bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer-related fatigue in carcinoma urinary bladder patients receiving chemotherapy: A single institutional study from northern India.
Authors: Talwar Vineet , Goel Varun , DASH Prasanta 
Published: March 2019

361 Background: Fatigue is one of the most disabling phenomenon among patients receiving anti cancer treatment, which has profound effect on their Quality of life (QOL). Although clinicians across the globe acknowledge the importance of regular assessment of fatigue, however it is seldom being assessed and documented in clinical practice in India and very few studies have reported Cancer Related Fatigue among Indian population. Methods: For this study an exploratory design was adopted, using a purposive sampling method. Patients (N=206,) undergoing chemotherapy at Rajiv Gandhi Cancer Hospital and Research Center, Delhi, India; aged 18-83 years were included. The level of fatigue was assessed using 16- item Multidimensional assessment of Fatigue (MAF) scale and a semi structured in depth interview schedule. These interviews were recorded, transcribed and analyzed. Results: Irrespective of age, and education, 81% patients experience clinically significant fatigue. Extreme level of fatigue was reported by 29% patients requiring immediate clinical intervention while 52% patients reported moderate level of clinically significant fatigue. Top four psychosocial issues reported were: apprehension of CT side effects (23.5%), fear of pain (19%), Loss of appetite (17.5%) and anxiety during CT (13.5 %), followed by financial issues (11%). Among all patients, (49.5%) were aware of their diagnosis of which 8% were either fully aware or partially aware about the prognosis (23%). Conclusions: Fatigue remains one of the most important clinical parameters among majority of Carcinoma Urinary Bladder patients receiving chemotherapy, and is neither assessed by clinicians nor reported by majority of the patients. While almost one fourth of the patients report fear of chemotherapy as their pressing psychosocial concern, others report fear of pain, loss of appetite, manifest anxiety symptoms or report financial and logistics issue during CT. Various exercise, educational material and psychotherapeutic interventions should be developed to prepare and support them during their treatment for better preparedness of side effects and their management, reduced symptoms and better quality of life.
Decreasing ureteral stent duration following radical cystectomy decreases readmissions and urinary infectious complications.
Authors: Beano Hamza Mustafa , He Jiaxian , Hensel Caitlin , Worrilow William Mills , Gaston Kris E , Clark Peter E , Riggs Stephen Boyd 
Published: March 2019

366 Background: Readmission following Radical Cystectomy with Urinary Diversion (RCUD) is often related to Urinary Tract Infection (UTI). We hypothesized that decreasing the duration of ureteral stenting postoperatively would decrease UTI-related complications without affecting ureteroenteric stenosis (UES) rates. Methods: We analyzed a prospectively and retrospectively collected dataset for cystectomy patients at our tertiary center. Adult patient who underwent RCUD for malignancy from January 2013-January 2018 were included. Patients with a history of abdominal/pelvic radiation and continent diversions were excluded. The patient population was divided to Late stent removal group (LSR- POD 14) and early stent removal group (ESR- POD 4). Statistical methods included t-test, chi-square test and multivariate logistic regression. Results: 177 patients were included in the final analysis after inclusion/exclusion criteria were applied. The LSR (n=75) and ESR (n=102) groups were similar in preoperative characteristics except higher intracorporeal ileal conduit formation in ESR. The LSR had higher 90-day overall readmission rates (OR=2.26, 95% CI;1.13,4.51, p-value=0.021), UTI-related readmissions (OR=3.05, 95% CI:1.32,7.04, p-value=0.010) and UAE (OR=3.02, 95%CI;1.47,6.18, p-value=0.003). Conclusions: Shorter ureteral stent duration following RCUD is associated with decreased readmissions and urinary infections complications without concurrent increase in UES. Strong consideration should be directed towards early stent removal. [Table: see text]
Hyperprogressive disease (HPD) in genitourinary (GU) cancer patients treated with PD-1/PD-L1 inhibitors.
Authors: Hwang Inhwan , Park Inkeun , Yoon Shin-Kyo , Lee Jae-Lyun 
Published: March 2019

369 Background: Post immunotherapy response and disease progression pattern are still under investigation. In terms of progression, rapid progression pattern called HPD has been observed during the early cycles of PD-1/PD-L1 inhibitors therapy in patients with various cancers. Data of HPD in patients with GU cancer are limited. Methods: This study included 203 patients with GU cancer treated with PD-1/PD-L1 inhibitors between February 2015 and June 2018. HPD was defined as greater than 50% increase in tumor burden compared with before-treatment computed tomography (CT) scan and greater than 2-fold increase in tumor growth rate (TGR) compared with previous TGR. Development of extensive new lesions were also regarded as HPD. Response was evaluated by RECIST v1.1 on at least two consecutive CT scan before the initiation of PD-1/PD-L1 inhibitors and one CT scan within 2 months after initiation of PD-1/PD-L1 inhibitors. Results: 102 patients with renal cell carcinoma (RCC) and 101 patients with urothelial cell carcinoma (UCC) were included. Median age was 64 years (range 56-71) and 141 patients (70%) were male. The most common metastatic site was lymph node (66%), followed by lung (51%) and bone (34%). HPD was observed in 13 out of 230 patients (5.7%; 95% CI, 5.0-6.3). Median OS for patients with progressive disease and HPD were 7.3 months and 3.5 months, respectively ( p=0.09). HPD was more frequently found in patients with UCC than RCC (11% vs. 0.9%, p=0.01). In multivariate analysis, patients of UCC ( p <0.001), presence of liver metastasis ( p=0.002), elevated LDH level (> upper normal limit, p=0.01), and hypoalbumimemia (< 3.5 gm/dL, p<0.001) were independent predictive factors for HPD. Conclusions: The incidence of HPD in GU cancer patients seems to be low compared to previous studies (9-10%). The majority of HPD developed in UCC and the incidence in RCC is negligible. Cares should be taken when treating patients with PD-1/PD-L1 inhibitors, especially when patients have UCC and liver metastases, elevated LDH and hypoalbuminemia.
Distinct genomic hallmarks exist between metastatic upper and lower tract urothelial carcinoma.
Authors: Winters Brian , De Sarkar Navonil , Arora Sonali , Bolouri Hamid , Vakar-Lopez, MD Funda , Cheng Heather H. , Yu Evan Y. , Kollath Lori , Grivas Petros , McFerrin Lisa , Montgomery Robert B. , Wright Jonathan , Lam Hung-Ming , Hsieh Andrew Caleb 
Published: March 2019

371 Background: Although the genomic landscape of LTUC is well studied, less is known about UTUC, including in the metastatic sites. We compared genomic features of metastatic UTUC and LTUC. Methods: We performed whole exome sequencing on 7 rapid autopsy patients with metastatic UC, with matched primary and metastatic tumor samples (N = 37). Single nucleotide variants (SNV) were identified using Mutect and Strelka. Focused analyses were performed on mutations with known significance in UC as well as mutations predicted to have functional impact using 11 mutation assessors. Genome scale copy number aberrations (CNA) were estimated using Sequenza (normalized for ploidy) to derive gene definition restricted copy number estimation outcomes. Multi-dimensional scaling (MDS) was used to visualize how copy number and mutation-derived genomic distances differed between LTUC and UTUC. Results: Three pts with UTUC (3 primary samples, 13 metastases) and four pts with LTUC (4 primary samples, 17 metastases) were examined. The majority of patients were male (5) and received cisplatin-based therapy (5). We found that SNV burden (mean mutation per megabase) was significantly higher in LTUC vs. UTUC overall (6.6 vs. 3.8, p = 0.001) and when stratified by primaries (6.1 vs. 2.9, p = 0.047); or metastases (6.7 vs. 4.1, p = 0.001). Mutational signature analysis revealed higher proportion of APOBEC signature in all LTUC vs. UTUC tumors. Both inter- and intra-individual genomic distances between primary and metastatic tissues were substantially larger in UTUC than LTUC, suggesting a wider spectrum of mutations at the level of individual nucleotides and chromosomal structure. Interestingly, Gene definition-restricted CNA analysis revealed MDM2 amplification exclusively in UTUC tumors which was associated with shallow p53 deletion. Conclusions: Metastatic UTUC appears to have a lower overall mutational burden but greater genomic variability compared to LTUC. Our relatively small dataset suggests that metastatic UTUC displays a greater spectrum of mutational divergence from LTUC which may partially explain differences in clinical behavior.
Risk for vascular thromboembolic events (VaTEs) in patients (pts) with advanced urinary tract cancer (aUTC) treated with chemotherapy.
Authors: Bamias Aristotelis , Tsironis George , Dimitriadis Ioannis , Tzanis Kimon , Tsiara Anna , Xirokosta Aikaterini , Kaparelou Maria , Kyriazoglou Anastasios , Cohen Abis , Barbarousi Despoina , Koutsoukos Konstantinos , Liontos Michael , Zakopoulou Roubini , Kostouros Euthymios , Pagoni Stamatina , Matsouka Charis , Dimopoulos Meletios A. 
Published: March 2019

383 Background: Venous thromboembolism (VTE) is a frequent complication of cancer or its treatment. Khorana (KRS) and Compass scores are two Risk Assessment Models for VTE. However, aUTC was not adequately represented and arterial events were not included, in these models. Methods: Data from pts with aUTC treated with at least one line of chemotherapy in our institution were analyzed. VaTE definition included: DVT and PE defined as venous events and peripheral arterial thrombosis or embolus, ischemic stroke and coronary events, grouped as arterial events. The association of baseline and treatment-related factors with the development of VaTE was assessed using competing-risk regressions. According to the results of our multivariate analysis we stratified patients according to the number of the identified risk factors. Results: 354 aUTC pts treated between 4/1995 and 9/2015 entered our study. 53% of pts had received cisplatin and 42% carboplatin-based regimens. 44 pts (12.4%) suffered 45 VaTEs (13 arterial, 32 venous) within a median time of 3.3 months. The cumulative and 6-month incidence was 14.8% (95% CI: 10.9-19.4) and 9.7% (95% CI: 6.8-13.1), [venous 10.5% (95% CI: 7.3-14.3)/7.5% (95% CI: 5-10.7); arterial 5.3% (95% CI: 2.8-9)/2.7% (95% CI: 1.3-5), respectively]. No association of the KRS and the COMPASS score with the incidence of VaTEs was observed. In the univariate and multivariate analysis, cumulative VaTE incidence was significantly increased in pts with “peripheral arterial disease (PAD) or history of VΤE” (adjusted SHR: 3.29; 95% CI: 1.65-6.55; p=0.001) and pts with other solid tumor (SHR: 2.20; 95% CI: 1.05-4.62; p=0.038). There was a strong correlation between the number of risk factors and the risk for VaTE development (p<0.001). Patients with 1 or 2, vs 0 factors had a 3-fold increased risk [cumulative incidence was 10.9% (95% CI: 7.4.-15.2) and 30.2% (95% CI: 18.4-42.8), respectively; SHR: 3.01 95% CI: 1.65-5.51]. Conclusions: Development of tumor-specific algorithms for the risk of vascular events is supported by our results. Pts with aUTC and a history of VTE, PAD and other solid tumor have a very high risk for VaTE. The role of prophylaxis should be prospectively studied.
Long-term follow-up after radiotherapy for prostate cancer with and without rectal hydrogel spacer: A pooled prospective evaluation of quality of life.
Authors: Seymour Zachary A , Daignault Stephanie , Bosch Walter , Gay Hiram Alberto , Michalski Jeff M. , Hamstra Daniel A. , Pinkawa Michael 
Published: March 2019

39 Background: Hydrogel spacers are a tool to improve dosimetry and overall quality of life with limited follow-up in men receiving radiotherapy for prostate cancer. This present study is a pooled analysis of a prospective cohorts with long-term follow-up quality of life (QOL) data with or without hydrogel spacers to minimize dose adjacent organs at risk. Methods: QOL was examined using the Expanded Prostate Cancer Index Composite (EPIC) to compare mean changes from baseline. A total of 215 patients from a randomized multi-institutional trial of radiation with or without hydrogel spacer with a QOL end-point were pooled with 165 non-randomized patients from a single institution with prospective QOL collection in both patients with or without hydrogel spacer. The proportions of men with minimally important differences (MIDs) relative to pre-treatment baseline in each domain were tested using repeated measures logistic models with pre-specified thresholds for clinically significant decline. Results: A total of 380 men were evaluated (64% with spacer and 36% without) with QOL data being available for 199 men beyond 24 months of follow-up (median: 39.5 months, range: 31-71.4 mo). Treatment with spacer was associated with less decline in average long-term bowel QOL (89.4 for control and 94.7 for experimental) with differences at > 2 years meeting the threshold of MID difference between cohorts (Bowel Score Difference from baseline: control = -5.1 spacer = 0.3 Diff = -5.4 p = 0.0003). When evaluated over time men without spacer were more likely to have 1xMID (5 points) declines in bowel QOL (p = 0.01). At long-term follow-up 1xMID was 36% without spacer vs 14% with spacer (p = 0.0006 OR = 3.5) while 2x MID was seen in 19% vs 6% (p = 0.008 OR = 3.6). The use of spacer was associated with improved bowel frequency (p = 0.002), reduced bleeding (p = 0.005) and less overall bowel problems (p = 0.007). Conclusions: In this pooled analysis of QOL after prostate radiotherapy with up to 5-years of follow-up utilization of a hydrogel spacer was associated with preservation of bowel QOL. This QOL benefit was preserved with long-term follow-up.
Real-world trends in first-line checkpoint inhibitor use (CPI) in advanced urothelial cell carcinoma (aUC).
Authors: Parikh Ravi Bharat , Galsky Matt D. , Baxi Shrujal S. , Adamson Blythe J.S. , Cohen Aaron Benjamin , Feld Emily , Christodouleas John Paul , Boursi Shimon Ben , Meropol Neal J. , Mamtani Ronac 
Published: March 2019

392 Background: Standard first-line treatment of aUC is cisplatin-based chemotherapy, with carboplatin-based chemotherapy or CPI reserved for cisplatin-ineligible individuals. However, given their favorable toxicity profile, there may be an indication drift of first-line CPI into cisplatin-eligible patients, despite no approved indication in this population. Methods: Using the Flatiron Health Database, a nationally representative electronic medical record-based dataset, we examined real-world prescribing patterns of first-line systemic therapies among 2090 patients with aUC diagnosed between the first quarter (q) of 2015 and 2018q1. Our analysis of cisplatin-eligible individuals excluded patients with pre-treatment (1) Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2, (2) creatinine ≥ 1.5 mg/dL, or (3) diagnostic codes for chronic renal failure, congestive heart failure, hearing loss, or peripheral neuropathy. We used nonparametric tests of trend to describe first-line CPI and chemotherapy use over time. Results: Between 2015 and 2018, the quarterly proportion of patients who received first-line CPI increased from 1.4% to 43%, while the proportion who received platinum-based chemotherapy decreased from 89% to 56% (ptrend< 0.001) Similarly, among cisplatin-eligible patients (n = 1181), the proportion of first-line CPI users increased from 1.0% in 2015q4 to 42% in 2018q1 (ptrend= 0.001), while the proportion of first-line cisplatin users fell from 53% in 2015q4 to 33% in 2018q1 (ptrend= 0.018). First-line CPI initiators were older (median age 76 vs 71) and had worse performance status (PS ≥ 2 17.8% vs 11.4%) relative to platinum initiators (Table). Conclusions: Our analysis suggests a dramatic rise in first-line CPI use, even in patients who may be cisplatin-eligible, for whom first-line CPI is not evidence-based. [Table: see text]
Identification of novel targets in non-muscle invasive bladder cancer: A systems biology approach.
Authors: Osterhout Robin , Kamal Adeela , Spigelman Samuel 
Published: March 2019

396 Background: Most bladder cancers are diagnosed as non-muscle invasive bladder cancer (NMIBC). Because of the high rate of recurrence and limited treatment options for recurrent disease, there is an urgent need to identify new treatment options. In this study, a network-based drug discovery approach was applied to identify novel targets in NMIBC. Methods: A computational systems-biology framework integrating genomic, transcriptomic, protein-protein, and protein-drug interactions was applied to identify and prioritize potential NMIBC targets and pathways. First, a NMIBC disease network module was constructed from genetic associations augmented with known protein-protein interactions. Independent NMIBC case/control expression data sets were leveraged to develop a phenotypic network module comprising genes differentially expressed in NMIBC. Proteins and pathways linking the disease model with the phenotypic module were identified, ranked, and benchmarked against known NMIBC pathways and drug targets from the literature. Results: NMIBC seed genes cluster significantly within the human interactome, reflecting an underlying disease module. The expanded disease module comprises 103 genes that show functional and literature-based enrichment. Genes differentially expressed in NMIBC were significantly connected to disease module genes compared with random expectation (z = 23.3), and are enriched in several biologically relevant pathways. Based on similarity to disease biology and network topology, 11 NMIBC pathways were identified as bridging genetic predisposition for and phenotypic expression of NMIBC. Within these overlapping pathways, known and novel drug targets were identified. Of these in silico targets, 19 are currently under development for treatment of bladder cancer, validating the approach. To further validate the approach, we observed overlap between in silico targets and hits from a chemogenomic library phenotypic screen. Conclusions: A network-driven systems biology approach identified both known NMIBC targets and novel proteins/pathways that are potential targets for the treatment of NMIBC. Further target validation is required.
Non-urothelial bladder cancer: Genomic alterations and patient outcomes.
Authors: Anari Fern , Miron Benjamin , Henson Donald , Arguello David , Plimack Elizabeth R. , Zibelman Matthew R. , Ramamurthy Chethan , Ghatalia Pooja , Heath Elisabeth I. , Burgess Earle Frederick , Dawson Nancy Ann , Vaena Daniel A. , Somer Bradley G. , Hogan Thomas F. , Hauke Ralph J. , Aragon-Ching Jeanny B. , Geynisman Daniel M. 
Published: March 2019

399 Background: Adenocarcinoma (ADA) and squamous cell carcinoma (SCC) are rare, aggressive subtypes of bladder cancer, for which no clear standard of care exists. We report on survival of pts with ADA and SCC and identify potential therapeutic targets using molecular profiling via next generation sequencing (NGS). Methods: Survival trends, demographics, pt characteristics were obtained from the Surveillance, Epidemiology, and End Results (SEER) Database. In a separate cohort, NGS results from 72 specimens (50% metastatic) were also analyzed, using either a hotspot 47 gene panel or a 592 gene assay (Caris Life Sciences, Phoenix, AZ). Results: In SEER, 235,537 cases of bladder cancer were extracted from 1988-2008, of which 3096 were SCC and 671 were ADA. 90% of pts were white, although more African-American patients (15%) were seen in those with ADA. Among all stages, median overall survival (mOS) and 5-yr survival rates were 17.9 mos and 58% for ADA and 15 mos and 37% for SCC. Via NGS testing, 43 patients (28 ADA, 15 SCC) were tested with a 47 gene panel and 29 (21 ADA, 8 SCC) with a 592 gene panel. In the 47 gene panel, among ADA pts, the highest mutation rates were TP53 (57.1%), KRAS (21.4%), SMAD4 (14.8%), PIK3CA (10.7%) and BRCA2 (7.7%). Among SCC pts, the highest mutation rates were TP53 (66.7%), PIK3CA (33.3%), HRAS (14.3%), FBXW7 (6.7%) and AKT1 (6.7%). In the 592 gene assay, the genes with the highest mutation rates in pts with ADA were TP53 (81%), SMAD4 (33.3%), KRAS (23.8%), KMT2C (11.8%), ARID1A (11.1%), BRAF (9.5%), CTNNB1 (9.5%), KMT2D (9.5%), TSC1 (9.5%), KDM6A (5.9%), CDKN2A (5%). Among SCC pts, the highest mutation rates were TP53 (75%), CDKN2A (42.9%), FGFR3 (25%), PIK3CA (25%), CIC (14.3%), KDM6A (14.3%), BRAF (12.5%), BRCA1 (12.5%), FH (12.5%), HRAS (12.5%) and KMT2D (12.5%). Only 1 pt had high TMB. Conclusions: Genomic profiling identifies differences in underlying tumor biology of bladder ADA and SCC, which on a population level are rare with poor survival. Overall, the alterations in the PIK3CA/ AKT/ mTOR and TP53 pathways are similar to what has been reported in UC. Future analyses of these malignancies should investigate the emerging actionable targets, such as TSC1, FGFR3, BRCA1/2 and BRAF.
Time to PSA nadir and the risk of death from prostate cancer following radiation and androgen deprivation therapy.
Authors: Pike Luke Roy George , Wu Jing , Chen Ming-Hui , Loffredo Marian , Renshaw Andrew A. , Pfail John , Kantoff Philip W. , D'Amico Anthony Victor 
Published: March 2019

4 Background: Whether the time to PSA nadir (TTN) has differential prognostic value in men who reach an undetectable versus detectable PSA nadir remains unknown. Methods: Two-hundred and four men from a prospective randomized controlled trial (RCT) involving radiation therapy with or without 6 months of androgen deprivation therapy (ADT) in unfavorable risk CaP at academic or community based centers in Massachusetts, enrolled between 1995 and 2001. Adjusted hazard ratios (AHR) of the risk of CaP-specific mortality (PCSM) calculated using Fine and Gray competing risk regression. Results: After a median follow-up of 18.17 years, 160 men died; 30 (18.75%) of CaP. Amongst men with a PSA nadir ≥ 0.2 ng/ml, a TTN < median (12 months) was significantly associated with an increased PCSM-risk versus the median or more (AHR 5.07, 95% CI 2.10-12.23, p<0.001); whereas this association was not observed among men with a PSA nadir of <0.2 ng/ml, (AHR 9.9, 95% CI 0.23-433.8, p=0.23). Conclusions: Men with both a short TTN and detectable PSA nadir could be considered for entry on RCTs at a novel entry point prior to PSA failure at the time of PSA nadir to complete planned conventional ADT versus that plus agent(s) shown to improve outcomes in men with or at high risk of having castrate-resistant CaP.