bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrophil extracellular trap as a predictive marker to cisplatin-based chemotherapy for patients with muscle-invasive bladder cancer.
Authors: Shang Bing-Qing , Gu Zhaoru , Qu Wang , Xie Rui-Yang , Wu Jie , Zhou Ai-Ping , Shou Jianzhong 
Published: June 2023

e16600 Background: Cisplatin-based chemotherapy is the recommended therapy for muscle-invasive bladder cancer (MIBC), in both the neoadjuvant and first-line settings. However, the efficacy of MIBC for chemotherapy is only about 40%~60%. Patients without clear benefits from cisplatin-based chemotherapy still suffer from the potential toxicity, possibly missing the timing for other effective treatments. Therefore, predictors of therapy response are urgently needed. Neutrophils form neutrophil extracellular traps (NETs), a network structure, and growing evidence indicated that it could be a prognostic and predictive marker in cancer. In bladder cancer, NETs were involved in radio-resistance, but the predictive role of chemotherapy is unclear. This study constructed a NET-related signature that predicted chemotherapy efficacy for MIBC patients. Methods: Transcriptome datasets were obtained from the transurethral resection of bladder tumor (TURBT) and metastatic lesion specimens. A dataset (GSE169455) of 149 MIBC patients who received preoperative cisplatin-based chemotherapy (neoadjuvant or induction) was enrolled for the training cohort. We used the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model to select candidate molecules based on the 250 NETs-initial biomarkers collected from the literature, and further developed a NETs-associated signature score (NETs-score) for therapeutic response prediction. The dataset reported by Taber A et al. of 96 MIBC patients who received cisplatin-based chemotherapy (neoadjuvant or first-line) was used as a validation cohort. Immunohistochemistry (IHC) was conducted to evaluate the potential role of NET-related genes in 51 patients who received neoadjuvant chemotherapy at our center from 2012 to 2019. Results: We constructed the NETs-score with 11 NETs-related genes by the LASSO Cox model. A higher NET score was observed in non-responders compared to responders in the training cohort (P<0.001). These results were confirmed in the validation cohort (P=0.006). Moreover, high NETs-score indicated reduced recurrence-free survival (RFS) [HR=2.07, 95% CI (1.26-3.40), P=0.003], cancer-specific survival (CSS) [HR=1.87, 95% CI (1.12-3.12), P=0.014], and overall survival (OS) [HR=1.83, 95% CI (1.13-2.94), P=0.012] among MIBC patients. Furthermore, in the IHC cohort, citrullinated histone H3 (H3Cit) as a hallmark of NETs, was an independent predictor of chemotherapy resistance as determined by the multivariate logistic regression analysis [OR=5.94, 95% CI 1.20–45.50, P=0.045]. Conclusions: In conclusion, our study suggested that NET was a predictive and prognostic biomarker for MIBC patients with cisplatin-based chemotherapy. [Table: see text]
A phase II study of toripalimab combined with gemcitabine-cisplatin as neoadjuvant therapy for patients with muscle-invasive bladder cancer (MIBC).
Authors: Xu Abai , Xu Peng , Chen Chunxiao , Liu Zhe , Jiang Ning , Bi Enguang , Cao Manming , Chen BinShen , LIU Chunxiao 
Published: June 2023

e16602 Background: Cisplatin-based neoadjuvant chemotherapy is the standard of care in MIBC with improved pathologic response (PaR) and overall survival (OS) compared to radical cystectomy (RC) alone. The efficacy of PD-1 inhibitor in combination with chemotherapy as a new neoadjuvant treatment option for MIBC still needs further confirmation. This study evaluated the efficacy and safety of toripalimab (an anti-PD-1 monoclonal antibody) combined with gemcitabine-cisplatin (GC) as neoadjuvant therapy for patients with MIBC. Methods: Eligible pts with MIBC (cT2-T4a, N≤1, M0) who were candidates for RC were enrolled. Toripalimab (240mg, d1) combined with GC (gemcitabine 1000mg/m2 d1,d8 plus cisplatin 35mg/m2 d1,d2) every 21 days, up to 4 cycles. RC was performed within 6 weeks after the last dose treatment. The primary endpoint was PaR (≤ pT1,N0). Secondary endpoints were PFS at 2 years and safety. Results: Between Apr 2021 and Jun 2022, 16 pts (4 pts cT2, 11 pts cT3, 1 pts cT4) were enrolled and received 4 cycles of neoadjuvant therapy, with median age of 63.5 and 75% male. 14 of the 16 pts underwent RC and two declined RC. Among 14 evaluable pts, PaR ≤pT1N0 was achieved in 12 pts (85.71%, 4 were pT0, 8 were pT1/a/is). Survival data are not yet mature. The most common adverse events (AEs) of any grade were anemia (14/16; 87.5%) and nausea/vomiting (11/16; 68.75%). One had Grade≥3 AEs (hemorrhagic shock) while on study that was unrelated to GC or toripalimab. Five pts experienced grade 1-2 immune related AEs, including thyroiditis (3/16, 18.75%) and rash (2/16,12.5%). Conclusions: Neoadjuvant toripalimab combined with GC showed promising safety and efficacy in MIBC with significant pathologic downstaging rates. Clinical trial information: NCT04861584 .
Detection of bladder cancer relapse after TURBT through urinary tumor DNA analysis: A prospective real-world evidence study.
Authors: Zhang Ruiyun , Zang Jingyu , Tang Haoran , Xie Feng , Zhang Yue , Jin Di , Qian Lei , Zhang Tianxiang , Jia Shidong , Zhuang Guanglei , Chen Haige 
Published: June 2023

e16605 Background: Bladder cancer is a common malignancy and detection of tumor recurrence is important to improve patient outcomes. Transurethral resection of bladder tumor (TURBT) is the standard treatment for early-stage bladder cancer, but the molecular detection of disease relapse remains a challenge. Reliable and non-invasive methods for monitoring the molecular changes in urine are crucial for timely intervention and disease management. Methods: In this study, 108 patients with early-stage bladder cancer who were selected for detection of disease relapse after the 1st TURBT (median timing 4.8 months after TURBT) were prospectively enrolled. The molecular recurrence in these patients was detected from the urinary tumor DNA (utDNA) using a targeted next-generation sequencing (NGS) assay (PredicineCARE). This assay identifies somatic alterations in utDNA, including single nucleotide variations (SNVs), gene fusions and copy number variations (CNVs), and based on these variations, the tumor fraction was called to identify molecular relapse in the patients. Results: 77 out of 108 (71.3%) patients were found to be tumor positive in utDNA with a tumor fraction ≥ 0.5%. The assay identified 525 SNVs and 32 CNVs in the tumor positive patients. The most frequently mutated genes in the urine samples were TP53 (38%), TERT (32%), KMT2D (28%), ARID1A (19%), FGFR3 (19%), PIK3CA (14%) and ERBB2 (12%). Conclusions: This study demonstrates the feasibility of using urine ctDNA assay to detect molecular recurrence in early-stage bladder cancer patients treated by TURBT. This information can be used to improve patient outcomes by enabling early detection of tumor recurrence and guiding treatment decisions. The findings of this study highlight the promising potential of urine-based NGS assays for cancer detection and disease surveillance.
A meta-analysis of local-regional therapy (LRT) in liver metastases from genitourinary cancers.
Authors: Behara Murali Ranjani , Findakly Dawood , Wang Jue 
Published: June 2023

e16606 Background: Liver metastases (Mets) from genitourinary cancers are difficult to treat and many of them are resistant to systemic therapy. Local-Regional Therapies (LRT) are becoming popular in treating Liver Mets. In this Meta-analysis, we analyze the outcomes of LRT for Liver Mets from Genitourinary Cancers. Methods: We searched PubMed, Google scholar for case reports, case studies, retrospective studies with patients who underwent LRT like Radiofrequency Ablation (RF), Chemoembolization (CE), Microwave Ablation (MA), Cryoablation for liver metastases for from Genitourinary Cancers including Prostate Cancer (PC), Testicular Cancer (TC) and Renal Cell Cancer (RCC). We also included 3 patients from Dignity Health Cancer Center, Phoenix, AZ. Results: Total number of patients in the study is 54, 3 of them from our Center. 39 are men and 15 are women. Mean and median age of the patients was 62.3, 65 years respectively. Number of patients with RCC, PC, TC are 43, 6, 5 respectively. 28 patients had CE, 23 had RFA and 3 had MA with the total number of procedures being 144, 41 and 5 respectively. Mean survival for all the patients is 62.7 months, mean survival for RCC, TC and PC are 68.9, 45.8 and 24.4 months respectively. Median number of systemic therapies received by the patients prior to getting LRT was 2 (range 1-4). We used RECIST criteria to quantify the benefit from LRT, 23 patients had Complete Response (CR), 6 had Partial Response (PR), 14 had Stable Disease (SD) and 8 had Progressive Disease (PD), there was no data for 2 patients. 43 patients had Clinical Benefit. We present a case of castration resistant metastatic PC from our facility. A 78-year man diagnosed metastatic PC in 2007 who had Prostatectomy, salvage radiation, intermittent androgen deprivation and Combined deprivation therapy. But his PSA continued to rise, flutamide was added. In 2017, he had liver metastasis, had RFA twice for 2 liver lesions and had CR. He continues to be on relugolix with good quality of life. Patients in the study are people with advanced metastatic cancer who underwent various systemic therapies like chemotherapy, radiation, immunotherapy and hormonal therapy prior to getting the LRT. LRT was done as the patients failed or did not tolerate systemic therapies. The mean survival for RCC patients in the study group is greater than the average survival of stage IV RCC, the lower mean survival for PC and TC can be explained by the limited number of this patient population in the study. Conclusions: Combination of LRT with systemic therapy for previously heavily treated Liver Mets from genitourinary cancers is a promising strategy for patients with otherwise poor prognosis. [Table: see text]
Outcomes of renal function and efficacy in patients with muscle invasive bladder cancer treated by tislelizumab-based immunochemotherapy.
Authors: Li Hong Zheng , Niu Yuanjie , Hu Hailong , An Zesheng , Shen Chong , Wu Zhouliang , Qie Yunkai , Chen Houyuan , Zhao Gangjian , Huang Shiwang , Bai Yiduo , Guo Shizheng , Li Peng , Lin Yuda 
Published: June 2023

e16608 Background: The occurrence PD-1 ICIs brings a new era of treatment for bladder cancer (BC). Although the safety and efficacy of most PD-1 ICIs have been certified progressively, whether they can be used in patients (pts) with renal impairment is always a concern for clinicians. Consequently, we intend to investigate the variation of renal function and efficacy of PD-1 ICIs based immunochemotherapy for pts with muscle invasive bladder cancer (MIBC) and renal insufficiency in short term. Methods: Our study relied on population of the TRUCE-01 trial (NCT04730219), an open-label, single-arm phase II study of tislelizumab based immunochemotherapy in pts with MIBC. Data of pts, including demographic information, imaging and pathological assessment of efficacy, and serum creatinine (SCr) level in baseline, after the first, second and third cycle (C1, C2 and C3) of treatment was collected and analyzed retrospectively. We calculated at estimated glomerular filtration rate (eGFR) according to CKD-EPI formula 2009, and divided pts into different groups according to baseline eGFR, in reference to CKD categories in the K-DIGO 2012 guidelines. Results: 74 pts have been included in our research in total. The median age was 69.5 years (IQR 61.7-75.0) and 56 (75.7%) were male. Median SCr in baseline was 77.4umol/L (IQR 67.8-96.6), while median eGFR was 84.6 (IQR 63.6-94.0) (the unit of eGFR is mL/min/1.73 m2). At baseline, 25 pts were classified as G1 (eGFR≥90), 36 as G2(eGFR <90 and≥60), 12 as G3 (eGFR <60 and ≥30), and 1 as G4 (eGFR <30 and≥15). No significant difference was found in eGFR between pts with CKD G1-2 in comparison to baseline and after C1, C2, C3 of treatment (All p>0.05). In pts with CKD G3-4, it is notable that eGFR may improve when the C1, C2 and C3 completed, in comparison to the baseline (p=0.087, p=0.046, p=0.114 in Wilcoxson test, p=0.082 in Repeated Measures ANOVA). 48 (64.9%) pts received 3 cycles of ICIs and underwent an operation. 24 of 48 (50%) pts received radical cystectomy (RC) and others were treated by maximal TURBT. All of them have conducted efficacy evaluation by both radiographic test and pathology. It is noted that no statistical difference in outcomes between Group G1-2 and G3-4 (p=0.772). Conclusions: Despite renal impairment is common in pts with MIBC, PD-1 immunotherapy is generally safe for kidney of MIBC patients with renal insufficiency and have no influence on efficacy in the short term. The potential improvement in eGFR of patients with worse renal function and its mechanism is essential to be revealed and verified. [Table: see text]
Efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in patients with high-risk UTUC.
Authors: Niu Yuanjie , Li Hong Zheng , Hu Hailong , An Zesheng , Shen Chong , Wu Zhouliang , Qie Yunkai , Bai Yiduo , Zhao Gangjian , Chen Houyuan , Guo Shizheng 
Published: June 2023

e16609 Background: Urothelial carcinomas (UCs) are the sixth most common tumor. Among them, UTUCs are uncommon, accounting for only 5-10% of UCs. Currently, radical nephroureterectomy (RNU) remains the gold standard of treatment for UTUC. Neoadjuvant chemotherapy treatment can be used for specific UTUC patients, especially for highly staged and/or grade tumors, such as kidneys with potentially decreased renal function after RNU. Neoadjuvant therapy is a series of treatments administered preoperatively for UTUC, mainly chemotherapy, and in recent years, novel therapies of immunotherapy have emerged. Since conventional cisplatin neoadjuvant regimens also require high preoperative renal function, neoadjuvant chemotherapy regimens such as immunotherapy provide more effective and feasible treatments for patients who are intolerant to current cisplatin chemotherapy regimens. However, there is a lack of valuable studies worldwide on novel regimens such as immunotherapy for UTUC. The aim of this study was to explore a novel preoperative neoadjuvant regimen of immunotherapy combined with chemotherapy for UTUC. To further observe the feasibility and effectiveness of this regimen in the field. Methods: 9 high-risk UTUC patients were included in this study. Among them, 7 had unilateral ureteral tumors. 1 had a unilateral renal pelvic tumor. 1 had unilateral pelvic ureteral tumor. Among them, 2 were combined with bladder tumor. All patients were given 3 cycles of tislelizumab 200 mg combined with albumin paclitaxel 200 mg after a thorough evaluation. The treatment cycles were 21 days. Imaging evaluation and surgical resection were given within 15-20 days after the end of the last treatment cycle. Results: 3 patients underwent radical nephroureterectomy with postoperative pathology suggesting SD status of the tumor. 1 patient underwent ureteral reimplantation with tumor-negative postoperative pathology (cCR) and 2 patients underwent ureteroscopic biopsy, 1 of whom had tumor-negative pathology (cCR). 2 patients declined surgical treatment with RNU, one patient had imaging confirmation that the tumor was in SD, and the other showed no evidence of tumor presence on imaging and cytology (cCR). 1 patient was treated intermittently for grade 2 myocardial adverse effects (the remaining patients had adverse effects mostly limited to grade 1, with alopecia and malaise as common symptoms). Conclusions: The characteristics of epithelial carcinoma of the upper urinary tract have led to a reduced intention of some patients to undergo RNU treatment after the completion of NAC treatment. Although the present study failed to obtain ideal pathological information after RNU, the clinical treatment effect (cCR 30%) presented in combination with imaging and cytological results reveals to some extent the promising prospect of future UTUC patients treated with NAC.
Early postoperative outcomes in stent vs stent-less ileal conduits after radical cystectomies.
Authors: Shah Yash , Simhal Rishabh , Wang Kerith Ruoyao , Prebay Zachary , Lallas Costas D. , Simon Daniel P , Gomella Leonard G. , Shah Mihir S 
Published: June 2023

e16612 Background: Placing stents at the ureteroileal anastomosis for radical cystectomy with ileal conduit (RCIC) diversion has been common practice for the vast majority of urologists. Recently, the practice has been called into question, as some institutions have shifted to not stenting their ileal conduits for patient comfort and convenience. In this study, we aim to investigate the difference in 30-day outcomes between patients who did and did not receive ureteroileal stents after RCIC. Methods: RCs performed between 2019-2020 were identified in NSQIP and the corresponding cystectomy-targeted database. Baseline demographics, comorbidities, and operative parameters were compared via Pearson’s chi-square and t-tests between stented and stent-less RCICs. Outcomes of interest included rates of urinary tract infections (UTIs), acute kidney injury (AKI), renal failure requiring dialysis, anastomotic leaks, ureteral obstruction, ureteral fistula formation, need for reoperation, and 30-day hospital readmissions. Outcomes were compared using Pearson’s chi-square. All statistical tests were two tailed, p<0.05 considered significant. Results: 3,865 RCICs were identified, of which 446 (11.5%) were stent-less. There was no difference in baseline demographics, comorbidities, or operative parameters between the stented and stent-less group, with the notable exceptions that significantly more stent-less patients had robotic-assisted instead of open RCs compared to the stented group (33% vs 21%, p<0.001), and significantly more stent-less patients were preoperatively on dialysis compared to the stented group (4.9% vs 0.5%, p<0.001). There was no significant difference in 30-day rates of UTIs, AKIs, renal failure, anastomotic leaks, ureteral obstruction, ureteral fistula formation, need for reoperation, and readmissions between the stented and stent-less cohorts. Conclusions: Stent-less ileal conduits have recently emerged in popularity. This study represents the largest multi-institutional analysis comparing outcomes between traditionally stented and stent-less RCICs, and shows that there is no significant difference in outcomes. Given the added cost and patient discomfort of ureteroileal stents, this study may indicate that these stents may not play as significant of a role in preventing early complications as previously thought. These findings warrant further investigation.
Phase Ib neoadjuvant CG0070 and nivolumab (N) for cisplatin (C)-ineligible muscle invasive bladder cancer (MIBC).
Authors: Li Roger , Spiess Philippe E. , Sexton Wade J. , Poch Michael Adam , Zemp Logan , Pow-Sang Julio M. , Zhang Jingsong , Dhillon Jasreman , Borjas Gustavo , Naidu Shreyas U , Dorman Denise , Burke James M. , Mule James J , Conejo-Garcia Jose , Jain Rohit K. 
Published: June 2023

e16613 Background: CG0070 is a replication-competent oncolytic adenovirus engineered to target RB deficient tumor cells and to express GM-CSF. CG0070 has previously demonstrated safety and efficacy against BCG-exposed high risk non-muscle invasive bladder cancer through tumor lysis and anti-tumor immune activation. We tested the safety and efficacy of CG0070 in combination with N as neoadjuvant therapy for MIBC in C-ineligible patients in this study (NCT04610671). Methods: C-ineligible pts with MIBC (cT2-4a, N≤1) were enrolled. Pts received 6 weekly intravesical CG0070 (1x1012vp) and 2 doses of N at wks 2 and 6, followed by radical cystectomy (RC). The primary objective is safety of CG0070+N as measured by CTCAEv5.0. Secondary objective is to assess pathologic response (PaR) (pT0N0) and 1yr event free survival (EFS). Exploratory objectives include the assessment of correlation between PaR with baseline 1) E2F expression; 2) immune infiltration; 3) PD-L1 expression; and 4) TLS expression. Results: Between Nov 2020 and Feb 2023, 21 pts were enrolled with median age 75yrs, 81% male, 33% > cT2; 1 pt refused RC but was included in the ITT population. Treatment was stopped after 1 infusion of CG0070 in 1 pt due to treatment unrelated worsening of renal function. The overall rate of >grade 3 AEs was 12/20 (60%), and the vast majority were related to RC (83%). Immune related AEs were seen in 1 pt, who had grade 2 autoimmune thyroiditis. There was no delay in time to RC and no unexpected surgical complications from treatment. Overall, 1 pt was unevaluable for efficacy, 2 pts progressed prior to RC, PaR was observed in 8/15 (53%) evaluable pts, and an additional pt had negative post-treatment biopsy but refused RC. On exploratory analysis, treatment response correlated with increased maturation of tertiary lymphoid structures and immunogenicity to bespoke tumor neoantigens. Conclusions: Neoadjuvant CG0070+N is safe and effective in C-ineligible pts with MIBC. This combination was well tolerated without any delays in RC and induced an overall response rate of 50%. Clinical trial information: NCT04610671 .
A single institution experience of multimodality radiation therapy for muscle-invasive bladder cancer.
Authors: Nair Monica , Scarborough Jessica , Gupta Shilpa , Gilligan Timothy D. , Nizam Amanda , Ornstein Moshe Chaim , Echle Jessica , Ciezki Jay P. , Stephans Kevin L. , Tendulkar Rahul D. , Scott Jacob , Mian Omar Y. 
Published: June 2023

e16614 Background: We studied a cohort of patients with localized muscle invasive bladder cancer (MIBC) who received organ preserving trimodality therapy (TMT) as definitive treatment at a single high-volume institution. Methods: A retrospective cohort analysis was performed for 231 bladder cancer patients treated with definitive radiation or chemoradiation therapy from 2006 to 2022 at a single institution. We assessed overall and disease-free survival as defined by any type of cancer recurrence. We analyzed survival outcomes based on stage, pathologic features, and patient characteristics. Results: 184 of 231 patients in this cohort received either definitive radiation therapy alone or with chemoradiation and had adequate follow-up data for analysis. The median overall survival for these 184 patients was 37mo (95%CI 28-67). Disease free survival (DFS) had a median time of 36mo (95% CI 23-69). On univariate analysis neither tumor size nor hydronephrosis showed a significant association with local recurrence. The presence of carcinoma in situ (CIS) was associated with shorter time to local recurrence (Log-Rank p = 0.039). Nine patients (4.9%) required cystectomy after initial definitive radiation therapy. When overall survival was compared between patients offered radical cystectomy who proceeded with definitive multimodal radiation therapy and radical cystectomy ineligible patients, there was a significantly longer overall survival for the cystectomy eligible patients (median 86mo (95%CI 35-206) vs median 31mo (95%CI 24-44), Log-Rank p = 0.0016). No differences were observed in cancer specific survival between cystectomy eligible and ineligible patients. Conclusions: Multimodality bladder preservation demonstrated cancer specific survival outcomes comparable to published radical cystectomy series. The presence of CIS at baseline was associated with increased local recurrence, but not CSS or OS. Eligibility for radical cystectomy was associated with longer overall survival in patients treated with TMT, highlighting the limitations of retrospective comparisons of all-cause mortality between different treatment approaches. Disease specific survival endpoints, propensity matching analyses, or randomized prospective trials are needed to draw comparative efficacy conclusions.