bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association between functional impairment pre- and post-cystectomy with neoadjuvant chemotherapy use in patients with muscle-invasive bladder cancer.
Authors: Osterman Chelsea K. , Deal Allison Mary , Nyrop Kirsten A. , Milowsky Matthew I. , Muss Hyman B. , Smith Angela 
Published: May 2020

e17008 Background: Standard of care treatment for muscle-invasive bladder cancer (MIBC) includes neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC), which can be associated with major toxicity. It is unknown whether patients who receive NAC have differences in functional impairment prior to RC, degree of functional decline post-RC, or time to return to baseline functional status post-RC compared to patients who do not receive NAC. Methods: A total of 80 patients were included in this study. Patients completed an initial geriatric assessment (GA) post-NAC but prior to RC, which was repeated at 30, 90 days, and 1 year post-cystectomy. Patients were classified as impaired or not impaired on each GA domain based on previously established cut points. Percentage impairment was calculated as the number of domains impaired out of the total number of domain assessments completed for each patient at each time point. Results: Median age was 68 for patients who received NAC (66% received gemcitabine/cisplatin) and 72 for patients who did not (p = 0.06), with elevated creatinine as the most common reason for not receiving NAC (57%). Overall, 74% of patients were impaired on at least 1 GA domain pre-surgery (NAC 75%; no NAC 71%) and 86% at 30 days post-RC (NAC 86%; no NAC 87%). Groups did not differ significantly in percentage of patients impaired on each GA domain or median percentage impairment at any time point. For both groups, median percentage impairment increased significantly at 30 days post-RC compared to pre-RC (NAC: 36% vs. 15%, p < 0.001; No NAC: 32% vs. 15%, p = 0.002), followed by a decrease in percentage impairment at 90 days post-RC compared to 30 days post-RC (NAC: 14% vs. 36%, p < 0.001; No NAC: 16% vs. 32%, p = 0.15). There was no difference in impairment at 90 days post-RC compared to pre-RC (NAC: 14% vs. 15%, p = 0.41; No NAC: 16% vs. 15%, p = 0.31). Conclusions: Patients with MIBC frequently have functional impairments at baseline, and their degree of impairment worsens in the short term post-RC. However, patients return to their baseline function by 3 months post-RC. Receipt of NAC was not associated with increased levels of functional impairment at any time point or a delayed return to baseline.
Evaluation of mood disorders in bladder cancer patients and their primary caregivers.
Authors: Au Daniel , Chestnut Connor , Brevik Andrew , Kirwan Mateo , Taylor John A , Harry Kadie , Dwyer Meagan L , Thompson Jeffrey , Wulff-Burchfield Elizabeth Marie 
Published: May 2020

e17013 Background: Mood disorders are prevalent in cancer patients in general and in bladder cancer specifically. New psychiatric diagnoses post-bladder cancer treatment are associated with decreased survival. Bladder cancer management is cost- and labor-intensive from a healthcare and social standpoint. Tools such as Enhanced Recovery After Surgery (ERAS) pathways have been developed to lower this burden of care, but focus entirely on physiologic parameters without addressing the psycho-social burden of bladder cancer or its treatment. Data is lacking regarding prevalence of mood disorders in bladder cancer patients, especially those with non-muscle-invasive disease, their caregivers, and regarding the relationship between patient and caregiver mood disorders. Methods: A cross-sectional dyadic study of 96 bladder cancer patients and their self-designated primary caregivers. Study utilized retrospective chart review and separate telephone interviews of patient and caregiver. Patients must have received initial diagnosis or proven recurrence within the past 24 and 12 months, respectively, and have no metastatic disease. Surveys included Patient Health Questionnaire 9 (PHQ-9) for depression, General Anxiety Disorder-7 (GAD-7) for anxiety, Short Form Health Survey (SF-12) for health-related quality of life, and a financial toxicity measure. Pearson correlation and regression models were used for analysis. Results: 49% (9.3% moderate to severe, 40.2% mild) of bladder cancer patients and 33% of caregivers (7.2% moderate to severe, 24.8% mild) had symptoms of depression. Patients’ PHQ-9 scores were moderately correlated with their caregiver, r = 0.49 (95% CI 0.32,0.63 p < 0.001). GAD-7 scores were not correlated between patient and caregiver r = 0.08 (95% CI 0.12,0.28 p = 0.45). Both patient (r = -0.31, 95%CI -0.48,-0.10 p < 0.004) and caregiver (r = -0.41, 95%CI -0.58,-0.22 p < 0.001) incomes were inversely associated with depression symptoms. Results were similar when stratified by non-muscle-invasive and muscle-invasive status. Conclusions: Depression is common among bladder cancer patients and their caregivers and these symptoms are correlated between patient and their caregiver. This correlation did not appear to hold true with respect to anxiety. Financial situation may play a role as increasing income was negatively correlated with depression symptoms. Patient and caregiver may both experience adverse psycho-social consequences from bladder cancer and treatments and pose a joint opportunity for intervention to lower burden of care.
Small cell bladder cancer: Treatment patterns and clinical outcomes.
Authors: Sekar Rishi Robert , Diamantopoulos Leonidas Nikolaos , Vakar-Lopez, MD Funda , Grivas Petros , Psutka Sarah P. , Schade George R. , Lin Daniel W. , Gore John L. , Montgomery Robert B. , Wright Jonathan L. 
Published: May 2020

e17014 Background: Small cell bladder cancer (SCBC) is a rare histologic variant associated with poor oncologic outcomes and propensity for metastasis, however, there remains a paucity of data regarding the role of chemoradiation. We review our institutional experience of patients with small cell bladder cancer (SCBC) treated with radical cystectomy (RC) versus concurrent chemoradiotherapy (CCRT). Methods: We retrospectively reviewed our institutional database for pts with SCBC treated with RC or CCRT and compared them to pts with conventional urothelial carcinoma (CUC) treated with RC. Clinicopathologic data and outcomes were captured and compared between treatment groups. Overall (OS) and recurrence-free survival (RFS) were estimated utilizing the Kaplan Meier method. T test, χ2 test and log-rank test were used for group comparisons. Factors significant in the univariate analysis for OS were included in multivariable Cox models. Results: We identified 38 consecutive pts with SCBC, of whom 24 (63%) had SC predominant ( > 50%) histology. At presentation, 31 (82%) had muscle invasion, 8 (22%) had nodal involvement, and 7 (18%) had distant metastasis. Twenty-eight (73%) pts proceeded to definitive therapy, with RC in 20 (53%) and CCRT in 8 (21%). Among pts treated with CCRT, 4 (50%) had complete response on cystoscopy, 2 (25%) had residual disease with 1 (12.5%) proceeding to salvage cystectomy, and 2 (25%) progressed with metastasis. Among pts treated with RC, 15 (75%) received neoadjuvant chemotherapy (NAC) with platinum/etoposide, of whom 3 (20%) experienced a pathologic complete response (pCR, ypT0N0), 3 (20%) had residual UC but no SCBC, and 9 (60%) had residual SCBC. Median OS was comparable between RC and CCRT groups (30.4 vs. 26.2 months, p = 0.633). Compared to pts with CUC treated with RC (n = 457), those with SCBC treated with RC had similar clinical stage, rates of carcinoma in situ, lymphovascular invasion, and positive surgical margins (all p > 0.05). Median OS and RFS were inferior for SCBC treated with RC (30.4 vs 109.7 months, p = .001; 13.1 vs 86.1 months, p = .002). On multivariable analysis among pts treated with RC, SCBC was significantly associated with shorter OS adjusting for pT and pN stage, performance status, and age. Conclusions: Pts with SCBC undergoing RC had significantly worse oncologic outcomes compared to pts with CUC, however RC and CCRT had comparable outcomes in pts with SCBC. The pCR rate to NAC was unexpectedly low. Larger sample size, assessment of other confounders and longer follow-up are needed for validation.
Associations between baseline body composition and cancer-specific mortality following neoadjuvant chemotherapy and radical cystectomy for bladder cancer.
Authors: Diamantopoulos Leonidas Nikolaos , Ngo Steven , Maldonado Reno , O'Malley Ryan Blair , Laidlaw Grace , Fintelmann Florian J. , Holt Sarah K , Gore John L. , Schade George R. , Lin Daniel W. , Grivas Petros , Montgomery Robert B. , Hsieh Andrew Caleb , Cheng Heather H. , Yezefski Todd , Schweizer Michael Thomas , Yu Evan Y. , Wright Jonathan L. , Psutka Sarah P. 
Published: May 2020

e17015 Background: Sarcopenia is a modifiable risk factor independently associated with cancer-specific mortality (CSM) in bladder cancer (BC). Sarcopenic obesity, where obesity is measured by fat mass index [FMI, total body fat (kg)/height(m)2], has been proposed as an additive insult. To date, studies have overwhelmingly been performed in patients treated without neoadjuvant chemotherapy (NAC). Herein, we evaluate associations between baseline skeletal muscle index (SMI), FMI, and CSM in patients treated with NAC and radical cystectomy (RC). Methods: Lumbar SMI (cross sectional area of skeletal muscle/height2, cm2/m2) was measured on a computed tomography (CT) image at the level of the third lumbar vertebral body, within 60 days prior to NAC. Total body FMI was calculated from visceral and subcutaneous fat cross-sectional areas. Patients were classified as being sarcopenic, according to sex-specific consensus definitions: Male: SMI < 55, Female: SMI < 39, and as obese if Male: FMI > 9, Female: > 13. Cancer-specific survival (CSS) was estimated using the Kaplan Meier method. Associations with CSM were summarized with multivariable Cox proportional hazards models. Results: 143 patients had CT scans of sufficient quality (2005-18). There were no significant differences in clinicopathologic characteristics between the study cohort and patients without available imaging (N = 261). Cisplatin-based NAC was given to 125 patients (87%), and 18 (13%) received other regimens. In total, 86 (60%) patients were sarcopenic, 52 (36%) obese, and 25 (17%) both sarcopenic and obese, while 48 (34%) were sarcopenic with normal FMI. Median follow-up was 2.7 years (IQR 1.2-6.2), and 43 patients died from BC. Three-year CSS was 61% (sarcopenic) vs. 77% (p < 0.05). Sarcopenic patients with normal FMI had the worst 3-year CSS (55%) compared to those with sarcopenia and FMI-obesity (79%), normal SMI with FMI-obesity (69%), and normal body composition (88%, p = 0.03). On multivariable analysis, neither FMI (HR: 0.77, 95% CI: 0.47-1.3, p = 0.3) nor SMI was independently associated with CSM (HR: 0.98, 95% CI: 0.96-1, p = 0.07) after adjustment for ASA score, pathologic tumor, and nodal stage. Conclusions: In patients treated with NAC+RC, pretreatment SMI trended towards independently predicting risk of CSM. Patients with sarcopenia and normal fat demonstrated the worst CSS. Further study is warranted on the impact of NAC on body composition and the role of the latter in risk stratification of this high-risk patient population.
Immune-related adverse events (irAEs) among urothelial carcinoma (UC) patients treated with PD-1 VS PD-L1 inhibitors: A real-world observational study.
Authors: George Saby , Bell Elizabeth , Engel-Nitz Nicole , White John C , Lal Lincy S. , Liu Frank Xiaoqing , Kim Ruth , Krulewicz Stan , Kasturi Vijay , Zheng Ying 
Published: May 2020

e17017 Background: Anti-PD-1/PD-L1 agents are US FDA-approved for patients with advanced or metastatic UC, but limited information exists on real world irAEs among this patient population. We examined the rates and time to onset of select irAEs in UC patients receiving PD-L1s vs PD-1s in the real world. Methods: This observational study included US commercial and Medicare Advantage health plan members from Optum Research Database with UC and treated with a PD-1 or PD-L1 agent between 01-Sep-14 and 30-Apr-19. Baseline characteristics were assessed ≤ 6-months prior to the first claim for anti-PD-1/PD-L1. 21 irAEs were chosen a priori based on the ASCO clinical guideline on irAE management, clinical input, frequency, and cost of treatment. Patients were followed for newly occurring irAEs, based on claims ICD codes, during the PD-1/PD-L1 therapy and up to 180 days after if no new treatment, study period end, death, or disenrollment. Kaplan-Meier method was utilized to calculate time to onset of irAEs. Results: The study included 240 patients receiving PD-L1s and 317 receiving PD-1s. Baseline demographics were similar (Table). The most common irAEs were 1) thyroid disorders, 2) impaired ventricular function with heart failure and vasculitis, 3) rash, and 4) nephritis. UC patients receiving PD-L1s had a lower rate of irAEs vs PD-1s, mainly driven by lower rates of hematologic and endocrine toxicities (Table). UC patients receiving a PD-L1 also had longer time to irAE onset (p-value = 0.05). Conclusions: UC patients receiving PD-L1s had a lower incidence rate of irAEs and longer time to irAE onset than patients on PD-1s. Findings suggest patients receiving PD-1s may require more intense monitoring for irAEs than patients taking PD-L1s. [Table: see text]
Marker of lipid peroxidation TBARS predicts survival in patients with metastaticurothelial carcinoma (MUC).
Authors: Slopovsky Jan , Kucharska Jarmila , Obertova Jana , Mego Michal , Kalavska Katarina , Gvozdjakova Anna , Palacka Patrik 
Published: May 2020

e17023 Background: Oxidative stress plays a significant role in cancer development and progression. A marker of lipid peroxidation TBARS is upregulated in various diseases. The objective of this prospective study was to explore predictive and prognostic values of TBARS in MUC patients (pts.) before the first-line platinum-based chemotherapy. Methods: Seventy-two consecutive pts. (57 men) with MUC (58 bladder, 14 upper GU tract) were enrolled into this study. Performance status ECOG ≥ 2 had 11 pts., visceral metastases were present in 34 pts. Most common type of treatment regimen was gemcitabine and cisplatin (65 pts.), gemcitabine and carboplatin received 7 pts. Based upon TBARS mean of 6,06 μmol/L, pts. were dichotomized into low and high groups. Progression-free survival (PFS), overall survival (OS) and their 95% CI were estimated by Kaplan-Meier method and compared with log-rank test. Results: At median follow-up of 9.6 months, 65 pts. experienced progression and 64 pts. died. Pts. with low TBARS had significantly better survival opposed to pts. with high TBARS (HR 0.44, 95% CI 0.27-0.74; P = 0,0009 for OS and HR 0.51; 95% CI 0.31-0.84; P = 0,006 for PFS, respectively). Pts. with ECOG ≤ 1 had significantly better both, OS and PFS in comparison to pts. with ECOG > 2. Conclusions: In this study, high plasma TBARS levels in patients with MUC before chemotherapy initiation were associated with poor survival. Therefore, this biomarker could be used for identification of patients with worse prognosis and could lead to better patient stratification and treatment decision making. The study was supported by VEGA 1/0614/12. Key Words: Metastatic Urothelial Carcinoma. Platinum-Based Chemotherapy. Lipid Peroxidation. TBARS. Survival.
Effect of epigenetic imprinting biomarkers in urine exfoliated cells (UEC) on the diagnostic accuracy of low-grade bladder cancer.
Authors: Zhou Ning , Cheng Tong , Li Xing , Pineda John P. , Shen Rulong , Wang Xiaonan , Si Han , Shi Panying , Zeng Shuxiong , Xu Chuanliang 
Published: May 2020

e17027 Background: Urine Exfoliated Cells (UEC) is the most widely used sample for noninvasive bladder cancer detection. However, current UEC-based methods including urinary cytology and other molecular detections showed low sensitivities especially for low-grade cancer (< 50% sensitivity). Epigenetic alterations such as elevated allelic expression of imprinted genes usually occur at early stages of malignancy, and can be considered as potential bladder cancer biomarkers. In this study, Quantitative Chromogenic Imprinting Gene In-Situ Hybridization (QCIGISH) was conducted to analyze the biallelic expression (BAE) and multiallelic expression (MAE) in UEC, and develop a more accurate method for early stage bladder cancer. Methods: 53 patients with urinary system diseases including 13 low-grade bladder cancer, 24 high-grade bladder cancer and 16 benign lesions, as well as 28 healthy volunteers were recruited in clinical trial NCT03563443 for validation. The total expression (TE), BAE and MAE of imprinted genes GNAS, PEG10, GRB10, SNRPN and HM13 were blindly detected by QCIGISH. The severity of malignancy was predicted by a grading model previously established on 229 tissue FFPE and cystoscopic biopsy samples, and subsequently validated with the pathology and clinical diagnosis results. Results: The QCIGISH method achieved 84.6% and 95.8% sensitivities for low- and high-grade bladder cancers, respectively, with an equally high specificity of 97.7%. The sensitivity of QCIGISH for low-grade bladder cancer is much higher than standard urinary cytology (16%), and FDA-approved molecular tests such as Hemoglobin Dipstick (38%), BTA Stat (36%), NMP22 BladderChek (25%), and ImmunoCyt (47%). Conclusions: The high accuracy of QCIGISH especially for low-grade bladder cancer demonstrated its great potential in becoming an important and powerful clinical tool for noninvasive diagnosis and large-scale screening for early bladder cancer.
Establishment of a primary cell culture of bone metastasis from urothelial carcinoma.
Authors: Spadazzi Chiara , Cocchi Claudia , Casadei Roberto , Brandolini Francesca , Pieri Federica , Bongiovanni Alberto , Recine Federica , Liverani Chiara , De Vita Alessandro , Miserocchi Giacomo , Calpona Sebastiano , Debonis Silvia Angela , Ibrahim Toni , Mercatali Laura 
Published: May 2020

e17030 Background: Urothelial carcinoma (UC) accounts for 90% of cases of bladder cancer. In advanced UC diagnosis, skeletal involvement is frequent. Here we report the establishment of a primary culture of bone metastasis (BM) from High Grade UC derived from 81 years-old patient with a previous diagnosis of papillary urothelial cancer in 2016. After 2 years, patient relapsed to bone and visceral sites and because of poor clinical condition, patient underwent palliative best supportive care. Methods: Patient-derived bone metastatic cell culture was obtained from a surgical specimen. Tumor cells were isolated by collagenase digestion. Cells were seeded on in vitro 2D plates or into 3D collagen scaffolds composed of bovine collagen type I. The establishment of tumor cell isolation was confirmed through the evaluation of cytomorphologic features and positive pan-citokeratin staining. Then, drug treatments was performed and cell survival was evaluated. The study was approved by Ethical Committee and patient signed an informed consent. Results: After a long-term culture, we were able to isolate from a 3D scaffold a tumor clone that successfully growth until passage 20. Stabilized cells generate spheroid-like aggregates, recreating acinar-structures typical of the primary papillary urothelial tumor. Next, we treated cells with: Gemcitabine (Gem), Carboplatin (Carbo), Docetaxel, Carbo+Gem and Bone targeted drugs (Zoledronic Acid and Denosumab). The most effective treatment was Gem+Carbo, in particular 24% of survival in 2D platform and 87% on 3D collagen scaffold. For all treatments, cells cultured on 3D scaffold were more resistant to drugs, mimicking more closely the in-vivo condition. Conclusions: We were able to isolate and establish a BM primary culture from UC using a 3D in-vitro collagen scaffold. This system can recreate microenvironmental conditions more similar to in-vivo ones and it promoted the isolation of tumor cell clones from stromal components of the heterogeneous primary culture. This cell line could be useful to investigate the molecular and genetic profile in order to identify promising molecular targets and to better understard the natural history of BM from UC.
Long-term outcomes among BCG-treated high-risk non-muscle invasive bladder cancer patients in an equal access setting.
Authors: Williams Stephen B. , Howard Lauren , Foster Meagan , Klaassen Zachary William Abraham , Sieluk Jan , Li Haojie , Imai Kentaro , Sbar Eric , De Hoedt Amanda M. , Freedland Stephen J. 
Published: May 2020

e17031 Background: Management of high-risk non-muscle invasive bladder cancer (HR NMIBC) represents a clinical challenge due to high failure rates despite prior bacillus Calmette-Guérin (BCG) therapy. We describe real-world patient characteristics, long-term outcomes, as well as the economic burden in the HR NMIBC population. Methods: We identified a random sample of 412 HR NMIBC patients who received ≥ 1 dose of BCG within Veterans Affairs (VA) centers across the United States from January 1, 2000, to December 31, 2016. HR NMIBC was defined as high-grade Ta (TaHG), T1, and/or carcinoma-in-situ (CIS). We analyzed the number of BCG instillations received, as well as used the Kaplan-Meier method to estimate event-free survival for cystectomy and bladder cancer-specific death. All-cause expenditures were summarized as medians with corresponding interquartile ranges (IQR) and adjusted to 2019 USD. Results: The median (IQR) age at diagnosis was 67 years (61-74), with most patients being white (84%) and male (81%). At HR NMIBC diagnosis, 69 (17%) patients had CIS +/- T1 or TaHG, and 341 (83%) had TaHG or T1, no CIS. The vast majority of patients [n = 363, (90%)] received six BCG instillations (range: 1-7) within 365 days of the first dose. The total follow-up was 2,694 person-years. From BCG initiation to end of follow-up, the median all-cause expenditures per patient were $358,593 (257,699 – 652,853). Conclusions: In this equal access setting, the vast majority of HR NMIBC patients received 6 instillations of BCG within 1 year, although the interval over which the instillations were given varied among patients. Patients with CIS appeared to have a worse prognosis, as 24% underwent cystectomy, and 13% died of bladder cancer at 10 years of follow-up. These findings also highlight the considerable economic burden of HR NMIBC. [Table: see text]