bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic analysis of disitamab vedotin combined with PD-1 inhibitor first-line treatment in advanced urothelial carcinoma: A propensity score analysis.
Authors: Jiang Yupeng , Xu Chao , Zou Wen , Chen Minfeng , He Wei , Li Yuan , Feng Yeqian , Fan Songqing , Wu Lin , Wang Jingjing 
Published: June 2024

e16565 Background: The combination of antibody-drug conjugates and PD-1 inhibitor has great prospects for first-line treatment of advanced urothelial carcinoma (UC). This real-world study explored the efficacy, safety, and prognostic biomarkers of disitamab vedotin (DV) combined with PD-1 inhibitor, and compared them with other first-line regimens without DV. Methods: Patients were enrolled retrospectively from July 2021 to December 2022 in two cancer centers. There were four first-line treatment regimens: DV (120-180mg) plus PD-1 inhibitor (Tislelizumab 200mg or Toripalimab 240mg) once every 3 weeks, chemotherapy (gemcitabine plus cisplatin/carboplatin) plus ICI, chemotherapy, and ICI. Then patients were classified into the DV group and No DV group. Treatment outcomes were compared between the two groups after 1:1 ratio PS matching adjusted for sex, PS score, stage, histological grade, and tumor location. In DV group, RNA-seq was used to analyze differential expressed genes (DEGs). Results: There are 63 patients enrolled with median age 68 years (44–90 years). The median follow-up time was 13 months (4–36 months). The 1-year overall survival and progression free survival (PFS) rates were 74.3% and 47%, respectively. There were 30 patients received DV plus ICI, 17 received chemotherapy plus ICI, 9 received chemotherapy, and 7 received ICI alone. PS score and first-line regimen containing DV are independent prognostic factors for PFS. After PS matching, there were 22 patients each in the DV group and No DV group. There were significant differences between the two groups in terms of objective response rate (81.8% vs.27.3%, p=0.003) and 1-year PFS rate (68.2% vs.33.5%, p=0.008) (Table). In safety, hematology and gastrointestinal toxicity were more likely to occur in the No DV group, while neurotoxicity and rash were more likely to occur in the DV group, and most of which were grade 1-2. In DV group, the top 5 most significantly DEGs between patients with long (>6 months) and short PFS (≤6 months)were SCGB1A1, AKR1C1, FAM205C, ACP7 and NLGN4X, and which are enriched in the pathway of cytoplasmic translocation and the function of ribosome. Conclusions: The first-line regimen of DV plus PD-1 inhibitor for patients with advanced UC was more effective and safer than the regimen without DV. The pathway of cytoplasmic translocation and the function of ribosome may be highly correlated to the effectiveness of the regimen of ADC plus ICI. [Table: see text]
TECIC bladder-sparing strategy for high-risk bladder cancer: Exploration and interim analysis of a multicenter, prospective, parallel controlled study (HSCRYO-104).
Authors: Jiang Haowen , Xu Chenyang , Chen Yiling , Zou Lujia , Zhang Limin , Jiang Shuai , Guo Jianming , Sheng Lu , Xu Bin , Luo Jianfeng 
Published: June 2024

e16585 Background: To evaluate the efficacy and safety of transurethral resection of bladder tumors (TURBt) plus endoscopic cryoablation (ECA) combined with Immunotherapy and Chemotherapy (TECIC) as a bladder-sparing therapy in treating high-risk bladder cancer, and to explore the synergistic mechanism between cryoablation and antitumor immunity during the treatment. Methods: The HSCRYO-104 study was a multicenter, nonrandomized, parallel controlled clinical trial with a noninferiority design to evaluate the efficacy of the TECIC modality in treating high-risk non-muscle invasive bladder cancer and early muscle invasive bladder cancer (stage T2). The ratio of the EBCA group and the control group was set as 1:3. In the ECA group, patients received TURBt with immediate ECA at the resection site, and subsequent adjuvant chemoradiotherapy and immunotherapy. The control group was treated with radical cystectomy with pelvic lymphadenectomy and urinary diversion. The primary outcome was overall survival (OS), and secondary outcomes included progression free survival (PFS), in-situ recurrence and incidence of adverse events (AEs). Alterations in the tumor microenvironment were explored. Results: Between December 2021 and August 2023, the interim analysis and exploratory study was completed. A total of 106 patients received screening at four medical centers in Shanghai, and 103 patients were included (25 in the ECA group and 78 in the control group). The two groups were well-balanced at baseline. In the per-protocol analysis, three of the 24 patients in the EBCA group experienced in-situ recurrence and were treated by TURBt and ECA again. No progression or cancer-specific death was observed. Six of 74 patients in the control group died due to disease progression. The interim analysis found that the ECA group was noninferior to the control group in both OS and PFS, with a lower incidence of AEs, enhanced recovery after surgery and shorter hospital stay. Exploratory studies found a significant increase in the proportion of effector memory T cells and upregulation of cytokines (e.g., IL-7 and IL-15) in patients after cryoablation. Conclusions: The TECIC modality as a bladder preserving therapy achieved non-inferior short-term survival to the radical cystectomy with a better quality of life. This strategy has great potential for application in treating patients with bladder cancer. Clinical trial information: ChiCTR2200057679 .
Development and validation of a novel prognostic model for overall survival in patients with micropapillary urothelial carcinoma.
Authors: Diamantopoulos Leonidas Nikolaos , Korentzelos Dimitrios , Bountziouka Vasiliki , Vadikolias Konstantinos , Lambropoulou Maria , Tripsianis Gregory 
Published: June 2024

e16618 Background: Micropapillary urothelial carcinoma (MUC) is a rare variant of bladder cancer with limited prognostic data in the literature. We hereby present a novel prognostic model for overall (OS), for patients with MUC, derived from the Surveillance, Epidemiology and End Results (SEER) database. Methods: The SEER database (18 registries/November 2020) was queried with the case listing method by using the ICD-10 topography codes C67.0-C67.9 (bladder cancer), and the morphologic code 8131 (MUC). Patients were randomly divided into a training (TC) and a validation cohort (VC) (7:3 ratio). Variables significantly associated with OS were identified with multivariate Cox regression and backwards stepwise conditional approach; each variable received “points” according to its beta coefficient, based on the formula: Probability of an event at time t=S0(t)exp(β1x1, β2x2...), (β = regression coefficients, x = observed covariate values, S0(t) = survival function). Cumulative risk points were assigned to each patient and three distinct risk categories for OS were constructed. Harrel’s optimism-corrected C-statistic with bootstrap resampling was used for internal (TC) and external (VC) validation. Discriminatory performance of the model was compared to the AJCC 8th edition with the likelihood ratio test (LRT). Results: 548 patients were included in the study (374 TC, 174 VC). No statistically significant differences in baseline characteristics and survival outcomes were identified between TC and VC. Age, marital status, tumor size, AJCC stage, radical cystectomy, radiation and chemotherapy were significant variables inserted in the multivariate model. Patients were stratified to three risk groups (low, intermediate, high) based on the total risk points collected (<100, 100-150 and >150, Table). Median OS was NR (95%CI; NR, NR), 41 (95% CI; 25-57) and 14 months (95% CI; 11-17) for the low, intermediate, and high-risk categories respectively (log-rank p<.001). Optimism-corrected C-statistic for the prognostic score was 0.74 (95%CI;0.71-0.78) in the TC and 0.70 (95%CI; 0.65-0.78) in the VC. C-statistic for AJCC 8th edition was 0.65 (95% CI; 0.61-0.69) and 0.62 (95% CI; 0.56-0.68) in the TC and VC respectively. The LRT demonstrated superior discriminatory performance of our prognostic model compared to AJCC (p<.001). Conclusions: We present a novel prognostic model for OS of patients with MUC composed of clinicopathologic and treatment variables. Our model had superior performance to the AJCC system and may serve as a useful tool for individualized risk assessment in patients with MUC. [Table: see text]
How febrile neutropenia affects hospitalization in patients with bladder cancer: Nationwide insights.
Authors: Rodriguez Evadne , Javaid Saad , Frasier Kelly , Li Vivian , Vinagolu-Baur Julia , Ortega Yaguachi Nataly , Del Castillo Olivia , Batista Raquel , Jonas Kenlee , Palma Laura 
Published: June 2024

e16625 Background: Bladder cancer is the most prevalent form of malignancy in the urinary tract and is a leading global health concern. Febrile neutropenia is a severe and potentially life-threatening complication of cancer treatment, and limited research exists on the impact of Febrile Neutropenia in bladder cancer. Our study examined its effects on adverse outcomes for hospitalized bladder cancer patients. Methods: The National Inpatient Sample (2017-2020) was employed to identify Bladder cancer patients with regional and advanced metastatic disease as the primary diagnosis and were stratified based on the presence or absence of a secondary diagnosis of Febrile neutropenia (FN). The primary outcome measure was mortality, while the secondary outcomes included length of stay, total cost of hospitalization, and other adverse in-hospital outcomes. Multivariate regression analysis was used to adjust for the confounding variables. Results: A total of 102,485 patients were hospitalized for Bladder cancer, among whom 865 had concurrent FN. The mean age of patients with FN was 67.31±17.44, while that of patients without FN was 72.19±11.48, p<0.001. As compared to Patients without FN, those with FN had a greater percentage of patients with Medicaid (8.77% vs. 6.15%) and private insurance (30.41% vs. 19.74%), while fewer patients with Medicare (58.48% vs. 72.17%), p=0.001. After multivariate regression analysis, patients with FN had increased odds of mortality (OR=4.33,(2.52-7.45); p<0.001). FN patients had a longer length of stay (+2.69 days (1.32-4.05); p<0.001) and higher total cost of hospitalization (+$23,229(3,907-4,255); p<0.001). Patients with FN were more likely to have fluid and electrolyte disorders (OR=1.57(1.11-2.20); p=0.009). However, no significant differences were observed in the odds of Sepsis (OR=1.34(0.62-2.85); p=0.45), Acute kidney injury (OR=1.10 (0.74-1.63); p=0.61), Acute respiratory failure (OR=1.11(0.50-2.50); p=0.78) and ICU admission (OR=0.56(0.20-1.57); p=0.27) between the two groups. Conclusions: In patients with bladder cancer, febrile neutropenia has been identified as an independent predictor of mortality. It is associated with increased healthcare resource utilization and fluid and electrolyte disorders. Proactive management of risk factors can help control febrile neutropenia and reduce the occurrence of adverse events in patients hospitalized with bladder cancer. [Table: see text]
Unveiling the pathologic predictor in patients with metastatic hormone-sensitive prostate cancer treated with abiraterone: Intraductal carcinoma of the prostate and its subtypes.
Authors: Wei Xinyuan , Zhao Jinge , Shi Yifu , Shen Pengfei , Liu Zhenhua , Zeng Hao 
Published: June 2024

e17077 Background: Intraductal carcinoma of the prostate (IDC-P) is a distinct pathological type of prostate cancer (PCa). Its association with poor prognosis in patients has gained widespread recognition. In this study, we aimed to assess whether metastatic hormone-sensitive prostate cancer (mHSPC) patients with different IDC-P statuses and subtypes exhibited varying responses to abiraterone treatment, with the goal of exploring its potential as a predictive pathological marker. Methods: We conducted a retrospective analysis of data from 165 mHSPC patients who received abiraterone treatment. Propensity score matching (PSM) was employed to minimize the potential impact of selection bias and confounding factors. We evaluated PSA response, PSA progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS), and overall survival (OS) based on IDC-P status and its subtypes (pattern 1: loose cribriform or micropapillary; pattern 2: solid or dense cribriform). We also conducted subgroup analyses to explore their predictive value in different patient populations. Results: Following PSM, a cohort of 108 mHSPC patients was established, among whom IDC-P was confirmed in 54 out of 108 (50%) individuals. Of these, 12/54 (22.2%) exhibited IDC-P pattern 1, while 42/54 (77.8%) had IDC-P pattern 2. The median follow-up duration for the entire cohort was 32.5 months, with median PSA-PFS, rPFS, and OS values of 24.3 months, 31.9 months, and not reached, respectively. No statistically significant difference was observed in PSA responses among patients with different IDC-P statuses. However, patients with IDC-P demonstrated poorer survival outcomes (PSA-PFS: 18.6 vs. NR months, p = 0.002; rPFS: 23.6 vs. NR months, p = 0.020). Patients with IDC-P pattern 1 exhibited clinical outcomes similar to those without IDC-P, whereas patients with IDC-P pattern 2 had significantly worse prognosis compared to those without IDC-P (PSA-PFS: 18.6 vs. NR months, p = 0.002; rPFS: 22.4 vs. NR months, p = 0.010). Subgroup analyses revealed a significant association between IDC-P pattern 2 and poorer prognosis across most population subgroups. Conclusions: Our study assessed the predictive value of IDC-P and its subtypes in prostate biopsy specimens of mHSPC patients undergoing abiraterone treatment. IDC-P, particularly IDC-P pattern 2, serves as an adverse prognostic indicator in these patients. Therefore, routine reporting of IDC-P and its pattern is important for treatment strategy making for prostate cancer patients.
Apa-RP: Multicenter phase 2 study of apalutamide (Apa) and androgen deprivation therapy (ADT) for the treatment of high-risk localized prostate cancer (HR LPC) following radical prostatectomy (RP)—Results in Black and non-Black patients (pts).
Authors: Hafron Jason , Saltzstein Daniel , Brown Gordon , Belkoff Laurence , Aggarwal Pankaj , Phillips Jennifer , Bhaumik Amitabha , McGowan Tracy , Shore Neal D. 
Published: June 2024

e17100 Background: Approximately 50% of pts with HR LPC have disease recurrence ≤2 years after RP. Apa-RP (NCT04523207) studied adjuvant Apa + ADT in pts with HR LPC who had undergone RP to determine if the combination improved biochemical recurrence (BCR)-free rate vs historical data from pts who received RP alone. Data are presented for subgroups of Black and non-Black pts. Methods: In this multicenter, open-label, single-arm, phase 2 study conducted at 28 US sites, treatment-naïve pts with HR LPC who had RP received Apa (240 mg; QD) for 12 cycles (28 day cycles) + ADT for 12 months. The study had a diversity goal to enroll ~15% Black pts. The primary endpoint was confirmed BCR-free rate at 24 months, where BCR is defined as two sequential prostate-specific antigen (PSA) levels of >0.2 ng/mL. Secondary endpoints included testosterone recovery (≥150 ng/mL) rate and safety. Modified intention-to-treat analysis set is reported. Results: 108 pts were enrolled (n=15 Black, n=93 non-Black). Black pts were younger than non-Black pts (mean 58.4 vs 66.3 years). Other baseline characteristics were similar, including: median pre-operative PSA 7.6 ng/dL (range 2.2–62.7) and baseline testosterone 340.0 ng/dL (range 43.0–939.0). Confirmed BCR-free rate was 100% (90% CI 93.4, 100.0) (Table); unconfirmed BCR-free rate was 98.4% (90% CI 92.2, 99.7) (Table). Serum testosterone recovery (≥150 ng/dL) event rate at 24 months was 77.4% (95% CI 66.6, 85.1) (Table). Treatment-emergent adverse events were reported in 99.1% (n=107) of pts; 22.2% (n=24) were grade 3–4, 14.8% (n=16) were serious AEs. In total, 13.0% (n=14) and 10.2% (n=11) of pts had treatment dose reductions/interruptions or discontinued due to AEs, respectively. Conclusions: Based on the high BCR-free rate, that persisted for 12 months following treatment, these results suggest that both Black and non-Black pts with HR LPC undergoing RP may benefit from 12 months of treatment intensification with Apa + ADT. Most pts had testosterone recovery. The safety profile of Apa + ADT was consistent with previous reports. Clinical trial information: NCT04523207 . [Table: see text]
Impact of surgical margins on mortality after robotic radical prostatectomy.
Authors: Ahlering Tom Edward , Zeidan Zaki , Tran Joshua , Hwang Yeagyeong , Huynh Linda My , Nguyen Mai Xuan , Zhang Whitney 
Published: June 2024

e17101 Background: Positive surgical margins (PSMs) following radical prostatectomy (RP) have long been seen as inherently unfavorable. Despite this belief, there has not been as much evidence supporting unifocal PSMs (UPSM) and prostate cancer-specific mortality (PCSM). Some have reported that multifocal PSM (MPSM) seems to be associated with PCSM. In this study, we examine and compare the impact on PCSM between percent tumor volume (PTV) and MPSMs. Methods: Prospectively collected data for 1552 patients with complete data who underwent RARP by a single surgeon between 2002 and 2018. The primary outcome was comparing risk of PCSM versus increasing pTV. Patients were categorized into pTV groups at a cutoff 40%. PSMs were categorized as negative (NSM), unifocal (UPSM), or multifocal (MPSM). Kaplan-Meier (KM) was used to assess time to OM and PCSM. Results: Men with 40-100% PTV were significantly older and had more advanced grades and stages. High PTV demonstrated a significantly greater risk of PSMs (both unifocal and multifocal), BCR, PCSM, and OM at 15 years. Before including PTV in the multivariate analysis, MPSM independently predicted PCSM, but UPSM did not. However, MPSMs lost their predictive significance when PTV was included. High-stage and Gleason grade group were independent predictors in both analyses. High PTV demonstrated shorter time to PCSM. Conclusions: Our study further challenges the common belief that PSMs are inherently oncologically adverse. Instead, MPSMs appear to signify more voluminous but more importantly aggressive underlying disease, which is the contributing factor for the adverse oncologic outcomes. We emphasize monitoring PTV as a key predictor of long-term adverse oncologic effects as a more reliable predictor of PCSM. Minimizing PSMs remains a critical surgical principle, but in prostate cancer, it needs to be weighed against urinary and sexual function outcomes.
Evaluation of body weight and race on pembrolizumab response in patients with endometrial cancer: A case control study.
Authors: Welp Annalyn , Johnson Kendall , Gehrig Paola A. 
Published: June 2024

e17579 Background: Recent studies demonstrate improvement in PFS when pembrolizumab, a humanized monoclonal antibody (mAB) that inhibits the PD-1 receptor, is used with platinum-based regimens for advanced or recurrent endometrial cancer (EC). ASCO recommends studies evaluate the effect of weight on efficacy of anticancer agents to guide dosing. In addition, most studies evaluating the pharmacokinetic effects of mABs typically include only white patients. Pembrolizumab is administered at a flat dose and there are currently no adjustments for weight or race. Therefore, this study was performed to evaluate the impact of weight and race on outcomes in patients with EC treated with pembrolizumab. Methods: This retrospective IRB-approved case-control study included EC patients from 04/2014-12/2022 treated with pembrolizumab. Any patient >18 years with EC who received pembrolizumab was included; carcinosarcoma excluded. Chart review was performed. Response was recorded using RECIST criteria and based on imaging and/or primary oncologist’s determination. Associated toxicities were graded by CTCAE. Statistical testing performed as appropriate. Results: Fifty patients met inclusion criteria, with a mean age of 66.0 years. The majority presented with advanced EC (Stage III or greater) at diagnosis (n=33, 66%). Twenty-eight (56%) had endometroid histology, and 42% (n=21) were MMRd. Most patients received single-agent pembrolizumab (n=26; 52%) or pembrolizumab with lenvatinib (42%), with an average of 8.44 cycles (either 200 mg every 3 weeks or 400 mg every 6 weeks). The table details the objective response rate (ORR) and PFS for patients by race and weight. There was no significant difference in PFS between non-obese (normal weight + overweight) and obese (obese + severely obese) overall. Conclusions: No difference was seen in ORR or PFS between non-obese and obese patients. The study was underpowered to perform tests of statistical significance by race. These data preliminarily suggest pembrolizumab may not need to be adjusted for weight. Larger scale multi-institution trials with a particular emphasis on the recruitment of non-Hispanic Black patients can help clarify whether race-based differences in dosing pembrolizumab may be needed. [Table: see text]