bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing the perioperative management of postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) in patients with pure seminomatous and nonseminomatous germ cell tumors (NSGCT).
Authors: Pfister D. J. , Busch J. , Winter C. , Schrader M. , Dieckmann K. , Schmelz H. U. , Albers P. , Heidenreich A. 
Published: February 2017

230 Background: PC-RPLND is a potentially complicated intervention. By the time the rate of complications and adjunctive surgery increased. Only few data are available concerning PC-RPLND in patients with advanced seminomas and residual retroperitoneal tumour lesions. We examined the intra and postoperative complications as well as the frequency of adjunctive surgeries in patients with seminoma and compared the data to a cohort of patients with NSGCT who underwent PC-RPLND. Methods: In our multicenter retrospective analyses 408 patients underwent PC-RPLND between 1989 and 2010. 47 patients with advanced seminomas and 327 patients with NSGCT. The surgical approach was preferred via a midline incision or a thoracoabdominal approach due to the location of the residual tumour. In one center a laparoscopic approach was preferred. Results: Of the 47 patients with seminoma a total number of 18 adjunctive surgeries were performed in 11 patients (8 nephrectomies, 3 inferior v.cava resections, 3 resections of the abdominal aorta, 2 resections of the colon, one nerv and 2 hepatic resections/biopsies). There was only one major intraoperative complication, injury of the v. cava and two postoperative complications, (prolonged intestinal paralyses). There were no significant differences adjunctive surgeries and postoperative complications (p=0.48 and p=0.133). There were significantly less intraoperative complications in favour of seminomas (p=0.006). Conclusions: PCRLND in seminomas and NSGCT is a demanding surgical intervention. In contrast to other series we did not find significant differences in the two patient groups concerning adjunctive surgeries and postoperative complications. The indication for PCLND in patients with seminoma is limited, but if necessary it can be performed safely in experienced centers. No significant financial relationships to disclose.
Anthropomorphic and hormone abnormalities in testicular cancer patients.
Authors: Singhera M. , Coffey J. , McDonald F. , Horwich A. , Dearnaley D. P. , Rapley E. , Huddart R. A. 
Published: February 2017

233 Background: Studies show a range of environmental and genetic associations with testicular cancer, specifically testicular dysgenesis, increased height, and multiple dysplastic naevi. To confirm these findings, we studied a cohort of testicular cancer patients and healthy controls. We also studied a cohort of unaffected relatives of patients to identify if any noted differences might be due to shared genetic/environmental background. Methods: We identified index cases from the hospital database. They nominated an unaffected relative and an unrelated friend. Controls were supplemented by recruitment of institutional staff. Results: 183 index cases (IC), 57 unaffected relatives (UR) and 103 unrelated controls (UC) were identified. Mean age was 47 years (25-78) IC, 44 years (18-74) in UR and 42 years (20-74) in UC. IC treated by chemotherapy (ch) had higher mean FSH than non chemotherapy patients (s)[18.98 v 13.22 (p=0.01)] and lower mean testosterone [ch:12.21, s:13.52 (p=0.04)] though mean LH [ch:7.94, s:6.05 (p=0.10)] and BMI (ch:27.38 s:26.81 (p=0.33) were not significantly different. Conclusions: In contrast to other studies, we found both testicular cancer patients and their relatives were shorter and with reduced arm length compared with controls; a sign of a possible shared genetic or environmental effect. There was no significant difference in weight, BMI, body fat %, lean body mass, and leg length. FSH and LH were significantly elevated and testosterone reduced in index cases (but not relatives) particularly in those who had chemotherapy. The lack of difference between relatives and controls suggests these are most in keeping with direct treatment effects. [Table: see text] No significant financial relationships to disclose.
Germline single-nucleotide polymorphisms (SNPs) associated with response of urothelial carcinoma (UC) to platinum-based therapy: The role of the host.
Authors: Gallagher D. , Joseph V. , Garcia-Grossman I. R. , Przybylo J. A. , Riches J. C. , Ostrovnaya I. , Hamilton R. , Milowsky M. I. , Offit K. , Bajorin D. F. 
Published: February 2017

236 Background: Platinum-based therapy improves outcome in neoadjuvant and metastatic UC. Since cell-line and human subject studies in other cancers show germline associations with platinum response, we hypothesized that germline variation also identifies genes that determine UC response to platinum-based therapy. Methods: Saliva or blood was prospectively collected from 651 UC patients (pts) diagnosed between 1984 and 2010. SNPs (n=80) were selected based on previously reported associations with UC and/or platinum response and genotyped using Sequenom MassArray iPLEX system. Samples and SNPs were filtered for genotyping rate (<0.8), minor allele frequency (<0.05) and departures from Hardy-Weinberg equilibrium (<1E-03). Clinical data were ascertained and linked with the genomic data in an anonymized manner. This analysis focused on 199 pts who received cisplatin or carboplatin and were eligible for response assessment (RES=partial response or complete response, n=90). Associations between SNPs and RES were tested using one and two degree of freedom tests. Results: Sixty-nine pts received neoadjuvant therapy (RES=54%), 126 chemo-naive pts received first-line metastatic treatment (RES=37%) and 4 received systemic treatment after prior chemoradiotherapy (RES=25%). We expected 4 associations due to chance alone at p < 0.05. However, on univariate analysis using a 2 degree of freedom test, 9 SNPs were associated (p < 0.05) with RES. Individual odds ratios (ORs) ranged from 0.32 to 3.29 with p-values ranging from 0.006 to 0.05. In analysis of rs9344 (CCND1) in all treated pts, 75/148 (51%) responded with AG/GG compared to 12/44 (27%) with AA [p=0.005312, OR 2.74 (CI 1.34, 5.92)]. In neoadjuvant pts treated with cisplatin, rs9344 analysis showed 29/48 (60%) responses in AG/GG pts compared to 5/17 (29%) with AA [p=0.026, OR 3.66 (CI 1.16, 13.1)]. Conclusions: We identified associations between 9 SNPs and response of UC to platinum-based therapy that are biologically and clinically relevant. A larger study will be required to independently validate these findings. Additional investigation of associations with time to metastasis and overall survival is ongoing. [Table: see text]
Effect of a therapeutic sphingosine 1-phosphate antibody on intratumoral hypoxia and sensitivity to standard chemotherapy in prostate cancer animal model.
Authors: Cuvillier O. , Ader I. , Bouquerel P. , Malavaud B. , Sabbadini R. A. 
Published: February 2017

24 Background: Hypoxia promotes neovascularization, metastasis, growth and resistance to treatments. The activation of HIF-1α has been identified as the master mechanism of adaptation to hypoxia. We recently identified the sphingosine kinase 1/sphingosine 1-phosphate (SphK1/S1P) pathway as a new modulator of HIF-1α activity under hypoxia in multiple cancer cell models (Ader et al, Cancer Res, 2008). S1P elicits proliferation, survival, or angiogenesis, and is believed to exert most of its actions as a ligand for a family of specific GPCRs to elicit paracrine or autocrine signaling. We have suggested that inhibiting SphK1/S1P signaling, which is up-regulated under hypoxia, may help normalizing the tumor microenvironment and increase sensitivity to chemotherapy, in the broader concept of normalization of tumor vessels as tumor oxygenation is known to enhance response to chemotherapy (Ader et al., Cancer Res, 2009). Methods: Quantitation of hypoxia and angiogenesis, and treatment efficacy using an orthotopic (o.t) xenograft model of fluorescent HRPC cells. Results: We provide in vitro evidence that inhibiting the S1P exogenous signaling, through pharmacological inhibition of its receptors or by taking advantage of a monoclonal antibody neutralizing S1P, blocks HIF-1α accumulation and its activity in prostate cancer cells under hypoxia. Second, using an o.t model of prostate cancer, we show that an anti-S1P antibody inhibits intratumoral hypoxia and modifies vessel architecture within 5 days of treatment. Third, we demonstrate that an anti-S1P strategy sensitizes to docetaxel, the “gold standard” treatment for HRPC. A 5-day anti-S1P antibody pretreatment markedly sensitizes to docetaxel in an o.t. PC-3/GFP model established in nude mice. The combination anti-S1P antibodytogether withdocetaxel was not only accompanied by a smaller primary tumor volume compared to docetaxel alone, but also significantly reduced the occurrence and number of metastases. Conclusions: These data establish the proof-of-concept that blocking the exogenous action of S1P reduces intratumoral hypoxia and sensitizes to chemotherapy in prostate cancer animal model. [Table: see text]
Effect of EGFR inhibition with cetuximab on the efficacy of paclitaxel in previously treated metastatic urothelial cancer.
Authors: Wong Y. , Litwin S. , Plimack E. R. , Vaughn D. J. , Song W. , Cohen S. M. , Lee J. W. , Dabrow M. B. , Tuttle H. , Hudes G. R. 
Published: February 2017

243 Background: The benefit of salvage chemotherapy such as weekly paclitaxel (TAX) is modest in metastatic (met) urothelial ca, with median TTP of ≤3 months and ORR of 10% (95% CI 4-18% [combined results, Vaughn 2002; Joly, 2009]). Cetuximab (CET) is a monoclonal antibody against the epidermal growth factor receptor (EGFR). High-grade urothelial cancer overexpress EGFR. We conducted a multicenter randomized, noncomparative phase II study to measure the efficacy of CET ± TAX in patients (pts) with previously treated met urothelial cancer. Methods: Pts with met urothelial cancer who received one line of chemotherapy in the adjuvant, neoadjvuant, or met setting were enrolled. Pts were randomized to CET 250mg/m2 (after 400 mg/m2 load) ± TAX 80 mg/m2 weekly. A cycle was 4 weeks (wks). Response (RECIST) was assessed by imaging every 8 wks. We used early progression to assess futility (Litwin Stats Med 2007). Either arm would close if 7 of the initial 15 pts in that arm progressed at the first disease evaluation. Either arm would be considered promising if ≥9/28 patients had PFS>16 wks (90.4% power to detect an improvement in Median [Med] PFS from 8 to 16 wks with a 7.1% type 1 error). Results: We enrolled 39 evaluable pts (30 male). Median age was 69 years (range 49-79). All pts received prior platinum-based chemotherapy. CET arm closed after 9 of the first 11 pts progressed by 8 wks (ASCO GU 2009). CET-TAX arm completed full accrual (28 pts), of which 11 had visceral disease and 13 received chemo for met disease. 10/28 pts had PFS>16 wks. Overall RR was 28.5%, (8/28 pts, 95% CI 13-49%) (2 CR, 6PR). 4 additional pts had unconfirmed PR. 2 pts have maintained PR 3 and 4 months after discontinuing CET-TAX. Med PFS for the CET-TAX was 115 days (16 weeks)(95% CI 58-174 days). Med PFS for pts with visceral disease was 84 days (95%CI 50-NR). Med PFS for pts who received prior chemo for met disease was 142 days (95% 58-NR). Med number of cycles for the CET-TAX was 3 (range 0-25). Grade 3 AEs occurring in more than 2 pts were rash (5), fatigue (4), anemia (4), low magnesium (3). Conclusions: EGFR inhibition with CET appears to augment the antitumor activity of TAX in pts with previously treated urothelial cancers. The CET-TAX combination merits further study to establish its role in treatment of urothelial cancers. [Table: see text]
Prognostic factors of cancer recurrence and progression in non-muscle-invasive urothelial carcinoma: A multicenter study of over 4,300 patients.
Authors: Chromecki T. F. , Svatek R. S. , Holmäng S. , Karakiewicz P. I. , Mazumdar M. , Dunning A. , Kamat A. M. , Tagawa S. T. , Scherr D. , Shariat S. F. 
Published: February 2017

249 Background: The outcomes of patients with non-muscle-invasive urothelial carcinoma of the bladder (NMIUCB) remain poorly understood. The aim of our study was to identify prognostic factors of cancer recurrence and progression in patients with primary UCB. Methods: We performed a combined analysis on individual data from 4,325 patients with primary NMIUCB. Results: Within a median follow-up of 64 months, 1,960 patients (45.4%) experienced disease recurrence, 498 (11.5%) experienced progression to muscle-invasive stage, 1,155 (26.7%) died of any cause, and 310 (7.2%) died of their cancer. In multivariable Cox regression analysis, advanced age, higher grade, larger tumor size, higher number of tumors, number of prior recurrences, and type of intravesical therapy were independent predictors of disease recurrence and progression. While treatment intravesical chemotherapy was only associated with decreased/delayed cancer recurrence, intravesical BCG therapy was associated with decreased/delayed cancer recurrence and progression. The predictive accuracies of the models for recurrence and progression were 63.5% and 71.3%, respectively. Conclusions: Even in a heterogenous patient population, BCG therapy appears to decrease frequency and delay time to cancer recurrence and progression in patients with NMIUCB. Predictive tools based on combination of multiple clinical variables which capture the biological and clinical potential of nonmuscle-invasive disease could help with patient counseling and individualized risk assessment for adjuvant intravesical therapy and clinical trial design. [Table: see text] No significant financial relationships to disclose.
Low-dose versus standard-dose gemcitabine infusion and cisplatin for patients with advanced bladder cancer: A randomized phase II trial.
Authors: Khaled H. , Abu-Taleb F. , Haggag R. , Zekri A. 
Published: February 2017

266 Background: Bladder carcinoma is the foremost oncologic problem in Egypt. Prolonged infusion of gemcitabine and cisplatin is an effective treatment for advanced bilharzial-related bladder cancer based on a previously published phase II trial. Methods: To compare efficacy and safety of both prolonged infusion and standard gemcitabine-cisplatin combination, this phase II randomized study of 60 untreated patients with stage III/IV bladder cancer was conducted. Patients were randomized to receive either gemcitabine (250 mg/m2) 6-hour infusion on days 1 and 8, and cisplatin (70 mg/m2) on day 2 every 21-day cycle (Arm1) or gemcitabine (1,250 mg/m2) 30-min infusion on days 1 and 8, and cisplatin (70 mg/m2) on day 2 every 21-day cycle (Arm 2). Results: The 47 males and 13 females had a median age of 60 years (range 40-73 years). A total of 44 patients had transitional cell, 12 had squamous cell, and 4 had undifferentiated cell carcinoma. Among the 53 evaluable patients (26 patients in arm1 and 27 patients in arm 2), complete response rate was achieved in 19.3% (5/26 patients of arm 1) and 7.4% (2/27 patients of arm 2). Eight patients in arm 1 (30.7%) and 7 patients (25.9%) in arm 2 had partial response on therapy. Thus the overall response rate of patients in arm1 and arm 2 was 50% (13/26 patients) and 33.3% (9/27patients), respectively (p = 0.21). No significant difference in median time to disease progression (6.7 months versus 7.9 months, p = 0.42), median survival (9.7 months versus 8.8 months, p = 0.3), and 1-year survival (27% versus 6%, p = 0.3) was detected between arms 1 and 2, respectively. No treatment- related deaths occurred. Main hematologic and nonhematologic toxicities were similar in both arms with no statistically significant differences. Conclusions: In the treatment of advanced bilharzial bladder cancer, gemcitabine in low dose and prolonged infusion in combination with cisplatin is not inferior to high-dose short infusion gemcitabine and cisplatin in terms of overall survival, time to disease progression, and response rates with favorable toxicity profile and less financial costs. No significant financial relationships to disclose.
Use of cytokeratin 18 and EAU score to predict tumor recurrence in patients with non-muscle-invasive bladder cancer following single postoperative immediate intravesical chemotherapy instillation.
Authors: Horinaga M. , Murata S. , Matsushima M. , Nakahira Y. , Yanaihara H. , Ueno M. , Asakura H. 
Published: February 2017

269 Background: We examined the prognostic factors for recurrence after TURBT using molecular markers as well as the scoring system of the EAU. Methods: Eighty-eight patients with primary or recurrent bladder tumors who underwent TURBT followed by the single postoperative immediate instillation of pirarubicin and no further instillations were enrolled between 2003 and 2006; the median follow-up period was 46 months. The time to first recurrence was the primary end point of this study. Patients were divided into EAU recurrence risk groups as follows: low-risk group (total score, 0), intermediate-risk group (total score, 1-9) and high-risk group (total score, 9-17). The intermediate-risk group patients were subdivided into a total score of 1-4 and a total score of 5-9. Immunostaining using Ki-67, pHH3, CK18 and Survivin were performed on the TURBT specimens. Results: According to the risk stratification, 5, 82, and 1 were assigned to the low-, intermediate-, and high-risk recurrence groups, respectively. During the follow-up, recurrences were observed in 0% of the low-risk group, 45% (37 out of 82) in the intermediate-risk group and 100% in the high-risk group. We evaluated various predictors of a recurrence-free outcome among the 82 intermediate-risk patients. In univariate analyses, EAU score (1-4, 32.1% vs 5-9, 62.1%; p = 0.0011), high CK18 expression (negative, 31.4% vs positive 88.8%; p < 0.0001), high Ki-67 index (< 5%, 35.4% vs > 5%, 52.5%; p = 0.017) and high Survivin nuclear staining (< 5%, 35.9% vs > 5%, 62.5%; p = 0.004) were associated with recurrence. In a multivariate analysis, EAU score (HR 2.95, p = 0.003) and a high CK18 immunostaining (HR 6.70, p < 0.0001) were independent predictors of disease recurrence. Conclusions: A single immediate chemotherapy instillation is, by itself, insufficient for the treatment of patients in the intermediate- or high-risk recurrence groups defined by the EAU guidelines. Strong immunohistochemical expression of CK18 and the EAU scoring system appeared to be independent predictors of clinical outcome among patients with urothelial carcinoma of the bladder. No significant financial relationships to disclose.
Role of heat shock protein 90 inhibition with 17-(allylamino)-17 (demethoxygeldenamycin) in muscle-invasive bladder cancer cells.
Authors: Williams H. 
Published: February 2017

273 Background: Muscle invasive bladder cancer portends a poor long term prognosis. Platinum based therapy is the mainstay of treatment but more effective agents are needed for management of this disease. Heat shock protein 90 (Hsp90) is a ubiquitous protein that has been shown to be overexpressed in tumor cells. It functions as a molecular chaperone responsible for the stability and function of a number of proteins critical to the oncogenic process. 17-(allylamino)-17 demethoxygeldanamycin (17 AAG) is a Hsp90 inhibitor that is currently in phase III trials in several tumor models. The purpose of this study was to evaluate the role of 17 AAG treatment for bladder cancer in vitro. Methods: Seven bladder cancer cell lines representing muscle invasive bladder cancer were treated in the presence and absence of 17 AAG. Both short term and long term treatments were evaluated for their effects on growth, motility and invasion of the cancer cells. Expression of proteins involved in cell growth, survival and metastasis were evaluated with Western blotting. Results: Our data demonstrated that 17 AAG treatment resulted in induction of apoptosis, inhibition of cell cycle progression through inhibition of MAP kinase pathway and cyclin D1 expression. Decreased tumor cell motility and invasion was observed with 17 AAG treatment. Several intracellular signaling pathways involved in cell proliferation, invasion and metastasis were inhibited. Conclusions: Hsp90 inhibition in muscle invasive bladder cancer cells impacts growth, motility and invasiveness by inhibiting numerous intracellular signaling pathways. Taken together, these findings suggest a possible role for Hsp90 inhibitors in bladder cancer tumorigenesis. No significant financial relationships to disclose.
Phase II trial of neoadjuvant cisplatin, gemcitabine, and bevacizumab followed by radical cystectomy (RC) in patients with muscle-invasive transitional cell carcinoma (TCC) of the bladder.
Authors: Chaudhary U. B. , Golshayan A. R. , Brisendine A. , Kraft A. S. , Clarke H. , Keane T. E. 
Published: February 2017

276 Background: Cisplatin-based neoadjuvant chemotherapy has shown survival advantage in patients (pts) with muscle-invasive bladder cancer. This benefit is strongly associated with downstaging of tumor to pT0. It was hypothesized that the addition of antiangiogenic therapy bevacizumab (Avastin [A]) to cisplatin (C) and gemcitabine (G) chemotherapy may offer improved outcomes in these pts. Methods: Patients with clinically localized, muscle-invasive, chemotherapy-naive TCC of bladder (T2-T4a), ECOG PS 0-1 received cisplatin 70 mg/m2 IV day 1, gemcitabine 1000 mg/m2 IV day 1 and 8, bevacizumab 15 mg/kg IV day 1 on a 21- day cycle for up to 4 cycles. After completion of neoadjuvant therapy all pts underwent RC. Those pts not achieving pT0 status received paclitaxel 175 mg/m2 IV day 1 and bevacizumab 15 mg/m2 IV day 1 on a 21-day cycle for up to 3 cycles. The primary objective of the trial was to achieve pT0 status. Results: By October 2010, 15 pts were enrolled, and 13 are evaluable for response. Median age was 64 (range 47-71), 9 (70%) males, 4 (30%) females. 2/13 (15%) developed PD after neo-adjuvant therapy and were taken off protocol.11/13 (85%) underwent RC. 4/13 (31%) pts were downstaged, 3/11 (27%) achieved pTis status and none achieved pT0 status. 2/11 (18%) pts received adjuvant paclitaxel chemotherapy with bevacizumab. Dose reduction or delays were noted in 12/15 (80%) pts. Grade 3 or 4 hematologic toxicity was observed in 5/15 (33%) pts. Grade 3 or 4 nonhematologic toxicity was observed in 3/15 (20%) pts: (renal dysfunction 2 pts, pulmonary embolism 1 pt). Postoperative complications were seen in 5/12 (42%) pts: enterovesicular fistula (1), delayed wound healing (1), prolonged ileus (2), and pelvic abscess (1). With a median follow-up time of 12 months (range 3-45), 8/11 (72%) pts have remained disease free. Conclusions: Neoadjuvant CGA is feasible in pts with clinically localized, muscle-invasive TCC of the bladder. The surgical complications rate appears rather high and close monitoring is needed. Accrual to the trial continuous and updated results will be presented. No significant financial relationships to disclose.