bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical impact of gemcitabine mono-maintenance versus best supportive care after first-line gemcitabine with platinum in patients with metastatic urothelial carcinoma.
Authors: Lee Seung-Hwan , Ha U-Syn , Hong Sung-Hoo , Lee Ji Youl , Kim In-Ho 
Published: March 2019

404 Background: To evaluate the clinical impact of gemcitabine (GEM) monotherapy after 1st line GEM with platinum in patients with metastatic urothelial carcinoma. Methods: We retrospectively reviewed the medical records of 113 patients who showed with radiological response or stabilization after 4-6 cycles of GEM with platinum.61 patients received maintenance of GEM-mono (GEM group) as 1000 mg/m2 on day 1 and 8 every three weeks until progression or development of unacceptable toxicity. And 52 patients received best supportive care (BSC) with regular radiologic evaluation (BSC group). Progression free survival (PFS) and overall survival (OS) from start date of GEM-mono or BSC was examined. Results: After a median follow-up of all population of 8.21 months, 43 (70%) patients had progressed and 32 (52%) died in the GEM-mono arm, compared to 45 (86%) and 39 (76%) in the BSC arm, respectively. Maintenance of GEM-mono was for a median 6 cycles (2-19). Median PFS was 7–12 months (range 1.5-13.0) in the GEM-mono arm and 4–8 months (range 1.4-8.6) in the BSC arm (Hazard Ratio 0.580, 95%CI 0.38-0.95, p=0.032). Most common grade 3/4 adverse events in the GEM arm were neutropenia (n=11; 18%) and fatigue (n=13; 21%). After progression, 42 (68%) patients received treatment at the GEM and 30 (58%) at the BSC arm. Conclusions: Our data suggest that maintenance of GEM-mono therapy in patients who responded to 1st line GEM with platinum provides a significant prolongation of PFS, and with a manageable toxicity profile.
Digital holography can differentiate between bladder cancer grades.
Authors: Haifler Miki , Yogev Almog , Goldstein Ofer , Zisman Amnon , Shaked Natan T 
Published: March 2019

413 Background: Treatment of high grade non-muscle invasive bladder cancer (HG NMIBC) is controversial with BCG instillation and early cystectomy as viable options. However, accurate predictive markers for HG NMIBC are lacking. Refractive index (RI) is an optical feature of tissues and has been shown to be correlated with various oncologic outcomes in prostate and breast cancers. The role of RI in NMIBC has not been explored yet. The aim of this study is to measure and compare RI values of benign and malignant low and high grade NMIBC. Methods: After IRB approval, tissue samples were obtained from high and low grade NMIBC patients. Measurements were performed on non-stained slides using digital holography. Areas of benign and malignant tissues were marked by a fellowship trained GU pathologist. The average RI (RIavg) and RI variance (RIvar) over malignant and benign cell nuclei were measured. Comparison between benign and malignant tissue and between low and high grade tumors was performed with the Student's t-test. Results: Multiple nuclei of LG and HG patients were measured . Mean difference of RIavg between malignant and benign cells was 0.03 in HG patients (p < 0.001). Mean difference of RIvar between malignant and benign tissues was 0.016 in HG patients (p < 0.001). In LG tissues, there was no significant difference in RIavg or RIvar between benign and malignant cells. Finally, there was a significant difference in RIavg between HG and LG cells (p < 0.001). Conclusions: For the first time, RI was measured in bladder cancer tissue by digital holography. The RI values and variance were different between malignant and benign cells in HG tissues. Furtheremore, we found a significant difference in RI values between HG and LG cells. This technology may assist in the future in tissue diagnosis and classification of bladder tumor.
Clinical impact of Bacillus Calmette-Guérin (BCG) Therapy on prognosis in patients with carcinoma in situ (CIS) of the upper urinary tract: A retrospective comparison with nephroureterectomy.
Authors: Yoneyama Takahiro , Soma Osamu , Suzuki Yuuichiro , Yoneyama Tohru , Mori Kazuyuki , Yamamoto Hayato , Imai Atsushi , Hatakeyama Shingo , Hashimoto Yasuhiro , Ohyama Chikara 
Published: March 2019

417 Background: Clinical benefit of bacillus Calmette-Guérin (BCG) therapy for the management of upper urinary tract carcinoma in situ (CIS) remain unclear. We investigated safety and long-term oncological outcome of BCG therapy for upper urinary tract CIS compared with nephroureterectomy. Methods: We treated consecutive 490 patients with upper urinary tract carcinoma Aomori, Japan. We retrospectively reviewed the post-treatment course of 60 patients with CIS of the upper urinary tract who had undergone either a radical nephroureterectomy (RNU group) or BCG therapy (BCG group). Clinical effectiveness, safety, and oncological outcomes were compared between the groups. Multivariate Cox regression analysis via inverse propensity treatment weighted (IPTW) methods was performed to identify the impact of BCG therapy on prognosis. Results: The number of patients in RNU and BCG groups were 22 and 38, respectively. Median follow-up was 59 months in this cohort. There was no significant difference in background of patients including age, sex, performance status between the groups. The reason of selection for BCG therapy were bilateral CIS of upper urinary tract (50%), solitary kidney (26%), and others (24%). The cytology became negative in 30 (79%) patients after 6-week course of BCG. BGC related adverse events were observed 92% of patients. Most common events were cystitis (76%) followed by fever (50%). Two patients experienced grade 3 sepsis after BCG therapy. 13 patients (43%) experienced tumor recurrence after BCG therapy. There were no significant differences in recurrence-free survival, cancer-specific survival, and overall survival between the RNU and BCG groups. Multivariate analysis revealed BCG therapy did not worse the prognosis of those patients. Conclusions: Although mild adverse events were frequented in BCG therapy for CIS of the upper urinary tract, it might be a useful alterative in patients with CIS of the upper urinary tract who are ineligible for radical nephroureterectomy. Further prospective studies are needed to confirm the benefits of BCG therapy for CIS of the upper urinary tract.
Randomized phase I trial of pembrolizumab with neo-adjuvant versus concomitant stereotactic body radiotherapy in metastatic urothelial carcinoma: Clinical and translational results.
Authors: Vandekerkhove Gillian , Sundahl Nora , Decaestecker Karel , Meireson Annabel , De Visschere Pieter , Fonteyne Valerie , De Maeseneer Daan Joost , Reynders Dries , Goetghebeur Els , Van Dorpe Jo , Verbeke Sofie , Annala Matti , Brochez Lieve , Van der Eecken Kim , Wyatt Alexander William , Rottey Sylvie , Ost Piet 
Published: March 2019

422 Background: Preclinical data indicates that stereotactic body radiotherapy (SBRT) works synergistically with pembrolizumab, but the effect and potential toxicity might depend on the timing of SBRT. The current study assessed the safety of two different SBRT schedules in combination with pembrolizumab for metastatic urothelial carcinoma (mUC), and explored correlative biomarkers including circulating tumor DNA (ctDNA). Methods: An open-label phase 1 trial was conducted at Ghent University Hospital in patients with mUC to assess the dose-limiting toxicity (DLT) of the combination of pembrolizumab (200mg intravenously, 3-weekly) and SBRT (3x8Gy to the largest lesion). Patients were randomized (1:1) to receive SBRT either prior to the first (arm A) or the third (arm B) cycle of pembrolizumab. Blood was collected throughout the trial for biomarker analysis. Adverse events (AEs) were assessed according to the Common Terminology Criteria for Adverse Events version 4.0. Secondary endpoints included best overall response measured per Response Evaluation Criteria in Solid Tumors v1.1 (RECISTv1.1). The trial was approved by the Ethical Committee of Ghent University Hospital and is registered on ClinicalTrials.gov (NCT02826564). Funding was provided by Merck Sharp & Dohme. Results: Eighteen patients were randomized (nine to each arm) and started trial treatment. No DLT occurred. Treatment-related AEs grade 1-2 occurred in 6/9 and 9/9 patients in arm A and B respectively. One patient in arm B experienced lymphopenia grade 3, unrelated to SBRT. No treatment-related AEs grade 4-5 occurred. An objective response rate as per RECISTv1.1 of 0% and 44·4% was noted in arm A and B respectively. Targeted sequencing of tissue DNA and ctDNA revealed high genomic concordance. A decline in ctDNA was observed in responding patients. Conclusions: Neo-adjuvant and concomitant SBRT combined with pembrolizumab is safe, with potentially superior responses in the latter. ctDNA monitoring is feasible during disease evolution and suggests a shared driver gene status throughout disease progression. Clinical trial information: NCT02826564.
Predictive role of CT texture analysis in patients with metastatic urothelial cancer treated with PD-1/PD-L1 inhibitors.
Authors: Alessandrino Francesco , Gujrathi Rahul , Nassar Amin , Alzaghal Arwa , Ravi Arvind , McGregor Bradley Alexander , Sonpavde Guru , Shinagare Atul B. 
Published: March 2019

424 Background: Reliable biomarkers to predict response of urothelial cancer to PD-1/PD-L1 inhibitors are still being investigated. Texture analysis represents underlying tumor heterogeneity and may serve as a predictor of response in urothelial cancer. The purpose of this study was to assess predictive ability of CT texture analysis for disease progression in patients with metastatic urothelial cancer treated with PD-1/PD-L1 inhibitor. Methods: In this IRB-approved HIPAA-compliant retrospective study, from total 93 consecutive patients with metastatic urothelial cancer treated with PD-1/PD-L1 inhibitors from 2013-2018, 43 patients with measurable disease per RECIST 1.1 criteria who had contrast-enhanced CT performed within three months after starting treatment were included. Progression-free survival was calculated based on serial follow-up CTs, and 11 patients without progression who did not reach 1 year follow-up were excluded. Texture features of measurable lesions on first follow-up CT were extracted (TexRAD Ltd, Feedback Plc, Cambridge, UK). Stepwise logistic regression analysis to identify patients who had progressive disease (PD) at 12 months was performed and performance assessed using receiver operator curves. Results: Of 32 included patients (24 men, 8 women; median age: 65 years) who had total 80 measurable lesions, 22 progressed by 12 months. On first follow-up CT, the entropy and mean of the lesions were higher (p = 0.04, p = 0.02) for patients with PD by 12 months. Calculated specificity and sensitivity of entropy (AUC = 0.79) were 90%, and 63%; of mean (AUC = 0.81) were 90%, and 50%. A predictive model including mean and entropy yielded 95% sensitivity, 80% specificity, 91% PPV, 89% NPV and 91% accuracy (AUC = 0.863) to identify patients with PD at 12 months. Conclusions: Texture analysis of CT performed within three months after starting PD-1/PD-L1 can help predict patients who progress by 12 months with high accuracy. Further studies investigating the correlation of texture analysis with survival endpoints may help validate the role of texture analysis as a biomarker to predict response to PD1/PD-L1 inhibitors.
Avelumab treatment for metastatic urothelial carcinoma in the phase Ib JAVELIN Solid Tumor Study: Updated safety and efficacy analysis with ≥ two years of follow-up.
Authors: Apolo Andrea B. , Ellerton John Allan , Infante Jeffrey R. , Agrawal Manish , Gordon Michael S. , Aljumaily Raid , Britten Carolyn D. , Dirix Luc , Lee Keun-Wook , Taylor Matthew H. , Schoffski Patrick , Wang Ding , Ravaud Alain , Xiong Junyuan , Rosen Galit , Gulley James L. , Patel Manish R. 
Published: March 2019

425 Background: Avelumab, a human anti‒PD-L1 IgG1 antibody, is approved for the treatment of metastatic urothelial cancer (mUC) progressing after platinum chemotherapy in the US, Canada, and Israel. Here, we report an updated pooled analysis of 2 cohorts of avelumab-treated patients (pts) with mUC from the JAVELIN Solid Tumor study (NCT01772004). Methods: Pts with mUC whose disease had progressed after platinum-based therapy or were cisplatin ineligible received avelumab 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by independent review (RECIST v1.1). Endpoints included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety (NCI CTCAE v4.0). Results: As of April 2018, 249 pts had received avelumab and had been followed for ≥2 years (median 2.7 years). Median treatment duration was 12.0 weeks (IQR, 6.0-32.1), and 12 pts (4.8%) remained on treatment. Confirmed ORR in all evaluable pts (n = 242) was 16.5% (95% CI: 12.1%-21.8%; complete response in 4.1%). Median DOR was 20.5 mo (95% CI: 9.7-not estimable), and the Kaplan-Meier (K-M) estimate of 12-mo DOR was 65.4% (95% CI: 47.0%-78.8%). Median PFS was 1.6 mo (95% CI: 1.4-2.7 mo), median OS was 7.0 mo (95% CI: 5.9-8.5 mo), and the K-M 12-mo and 24-mo OS rates were 35.9% (95% CI: 29.9%-42.0%) and 20.1% (95% CI: 15.2%-25.4%), respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 71.1% of pts (177/249), most commonly infusion-related reactions (24.1%), fatigue (18.1%) and rash (18.1%). Grade ≥3 TRAEs occurred in 11.6% of pts (29/249), most commonly fatigue (1.6%), elevated lipase (1.6%), and pneumonitis (1.2%). Ten pts (4.0%) discontinued avelumab due to a TRAE. There was 1 treatment-related death (pneumonitis). Conclusions: Avelumab showed durable clinical activity and had a manageable safety profile in pts with mUC. A phase 3 trial of avelumab in the maintenance setting after first-line platinum-based therapy for mUC is ongoing. Clinical trial information: NCT01772004.
Avelumab treatment in metastatic urothelial carcinoma: Association between early response and durable outcomes in the phase Ib JAVELIN Solid Tumor Study.
Authors: Patel Manish R. , Gulley James L. , Lee Keun-Wook , Infante Jeffrey R. , Manitz Juliane , Kasturi Vijay , Zhang Hao , Rosen Galit , Apolo Andrea B. 
Published: March 2019

429 Background: Avelumab is a human anti‒PD-L1 IgG1 antibody approved in the US, Canada, and Israel for the treatment of locally advanced or metastatic urothelial carcinoma (mUC) progressed after platinum chemotherapy. In the JAVELIN Solid Tumor study, avelumab treatment in post-platinum patients (pts) has shown promising and durable antitumor activity and favorable overall survival (OS) outcomes. Here, we report post hoc analyses to assess if early response to avelumab is associated with long-term treatment outcomes. Methods: Pts with mUC that had progressed after platinum-based therapy in the JAVELIN Solid Tumor study were analyzed. Tumors were assessed every 6 weeks by independent review (RECIST v1.1). A Kaplan-Meier subgroup analysis has been performed for duration of response (DOR); response by week 7 (first tumor scan ± 5 days) define balanced subgroups. A landmark analysis was used to assess the association between time-to-response and OS. The landmark was 3 mo (second tumor assessment; 12 weeks ± 5 days). Results: 242 pts with platinum-treated mUC received avelumab and were followed up for ≥2 years (median, 2.7 years; data cutoff, Apr 2018). No difference in DOR was found between pts who had responded by the first tumor assessment (n=15) and those who responded later (n=25; HR, 0.8 [95% CI: 0.3-2.0]). In a landmark analysis for OS, the median OS was not reached (NR [95% CI: 18.9 mo-NR]) in pts who had responded within 3 mo (n=29) compared with 9.5 mo (95% CI: 6.5-14.4) in pts with late response or stable disease (n=74), and 4.3 mo (95% CI: 2.8-7.1) in other pts (progressive disease [PD] or not evaluable; n=70). Further sensitivity analyses found that survival did not vary between pts who continued treatment beyond investigator-confirmed PD (n=46) vs those that did not (n=24; median survival, 5.0 mo [95% CI: 2.8-8.8] vs 4.3 mo [95% CI: 0.9-8.3], respectively). Conclusions: Responses to avelumab have similar durability irrespective of time to response. Pts with an early response to avelumab tend to survive longer than pts with stable disease, and both groups have longer OS than nonresponders. Clinical trial information: NCT01772004.
The cost of obesity in radical cystectomy.
Authors: Huynh Melissa , Wang Ye , Pucheril Daniel , Zlatev Dimitar V. , Chang Steven Lee , Mossanen Matthew , Yu Alice 
Published: March 2019

434 Background: The Centers for Disease Control and Prevention estimates that nearly 40% of the U.S. population meets the criteria for obesity classification. Several studies have shown that obesity is associated with increased medical morbidity and costs. In this study, we investigated the impact of obesity on the financial burden of radical cystectomy. We hypothesize that the cost of radical cystectomy is greater in obese and morbidly obese patients compared to overweight patients. Methods: We performed a retrospective observational study within the Premier Healthcare Database (Premier Inc., Charlotte, NC), a large, U.S. hospital-based, all-payer database representing approximately 20% of annual inpatient discharges. ICD-9 procedure codes were used to identify all patients who had undergone elective radical cystectomy (57.71, 57.79) from 2003 to 2015, and administrative data was used to extract the costs associated with the index hospitalization. Patients were stratified into three body mass index (BMI) categories: overweight (25 BMI <30), obese (30 ≤ BMI < 40) and morbidly obese (BMI ≥ 40). Quantile regression analysis was performed to examine the effect of BMI category on cost. Results: We identified 12,056 patients who underwent radical cystectomy, 1,406 of whom had data available regarding BMI category. The crude cost of the index hospitalization for radical cystectomy was $24,596 for overweight patients. The costs associated with patients in the obese and morbidly obese categories were $2,158 ( p=0.059) and $5,308 ( p<0.001) higher compared to overweight patients, respectively. Median operative time for overweight, obese, and morbidly obese patients was 346, 391, and 420 minutes, respectively (p=0.0001). Multivariable models were constructed controlling for clinicodemographic, and surgical factors. After adjustment for operative time, there were no longer any statistically significant differences in cost between the BMI categories. Conclusions: The cost of radical cystectomy is significantly greater for obese and morbidly obese patients compared to overweight patients. This increased financial cost associated with obesity difference is driven by increased operative times encountered in obese patients.
Neoadjuvant chemotherapy utilization in muscle-invasive bladder cancer: Increasing yet inappropriate use?
Authors: Nyame Yaw A. , Holt Sarah K , Winters Brian , Psutka Sarah P. , Dash Atreya , Schade George R , Lin Daniel W. , Yu Evan Y. , Gore John L. , Wright Jonathan L. 
Published: March 2019

441 Background: Neoadjuvant cisplatin-based chemotherapy (NAC) is associated with improved overall survival in patients with muscle-invasive bladder cancer (MIBC); however, utilization nationally has been low. Over the past decade, the use of NAC has increased to approximately 20% of patients with MIBC. We investigate whether this increase in NAC is with appropriate cisplatin-based regimens using registry data. Methods: This is a population-based analysis of linked SEER-Medicare data from 2004-2011. We identified 4,534 patients with cT2-4N0-1 bladder cancer undergoing cystectomy. Specific chemotherapy drugs administered were identified using pharmacy records. The cohort was stratified into three groups, standard of care (SOC: i.e., appropriate cisplatin-based chemotherapy), non-SOC, and no NAC. Descriptive statistics were performed to compare each group and multivariate logistic regression performed to determine factors associated with receiving SOC NAC. Results: Over the study period, 694/4534 (15.3%) of patients in the study received NAC, increasing from 11.0% in 2004 to 24.8% in 2011. From 2004-2011, 345/694 (49.7%) of patients who were given NAC received a non-SOC regimen. Among patients that received non-SOC NAC, the most common regimens included gemcitabine-carboplatin in 170/345 (49.3%), gemcitabine monotherapy 73/345 (21.2%) carboplatin monotherapy in 51/345 (14.8%), cisplatin monotherapy 29/345 (8.4%), and MVA with carboplatin 3/345 (0.8%). On multivariate analysis, age (OR 0.91[95% CI 0.88-0.94]) and moderate/severe renal disease (OR 0.2[95% CI 0.08-0.51]) were negatively associated with SOC NAC. The year of diagnosis (OR 1.32[95% CI 1.23-1.42]) was positively associated with the receipt of SOC NAC in the cohort. Conclusions: Although NAC for MIBC has increased, nearly half of these patients are not receiving SOC cisplatin-based regimens. This underscores the importance of better identifying patients eligible for neoadjuvant therapy, the need for appropriate drug selection which may be facilitated through centers of excellence and multidisciplinary clinics, and the need for more clinical trials for cisplatin ineligible patients.
Hyperprogressive disease in patients with metastatic genitourinary tumors treated with immune checkpoint inhibitors.
Authors: Suárez Cristina , Morales-Barrera Rafael , Garcia-Ruiz Alonso , Gonzalez Macarena , Ligero Marta , Valverde Claudia , Serrano Cesar , Mateo Joaquin , Perez-Lopez Raquel , Carles Joan 
Published: March 2019

448 Background: Hyperprogressive disease (HPD) is a new pattern of progression in cancer patients (pts) treated with immune checkpoint inhibitors (ICI). The rate and outcome of HDP in pts with metastatic renal carcinoma (RCC) and urothelial carcinoma (UC) are unknown. Here, we report the percentage of HPD in a cohort of pts with GU malignancies treated at our center and explore associations with clinical variables. Methods: Medical records from pts treated in phase I-III clinical trials with ICI alone or in combination between July 2013 and June 2018 were retrospectively reviewed. We defined HPD according to the radiologic VHIO´s criteria (ASCO 2018). Associations between HPD and categorical or continuous variables were evaluated using Fisher exact test and Wilcoxon test respectively. OS were estimated with the Kaplan-Meir method. Statistical analyses were performed using the R statistical software (R version 3.5.0). Results: Overall, 104 pts received therapy with ICI. Of these patients, 16 were not included for the analysis (6 pts with absence of measurable disease, 6 pts did not have CT scan available after the clinical progression and 4 pts treated with ICI plus chemotherapy). Thus, 88 pts were included for the analysis, 29 (33%) with RCC and 59 (67%) with UC. Median follow-up was 7.4 months. Median age was 66.5 years (range 29-91 y).Twenty-three pts (26%) were treated with ICI monotherapy and 65 pts (74%) in combination (anti-CTL4, antiangiogenics, PARP inhibitors, FGFR inhibitors). Forty-seven pts (53%) received ICI as second-line therapy or later. By RECIST v1.1, 26 (30%), 19 (21%) and 43(49%) pts had a best response of progressive disease, stable disease or partial+complete response, respectively. We identified 9 pts (10%) who meet the HPD criteria, 2 pts with RCC and 7 with UC. HPD was associated with anemia at baseline (p = 0.058). Pts with HPD had a trend toward lower overall survival (OS) compared with pts with non-HPD (8.87 vs 4.77 months; p = 0.065). Conclusions: These findings demonstrate that HPD is a phenomenon seen in a significant proportion of pts with RCC and UC and should be taken in account. We found that HPD is associated with poor OS and the anemia at baseline was correlated with HPD.