy, GU metastatic NEC (mNEC) have limited data to support next therapies. Lurbinectedin, a marine-derived alkylating drug and a selective inhibitor of oncogenic transcription and DNA repair pathways, is FDA-approved for small cell lung cancer (SCLC) after progression on frontline platinum-based therapy, with a disease control rate (DCR) of 68.6%. It is unknown whether DCR is similar in SCLC and GU mNEC. Methods: We report the first multi-institutional series (n=14) of lurbinectedin in GU mNEC. Imaging-based best overall responses (BOR) were noted as complete (CR), partial (PR), stable (SD), progressive (PD) or non-evaluable (NE). DCR includes CR, PR, and SD. We use the Kaplan-Meier method for overall survival (OS) and progression-free survival (PFS) from lurbinectedin start date. We define duration of response (DoR) from response date to progression or last contact date for patients (pts) with CR or PR. Results: Most pts had a median age at metastasis of 70.5 years (ICR: 64-74.5) [Table]. Primary locations were bladder (7/14, 50%), prostate (5/14, 35.7%) and ureter (2/14, 12.3%). Histology at diagnosis mostly consisted of mixed or pure SCNEC, with one exception of LCNEC. Most pts had visceral disease, prior immunotherapy and at least 2 prior lines of therapy for mNEC before lurbinectedin (8/14, 57.1%). DCR was 6/14 (42.8%), including 5 bladder pts and 1 prostate pt. Among bladder pts, BOR included one CR (1/7, 14.3%) for the LCNEC case, 2 PR (2/7, 28.6%), 2 SD (2/7, 28.6%) and 2 PD (2/7, 28.6%). Most prostate and ureteral pts either progressed on lurbinectedin or were NE (Prostate: 1 PR, 2 PD, and 2 NE; Ureteral: 1 PD and 1 NE). For all 14 pts, median OS was 11.47 months (95% CI: 2.17-13.63) and median PFS was 2.8 mo (1.4-10.9). Median DoR was 7.38 mo (2.3-9.53) for 4 responding pts (CR or PR). Treatment was stopped due to progression (9/14, 64.3%), three adverse events [thrombocytopenia, electrolyte abnormalities, cerebrovascular accident] (3/14, 21.4%), and pt preference (1/14, 7.1%). Conclusions: Lurbinectedin offers encouraging responses (DCR: 5/7, 71.4%) close to those in SCLC, in previously treated bladder mNEC. One CR was noted for a bladder pt with LCNEC. Responses were less appreciated in prostate and ureteral mNEC due to NE responses and limited number. Larger cohorts are needed to confirm survival benefit and genetic analyses are warranted to identify characteristics of responders. [Table: see text]
Tislelizumab in combination with gemcitabine plus cisplatin as neoadjuvant therapy for lymph node‐positive bladder cancer: Results of a prospective study.
Authors: Yang Xiao , Zhuang Juntao , Cao Qiang , Cai Lingkai , Wu Qikai , Lu Qiang 
Published: January 2024

619 Background: Although multiple single-arm clinical trials have shown promising pathologic complete response (pCR) rates with neoadjuvant ICIs combined with gemcitabine plus cisplatin in MIBC, lymph node‐positive bladder cancer is generally excluded. In this study, our specific aim was to compare the efficacy and prognosis of neoadjuvant tislelizumab combined with gemcitabine plus cisplatin in patients with lymph node‐positive bladder cancer. Methods: In this investigator-initiated study, eligible patients had cT2-T4 N+ M0 MIBC, cisplatin-eligible, and to be planned radical cystectomy (RC). Patients received tislelizumab 200 mg in day 8 (D8), cisplatin 70 mg/m2 D2-4, and gemcitabine 1000 mg/m2 D1 and D8 every 21 days for 3 or 4 cycles. RC was performed within 6 weeks after last dose treatment. The primary endpoint was pathologic complete response (pCR, ypT0). Secondary endpoints included pathologic downstaging (<ypT2), EFS, OS and safety. Results: A total of 15 pts were enrolled,14 pts (2 cT2, 7 cT3, 5 cT4) have completed neoadjuvant therapy and underwent RC. One patient declined surgery for personal reasons and received further systemic therapy. In 14 pts evaluable for efficacy, the investigator-assessed confirmed clinical complete response was 21.4% (3/14). Final pathologic results showed that 5 pts (50%) achieved pCR (ypT0N0), 4 ypT1, and 5 ypT2/T3, and 9 patients (<ypT2N0,64.2%) had staging downgrades, with no patients experiencing progression. A complete nodal response (pN0) occurred in 11 (78.5%) pts after tislelizumab +chemotherapy. The median follow-up was 8.9 months, with one death due to multiple metastases and the remaining patients showing no signs of recurrence or metastasis. Median EFS and OS was not reached. Most common neoadjuvant therapy-related AEs of any grade were hematologic toxicities (11/14,78.5%), nausea (9/14,64.2%), vomiting (8/14,57.1%). Grade ≥3 neoadjuvant therapy-related AEs were neutropenia (n = 3), thrombocytopenia (n = 2), anemia (n = 2). One patient discontinued tislelizumab due to AEs. Conclusions: The combination of tislelizumab and gemcitabine/cisplatin is clinically active with a manageable safety profile as a neoadjuvant therapy for lymph node‐positive bladder cancer. Clinical trial information: NCT04570410 .
Time to next systemic therapy after stereotactic body radiation therapy for oligoprogressive metastatic castrate-resistant prostate cancer.
Authors: Eule Corbin J. , Candelario Nellowe , Robin Tyler P. 
Published: January 2024

62 Background: Patients with castrate-resistant prostate cancer (CRPC) with progressive disease are generally require a change/escalation in systemic therapy. For patients with limited ( ≤3) sites of progressive disease (oligoprogression), metastasis-directed therapy with stereotactic body radiation therapy (SBRT) may allow a longer interval before next line systemic therapy, but there is limited data describing this approach. Methods: This is a retrospective study of patients with oligoprogressive metastatic CRPC (omCRPC) treated with SBRT at a single center between 2011-2022. The primary endpoint was time to next systemic therapy (TTNST) after SBRT. Secondary endpoints included overall survival (OS) after SBRT and TTNST stratified by presence of untreated non-progressing metastases. Results: Thirty-two patients with omCRPC received SBRT to 38 metastases. Patients had a median age of 72.5 years (range 50.6-84.3) and median PSA 6.85 ng/mL (range 0.39-922.0) at time of SBRT. The majority had an ECOG of 1-2 (29 patients, 90.6%) and metastases detected on conventional CT and/or bone scans (26 patients, 81.3%). The most commonly utilized SBRT regimen was 3000 cGy in 5 fractions (18 metastases, 47.4%) (Table). Sixteen patients were treated to all known sites of disease, whereas 16 patients received SBRT to oligoprogressive metastases but had at least one untreated non-progressing metastasis at the time of SBRT. Of 32 patients, 23 (65.7%) received SBRT to bone only, 3 (9.4%) to lymph node (LN) only, and 6 (18.8%) to other sites (pelvic tumor, n=2; pelvic tumor + LN, n =1; LN + bone, n=1; dura + bone, n=1; liver, n=1). Patients had received a median of 1.0 prior line of androgen receptor signaling inhibitors and were predominantly (26 patients, 81.3%) chemotherapy naïve. Following SBRT, the median TTNST was 10.1 months and median OS was 41.3 months. For patients with 0 versus ≥1 untreated non-progressing metastasis, TTNST was 11.3 versus 8.7 months, respectively (HR 0.67, 95% CI 0.33-1.36, logrank p=0.24). There were no grade ≥3 toxicities due to SBRT. Conclusions: In this cohort, patients with omCRPC treated with SBRT delayed the next line of systemic therapy for a median of 10.1 months. SBRT in patients with omCRPC may delay initiation of next line systemic therapy in well selected patients, including those with ≥1 untreated non-progressing metastases. [Table: see text]
The pretreatment neutrophil-to-lymphocyte ratio to predict clinical response to maintenance avelumab therapy in patients with metastatic urothelial cancer.
Authors: Inoue Satoshi , Sai Hiroki , Hayakawa Akira , Morishita Koya , Yuguchi Yuri , Suzuki Tomohide , Matsui Hirotaka , Maeda Motohiro , Asano Akiyuki , Tochigi Kosuke , Akamatsu Shusuke 
Published: January 2024

620 Background: It has not been elucidated how preceding first-line chemotherapy affects neutrophil-to-lymphocyte ratio (NLR) and maintenance avelumab therapy. We investigated the relationship between NLR levels just before the initiation of treatment with maintenance avelumab therapy and clinical outcomes in metastatic urothelial cancer (mUC) patients. Methods: This retrospective study was analyzed for patients with mUC who received maintenance avelumab therapy between February 2021 and July 2023 at Nagoya University and several affiliated hospitals in Japan. We investigated the relationship between NLR levels just before avelumab therapy and clinical outcomes. All patients were divided into two groups according to NLR levels just before avelumab therapy. A NLR level of ≥3.00 was defined as elevated according to a calculation by a receiver-operation curve analysis. Progression-free survival (PFS) and overall survival (OS) rates were estimated using Kaplan–Meier curves and Cox proportional hazards models. Results: The median age and follow-up duration were 73 years (range 49-83 years) and 11.6 months (range 2.4-26.5 months), respectively. The high NLR group consisted of 29 patients (45.3%). Patients in the high NLR group had significantly shorter PFS and OS than those in the low NLR group (p=0.018 and p=0.027, respectively). Similarly, PFS and OS was significantly shortened in patients with NLR levels that had increased during first-line chemotherapy than their counterparts (p=0.018 and p=0.008, respectively). Furthermore, patients in the high NLR group had a significantly lower disease control rate than those in the low NLR group (58.6% vs 91.4%, p=0.003). While there was not a significant association between OS and NLR at the start of first-line chemotherapy (p = 0.763). Multivariate analyses revealed that stable disease as best response to first-line chemotherapy was significantly associated with PFS [hazard ratio (HR), 4.55; p=0.001] and OS (HR, 21.58; p=0.001). Conclusions: High NLR levels just before avelumab therapy might be a prognostic factor for mUC patients undergoing maintenance avelumab therapy.
Clinical impact of C-reactive protein flare response in patients with advanced urothelial carcinoma who received pembrolizumab.
Authors: Tomisaki Ikko , Harada Mirii , Minato Akinori , Higashijima Katsuyoshi , Takaba Tomohisa , Nagata Yujiro , Harada Kenichi , Fujimoto Naohiro 
Published: January 2024

634 Background: C-reactive protein (CRP) has been reported as one of the useful predictive markers in patients with advanced urothelial carcinoma (UC). Not only baseline revel, kinetics of CRP during medical treatment also has been demonstrated. However, there are extremely limited data on temporary elevated CRP levels followed by decreasing below baseline (CRP flare response) after administration of immune checkpoint inhibitors. The aim of this study was to clarify the clinical significance of CRP flare response after administering pembrolizumab in patients with advanced UC. Methods: We retrospectively reviewed patients with advanced UC who consecutively received pembrolizumab as second-line or later therapy between March 2018 and January 2023 at one academic center and six general hospitals. Patients were categorized into 3 groups according to early CRP kinetics: flare-responder (CRP levels had increased to more than double from baseline within 1 month after pembrolizumab administration (CRP flare) and decreasing to below-baseline levels within 3 months); responder (CRP levels decreased ≥30% from baseline within 3 months without CRP flare); non-responder (the remaining patients). Tumor responses, overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were compared among the groups. Results: A total of 97 eligible patients, 15, 25, and 57 patients were classified into flare-responder, responder, and non-responder group, respectively. Objective response rates of flare-responder (43%) and responder (52%) were higher than that of non-responder groups (17%). Median follow-up was 7.8 months. Progression and death were observed in 83 and 70 patients during follow-up, respectively. Median OS was 19.8, 15.2, and 7.8 months in the flare-responder, responder, and non-responder group, respectively (P= 0.03). Furthermore, Median PFS was 8.1, 6.3, and 2.7 months in the flare-responder, responder, and non-responder group, respectively (P= 0.006). In multivariate analysis, CRP-flare response was a significant favorable predictive factor associated with OS. The patients who developed any grade AEs were 33, 40, 20.7% in the flare-responder, responder, and non-responder group, respectively (P= 0.16). Similarly there were no significant differences in occurrence of severe AEs (≥Grade 3). Conclusions: CRP flare response was observed in 15% of patients with advanced UC who received pembrolizumab and favorable oncological outcomes were observed in these patients. CRP-flare might be a promising predictive and prognostic marker in patients with advanced UC who underwent pembrolizumab therapy.
Safety of intraoperative tranexamic acid use on the risk of venous thromboembolism (VTE) in patients undergoing robotic assisted radical cystectomy (RARC).
Authors: Ahmed Mohamed E. , Andrews Jack R. , Mahmoud Ahmed M. , Thapa Prabin , Khanna Abhinav , Shah Paras , Sharma Vidit , Thompson R. Houston , Frank Igor , Karnes R. Jeffrey , Tollefson Matthew K. 
Published: January 2024

641 Background: Perioperative blood transfusion is associated with an increased risk of adverse events and tranexamic acid (TXA) use has been proposed to decrease the need for perioperative blood transfusion. Herein, we seek to investigate the impact of intraoperative TXA on perioperative risk of VTE in a subset of patients who underwent robotic-assisted radical cystectomy (RARC) for bladder cancer. Methods: We queried the prospectively maintained Mayo Clinic Radical Cystectomy registry and identified patients who underwent RARC between 2004-2021 and received TXA intraoperatively. In univariable and multivariable analyses, we investigated factors associated with bleeding and VTE within 30 days post-operatively. Results: Of 2862 patients, we identified 94 patients who received TXA (IV) intraoperatively (Group A) and were propensity score matched 1:1 for age, neoadjuvant chemotherapy, pT stage, pN stage, and preoperative hemoglobin with a group who did not receive TXA; 38 patients (Group B). In univariable and multivariable models, use of TXA has no statistically significant impact on patient’s risk of bleeding or VTE. In a univariable model, number of positive lymph nodes and extent of lymph node dissection were associated with increased risk of VTE (Table 1). Conclusions: In our study, use of TXA in patient’s undergoing RARC was safe and was not associated with increased risk of VTE. [Table: see text]
Clinical efficacy of enfortumab-pembrolizumab combination therapy in locally advanced/metastatic urothelial carcinoma (UC): A real-world experience.
Authors: Tripathi Nikita , Naqvi Syed Arsalan Ahmed , Ballouz Tara , Saxena Akshat , Bibi Arifa , Khan Muhammad Ali , Channar Aneeta , Riaz Irbaz Bin , Tyson Mark , Bryce Alan Haruo , Singh Parminder 
Published: January 2024

643 Background: The FDA approval of enfortumab (EV) and pembrolizumab (Pembro) combination therapy as a first-line treatment for cisplatin-ineligible patients with locally advanced/metastatic urothelial carcinoma (la/mUC) was based on the EV-103 trial. We aim to assess the clinical response rate of this combination therapy in our institution's patients with locally advanced and metastatic UC. Methods: This retrospective cohort study included 20 patients diagnosed with locally advanced/metastatic UC(la/mUC) who were treated with EV-Pembro combination for at least 2 cycles, from June 2022 to August 2023 at the Mayo Clinic. Patients who were treatment naïve or who progressed one or more lines of therapy were included in the study cohort. Main outcome of interest included imaging-based best overall response rate in terms of complete (CR) and partial (PR) response, stable disease (SD), and progressive disease (PD). Results: Out of 20 patients, the number of males and females were 16 (80%) and 4 (20%) respectively; the median age was 77 years (IQR: 51-92). 3 (15%) of patients had involvement of upper urinary tract disease along with bladder cancer. The common sites of visceral metastasis at the time of initial presentation include liver 2(10%), lung 6(30%) and lymph nodes12(60%). Common toxicities of this regimen included rash, pruritis, peripheral neuropathy, fatigue, transaminitis, dysgeusia, and diarrhea. The treatment was stopped in 10 (50%) patients due to completion of planned therapy (achieved CR or proceeded with resection of residual disease) (30%), 5 patients due to progression (50%), 1 patient due to therapy side effects (10%) and in 1 patient due to death (10%). The objective response was 45% (N =9); 5 (25%) had PR, and 4 (20%) had CR. A total of 2 (10%) had SD while 2 (10%) experienced PD. Histological correlation with clinical benefit is shown in the table. Conclusions: EV-Pembro combination therapy shows promising responses in patients who have progressed after previous lines of therapy, consistent with previously published data on EV 201 in small cohorts. However, ongoing expansion of this cohort and data from larger studies will help further elucidate survival benefits and their correlation with genetic testing. [Table: see text]
RC48-ADC versus BCG in adjuvant treatment of high-risk non-muscle-invasive bladder cancer with HER2 over-expression: A real-world retrospective study.
Authors: Liu Haoyang , Chen Junru , Liu Haolin , Zhu Qiyu , Liao Banghua , Liu Zhenhua , Shen Pengfei , Zeng Hao 
Published: January 2024

644 Background: Bladder cancer ranks as the tenth most prevalent malignancy globally, with non-muscle invasive bladder cancer (NMIBC) accounting for approximately 75% of cases. Patients diagnosed with high-risk NMIBC (HR-NMIBC) face a grim prognosis, characterized by a 5-year disease progression rate of up to 40%. Currently, the standard treatment for HR-NMIBC involves transurethral resection of bladder tumor (TURBT) followed by adjuvant intravesical Bacillus Calmette-Guérin (BCG) therapy. However, BCG infusion therapy is associated with prolonged duration, substantial costs, and a high frequency of toxic side effects. RC48-ADC, a novel humanized anti-HER2 antibody conjugated with monomethyl auristatin E, has shown promising efficacy with a manageable safety profile in patients with locally advanced or metastatic urothelial carcinoma (mUC) in a Phase II clinical trial (NCT03507166). Therefore, investigating the therapeutic potential of RC48-ADC in HR-NMIBC patients holds significant clinical importance. Methods: We conducted a retrospective analysis on patients diagnosed with HR-NMIBC exhibiting HER2 overexpression (≥ HER2 2+) who underwent adjuvant therapy with either RC48-ADC, a HER2-targeting antibody-drug conjugate, or BCG, at West China Hospital of Sichuan University between 2019 and 2023. The primary study endpoint was the twelve-month recurrence-free survival (RFS) rate, with safety assessments as secondary endpoints. Results: A total of thirty patients diagnosed with HR-NMIBC displaying HER2 overexpression were included in the study. Following TURBT, eleven patients received adjuvant therapy with RC48-ADC, while nineteen received adjuvant therapy with BCG. The median follow-up duration for patients receiving RC48-ADC and BCG adjuvant therapy was 7.3 and 16.43 months, respectively. Among patients treated with RC48-ADC, the twelve-month RFS rate was 100%, with one out of the 11 patients experiencing relapse after 14.2 months of RC48-ADC adjuvant therapy. In the BCG-treated group, the twelve-month RFS rate was 57.6%. However, Kaplan-Meier analysis revealed no statistically significant difference between these two groups (P=0.22). In the RC48-treated group, the most commonly reported treatment-related adverse events (TRAEs) included alopecia (45.5%), arthralgia (18.2%), and nausea (18.2%). A total of 27.7% of patients experienced grade 3 TRAEs, including alopecia, rash, and hypoesthesia, with no observations of grade 4 or grade 5 TRAEs. Conclusions: RC48-ADC has demonstrated promising efficacy with a manageable safety profile as an adjuvant therapy in patients with HR-NMIBC. RC48 may be an alternative adjuvant therapy for BCG in terms of the 12-month recurrence-free survival rate.
A study of blood myeloid-derived suppressor cells for predicting pembrolizumab efficacy in patients with metastatic urothelial carcinoma.
Authors: Kato MInoru , Yamamoto Shoma , Azuma Yukari , Takeyama Yuji , Uchida Junji 
Published: January 2024

658 Background: Immune checkpoint inhibitors (ICIs) are crucial for treating metastatic urothelial carcinoma (mUC) patients, yet current prognostic biomarkers fail to predict ICI efficacy. Previous preclinical models have suggested myeloid-derived suppressor cells (MDSCs) as a potential therapeutic target in bladder cancer. This study aims to evaluate the predictive value of blood MDSCs in mUC patients undergoing pembrolizumab treatment. Methods: Ninety-eight mUC patients who progressed with platinum-based chemotherapy at Osaka Metropolitan University received pembrolizumab. Among them, 30 patients were assessed for blood MDSCs. Peripheral blood samples were collected from healthy individuals (n = 6) and mUC patients (n = 30) before pembrolizumab initiation. The mononuclear cell layer was isolated using density gradient centrifugation for MDSC analysis through flow cytometry. Monocytic and polymorphonuclear MDSCs were defined as CD11b+ HLADR – CD33 high CD14 + CD15 – and CD11b+ HLADR – CD33 low CD14 – CD15 +, respectively. The neutrophil-lymphocyte ratio (NLR) in blood served as a control. Treatment response was assessed via CT images using RECICT v1.1. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method, with log-rank test for between-group comparison. Results: First, blood MDSCs were significantly elevated in mUC patients compared to healthy controls (p = 0.0024, Mann Whitney test). Secondly, patients with MDSClow (≤ median, n = 15) had significantly longer PFS than those with MDSChigh (> median, n = 15) (17.6 vs. 1.9 months, p = 0.0126). However, no significant difference was observed in OS. In contrast, when the NLR cutoff was set at 3.5, no significant association was found for PFS and OS. Conclusions: Blood MDSCs show promise as a predictive marker for pembrolizumab therapy efficacy.