bluuebunny/crossref_metadata_2025_split huggingface dataset:
VICTOR: Vinflunine (Vin) in advanced metastatic transitional cell carcinoma of the urothelium (TCCU)—A retrospective analysis of use of Vin in multicenter, real life setting as second-line chemotherapy (ChT) through free-of charge-programme (FOCP) for patients (pts) in the UK.
Authors: Hussain Syed A. , Ansari Jawaher , Huddart Robert Anthony , Wylie James , Vilarino-Varela Maria , Faust Guy , Tan Melissa , Lyons Jeanette , Hassall Alison , Escriu Carlos , Chauhan Seema , Jackson Richard 
Published: February 2017

352 Background: There is no standard of care currently in UK for second line ChT for pts with advanced TCC. Vin is approved for TCCU for pts who have failed a platinum-based regimen and is now the standard ChT in 2nd line in Europe based on large phase III randomised trial data showing 2.6 months survival advantage. ESMO guidelines recommended it as the only option for pts in the 2nd line setting. Vin is not currently available in NHS practice in UK as it is not on the approved list of drugs on cancer drug fund. Methods: Data are collected retrospectively on pts who received Vin as a 2nd line treatment through FOCP. The dose of Vin was 240-320 mg/m2 every 3 weeks. The aim was to document the toxicity, radiological RR and OS for pts treated with Vin in real life setting within the FOCP. Results: At the time of analysis data from 37 pts from 6 sites were available. Median pts age was 64 years(range: 57-69), 24m; 13 f. All pts had advanced metastatic TCC. 9 pts had bone or liver mets, 3 pts had PS 2 and 5 pts had HB <10, all known poor prognostic indicators in palliative ChT setting. Total of 179 cycles have been delivered (median 3 ; mean 5; range1-16). Grade 3 / 4 toxicity: Anaemia 2/179, Neutropenia 2/179, Neutropenic infection 2/179, Constipation 4/179, Fatigue 3/179. Grade 2 toxicity; Anaemia 5/179, Neutropenia 13/179, Thrombocytopenia 2/179, Febrile infection 1/179, Constipation 9/179, Fatigue 20/179, Abdominal pain 2/179, Vomiting 8/179. 30 pts were evaluable for response. 11 pts had PR, 6 had SD, 13 had PD and 7 were not evaluable. Partial RR was 30 % with ITT and 37% for evaluable pts. Median OS was 9.5 (95% CI; 5.9- 16.9) months. Conclusions: Real life data showing a median OS of 9.5 m by ITT for all pts are encouraging and consistent with real life data from Europe (Spanish, German and French) presented at ESMO 2013. Toxicity has further improved with the use of prophylactic laxatives and oral antibiotics.
Programmed death-ligand 1 characterization of circulating tumor cells and white blood cells in muscle-invasive and metastatic bladder cancer patients.
Authors: Friedlander Terence W. , Lu David , Krupa Rachel , Premasekharan Gayatri , Welty Christopher J. , Paz Rosa , Jendrisak Adam , Landers Mark , Louw Jessica , Orr Sarah , Marrinucci Dena , Fong Lawrence , Dittamore Ryan Vance , Paris Pamela 
Published: February 2017

353 Background: Muscle invasive(MIBC) and metastatic (mBCa) bladder cancer patients have few options to extend survival. Recent studies have shown that PD-1 and programmed death-ligand 1 (PD-L1) checkpoint inhibitors have activity even in chemotherapy refractory patients and it has been proposed that PD-L1 expression on tumors or lymphocytes may correlate with response to therapy. To identify potential patients who may benefit from PD-1/PD-L1 targeted immunotherapeutics, we utilized a non-invasive, real-time blood test for PD-L1 protein expression in circulating tumor cells (CTCs) and white blood cells (WBCs) of bladder cancer patients. Methods: Twelve blood samples from unique patients with MIBC or mBCa were collected and shipped to Epic Sciences. All nucleated cells were plated onto glass slides and subjected to IF staining and CTC identification by fluorescent scanners and algorithmic analysis. CTCs, defined as traditional (CK+ CD45- w/ intact DAPI nuclei and morphologically distinct) or CK- (CK-, CD45-, intact and distinct) were identified. PD-L1 biomarker characterization was assessed by IF staining, and UroVysion FISH testing was used to assess genomic abnormalities in a subset of patient samples. Additionally, WBCs (CD45+ cells) were assessed for PD-L1 expression. Results: Traditional CTCs were detected in 6/12 (50%) patients. 3/12 (25%) patients had PD-L1+ cells, 2 of these patients were exclusively CK-/PD-L1+ CTCs, which were confirmed as cancer via FISH. CK- CTCs were detected in 83% (10/12) patients. 5 patients had greater than 4 fold PD-L1 positivity in WBCs as compared to healthy donor controls. Conclusions: MIBC and mBCa patients have detectable CTCs with a high frequency of CK-/PD-L1+ CTCs. Utilization of a liquid biopsy to identify patients with PD-L1+ CTCs and PD-L1+ WBCs may enable both patient selection or short term therapeutic monitoring for measuring pharmacodynamics to ensure therapy effectiveness. Further studies are planned to investigate association of PD-L1+ CTCs and WBCs with response to PD-1 and PD-L1 checkpoint immunotherapy.
A novel tool to predict outcomes following radical cystectomy using age and co-morbidity status.
Authors: Nayak Jasmir Gopal , Holt Sarah , Gore John L. , Dash Atreya 
Published: February 2017

354 Background: Substantial morbidity and mortality is associated with radical cystectomy. Utilizing administrative data, we sought to develop a novel model combining age and co-morbidity status to determine the risk of clinically relevant outcomes including: prolonged length of stay (LOS), disposition to skilled nursing facility (SNF), mortality on index admission, and hospital readmission rates following radical cystectomy. Methods: From the Premier Perspectives Database, we identified patients who underwent radical cystectomy for bladder cancer between 2007-2013 using ICD-9 codes. Comorbidity was determined using the Elixhauser method. Prolonged LOS was defined as admissions exceeding 10 days. Hospital readmissions were flagged if they occurred in the month of surgery or the month after regardless of the reason. Probabilities were derived from multivariable logistic regression models that additionally adjusted for provider volume (based on quartiles), payer, patient marital status, and hospital urban/rural status. Results: We identified 6,460 radical cystectomy patients, of whom 16% were discharged to a SNF, 37% had a prolonged LOS, and 2% died during the index admission. Among patients who were discharged home after surgery, 27% were readmitted. Prolonged LOS was associated with increasing comorbidities and age >70 (p<0.001). The adjusted likelihood of readmission increased with increasing burden of comorbid conditions (p<0.001) (Table), however, was not associated with age group. The likelihood of being discharged to a SNF increased with increasing age and increasing number of comorbidities (p<0.001). Mortality was associated with 3 or more comorbidities and age >70. Conclusions: We present adjusted disposition and mortality rates following radical cystectomy for bladder cancer stratified by patient age and comorbidity. These data may inform preoperative patient counseling regarding the potential for prolonged recovery and mortality and facilitate improved shared decision-making between patients and clinicians anticipating cystectomy for bladder cancer.
Genetic variants of the organic anion transporter SLCO2B1 as pharmacogenomic determinants of response to androgen deprivation therapy (ADT) for prostate cancer.
Authors: Kantoff Philip W. , Wang Xiaodong , Xie Wanling , Nakabayashi Mari , Pomerantz Mark , Lee Gwo-Shu Mary 
Published: February 2017

137 Background: Genotypes at three SNPs (rs12422149; rs1789693; rs1077858) within SLCO2B1 were associated with time to progression (TTP) on ADT in the Dana-Farber Cancer Institute (DFCI) Prostate CRIS ADT cohort (J Clin Oncol. 2011 29(18): 2565). Variation at exonic SNP rs12422149 (Gln to Arg) allows more efficient import of DHEAS, enhances AR signaling and cell growth, and as a result, is associated with shorter TTP on ADT. We further externally validated the association of SLCO2B1 variants with TTP on ADT in an independent ADT cohort and estimate their association with overall survival (OS) in both cohorts. Methods: An independent ADT cohort (N=616) was established for validation. TTP was defined using the same criteria as for the original cohort. The associations of genetic variants with TTP on ADT and OS were estimated from multivariable Cox regression and adjusted by known prognostic factors. Effects of one intronic SNP rs1077858 on SLCO2B1 and DHEAS uptake activity were characterized in cell cultures. Results: Association between genotype at rs12422149 and TTP on ADT was confirmed in univariable (P= 0.0187) and multivariable (adjusted HR= 1.31 for GG vs AA/AG, P= 0.0489) analyses. The Median OS from ADT initiation was 6.5 years in all patients (N= 1094, original plus validation cohort). The intronic SNP rs1077858 was significantly associated with the OS from ADT initiation in both univariable (P= 0.0091) and multivariable (adjusted HR= 1.34 for GG vs AA/AG, P= 0.014) analyses. The difference of median OS was 18 months. SLCO2B1 expression in normal prostate tissue carrying the major allele of SNP rs1077858 (AA) was significantly lower than those carrying the risk allele (GG) (Ptrend= 0.0193), suggesting that the association of the SNP rs1077858 with the OS on ADT may be due to its impact on the SLCO2B1 expression. SLCO2B1 knockdown in vitro decreased DHEAS uptake and diminished DHEAS-induced prostate cancer cell growth. Conclusions: Germline variants within SLCO2B1 modulate function or expression of SLCO2B1, subsequently affecting the uptake of androgen precursors and affecting TTP or OS in prostate cancer patients.
A retrospective analysis of the effect of time from diagnosis to cystectomy on survival in patients with muscle-invasive bladder cancer receiving neoadjuvant chemotherapy.
Authors: Park Jong Chul , Gandhi Nilay M , Bivalacqua Trinity , Schoenberg Mark , Carducci Michael Anthony , Eisenberger Mario A. , Baras Alexander S , Netto George J. , Liu Jen-Jane , Drake Charles G. , Hahn Noah M. 
Published: February 2017

360 Background: Retrospective population-based studies have shown that an interval longer than 12 weeks between diagnosis and cystectomy is associated with worse outcomes in patients with muscle-invasive bladder cancer (MIBC). Neoadjuvant chemotherapy (NAC) is widely used however the impact of duration from diagnosis to cystectomy is unclear in MIBC patients treated with NAC. Methods: We performed a retrospective analysis of patients with MIBC who received NAC followed by cystectomy between 1996 and 2014 at a single institution. Total therapy duration was defined as the time interval between diagnosis of MIBC on biopsy and the date of cystectomy. Cox proportional hazards regression models were used to investigate the effect of total therapy duration and other factors on overall survival (OS). Results: 201 patients who met the study criteria were analyzed.Demographics included: median age 62, 79% male, 62% cT2N0, 10% cN+, 29% w/variant histology (VHx). Cisplatin-based therapy was given to 91% of patients for a median of 3 cycles. The median time from diagnosis to the cystectomy was 28 weeks. A total therapy duration < 28 weeks did not impact OS (hazard ratio [HR], 0.68; p=0.39). Pretreatment clinical covariates associated with improved OS included age< 62 (HR 0.56; p=0.034) and absence of VHx (HR, 0.40, p=0.001). Post-treatment factors of significance included less than 3 cycles of chemotherapy received (HR 1.75, p=0.037), pT3/T4 or N+ (HR 5.18, p<0.001), and N- (HR 0.58, p=0.048). Conclusions: Total therapy duration does not significantly impact OS in patients with MIBC receiving NAC. This data adds to the evidence supporting the use of NAC in MIBC patients fit to receive cisplatin-based regimens.
Primary prevention of bladder cancer: Does the public know the risk factors?
Authors: Wood Erika L. , Golla Vishnukamal , Goswamy Rohit , Fellman Bryan , Urbauer Diana L , Canfield Steven , Shah Jay Bakul 
Published: February 2017

366 Background: Smoking is the single most significant modifiable risk factor for bladder cancer, yet this is not well known outside of the medical community. Previous studies from tertiary referral centers have found that 36-58% of urology patients can identify smoking as a risk factor for bladder cancer. Since those patients may not be representative of the general population, we studied the knowledge base of bladder cancer risk factors among people encountered in the general waiting room of an urban county hospital. Methods: 215 participants over 18 years of age were recruited from the waiting room of an urban county hospital to participate in a brief survey on risk factors for various cancers. Fisher’s exact test and McNemar’s test were used to detect differences in knowledge between bladder cancer and other cancers. Results: The survey participant population was mostly female (65.6%), Hispanic (54%), and middle-aged (67% age 35-64). Most (54.8%) had an annual household income of less than $20,000, attained a high school education (49.1%) or below (24.1%), and 40.3% were current or former smokers. An overwhelming majority of participants chose smoking as a risk factor for lung cancer (92.2%), with 80.7% identifying smoking as the primary risk factor for lung cancer. In contrast, only 31.6% of participants chose smoking as a risk factor for bladder cancer with 7.4% selecting it as the primary risk factor for bladder cancer. Knowledge of smoking as a risk factor for bladder cancer was not impacted by education, income, smoking status, or personal/family history of cancer. Male gender and exposure to industrial chemicals were identified as risk factors for bladder cancer by a minority of patients (19.3% and 28.0%, respectively). Almost half of all participants surveyed (49.1%) incorrectly identified alcohol use as a risk factor for bladder cancer. Conclusions: Among participants of low socioeconomic status presenting to an urban county hospital, there is a concerning lack of knowledge about the major risk factors for bladder cancer. Given that smoking is a modifiable risk factor, future public education initiatives to prevent bladder cancer should focus on populations with low socioeconomic status as high-yield targets to affect change.
Potent suppression of proliferation of carcinoma cells by a novel non-nucleoside reverse transcriptase inhibitor.
Authors: Fisch Alexander , Schroeder William , Smart Robert , Patel Osman 
Published: February 2017

367 Background: The treatment of choice for many patients with advanced carcinomas is surgery in combination with aggressive chemo- and radiotherapy. Unfortunately, even with the aggressive regime of therapy against carcinomas, there is neither guarantee of life-long remission nor of further spread to other organs including the urogenital system. However, recent advances have identified the reactivation of telomerase as a pivotal element in the development of cancer. Therefore, the objective of this study was to evaluate the efficacy of a novel anti-telomerase (GV6) developed at our Institution on MCF7 (ER+, PR+, HER2+) and MDA-MB 231 (ER-, PR-, HER2-) cell lines. Methods: Seeded flasks (T-75) were supplemented with 25μm GV6 (n=4-6) or solvent alone (control, n=3) for 14 (short-term) or 27 (long-term) days. Cell viability and replicative senescence were both assessed using the Trypan Blue (Gibco) and SA-β-Gal (Cell Signaling Tech) methods, respectively. Results: By day 27, MCF7 flasks had a greater (p<0.05) number of viable cells (35.4% vs. 29%) compared to MDA-MB 231 cells. More senescent cells were observed in GV6 supplemented MDA-MB 231 (~75%) cells than in MCF7 (~60%) by day 27. Conclusions: Our results indicate that GV6 is an equally potent inhibitor of telomerase and merits further studies.
Results of the phase I trial of cetuximab with mitomycin c and 5-fluorouracil concurrent with radiotherapy treatment in patients with muscle-invasive bladder cancer.
Authors: Hussain Syed A. , Hendron Carey , Buckley Laura , Dickinson Lynne , Syndikus Isabel , Malik Zafar , Eswar Chinnamani , James Nicholas David 
Published: February 2017

368 Background: Synchronous chemo-radiotherapy is an alternative to cystectomy in patients with muscle invasive bladder cancer (MIBC). BC2001 trial reported improved local control in patients randomised to synchronous chemo-radiotherapy compared to radiotherapy alone (James, Hussain, Hall et al NEJM 2012). TUXEDO trial reports phase I trial results with additional weekly cetuximab (Cet) in combination with Mitomycin c (MMC), 5-Fluouracil (5-FU) and concurrent radiotherapy (RT). Methods: This two centre phase I trial recruited 7 patients with MIBC in Queen Elizabeth Hospital Birmingham and Clatterbridge Cancer Centre Liverpool to synchronous chemotherapy using Loading dose of Cet 400 mg/m2 followed by weekly Cet 250 mg/m2, continuous infusion 5-FU 500mg/m2/day during fractions 1-5 and 16-20 of RT and MMC12mg/m2on day 1 in combination with radical RT treatment 64 Gys in 32 fractions. The primary endpoint was to assess toxicity. Secondary end- points included 3 months pathological complete response, loco-regional disease-free survival and overall survival. Results: Median age of patients was 70 (range: 60-75) years, all were male, 6 had received prior neoadjuvant chemotherapy. Two patients had T2B, 3 T3A and 2 T3B disease, all had G3, TCC disease, 6 patients had neo-adjuvant chemotherapy. All 7 patients completed RT as planned except for 1 who withdrew from trial after 5 weeks of protocol treatment due to relocation. Median dose intensity for Cet and MMC was 97.6% and for 5-FU was 99.4%. Grade 3 toxicity to report was maculopapular rash in 3 patients. Grade 2 toxicities include UTI/ frequency/ nocturia / fatigue /constipation / hypokalemia/epistaxis/palmar-plantar reported in 3/1/1/1/1/1/1/2 cases respectively. Grade 2 maculo-papular rash was reported in 3 cases. All seven patients have achieved complete responses at 3 months cystoscopic assessment. Patients continue on surveillance as per TUXEDO trial protocol. Conclusions: Synchronous chemotherapy with Cet and 5FU/MMC concurrent with radical RT is safe to deliver. Complete response rates are encouraging and a phase II trial with added centres within UK is being launched. Clinical trial information: NOT KNOWN.
Outcomes of preoperative chemotherapy in bladder cancer patients including node-positive disease.
Authors: Faltas Bishoy , Date Pravin R. , Scherr Douglas , Nguyen Daniel P. , Al Awamlh Bashir Al Hussein , O'Malley Padraic , Christos Paul J. , Beltran Himisha , Nanus David M. , Tagawa Scott T. 
Published: February 2017

370 Background: Neoadjuvant chemotherapy is associated with improved overall survival benefit and the concept of systemic therapy followed by local consolidation may also lead to favorable long-term outcomes for those with lymph node (LN) metastases at presentation. Our goal was to examine the outcome of preoperative chemotherapy in patients (pts) with and without clinical evidence of LN metastases. Methods: After informed consent, patients were enrolled in a prospective database prior to radical cystectomy with lymph node dissection for bladder cancer between December 2001 to February 2014. Data were analyzed using descriptive statistics. Results: Our cohort included 63 patients receiving pre-operative chemotherapy with a median age 68 (range 38-91), 46 (72%) were male, and 17 (27%) had gross metastatic disease to lymph nodes (LNs). 13 pts received MVAC (20%), 44 gemcitabine and cisplatin (GC) (69%), 1 gemcitabine and carboplatin, 1 received ifosfamide, paclitaxel, and cisplatin and 4 pts had unknown neoadjuvant chemo outside of the institution. Most patients with LN positive (71%) disease received GC preoperative regimens. The median and the modal number of cycles were 4 (range 1-6). 44 patients underwent robotic-assisted radical cystectomy (RARC) (69%), 19 underwent open radical cystectomy (30%), and another pt. had RARC converted to an open procedure. Overall, 20 (31%) patients achieved pathologic complete response (pCR). Four pts (24%) with initial metastatic disease achieved pCR after preoperative chemotherapy. Overall pCR rates were similar between MVAC (38%) and GC (33%). All LN positive patients who achieved pCR had received gemcitabine-cisplatin preoperatively and underwent RARC. Recurrence-free and overall-survival data will be presented at the meeting. Conclusions: Preoperative chemotherapy was associated with a significant pCR rate in all bladder cancer patients including LN positive patients.
Multi-institutional validation of the predictive value of Ki-67 in patients with high-grade urothelial carcinoma of the upper urinary tract.
Authors: Krabbe Laura-Maria , Bagrodia Aditya , Haddad Ahmed Q , Kapur Payal , Khalil Dina , Hynan Linda S. , Wood Christopher G. , Karam Jose A. , Weizer Alon Z. , Raman Jay D. , Remzi Mesut , Rioux-Leclerq Nathalie , Haitel Andrea , Roscigno Marco , Bolenz Christian , Bensalah Karim , Sagalowsky Arthur I. , Shariat Shahrokh F. , Lotan Yair , Margulis Vitaly 
Published: February 2017

371 Background: To validate the independent predictive value of Ki-67 in patients with high-grade upper tract urothelial carcinoma (UTUC). Methods: 475 patients from the international UTUC collaboration who underwent extirpative surgery for high-grade UTUC were included in this study. Immunohistochemical staining for Ki-67 was performed on tissue microarray (TMA) formed from this patient cohort. Ki-67 expression was assessed in a semi-quantitative fashion and considered overexpressed at a cut-off of 20%. Multivariate analyses (MVA) were performed to assess independent predictors of oncological outcomes and Harrell’s C indices (HCI) were calculated for predictive models. Results: Median age of the cohort was 69.7 years and 55.2% of patients were male. Ki-67 was overexpressed in 25.9% of patients. Ki-67 overexpression was significantly associated with ureteral tumor location, higher pT-stage, lymphovascular invasion, sessile tumor architecture, tumor necrosis, concomitant carcinoma in situ (CIS), and regional lymph node metastases. In Kaplan-Meier analyses, overexpressed Ki-67 was associated with worse recurrence-free (RFS) (HR 12.6, p<0.001) and cancer-specific survival (CSS) (HR 15.8, p<0.001). In MVA, Ki-67 was an independent predictor of RFS (HR 1.6, 95% CI 1.07-2.30, p=0.021) and CSS (HR 1.9, 95% CI 1.29-2.90, p=0.001). Ki-67 improved HCI from 0.66 to 0.70 (p<0.0001) for both RFS and CSS in our preoperative model, and from 0.81 to 0.82 (p=0.0018) for RFS and 0.81 to 0.83 (p=0.005) for CSS in our post-operative model. Conclusions: Ki-67 was validated as an independent prognostic predictor of RFS and CSS in patients treated with extirpative surgery for high-grade UTUC in a large, multi-institutional cohort.