bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and pathological outcomes of nephrectomy/metastasectomy in patients with metastatic renal cell carcinoma after prior immune checkpoint inhibitor exposure.
Authors: Amaral Paulo Siqueira , Beckermann Katy , Hillis Mikala , Schaffer Kerry Roe , Ancell Kristin Kathleen , Lambrecht Morgan , Kaiser Elizabeth , Rini Brian I. 
Published: June 2024

e16515 Background: The landscape of metastatic renal cell carcinoma (mRCC) treatment has changed with the emergence of immune checkpoint blockade (ICB) which leads to enhanced responses and prolonged survival compared to tyrosine kinase inhibitors (TKI). The higher objective response rates and durable disease control has resulted in consideration of consolidative surgery in a subset of patients. Methods: A single-center retrospective analysis of mRCC patients who had cytoreductive nephrectomy or metastasectomy between October 2017 and January 2024 after prior ICB exposure was conducted. Clinical and pathological characteristics, response to ICB, and safety outcomes were evaluated. We also assessed the time off systemic therapy after surgery. Results: Seventeen patients were identified. The median age was 59 years, and the median follow-up was 24.8 months after starting ICB. 76.5% received combination regimens (six with dual ICB and seven with ICB plus TKI), while the remaining four patients had anti-PD1 monotherapy. Fourteen patients initiated ICB as first- line treatment while the remaining three patients had ICB in the second line. Median ICB exposure time before surgery was 10.9 months (range, 0.8 - 41.5). 70.6% were International mRCC Database Consortium (IMDC) intermediate risk and 29.4% were poor risk. Fifteen patients had radical nephrectomy, and one had a renal bed resection. The best overall response before surgery included 6% complete response, 35.2% partial response, 41.1% stable disease, 17.6% disease progression (PD of primary tumor only). Pathological findings revealed 76.5% clear cell, 11.8% unclassified and 11.8% papillary RCC. 58.8% showed Fuhrman grade 3 or 4 and 11.8% had a sarcomatoid component. Notably, three (17%) patients had a complete pathological response in the primary tumor and 88.2% displayed necrosis. One patient (6%) had a 30-day post-operative complication of deep vein thrombosis. Fourteen (82.4%) patients had residual disease after surgery, but ten patients (58.8%) discontinued systemic treatment. Among the seventeen patients, nine resumed systemic therapy after a median time of 8.3 months off therapy (range, 2.8 -15.5). Conclusions: Surgical consolidation after ICB is safe and may allow patients time off systemic therapy. ICB is active in primary renal tumors, with complete pathological responses and necrosis observed.
The prognostic significance of venous tumor thrombus grading for patients with renal cell carcinoma.
Authors: Ge Silun , Qu Le , Wang Linhui , Ge Jingping 
Published: June 2024

e16520 Background: Venous tumor thrombus (VTT) is observed in 4−10% of newly diagnosed RCC patients, and a successful radical nephrectomy and thrombectomy provides considerable palliation to a proportion of nonmetastatic RCC patients with VTT. However, the reported postsurgical survival varies significantly with the 5‐year overall survival (OS) rate ranging from 37.0 to 71.0%. Hence, accurate risk factors are critically needed for these patients. Here we evaluate the prognostic significance of VTT grading for these patients. Methods: The final evaluable dataset enrolled 706 consecutively nonmetastatic ccRCC patients who underwent radical nephrectomy and thrombectomy, including 304 in the Training cohort from the Eastern China Renal Cancer Collaborative Group, 320 in the China‐Validation cohort and 82 in the Poland‐Validation cohort. All pathological specimens were centrally reviewed by three genitourinary pathologists blinded to clinical information. Univariable and multivariable Cox regression analyses were performed to identify independent predictors associated with survival outcomes. Results: To comprehensively evaluate the potential of VTT in risk assessment, multiple characteristics of VTT were incorporated, including VTT height, consistency and the pathological nuclear grading of VTT (VTT grading), which has not been studied yet. Although higher pathological grading of primary tumor (PT) and VTT were both significantly correlated with dismal prognosis, only VTT grading remained as an independent predictive factor for OS and DFS after multivariable Cox regression. Furthermore, VTT grading showed superiority in risk assessment compared with PT grading and other variables by c‐index analysis (OS: 0.663 vs. 0.501–0.610, 0.667 vs. 0.544–0.651, and 0.719 vs. 0.511–0.700 for Training, China‐Validation, and Poland‐Validation cohorts, respectively; DFS: 0.664 vs. 0.501–0.606, and 0.672 vs. 0.530–0.640 for Training, and China‐Validation cohorts, respectively), which was confirmed by the receiver operating characteristic (ROC) analysis (OS: area under the curve [AUC] 0.764 vs. 0.650–0.664, 0.684 vs. 0.650–0.667, and 0.814 vs. 0.641–0.711 for Training, China‐Validation, and Poland‐Validation cohorts, respectively; DFS: AUC 0.753 vs. 0.648–0.651, and 0.704 vs. 0.601–0.665 for Training, and China‐Validation cohorts, respectively). Conclusions: VTT grading displayed superior accuracy and discriminatory ability in predicting survival risk for nonmetastatic ccRCC patients with VTT. Assessing VTT grading in routine pathology reports may provide further information for stratification of patient risk.
A phase 1 study of BAT8007, an anti-nectin-4 monoclonal antibody-exatecan conjugate, in patients with advanced solid tumors.
Authors: Jiang Lijuan , Song Zhengbo , Gong Yi , Jin Jianan , Ding Yao , Tang Long , Deng Xia , Li Xiangdong , Li Su , Cheng Xiangdong , Zhou Fangjian , Zhou Xiaoyan , Fu Ziyi , Yu Jin-Chen 
Published: June 2024

e16567 Background: BAT8007 is an antibody-drug conjugate targeting Nectin-4. In this phase 1 study, the authors investigated BAT8007 in subjects with advanced solid tumors. Methods: Subjects with advance solid tumor received BAT8007 on day 1 of a 21-day cycle until subject intolerance or disease progression. The study objectives were tolerability, safety, pharmacokinetic characteristics, immunogenicity, and preliminary efficacy. Results: As of January 30, 2024, 16 Chinese subjects with urothelial carcinoma (UC), non-small cell lung cancer (NSCLC), prostatic cancer, esophageal squamous cancer, hepatocellular carcinoma, ovarian cancer were allocated into five cohorts of 0.8, 1.6, 2.4, 3.0, 3.6mg/kg dose levels. The Nectin-4 expression on tumor tissue was not a requirement for eligibility. There was no dose-limiting toxicity observed, the dose escalation beyond 3.6mg/kg is continuing to be explored. The maximum tolerated dose has not yet been reached. In 16 subjects who have received at least one dose of BAT8007, at least one treatment-emergent adverse events (TEAEs) were reported in 13/16 (81.25%) subjects. The most common TEAEs (≥20%) of any grade were anemia, neutropenia, leukopenia, nausea, vomiting, hypoalbuminemia, hypertriglyceridemia and fatigue. The majority of the treatment-emergent adverse events were Grade 1 or 2; 18.75% subjects experienced Grade 3 or greater AEs, including thrombocytopenia 1/16 (6.25%), worsening anemia 1/16 (6.25%), neutropenia 1/16 (6.25%). The gastrointestinal toxicity was mild. There were no subjects terminated the study treatment due to TEAE. No skin, ocular toxicity and interstitial lung disease were reported. Six subjects with UC were recruited and distributed in 0.8mg/kg(n=1), 1.6mg/kg(n=1) and 3.0mg/kg(n=4) cohort. All of them had undergone prior 3-5 lines of systemic treatments including PD-1 antibodies and platinum-based regimens. Four subjects with UC were enrolled, and 2 of them performed one tumor assessment as data cut off. Both of them showed stable disease with target lesion reductions of -14% and -16.3%, respectively. Both of these two UC subjects had been treated with RC48 (disitamab vedotin, an anti-HER2 ADC) treatment prior to this assessment. Additionally, 1 subject with NSCLC achieved a confirmed partial response (target lesion reduction of -61.0%) in 2.4 mg/kg cohort, and is still benefiting from BAT8007. Conclusions: BAT8007 was well-tolerated with manageable toxicity and demonstrated preliminary antitumor activity in urothelial carcinoma and NSCLC. Clinical trial information: NCT05879627 .
Maintenance therapy with avelumab as the first-line treatment in patients with metastatic urothelial carcinoma: A real-world, ambispective RAVE-Bladder study.
Authors: Gridneva Yana , Sultanbaev Alexander , Anzhiganova Yulia , Gluzman Mark , Mochalova Anastasia , Shkurat Alexey , Parsadanova Elvira , Israelyan Edgar , Murzina Yulia , Kalpinsky Aleksey , Stativko Olesia , Karabina Elena , Kеln Artyom , Petkau Vladislav , Tovbik Natalya , Turganova Maria , Safina Sufiia , Kopyltsov Evgeny , Volkova Maria , Tsimafeyeu Ilya 
Published: June 2024

e16569 Background: The RAVE-Bladder study was designed to assess the efficacy and safety of avelumab maintenance in patients with metastatic urothelial carcinoma in a real-world population. Methods: In this non-interventional, ambispective study, eligible patients had metastatic urothelial carcinoma and measurable disease that had not progressed with first-line platinum-based chemotherapy. Patients received maintenance avelumab according to a standard regimen (800 mg, administered every 2 weeks). Tumor imaging was performed at baseline and then every 12 weeks. The primary endpoint was overall survival (OS) at the initiation of avelumab treatment, while secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Results: At data cutoff (February 02, 2024), 110 patients (81% male, 19% female) were recruited from 21 sites and median follow-up was 9.71 months. Median age was 65 (range, 36-84) years. All patients had confirmed urothelial carcinoma (high grade, 62.8%). Primary tumor site was upper urinary tract in 26 (23.6%) and bladder in 84 (76.4%) cases. Forty-five (40.9%) patients had radical surgery; 68 (61.8%) had metastatic disease at time of diagnosis; 44 (40%) had 2 and more metastatic sites. First-line chemotherapy included gemcitabine + cisplatin, gemcitabine + carboplatin, cisplatin only, carboplatin only, and MVAC in 51 (46.4%), 32 (29%), 19 (17.3%), 7 (6.4%), and 1 (0.9%) patients, respectively. Median number of chemotherapy cycles was 4 (range, 3-9) and median number of avelumab infusions was 16 (range, 2-43). ORR to chemotherapy was 48.2%. An additional 38 patients (34.6%) responded to avelumab therapy (16 CR, 22 PR). Median OS was not reached and 1-year OS rate was 78.7%. Median PFS was 9.5 months (95% CI 7.8 – 11.2 months). Thirteen (11.8%) patients experienced grade 3 adverse events during avelumab therapy. Conclusions: The findings illustrate the favorable tolerability of maintenance therapy with avelumab, a remarkable progression-free interval subsequent to standard platinum-containing chemotherapy and prominent additional response rate among patients with metastatic urothelial carcinoma. Ongoing follow-up continues to provide additional insights. Clinical trial information: KCRB01012022 .
Noninvasive early detection and recurrence monitoring for non-muscle-invasive bladder cancer via urine tumor DNA.
Authors: Wu Junlong , Cheng Huanqing , Wang Huina , Chen Libin , Liu Lei , Cao Shanbo , Lou Feng , Ye Ding-Wei 
Published: June 2024

e16586 Background: Traditional methods for the detection and surveillance of non-muscle-invasive bladder cancer (NMIBC) were generally invasive, costly, and not effective for early-stage, low-grade, and minimal residual disease (MRD) tumors. Whether urine tumor DNA could be used to early detect urothelial carcinoma and monitor MRD with high sensitivity should be explored. Methods: We conducted a perspective study to determine the performance of utLIFE-UC (our previously reported urine tumor DNA multidimensional bioinformatic predictor) in early detection and recurrence monitoring of NMIBC (Trial No. ChiCTR2300072635). We prospectively recruited 49 patients initially diagnosed with NMIBC. Urine samples were collected prior to transurethral resection of bladder tumor (TURBT) and repeat TURBT (Re-TURBT) if needed. Postsurgical samples were collected every 3-6 months when patients underwent routine cystoscopy. The utLIFE-UC score > 60 indicates a positive clinical significance. Results: Overall, utLIFE-UC could discriminate NMIBC with high sensitivities of 91.8% (45/49), both in different T stages (Ta, 84.0%; T1, 100%; P = 0.110) and grades (low-grade, 88.2%; high-grade, 93.3%; P = 0.613). Twenty patients underwent Re-TURBT, of whom 8 cases had residual tumor. The utLIFE-UC correctly diagnosed 8 of 8 (100%) patients with residual tumor. In addition, the assay showed a high NPV of 100%, implying that it may aid in avoiding Re-TURBT in patients predicted to have no residual tumor. Notably, utLIFE-UC score before Re-TURBT in patients with multiple tumors (MT) was markedly increased than that of patients with single tumor (ST) (P = 0.028). MRD-positive rate in MT patients was 100%, whereas 50% of ST patients were MRD-negative. During follow-up, recurrence status of 27 patients was collected, and 18.5% (5/27) of them recurred. The median follow-up time was 211 days (range 39 to 326 days). For patients receiving Re-TURBT, all the tumors with MRD-negative results before Re-TURBT, had no recurrence, further supporting the possible unnecessity of Re-TURBT in this population. The prognostic value of postsurgical utLIFE-UC results in NMIBC was explored. MRD-positive patients showed a worse recurrence-free survival than MRD-negative ones (median 200 days vs unreached; P = 0.001). However, it was not observed the correlation between prognosis and clinical features, including age, sex, tumor number, T stage, and grade. Compared to clinical confirmed recurrence, utLIFE-UC could predict recurrence with a median lead time of 100 days (range 17 to 140 days; P = 0.056). Conclusions: TheutLIFE-UC assay for early diagnosis, MRD detection and surveillance in NMIBC is a noninvasive and effective approach, which may contribute to reducing the burden of cystoscopy and invasive examination. Clinical trial information: ChiCTR2300072635 .
Effectiveness of adjuvant immunotherapy in muscle-invasive urothelial cancer: A systematic review and meta-analysis of randomized controlled trials.
Authors: Silva Isadora Mamede Mendes da , Silva Caroliny , Alves Ana Caroline Fonseca , Oliveira João Pedro , Maia Melissa , de Liz Caio Dabbous , Oliveira Audrey Cabral Ferreira de 
Published: June 2024

e16599 Background: Neoadjuvant platinum-based chemotherapy followed by radical surgery is the established treatment for muscle-invasive urothelial cancer (MIUC). However, over 50% of patients face lethal metastatic recurrence, and adjuvant chemotherapy's efficacy lacks consensus for high-risk cases, with others encountering eligibility issues. Recent breakthroughs highlight adjuvant pembrolizumab's significant enhancement of disease-free survival. In response, a meta-analysis was conducted to assess immunotherapy's effectiveness in managing high-risk MIUC. Methods: A systematic search across PubMed, Embase, Cochrane, ClinicalTrials.gov, and ASCO GU abstracts identified randomized controlled trials (RCTs) comparing adjuvant PD-1 and PD-L1 inhibitors against control (placebo or observation) for MIUC. Key outcomes included disease-free survival (DFS), grade 3 or higher adverse events (AE), and overall survival (OS). Heterogeneity was assessed using I2 statistics, employing a random-effects model for analysis. Statistical analyses utilized R software version 4.3.2. Results: In a cohort of 2,220 patients from three RCTs, 1,113 (50.14%) received immunotherapy. Immunotherapy significantly improved DFS (HR 0.73; 95% CI 0.59-0.90; p < 0.01), particularly in lower tract tumors (HR 0.71; 95% CI 0.56-0.91; p < 0.01). No significant DFS improvement was observed in the upper tract subgroup (HR 1.21; 95% CI 0.87-1.68; p = 0.25) (p-interaction = 0.01). Further analyses showed no significant subgroup differences in PDL1+/- (p-interaction = 0.85) and previous neoadjuvant chemotherapy use (p-interaction = 0.12). However, immunotherapy exhibited a higher incidence of grade ≥ 3 AE (RR 1.47; 95% CI 1.13-1.91; p < 0.01). No differences in OS were found (HR 0.94; 95% CI 0.80-1.11; p = 0.46). Conclusions: Adjuvant PD-1 and PD-L1 inhibitors significantly enhance MIUC disease-free survival, irrespective of PD-L1 status. However, this benefit comes with an increased risk of grade 3 or higher adverse events. These results offer compelling evidence supporting immunotherapy as a valuable adjuvant treatment option for high-risk MIUC patients.
Efficacy of first line (1L) poly ADP-ribose polymerase inhibitors (PARPi) in combination with androgen pathway inhibitors (API) by homologous recombination repair (HRR) genes in metastatic castration-resistant prostate cancer (mCRPC): A living meta-analysis.
Authors: Bibi Arifa , Naqvi Syed Arsalan Ahmed , Khan Muhammad Ali , Raina Ammad , Khakwani Kaneez Zahra Rubab , Orme Jacob , Childs Daniel S , Kase Adam McLain , Baca Sylvan C. , Sartor Oliver , Singh Parminder , Bryce Alan Haruo , Riaz Irbaz Bin 
Published: June 2024

e17059 Background: It is unclear if patients with different HRR gene-mutated mCRPC derive consistent benefit from treatment with PARPi and API combination. Approval labels for PARPi+API are inconsistent across regulatory bodies in the US (Food and Drug Administration, FDA) and Europe (European Medical Agency, EMA), adding to confusion among practicing clinicians. Therefore, we aimed to assess the differential efficacy of PARP+API therapy by different genes using up-to-date trial evidence. Methods: We maintain a living meta-analysis on mCRPC treatments that is updated when new data becomes available. Here, we report data from phase III randomized control trials (RCTs) assessing PARPi+API in 1L mCRPC. The outcomes of interest included radiographic progression-free survival (rPFS) and overall survival (OS). Hazard ratios (HR) for rPFS and OS by different genes were summarized using random effects meta-analysis via inverse variance approach. Results: We have screened 27376 references since the inception of this living review. Here, we report data from three trials (15 references) with a total of 1618 patients. Frequently reported HRR gene mutations in the included trials were BRCA2 (35%), ATM (21%), CDK12 (12.2%), CHEK2 (12.2%), BRCA1 (4.6%), and PALB2 (3.4%). In terms of rPFS, statistical benefit was observed in BRCA (0.28; 95% CI: 0.13-0.59) and CDK12 (0.58; 95% CI: 0.35-0.95) subgroups, whereas no statistically significant benefit was seen in PALB2 (0.53; 95% CI: 0.21-1.32), ATM (0.93; 95% CI, 0.57-1.53), and CHEK2 (0.92; 95% CI: 0.53-1.61) subgroups. For OS, benefit was observed in BRCA (0.47; 95%CI: 0.31-0.71) subgroup. While not statistically significant, a signal of meaningful OS benefit was observed in PALB2 (0.33; 95%CI: 0.10-1.16) but no OS benefit was observed in ATM (0.97; 95% CI: 0.57-1.67), CDK12 (0.80; 95% CI: 0.36-1.78), and CHEK2 (0.81; 95% CI: 0.37-1.75) subgroups. Conclusions: Current results show that mCRPC patients with BRCA and CDK12 alterations had delayed disease progression with PARPi+API as 1L therapy. BRCA mutations are also associated with improved OS, while patients with CHEK2 and ATM derived no significant benefit with PARPi+API combination. [Table: see text]
Exploring the prognostic value of the TRAQinform Profile applied to end-of-treatment PSMA PET/CT in patients with mCRPC and treated with 177Lu-PSMA radioligand therapy: A retrospective, single-center analysis.
Authors: Murthy Vishnu , Lokre Ojaswita , Perk Timothy G. , Thin Pan , Nguyen Kathleen , Chen Lucia , Gafita Andrei , Czernin Johannes , Calais Jeremie 
Published: June 2024

e17060 Background: To explore the prognostic value of the TRAQinform Profile trained on mid-treatment prostate-specific membrane antigen (PSMA) PET/CT (PSMA-PET) when applied to end-of-treatment PSMA-PET (ePET) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with 177Lu-PSMA Radioligand Therapy (PSMA-RLT). Methods: This was a single-center retrospective study. mCRPC patients who underwent PSMA-RLT with available baseline PSMA-PET (bPET) and ePET within 6 mo of the last PSMA-RLT cycle were eligible. Overall survival (OS) from ePET was collected. TRAQinform IQ technology (AIQ Solutions, Madison, WI) was used to conduct lesion region of interest (ROI)-based analyses at bPET and ePET, and changes in SUVmax, SUVmean, volume (cm3), and SUVtotal (SUVmean x volume) across all lesion ROI from bPET to ePET were extracted. Lesion ROI were matched across time points and categorized into new, increasing, stable, decreasing, and disappeared based on changes in SUVtotal. Associations between % new, % increasing, % stable, % decreasing, and % disappeared lesions and OS were evaluated using univariate Cox regression models. This study applied TRAQinform Profile (a random forest model), trained on 185 external PSMA-PET, to generate TRAQinform Profile scores for early identification of optimal vs. suboptimal responders to PSMA-RLT. Associations between TRAQinform Profile scores and OS were evaluated by Kaplan-Meier analysis. Results: Twenty mCRPC patients were included. Thirteen of 20 patients (65%) had died at the last follow-up. The median survival time from ePET was 14.5 mo (IQR, 10.2–44.3). The median number of lesion ROI identified on bPET and ePET were 13.5 (IQR: 5.8-59.5) and 33 (IQR: 2.8-86.3) respectively. The median % changes in SUVmax, SUVmean, volume, and SUVtotal from bPET to ePET were -33.9%, -20.7%, 4.3%, and -13.9% respectively. An increase in percent new and percent new or increasing lesions was associated with a higher risk of death (HR = 1.03; p = 0.002, HR = 1.03; p = 0.003 respectively), while an increase in percent disappeared or decreasing lesions was associated with a lower risk of death (HR = 0.97; p = 0.006). The median TRAQinform Profile score was 0.27, and patients with a TRAQinform Profile score above the median had shorter OS compared with patients with a TRAQinform Profile score below the median (median OS, 10.9 mo [IQR, 5.0-13.3] vs. median OS, 44.3 mo [IQR, 14.5-44.3]; p = 0.02). Conclusions: In this retrospective study of 20 mCRPC patients treated with PSMA-RLT, the TRAQinform Profile score was prognostic for OS. Percent new, percent new or increasing, and percent disappeared or decreasing lesions were significantly associated with OS. Validation in larger, prospective multicentric clinical trials is warranted.