bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subgroup analyses from READY: Real-world data from an Italian compassionate use program (CUP) of avelumab first-line maintenance (1LM) treatment for locally advanced or metastatic urothelial carcinoma (la/mUC).
Authors: Bracarda Sergio , Antonuzzo Lorenzo , Maruzzo Marco , Santini Daniele , Tambaro Rosa , Buti Sebastiano , Carrozza Francesco , Calabrò Fabio , Di Lorenzo Giuseppe , Fornarini Giuseppe , Iacovelli Roberto , Cullurà Daniela , Messina Carlo , Cerbone Linda , Fazzi Gennaro , Venturini Filippo , Colasanto Raffaele , Necchi Andrea , De Giorgi Ugo 
Published: January 2024

558 Background: A multicenter CUP provided early access to avelumab 1LM in Italian patients (pts) with Ia/mUC before reimbursement. Real-world pt characteristics and outcomes with avelumab 1LM from READY were reported previously. Here, we report updated data and subgroup analyses of effectiveness with avelumab 1LM. Methods: This prospective, noninterventional CUP included pts with la/mUC who were progression free after 1L platinum-based chemotherapy (PBC; 4-6 cycles, starting avelumab 1LM 4-10 wk after last PBC dose). Pts were enrolled from Jan 18, 2021 to Mar 7, 2022. Avelumab was provided per physician request and after approval by local ethics committees, per Italian compassionate-use regulations. Pts who had a relapse within 12 mo of prior adjuvant or neoadjuvant systemic therapy, including immune checkpoint inhibitors, were excluded. Results: 464 pts were included (78.45/21.55% male/female; median age, 70.0 y [interquartile range, 63.0-76.0]). At data cutoff (July 30, 2023), median follow-up from start of avelumab 1LM in 411 evaluable pts was 20.24 mo (95% CI, 19.78-20.93); median overall survival (OS) and progression-free survival (PFS) from start of avelumab were 26.22 mo (95% CI, 19.97-not estimable [NE]) and 7.63 mo (95% CI, 5.79-9.24), respectively. In pts aged <60 y (n=53), 60-70 y (n=150), and >70 y (n=208), median OS (95% CI) was not reached (NR; 12.86 mo-NE), NR (24.21 mo-NE), and 24.01 mo (16.94-NE), and median PFS was 5.20 mo (2.83-6.71), 7.70 mo (5.26-10.07), and 8.82 mo (6.05-12.93), respectively. In pts who received 1L cisplatin + gemcitabine (n=183) and 1L carboplatin + gemcitabine (n=219), median OS (95% CI) was NR (16.05 mo-NE) and 25.10 mo (19.97-NE), and median PFS was 6.61 mo (5.30-9.18) and 8.42 mo (6.05-12.73), respectively. The table shows OS and PFS in other subgroups defined by best response to 1L PBC and number of 1L PBC cycles received. Conclusions: Real-world outcomes with avelumab 1LM in this CUP in Italy show clinical benefit across various subgroups. These data are clinically relevant and are consistent with other real-world country-based studies and the phase 3 JAVELIN Bladder 100 trial. Findings further support the use of avelumab 1LM as standard of care in pts with la/mUC who are progression free after PBC. [Table: see text]
Treatment (Rx) trends and attrition with lines of therapy in patients (pts) with advanced urothelial carcinoma (aUC).
Authors: Mathew Thomas Vinay , Jo Yeonjung , Tripathi Nishita , Roy Soumyajit , Chigarira Beverly , Dal Emre , Gebrael Georges , Hage Chehade Chadi , Sayegh Nicolas , Fortuna Gliceida Galarza , Ji Richard , Campbell Patrick , Li Haoran , Agarwal Neeraj , Gupta Sumati , Swami Umang 
Published: January 2024

562 Background: The Rx landscape of aUC has evolved significantly with the approval of novel therapeutic agents. However, even with the advent of new therapeutic options, aUC remains a lethal malignancy with poor outcomes. Here, we use a large real-world database to describe Rx trends and attrition in pts with aUC. Methods: Patient data was extracted from the Flatiron Health EHR-derived deidentified database. Inclusion criteria: pts with histological diagnosis of metastatic or aUC between 1/1/11-1/10/2023 and Rx receipt at participating site. Pts receiving Rx for two or more cancers were excluded. Rx were grouped into categories based on NCCN approved regimens. Rx in each line (L) of therapy were summarized using frequency and percentages. All the analysis was done using R version 4.2.3. Results: Of the identified 12,157 pts in the dataset, 8,660 had Rx information and 7,260 were included in the analysis based on eligibility criteria. Details of each line of therapy are presented in the table. Of all pts receiving 1L, only 37% receive 2L and only 12% receive 3L of therapies. Carboplatin containing regimen were most commonly used in 1L followed by PD-1/L1 therapies. PD-1/L1 therapies were most commonly used regimens in 2L and 3L. Over time, there has been a steady decline in the overall use of platinum-based regimens, and since 2015 an increase in uptake of PD-1/L1 agents has been observed. The use of novel therapeutic agents, such as enfortumab vedotin (EV), erdafitinib, and sacituzumab govitecan (SG), has increased since 2019, especially in the 2L and 3L of therapy. Conclusions: Approximately two-thirds of aUC patients don’t receive 2L or beyond systemic therapy. Majority of real-world patients (61%) did not receive cisplatin-based regimens and instead received carboplatin or PD- 1/L1i based therapies. These data warrant the need for more effective and tolerable Rx in front-line setting. [Table: see text]
HER2 mutation and bladder cancer (BC): Prevalence and clinical outcomes.
Authors: Shah Neil J. , Aggen David H , Zheng Junting , Niederhausern Andrew , Alam Syed Muneeb , Balar Om , Bahadur Nadia , Watson Adam , Regazzi Ashley M. , Ratna Neha , Funt Samuel A , Teo Min Yuen , Pietzak Eugene J. , Solit David B. , Bajorin Dean F. , Philip John , Rosenberg Jonathan E. , Ostrovnaya Irina , Al-Ahmadie Hikmat A. , Iyer Gopa 
Published: January 2024

574 Background: Novel HER2-directed targeted therapies have revolutionized the treatment paradigm for patients with breast cancer and are being actively investigated in BC. The impact of pathogenic HER2 mutation and/or its amplification on clinical outcomes across various stages of BC is underdefined. Methods: In our retrospective study, we identified 999 BC patients who underwent genetic profiling using MSKCC IMPACT and had at least one year of follow-up. The BC disease states included non-muscle invasive (NMIBC), muscle-invasive (MIBC), and metastatic (MetBC). Patient demographics and HER2 alteration (mutation or amplification) were analyzed and compared closest to the time of IMPACT sampling, using the Kruskal-Wallis rank sum test or the Fisher’s exact test. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS) for MIBC and MetBC, and advanced disease-free survival (ADFS) for NMIBC. The log-rank test and Cox proportional hazard regression were used in survival analyses. Results: The study cohort included NMIBC:359, MIBC:429, and MetBC:211 patients at the time of profiling and the overall incidence of HER2 alteration (mutation or amplification) was 13% (48), 17% (75), and 19% (41), respectively. HER2 Amplification was significantly lower for NMIBC (2.8%) compared to MIBC (9.3%) and MetBC (10%), p<0.001. HER2 S310F and S310Y were the most common pathogenic mutations. Age, race, gender, and smoking status were not associated with the incidence of HER2 alteration for any BC disease states. The median follow-up for NMIBC, MIBC, and MetBC was 5.3, 3.6, and 6.5 years, respectively. HER2 status did not influence ADFS for NMIBC; PFS and OS for MIBC regardless of neoadjuvant cisplatin chemotherapy (chemo); OS for 1st line (1L) MetBC treated with gemcitabine plus platinum (GC) chemo or 2nd line (2L) immune checkpoint inhibitor (ICI) therapy post 1L-chemo (table). Conclusions: We present one of the largest and comprehensive study of HER2 mutation in BC. Overall, HER2 amplification was significantly less frequent for NMIBC. HER2 alterations were not a prognostic marker for NMIBC or MIBC independent of neoadjuvant cisplatin-based chemo, MetBC- 1L GC-chemo and 2L ICI post GC-chemo. Further studies examining IHC and functional HER2 PET imaging are needed to further define the HER2 BC landscape. [Table: see text]
20-year trends in perioperative outcomes in patients with bladder cancer undergoing radical cystectomy with ileal conduit urinary diversion.
Authors: Xu Kevin Lou , Ryu Grace , Makarova Elizaveta , Bakhl Katrina , Boltz Suzanne , Demirsoy Seyma , Raman Jay D. , Truong Hong 
Published: January 2024

583 Background: Radical cystectomy is associated with considerable postoperative morbidities. Enhanced recovery after surgery protocol is a multimodal perioperative pathway implemented to improve post-surgical outcomes over the past decade. We sought to compare the 30- and 90-day postoperative morbidity and mortality rates following RC and ileal conduit urinary diversion between 2000-2010 and 2010-2020 to evaluate the trends in patient outcomes and areas that need improvement. Methods: This retrospective cohort study used data from TriNetX US Collaborative network which allowed access to de-identified patient health records from over 43 healthcare organizations. ICD-10 codes were used to identify patients with bladder cancer who underwent radical cystectomy and ileal conduit urinary diversion from 01/01/2000 to 01/01/2020. The rates of 30 and 90-day postoperative morbidities and mortalities were compared between 2000 – 2010 and 2010 – 2020 using the chi-squared test. Results: The 30 and 90-day complications by decade were summarized in Table. There were 738 cases reported from 22 HCOs from 2000 to 2010 and 10,052 cases reported from 43 HCOs from 2010 to 2020. The overall all-cause mortality at 30 and 90-days postop were 1.5% and 4.4%, respectively, and remain unchanged over the past 20 years. The most common complications within 90-days postop were urosepsis (19.1%), acute kidney injury (16.3%), and UTI (15.6%). While most complication rates remain stable, the rates of urosepsis, acute kidney injury, and UTI were higher between 2010 to 2020 compared to 2000 to 2010. Conclusions: Radical cystectomy and urinary diversion procedure is associated with high perioperative morbidities with up to 1 in 5 patients experiencing a complication within 90-days postop. Despite reported improvement in cancer-specific survivals from recent reports, the overall morbidity and mortality rates associated with the procedure have not improved over the past two decades. Further research is needed to improve surgical outcomes, especially in infectious complication and renal function, for patients with bladder cancer undergoing radical cystectomy. [Table: see text]
Characterizing psychological resources and resilience in patients with bladder cancer: Associations with frailty and quality of life.
Authors: Petersen Erin , Holt Sarah K , Browning Anne , Jannat Samia , Cavanaugh Dana , Wright Jonathan L. , Gore John L. , Schade George R. , Psutka Sarah P. 
Published: January 2024

585 Background: Bladder cancer (BC) profoundly affects patients’ mental and physical well-being, with significant impacts to quality of life (QOL), mental health, and ability to perform activities of daily living. Understanding factors that influence patients’ responses to BC is crucial to tailored care. One such factor that has yet to be studied in BC patients is resilience, or the ability to maintain or restore baseline function following a stressor. Our objective was to demonstrate the feasibility of prospectively characterizing baseline resilience and frailty in patients with BC. We hypothesized that resilience and psychological resources (PsyResources) would be positively associated with improved QOL and inversely associated with frailty. Methods: With IRB approval, we enrolled patients with BC (N=67) from a urology clinic (6/20-7/2021). Patients completed a comprehensive geriatric assessment incorporating validated assessments of frailty and PsyResources: University of Washington Resilience Survey (UWR), Psychological Capital (PsyCap), Brief Inventory of Thriving (BIT), and Self-Compassion Survey (SCS) which measure resilience, psychological capital, mental health, and self-compassion, respectively. Validated QOL surveys were completed at 2 weeks, 3 and 6 months post-treatment. Correlation matrices evaluated PsyResources’ links with baseline frailty and Spearman’s correlation coefficient (ρ) was reported. Associations between PsyResources, anxiety and depression, and QOL were evaluated with linear regression. Results: The median age of the cohort was 71 (83.6% male) and 77.6% had muscle-invasive BC (cN+:20.9%, M1: 7.6%). PsyResource assessment completion rates ranged 96-100% and had strong inter-assessment associations (ρ=0.52-0.81, p< 0.0001 for all). Baseline PsyResources were strongly inversely correlated with the geriatric depression scale, (ρ=-0.50-0.65, p<0.0001). Negative correlations were found between functional frailty and SCS (ρ=-0.37, p=0.006). A higher baseline of each PsyResource was associated with improved global symptoms, emotional function, and body image (BIT and SCS) (p<0.05) and decreased anxiety and depression over time (B:-0.167 to -2.46; p<0.02). Conclusions: We present the first prospective characterization of baseline PsyResources in patients with BC, revealing positive correlations with mental health and inverse correlations with functional frailty. Interestingly, PsyResources were associated with improved QOL outcomes over time. Ongoing work is exploring the relationship between resilience and different domains of frailty and the potential role of functional recovery and decline following BC treatment. Future work will also evaluate associations with survival outcomes and the ability to modify resilience to facilitate recovery of functional status and quality of life after treatment.
Thromboembolic events associated with neoadjuvant chemotherapy for muscle invasive cancer of the bladder.
Authors: Qureshi Muneeb , Rehan Ahmed , Mok Wai Kit , Salawu Abdulazeez , Goktas Aydin Sabin , Tay Jessica , Hubbard Rachel , Catto James W.F. , Hussain Syed A. 
Published: January 2024

586 Background: Patients with muscle invasive bladder cancer who undergo platinum-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy or radiotherapy are at high risk of venous and arterial thromboembolic events (TEE). TEE is associated with delay to radical cancer treatment, significant morbidity and even mortality. This study aimed to document the incidence and characteristics of TEE during NAC and prior to radical treatment. Methods: Retrospective data was collected on all patients in our centre who underwent NAC prior to radical treatment. TEE events were identified based on routine imaging to assess for response to NAC; or imaging based on clinical symptoms developed during (or within 28 days) of NAC but prior to radical treatment. Results: Data was collected on 148 patients between January 2015 and September 2023. Age range: 44 - 82 years, the majority (73.6%) of whom were male. All patients received platinum-based chemotherapy (median 4 cycles). A total of 31 patients (20.9%) developed 35 TEE, including 27 venous events (24 pulmonary emboli and 3 deep venous thromboses), and 8 arterial events (3 aortic thrombus, 4 limb ischaemia, 1 ischemic stroke). Four patients had a venous and arterial TEE. The majority of pulmonary venous TEE were subclinical. Conclusions: Our single-centre study demonstrates that the incidence of TEE during NAC prior to radical treatment for bladder cancer is high. Improved imaging techniques and routine scans post-NAC led to identification of subclinical TEE that require treatment as they are likely to become clinically significant. The high rate of TEE in this patient population is likely to benefit from prophylactic anticoagulation during NAC and should be investigated in future prospective clinical trials.
Clinical outcomes with split-dose cisplatin-based regimens in patients (pts) with locally advanced or metastatic urothelial carcinoma (la/mUC): Results of a systematic literature review (SLR) and network meta-analysis (NMA).
Authors: O'Dwyer Richard Thomas , Kearney Mairead , Musat Mihaela , Gulas Ioana , Guenther Silke , Hubscher Elizabeth , Moradian Hoora , Sridhar Srikala S. 
Published: January 2024

589 Background: Gemcitabine + cisplatin (GC) is one of the most effective and commonly used regimens in la/mUC. In GC, cisplatin is dosed at 70 mg/m2 on day 1 of a 3-week cycle; however, for many pts, impaired renal or cardiac function, neuropathy, or poor performance status can preclude use of cisplatin. A promising alternative is split-dose GC, where the cisplatin dose is divided over 2 days. We conducted an SLR and NMA to better understand outcomes, toxicity, and comparative effectiveness of split-dose GC vs GC, GCarboplatin (GCa), and methotrexate + vinblastine + doxorubicin + cisplatin (MVAC). Methods: An SLR, performed on March 8, 2023, followed Cochrane guidelines to identify observational studies of treated pts with la/mUC and randomized and nonrandomized trials investigating split-dose cisplatin regimens for this indication. No limits were placed on publication year or geography, and studies reported in English, Spanish, French, and German were included. An NMA was conducted for objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results were reported as odds ratios or hazard ratios (HRs) with 95% credible intervals (Crls). Results: Among 120 studies that met SLR inclusion criteria, 16 (6 clinical trials, 10 retrospective studies) conducted in the US, Europe, and Asia published from 1999-2023, representing 1,767 pts, included split-dose GC. Common reasons for choosing split-dose GC were impaired renal function (creatinine clearance ≤60 mL/min), age >70 years, comorbidities, and physician preference. Most often, cisplatin was split (35 mg/m2) on days 1+8 or 1+2, and pts received a median of 3-5 cycles. In studies reporting outcomes with split-dose GC (12 studies), ORRs were 39-80% (11 studies), median PFS was 3.5-9.9 months (7 studies), and median OS was 8.5-18.1 months (11 studies). Discontinuation rates due to adverse events were 8-38% (5 studies). In the NMA, ORR for split-dose GC was significantly higher than GCa but not GC and MVAC. PFS and OS for split-dose GC were not significantly different from GCa, GC, or MVAC (Table). Conclusions: This is the first SLR and NMA of split-dose GC in la/mUC. Despite heterogeneity in the limited studies included, survival with split-dose GC was numerically better than GC and worse versus MVAC but not statistically different in either case. Split-dose GC has the potential to extend the la/mUC population eligible to receive cisplatin-based regimens and warrants further study. [Table: see text]
Effects of perioperative chemotherapy on prognosis in muscle invasive bladder cancer treated with radical cystectomy.
Authors: Hatakeyama Shingo , Taoka Rikiya , Miki Jun , Saito Ryoichi , Fukuokaya Wataru , Matsui Yasuyuki , Kawahara Takashi , Matsuda Ayumu , Kawai Taketo , Kato MInoru , Sazuka Tomokazu , Sano Takeshi , Urabe Fumihiko , Kashima Soki , Naito Hirohito , Murakami Youji , Nishiyama Naotaka , Nishiyama Hiroyuki , Kitamura Hiroshi , Ohyama Chikara ,   The Japanese Urological Oncology Group
Published: January 2024

592 Background: We aimed to evaluate the effect of the number of neoadjuvant chemotherapy (NAC) cycles and the adding adjuvant chemotherapy (AC) after NAC in muscle-invasive bladder cancer (MIBC) on overall survival (OS). Methods: This multicenter retrospective study included 2674 patients with MIBC who underwent radical cystectomy (RC) from 36 institutions within the Japanese Urological Oncology Group. Among them, we selected 1687 patients with cT2-4NxM0 who were treated with RC alone or RC plus perioperative chemotherapy. We compared the effect of the number of NAC cycles (2 vs. ≥3 cycles) and the addition of AC on OS. Cox proportional-hazards regression was used to assess the association of treatment received with OS. Results: Of 1687 patients, 946 were treated with NAC with a median of 3 cycles. Use of NAC significantly prolonged OS compared to the RC alone. The pathological complete response rate was not significantly different between the 2 cycles (22.9%) and ≥3 cycles (27.5%, P = 0.112) groups. OS was not significantly different between the groups (P = 0.559). Multivariable Cox regression analysis showed that pathological high-risk (ypT2–4, pT3–4, or pN+) or cisplatin ineligibility were significantly associated with poor OS, but not the number of NAC cycles (P = 0.238). We identified 942 pathologically high-risk patients after RC who were eligible for AC. We observed no significant OS improvement with addition of AC after NAC as intensive perioperative chemotherapy. The primary limitation is selection bias from confounding by clinical indication. Conclusions: The impact of 3 or more NAC cycles and the addition of AC on OS in MIBC patients treated with RC may be limited.
Bladder-sparing treatment for muscle-invasive bladder carcinoma: A single-center, single-arm clinical study of sequential neoadjuvant chemotherapy followed by tislelizumab neoadjuvant immunotherapy.
Authors: Zeng Yu , Li Changqi , Lv Chengcheng , Fu Cheng , Chen Ang , Fu Shui , Bi Huan , Shan Guangyi , Wang Yiding , Wang Zhe , Liu Qiang , Shao Bo 
Published: January 2024

596 Background: Althoughradical cystectomy (RC) in combination with cisplatin-based neoadjuvant chemotherapy is the gold-standard for muscle-invasive bladder carcinoma (MIBC), bladder-sparing treatment have emerged to be an alternative choice for patients who are concerning about the life quality after surgery. The optimal strategy for bladder-sparing treatment such as trimodal therapy (TMT) showed similar effect with RC. Since the TRUCE-01 has illuminated considerable response of neoadjuvant immunotherapy in MIBC, we aim to study whether neoadjuvant chemotherapy plus immunotherapy can improve the bladder-sparing rate in MIBC patients. Methods: 30 planned patients with MIBC (T2-4a N0-1 M0) received cisplatin 70 mg/m2 or carboplatin AUC 4.5 on days 1 every 3 weeks (Q3W) plus gemcitabine 1000 mg/m2 on the 1st and 8th day of each 21-day cycle x 4 cycles. Tislelizumab 200 mg was administered on the 14th day of each 21-day cycle at the 3rd and 4th cycles. CT and cystoscopy imaging were carried out to evaluate disease progression. After the 4th treatment, radical cystectomy, partial cystectomy or TURBT were perform in accordance with the disease status. For continuous bladder-spare treatment, 2 additional cycles of tislelizumab were performed. Bladder-sparing rate was settled as exploratory endpoints based on 2-years follow-up and predictive biomarker will be analyzed. Results: To date, 21 of 30 pts have been enrolled and 17 pts have completed the regimen. 2 pts were excluded because of complicating with other disease (suffering cerebral infraction or rectal cancer during the trail), and 2 pts voluntarily quitted due to intolerance of chemotherapeutic adverse effect (fatigue and gastrointestinal symptoms). 2 pts partially response to the therapy and received RC after disease progression. 1 pt have no response to the therapy and received palliative care as unsuitable for surgery. The resting 10 of 17 pts successfully preserved their bladder by achieving pT0 (58.8%) after treatment. Among them 3 pts have been followed up over 1 year and no relapse was observed. Conclusions: These data support neoadjuvant chemotherapy plus immunotherapy a feasible bladder-sparing choice for patients with MIBC. Further completed follow-up data and biomarker analysis will accurately identify patients who are suitable for this therapy. Clinical trial information: ChiCTR2100050763 .