bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causes of death in intermediate- and high-risk prostate cancer treated with radiotherapy with or without androgen deprivation therapy: Analysis from two phase III trials.
Authors: Nabid Abdenour , Carrier Nathalie , Vigneault Eric , Martin André-Guy , Souhami Luis , Duclos Marie , Bahary Jean-Paul , Nguyen-Huynh Thu-Van , Lemaire Céline , Brassard Marc-André , Vass Sylvie , Bahoric Boris , Archambault Robert , Vincent François 
Published: February 2017

34 Background: The purpose of this analysis was to establish causes of death in a population of intermediate-risk (IR) and high-risk (HR) prostate cancer treated on two phase III trials. Methods: From October 2000 to September 2010, 1,230 patients were randomized: 630 with HR (ClinicalTrials.gov, #NCT00223171) and 600 with IR (#NCT00223145). HR was defined as T3-4, PSA >20 g/ml, Gleason >7 (with at least one of these 3 factors). IR was defined as T1-T2, Gleason < 6 and PSA 10-20 ng/ml or T1-T2, Gleason 7 and PSA < 20 ng/ml. Causes of death were compiled until July 2015 and were established from data sent by the different investigators and centrally reviewed. Causes of death were mainly based on data from clinical records, then by family members, obituaries, death certificates and family physicians. Results: The median follow-up for the 1,230 patients was 7.5 years (HR 8 vs. IR 6.8 years, p<0.001). 30.2% (372/1,230) patients had died: (HR 37% vs. IR 23.2%, p<0.001). A total of 8% (99/1,230) patients developed local, regional, and metastatic prostate cancer recurrences: (HR 11.6% vs. IR 4.3%, p<0.001) and 4.4% (54/1,230) died from prostate cancer: (HR 7.3% vs. IR 1.3%, p<0.001). The most frequent cause of death was a second cancer (120/1,230, 9.8%): (HR 10.6% vs. IR 8.8%, p=NS). Cardiovascular deaths occurred in 6.3% (78/1,230) (HR 7.1% vs. IR 5.5%, p=NS) with no statistical difference between the different durations of androgen deprivation therapy (ADT) 0, 6, 18, or 36 months. Other causes of death were pulmonary (3.7%), digestive (1.1%), others (3.3%), and unknown (1.7%). Majority of deaths occurred between 3 and 9 years after randomization (HR 70% and IR 73%). Prostate cancer deaths were distributed over all the follow-up period. The 5/10 year overall survival between HR and IR were 88.6%, 91.8%, and 61.6%, 69.8%, respectively with significant differences (p=0.045 and p=0.016). Conclusions: In patients with localized HR and IR prostate cancer, the first cause of death was a second cancer and prostate cancer came as the third one after cardiovascular disease. There was no statistical difference in the incidence of cardiovascular deaths in patients treated with different durations of ADT. Clinical trial information: Clinical Trials, gov. #NCT00223145 - Clinical Trials, gov. #NCT00223171.
Prognostic role of body mass index (BMI) in patients with metastatic castration resistant prostate cancer (mCRPC) receiving chemotherapy: Preliminary results from a retrospective Italian multicenter study.
Authors: Lutrino Stefania Eufemia , Fontanella Caterina , Caffo Orazio , Massari Francesco , Atzori Francesco , Maggi Claudia , Calvani Nicola , Sacco Cosimo , Veccia Antonello , Modena Alessandra , Cugudda Silvia , Verzoni Elena , Caliolo Chiara , Ermacora Paola , Maines Francesca , Tortora Giampaolo , Procopio Giuseppe , Ferrara Pasqualinda , Fasola Gianpiero , Cinieri Saverio 
Published: February 2017

342 Background: Body mass index (BMI) is linked to an increased risk of cancers and a poorer prognosis. However, the evidence on the relationship between high BMI and metastatic castration resistant prostate cancer (mCRPC) is not entirely consistent and the data are conflicting. The aim of this observational, retrospective, multicenter study was to evaluate the correlation between BMI and progression-free survival (PFS) and overall survival (OS) in patients (pts) with mCRPC treated with chemotherapy. Methods: We collected mCRPC pts who received docetaxel 75 mg/m2 every 21 days as first line therapy in6 Italian Cancer Centers from 2005 to 2015. We classified BMI group according with the World Health Organization definition : normal weight BMI < 25kg/m2, overweight 25 ≤ BMI < 30kg/m2, and obese BMI ≥ 30kg/m2. Baseline characteristics and treatment information has been recorded in an anonymized excel file. Results: We collected 113 pts with a median age of 70.7 years (62 to 87) at the time of mCRPC diagnosis. In our cohort 33.6% of pts were normal weight at the HRPC diagnosis, 50.9% were overweight, and 15.5% were obese. At the baseline, 83.3% of obese pts had at least 1 co-morbidity versus 64.9% of normal/overweight pts. Moreover, 27.8% of obese pts needed a docetaxel dose reduction versus 17.5% normal/overweight pts. Only a non-significant trend for the detrimental effect of high BMI on PFS and OS has been documented. Median PFS in obese pts 6.4 months vs 7.0 months in of normal/overweight pts (p = 0.439); median OS in obese pts 38.8 months vs 43.4 months in of normal/overweight pts (p = 0.157). Conclusions: The relationship between BMI and mCRPC is extremely complex and unclear. Even if in this preliminary analysis we failed to confirm a significant association between BMI and survival, the data suggests that obesity may be associated with a lower tolerance to chemotherapy. Overall, we expected to enroll approximately 500 pts and data collection is currently ongoing.
Comparison of docetaxel and cabazitaxel efficacy on prostate cancer cells both in vitro and in vivo.
Authors: Nelius Thomas , Jarvis Courtney , Martinez-Marin Dalia , Filleur Stephanie 
Published: February 2017

351 Background: Despite recently approved novel agents, taxane-based chemotherapy remains the major therapeutic strategy for metastatic castration-refractory prostate cancer/mCRPC. Still mCRPC continues to be incurable. Besides, patients often experience severe side effects, prompting a re-evaluation of standard regimen. Past studies have demonstrated promise for Low-Dose Metronomic/LDM chemotherapy, defined as the frequent administration of low doses of chemotherapeutic drugs with no prolonged drug-free breaks. Yet relative activities of LDM taxanes and combinations with known anti-neoplasic agents have to be investigated. Methods: PC3, Du145 and LNCaP-derivative CL1cell lines were used to compare the effect of increasing doses of taxanes on cell proliferation, cell cycle distribution and apoptosis by crystal violet, propidium iodide and AnnexinV stainings, respectively. Autophagy was assessed by western blotting against Beclin1. In vivotumor growth was measured using CL1 control and CL1-PEDF xenografts. Phagocytosis was determined by cytotoxicity assay in CL1-macrophages co-cultures. Results: Our data showed that cabazitaxel/cbz-treated cells had a significantly lower EC50 compared to docetaxel/doc, with Du145 cells presenting the greatest differences. Both low-dose taxanes increased the sub-G0 cells population. However, the sub-G0 increase was significantly greater in cbz- than doc-treated Du145 cells, but not in PC3 and CL1. Accordingly, plasma membrane Annexin V elevation occurred in Du145 cells at lower doses of cbz than doc validating a higher efficacy due to increased apoptosis. Although Beclin1 levels remain unchanged in PC3 and CL1 cells, it was found up-regulated for all doses of cbz in Du145. In vivo, LDM cbz was significantly more efficient in curbing tumor growth than doc. This effect was markedly increased when cbz was combined with the angio-inhibitor and anti-tumor Pigment Epithelium-Derived Factor (PEDF); an effect that could be explained by increased phagocytosis. Conclusions: Our data demonstrate a higher efficacy of cbz on CRPC both in vitro and in vivo, and suggest that LDM taxane chemotherapy/PEDF combination could be used as a novel therapeutic strategy for CRPC.
Neutrophil-to-lymphocyte ratio as a prognostic biomarker in bladder cancer: A REMARK-guided secondary analysis of SWOG 8710.
Authors: Ojerholm Eric , Smith Andrew , Hwang Wei-Ting , Baumann Brian Christopher , Tucker Kai N. , Lerner Seth P. , Christodouleas John Paul 
Published: February 2017

361 Background: Pre-operative risk stratification is a major challenge in bladder cancer (BC), and a biomarker is needed. Recent studies suggest baseline neutrophil-to-lymphocyte ratio (NLR) correlates with survival in BC, but these results are threatened by methodological limitations. We tested whether NLR is prognostic for overall survival (OS) in BC following principles detailed by the REMARK biomarker guidelines. Methods: SWOG 8710 was a randomized, phase III trial assessing radical cystectomy (RC) ± neoadjuvant chemotherapy (NAC). It enrolled 317 patients with T2-T4aN0 BC. Baseline NLR was calculated from prospectively-collected pre-treatment complete blood counts. We performed a secondary analysis on 230 patients with valid NLR who successfully completed RC (119 patients) or NAC + RC (111 patients). We evaluated the association of NLR with OS in univariable and multivariable Cox regression models, adjusting for pre-specified factors (age, gender, T-stage, lymphovascular invasion [LVI], and treatment received). Model assumptions of linearity and proportional hazards were checked. We estimated an 80% power to detect a hazard ratio (HR) of ≥ 1.11 for death with each unit increase in NLR at α = 0.05. We addressed missing values via multiple imputation and defined OS from date of treatment to death. Results: There were complete data for all covariates except a small portion ( < 7%) of LVI values. Median baseline NLR was 2.7 (IQR 2.0-4.1), and NLR was not significantly associated with any other covariate. During a median follow-up of 18.6 years, there were 172 deaths. On multivariable analysis, older age (HR 1.05, 95% CI [1.04-1.07], P < 0.001) and treatment with RC alone (HR 1.39, 95% CI [1.03-1.88], P = 0.03) were associated with worse OS. Baseline NLR was not associated with OS in either univariable (HR = 1.03, 95% CI [0.97 – 1.10], P = 0.30) or multivariable models (HR = 1.04, 95% CI [0.98 – 1.11], P = 0.24). Conclusions: In contrast to previous studies, this analysis of prospectively-collected trial data suggests baseline neutrophil-to-lymphocyte ratio is not prognostic for OS in patients with muscle-invasive bladder cancer.
Safety, clinical activity, and PD-L1 expression of avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with metastatic urothelial carcinoma from the JAVELIN Solid Tumor phase Ib trial.
Authors: Apolo Andrea B. , Infante Jeffrey R. , Hamid Omid , Patel Manish R. , Wang Ding , Kelly Karen , Mega Anthony E. , Britten Carolyn D. , Mita Alain C. , Ravaud Alain , Cuillerot Jean-Marie , von Heydebreck Anja , Gulley James L. 
Published: February 2017

367 Background: Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody being investigated in multiple clinical trials. We report safety and clinical activity of avelumab as a second-line therapy in patients (pts) with metastatic urothelial carcinoma (mUC) based on level of PD-L1 expression (NCT01772004). Methods: Pts with mUC unselected for PD-L1 expression received avelumab at 10 mg/kg Q2W by IV infusion until confirmed progression, unacceptable toxicity, or any criterion for withdrawal occurred. Tumors were assessed every 6 wks (RECIST 1.1). Best overall response rate (ORR) and progression-free survival (PFS) were evaluated. Adverse events (AEs) were graded by NCI-CTCAE v4.0. PD-L1 expression was assessed by immunohistochemistry. Results: As of 19 Mar 2015, 44 pts (30 men, 14 women) with mUC were treated with avelumab (median 13 wks [range 2-28]) and followed for a median of 3.5 mo (range 3.0-5.0). Median age was 68y (range 30-84), ECOG performance status was 0 (43.2%) or 1 (56.8%), and pts had received a median of 2 prior therapies (range 1- ≥ 4). Treatment-related treatment-emergent AEs (TR-TEAEs) of any grade occurred in 26 pts (59.1%); those occurring ≥ 10% were grade 1/2 infusion-related reactions (8 [18.2%]) and fatigue (7 [15.9%]). One pt had grade 3 asthenia. There were no treatment-related deaths. ORR was 15.9% (7 pts; 95% CI: 6.6, 30.1) with 1 CR and 6 PRs; 6 responses were ongoing at data cutoff. Stable disease (SD) was observed in 19 pts (42.3%) and disease-control rate (CR+PR+SD) was 59.1%. PD-L1 expression was evaluable in 32 pts. Using a ≥ 5% cutoff (10/32 [31.3%] were PD-L1+), ORR was 40.0% in PD-L1+ pts (4/10) vs 9.1% in PD-L1– pts (2/22; p= 0.060). PFS rate at 12 wks was 70.0% (95% CI: 32.9, 89.2) in PD-L1+ pts vs 45.5% (95% CI 22.7, 65.8) in PD-L1− pts. Conclusions: Avelumabshowed an acceptable safety profile and had clinical activity in pts with mUC. There was a trend towards higher ORR and prolonged PFS rate at 12 wks in pts with PD-L1+ mUC. Further analyses of PD-L1 expression and clinical activity of avelumab in UC are ongoing. *Proposed INN. Clinical trial information: NCT01772004.
Variant isoforms of CD44 expression as predictive markers for mortality in surgically treated patients with locally advanced upper tract urothelial carcinoma.
Authors: Kikuchi Eiji , Hagiwara Masayuki , Hayakawa Nozomi , Mizuno Ryuichi , Kosaka Takeo , Mikami Shuji , Miyajima Akira , Saya Hideyuki , Oya Mototsugu 
Published: February 2017

388 Background: The variant isoforms of CD44 (CD44v), which are some of the new cell surface markers for cancer stem cells, have been associated with tumor growth, treatment resistance, and cancer death in several cancers. We investigated the role of CD44v8-10, which is a CD44v, on the clinical outcome of patients with advanced upper tract urothelial cancer (UTUC). Methods: The protein expression of CD44v8-10 was immunohistochemically evaluated using CD44v9 antibody, which detects immunogen of CD44v8-10, and investigated the association with clinical characteristics and outcome in surgical specimens obtained from 110 patients who had been treated with radical nephroureterectomy for ≥pT2 UTUC. The mean percentage of positive cancer cells stained with CD44v9 antibody in each tumor was estimated. Results: The median percentage of CD44v9 positivity was 5.50±7.74%. Patients were subsequently stratified into a CD44v9-positive group (n = 82) and a CD44v9-negative group (n = 28) based on a cut-off level of 5%. During the mean follow-up of 4.8 years, disease recurrence was observed in 49 patients (59.8%) in the CD44v9-positive group and in 8 patients (28.6%) in the CD44v9-negative group. The 5-year recurrence-free survival rates were 47.6% in the CD44v9-positive group and 66.6% in the CD44v9-negative group (p= 0.038). Multivariate analysis showed that tumor grade G3 (p= 0.005, HR = 3.77), the presence of lymphovascular invasion (p= 0.041, HR = 1.84), and CD44v8-10 expression (p= 0.028, HR = 2.33) were independent risk factors for disease recurrence. In this series, 37 patients in the CD44v9-positive group (45.1%) and 5 (17.9%) in the CD44v9-negative group died of the disease. The 5-year cancer-specific survival rates were 57.8% in the CD44v9-positive group and 80.4% in the CD44v9-negative group (p= 0.032). The CD44v9 expression (p= 0.040, HR = 2.67) in addition to tumor grade G3 (p= 0.003, HR = 8.35) were independently associated with cancer death. Conclusions: The expression ofCD44v8-10 may be a new biomarker of malignant potential in locally advanced UTUC and could provide additional prognostic information in patients with UTUC.
A phase I study of chemoradiation with weekly panitumumab following neoadjuvant chemotherapy and pelvic lymph node dissection as an organ preserving treatment of invasive bladder cancer.
Authors: Fransen van de Putte Elisabeth E. , Pos Floris J. , Doodeman Barry , van Rhijn Bas W.G. , van der Laan Elsbeth , Van Der Heijden Michiel Simon , Kerst Jan M. , Horenblas Simon , Bergman Andre M. 
Published: February 2017

392 Background: Radical Cystectomy (RC) is the standard treatment of Invasive Bladder Cancer (IBC). Although organ sparing, external beam Radiation Treatment (RT) alone is considered inferior to RC. Since the Epidermal Growth Factor receptor (EGFr) is frequently overexpressed in IBC, combined EGFr inhibition by Panitumumab (P) and RT might improve treatment outcome. In this study, the safety and efficacy of concurrent RT and P (RT/P) following Neoadjuvant Chemotherapy (NAC) and Pelvic Lymph Node Dissection (PLND) was evaluated. Methods: cT2-4N0-2M0 or cT1N1-2M0 bladder cancer patients were enrolled in the study. NAC consisted of a maximum of 4 cycles platinum-based chemotherapy. cN0 patients received NAC after PLND, while cN+ patients (confirmed by fine needle aspiration) received NAC prior to PLND. RT/P consisted of concurrent P (7 weekly doses of 2.5 mg/kg) and bladder RT (66Gy in 33 fractions). Primary end-points were treatment-related toxicity and complete clinical response (CR) assessed by Computed Tomography and cystoscopy 3 months after therapy completion. Partial response (PR) was defined as cT < 2N0. Results: A total of 31 patients were included (mean age: 60±10 years), 3/31 patients were cN1-2. Three patients discontinued NAC after 3 cycles due to toxicity. After NAC (24 cisplatin-based and 7 gemcitabine/carboplatin) 13 (41.9%) patients had remaining visible disease. All patients completed RT, while 4/31 patients terminated P prematurely (2-6 doses) due to toxicity. Preliminary response results after RT/P were available for 29/31 patients. Twenty-six/29 (89.7%) patients had a CR, 3 patients PR (10.3%) of which 2 were treated with transurethral resection and intravesical treatment (TaG1-2) and 1 patient underwent immediate cystectomy after histologic confirmation of T1G3. Conclusions: These preliminary results suggest that concurrent P and RT following NAC and PLND is an organ-preserving option for IBC. Toxicity, EGFr expression, mutational status and long-term oncologic outcomes have to be awaited. Clinical trial information: NL31148.031.10.
Effect of chemotherapy and/or TURBT on pathologic response in patients receiving neoadjuvant chemotherapy for muscle-invasive bladder cancer.
Authors: Brant Aaron , Kates Max , Chappidi Meera , Patel Hiten D. , Sopko Nikolai A. , Bivalacqua Trinity J. 
Published: February 2017

395 Background: Neoadjuvant chemotherapy (NAC) for muscle−invasive bladder cancer (MIBC) has been associated with a survival benefit in patients who achieve pathologic response. However, a smaller but significant group of patients who receive transurethral resection of bladder tumor (TURBT) without NAC will also be down−staged. We estimated the prevalence of pathologic response to TURBT in patients who receive NAC. Methods: Of 737 serial patients who received radical cystectomy (RC) at Johns Hopkins Medical Center from 2005–2014, 328 with cT2 urothelial carcinoma were identified. 172 patients received NAC and TURBT, while 156 received only TURBT prior to RC. Demographic, clinical, and pathologic information was compared between groups using Wilcoxon−Mann−Whitney for continuous and chi−squared for categorical variables. Pathologic response was defined as < pT2 at RC. A Poisson regression model with robust error variance was used to determine relative risk (RR) of pathologic response in NAC vs. non−NAC patients, adjusting for age, body mass index (BMI), race, gender, Charlson score, smoking status, days from MIBC diagnosis to surgery, and history of prior non−MIBC (NMIBC). Results: Pathologic response was higher in NAC patients compared to non−NAC patients (62% vs. 21%, RR = 3.00). NAC patients were significantly younger than non−NAC patients (64.8 vs. 71.2 years, p < 0.01), with higher BMI (28.1 vs. 26.7 kg/m2, p < 0.01), lower frequency of Charlson score ≥ 3 (13.4% vs. 26.7%, p < 0.01), and lower frequency of prior NMIBC (9.4% vs. 22.4%, p < 0.01). Adjustment resulted in a RR of pathologic response in NAC vs. non−NAC patients of 2.50 (95% CI: 1.69−3.69, p < 0.01). Assuming no interaction between NAC and TURBT, this adjusted model suggests that in a cohort of patients who receive NAC, 40% (95% CI: 27–59%) of pathologic response can be attributed to TURBT. Conclusions: An adjusted model suggests that in a cohort of patients who receive NAC and TURBT prior to RC, 40% of pathologic response can be attributed to TURBT. An understanding of which patients are true responders to chemotherapy and which receive a therapeutic TURBT is needed to select optimal candidates for NAC.
Diagnostic and therapeutic workup of patients with hematuria: Analysis of 1048 consective patients in a German outpatient service.
Authors: Eisenhardt Andreas , Heinemann Daniel , Niedworok Christian , RÃƒÂ¼bben Hebert 
Published: February 2017

399 Background: The diagnostic workup of patients with hematuria especially microhematuria is discussed controversially. For this reason the diagnostic and therapeutic procedures of 1049 patients with hematuria referred to our urological outpatient service in the years 2011-2012 were analysed. Methods: A number of 1049 consecutive patients with hematuria referred to the outpatient service Praxisklinik Urologie Rhein-Ruhr in the years 2011-2012 were retrospectively included into the analysis. The following parameters were measured: demographic data, concomittant diseases, clinical symptoms regarding the urinary tract, history of cancer or radiation of the pelvis, diagnostic and therapeutic procedures. Results: The median age was 58 years and the study group comprised 479 men and 570 women. A number of 160 patients had a urinary tract infection within 4 weeks of presentation and 89 individuals presented with macrohematuria. Symptoms of urolithiasis occured in 148 patients. All patients had ultrasound of the genitourinary tract and 731 were examined by excretion urogram, 111 patients via CT-scan of the abdomen and 888 individuals via urethrocystoscopy. Further workup revealed 77 stones via radiological examination and a total of 11 renal cell cancers, 57 papillary urothelial tumors of the bladder, 1 tumor of the ureter and 6 muscle-invasive bladder tumors were detected. Conclusions: Our data presented here reassures invasive diagnostic workup of patients with hematuria due to the fact that cancer of the genitourinary tract is detected in more than 5 percent of patients.