bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of prior platinum on patients receiving salvage systemic therapy for advanced urothelial carcinoma (UC).
Authors: Sonpavde Guru , Pond Gregory Russell , di Lorenzo Giuseppe , Buonerba Carlo , Rozzi Antonio , Lanzetta Gaetano , Necchi Andrea , Giannatempo Patrizia , Raggi Daniele , Matsumoto Kazumasa , Choueiri Toni K. , Mullane Stephanie A. , Niegisch Guenter , Albers Peter , Lee Jae-Lyun , Kitamura Hiroshi , Kume Haruki , Bellmunt Joaquim 
Published: February 2017

386 Background: Trials of salvage therapy for advanced UC have required prior platinum-based therapy. This practice requires scrutiny since non-platinum-based first-line therapy may be offered to cisplatin-ineligible patients (pts). We examined the impact of prior exposure to first-line platinum vs. non-platinum based chemotherapy on overall survival (OS) with salvage systemic chemotherapy. Methods: Data of pts receiving salvage systemic chemotherapy were collected retrospectively or from trials. Data on prior first-line platinum exposure were required in addition to the known prognostic factors: treatment free interval, hemoglobin, performance status, albumin and liver metastasis status. Cox proportional hazards regression was used to evaluate their association with OS after accounting for salvage therapy with single agent chemotherapy or combination chemotherapy. Results: Data was obtained from 455 pts exposed to prior platinum and 37 pts not exposed to prior platinum. In the group exposed to prior platinum, salvage therapy consisted of a single agent taxane (n = 184) and taxane containing combination chemotherapy (n = 271). In the group not exposed to prior platinum, salvage therapy consisted of single agent taxane or vinflunine (n = 20), single agent 5-fluorouracil (n = 1), taxane containing combination chemotherapy (n = 12), carboplatin-based combinations (n = 2) and cisplatin-based combinations (n = 2). The median OS for the prior platinum group was 7.8 (95% CI: 7.0, 8.1) months (mo), and for the prior non-platinum group was 9.0 (6.0, 11.0) mo (p = 0.50). In a multivariable analysis including major prognostic factors and after controlling for single agent or combination salvage chemotherapy, prior platinum vs. no prior platinum exposure conferred no independent impact on OS (HR 1.10 [0.75, 1.64], p = 0.62). Conclusions: Prior platinum vs. non-platinum based chemotherapy did not confer a prognostic impact on OS after accounting for major prognostic factors in pts receiving salvage systemic chemotherapy for advanced UC. Lack of exposure to prior platinum should not disqualify pts from inclusion in trials of salvage therapy after accounting for the 5 known prognostic factors.
Impact of tumor location on local recurrence after nephroureterectomy for upper tract urothelial carcinoma: Implications for adjuvant radiotherapy.
Authors: Yoo Sangjun , You Dalsan , Jeong In Gab , Song Cheryn , Hong Bumsik , Hong Jun Hyuk , Ahn Hanjong , Kim Choung-Soo 
Published: February 2017

390 Background: To date, risk factors for local recurrence after complete removal of upper tract urothelial carcinoma (UTUC) have not been clearly identified. We evaluated the impact of tumor location on local recurrence in UTUC patients underwent radical nephroureterectomy. Methods: Among UTUC patients who underwent radical nephroureterectomy between 1998 and 2012, 192 (54.4%) patients with renal pelvic tumor and 161 (45.6%) patients with ureter tumor were included. Local recurrence was divided into regional lymph node recurrence (LNR) and surgical bed recurrence (SBR). The significance of tumor location and other variables on local recurrence were evaluated. Results: Lymphovascular invasion (p = 0.003), carcinoma in situ (p = 0.006) and high grade tumor (p < 0.001) were more common in ureter tumor. During median follow-up period of 73 months, local recurrence was occurred in 33 (9.3%) patients. Among subtype of local recurrence, SBR (8.1 vs. 2.1%, p = 0.011) were more common in patients with ureter tumor compared to renal pelvic tumor although the probability of regional LNR was not significantly different according to tumor location (7.5% vs. 3.1%, p = 0.088). 5-year local recurrence-free survival (80.5% vs. 94.2%, p = 0.002), LNR-free survival (89.8 vs. 96.5%, p = 0.046) and SBR-free survival (88.3% vs. 97.6%, p = 0.005) were inferior in ureter tumor compared to renal pelvic tumor. Ureter tumor (HR; 2.552, p = 0.017), high grade tumor (HR; 3.064, p = 0.016) and advanced tumor stage (≥T3) (HR; 3.236, p = 0.002) were associated with local recurrence. Ureter tumor (HR; 4.704, p = 0.002) and advanced tumor stage (HR; 4.840, p = 0.006) were risk factors for SBR. However, tumor location was not associated with LNR although lymphovascular invasion (HR; 5.451, p < 0.001) and high grade tumor (HR; 4.191, p = 0.012) were related with LNR. Conclusions: Ureter located tumor was associated with local recurrence which comes from the SBR. Adjuvant radiotherapy or surgical technique for reducing the risk of SBR should be considered in patients with ureter tumor.
Metastatic bladder neoplasms treated with stereotactic body radiosurgery.
Authors: Lederman Ariel Joseph , Loksen Mordecha , Lowinger Thomas , Izon Daniel , Lederman Gilbert S. 
Published: February 2017

397 Background: Stereotactic Body Radiosurgery (SBR) as treatment for metastatic bladder cancer delivers high dose radiation precisely to the site of cancer. In our prospective data analysis, 20 sites of extravesical bladder cancer treated with SBR were analyzed. Methods: Twenty metastatic bladder neoplasms were treated in 15 patients. Sixteen were transitional cell carcinoma, 2 adenocarcinoma, 1 squamous cell carcinoma, and 1 rhabdomyosarcoma. Ages ranged from 39 to 82 years (mean 64) with 4 females and 11 males. Tumor volumes ranged from 10.2 to 563 cc (mean 129.8 cc). Patients were treated with 500-900 cGy (median 800) in 5-8 fractions (median 5) for a total dose of 3000-4500 cGy (median 4000). Cancers were radiographically evaluated with contrast CT and/or MRI studies and reviewed independently by radiologists. Disease control is defined as cessation of growth, shrinkage or disappearance of the tumor after treatment. Results: Follow-up ranged from 1 to 20 months (mean 8 months). The overall control rate was 90%. Both patients who did not respond to treatment were males with transitional cell carcinoma. By dose, volume, age, sex and prior treatment, there was no statistically significant difference in outcome among the 20 patients treated. Conclusions: SBR for metastatic bladder cancer offers a well-tolerated, non-invasive technique with a high rate of tumor control. Patients continue to be evaluated for longer follow up, possible benefits of local control and potential survival advantage. SBR remains an option for those whom standard approaches have not produced desired results or in patients seeking an alternative to surgical or chemotherapeutic treatment.
NBI-assisted cystoscopy to improve follow-up of patients with transitional cell carcinoma of the bladder.
Authors: Eisenhardt Andreas , Hirner Lucas , Ruebben Herbert 
Published: February 2017

400 Background: Narrow Band Imaging (NBI) is a new technique of urethrocystoscopy, in which only a certain bandwidths of illumination (415 (blue) and 540nm (green)) of the spectrum is used to detect urothelial carcinoma. The aim of the investigation was to analyse the potential benefit of NBI in the follow up of patients with transitional cell carcinoma of the bladder. Methods: In the time between August 2013 until August 2014, patients with history of transitional cell carcinoma of the bladder, who presented for follow-up cystoscopy , were either examined via flexible white light endoscopy [WLE] plus second look WLE (n = 317, controls) or second look NBI-cystoscopy alone (n = 308) in the same session. Results: Rates of recurrences were similiar in both groups (NBI 95 (25%); WLE 85 (26.8%)). NBI after WLE identified more tumours in 21 patients (6.1 vs. 3.81). In 9 patients NBI showed no vascularization in suspicious areas. In the control arm, in 9 cases more tumours (4,67 vs. 3.33) were identified in the second WLE. After macroscopical identification of a recurrence, the time since the last resection was measured (WLE 10,67 months, NBI 16,85 months). Conclusions: While the number of patients with recurrent bladder cancer is not influenced by the use of NBI, the additional use of NBI in the follow-up cystoscopy of patients after transurethral resection of superficial bladder cancer (TUR) leads to an increased number of detected tumors. A part of the additionally detected tumors can be explained by the double examination. In addition NBI appears to provide a hint in individual cases whether a TUR is necessary at all.
Development and validation of contouring guidelines for post-cystectomy adjuvant radiation of bladder cancer.
Authors: Baumann Brian C. , Bosch Walter , Bahl Amit , Birtle Alison J. , Breau Rodney H. , Challapalli Amarnath , Chang Albert , Choudhury Ananya , Daneshmand Siamak , Feldman Adam S. , Guzzo Thomas J. , Hilman Serena , Jani Ashesh B. , Malkowicz S. Bruce , Master Viraj A. , Mitra Anita , Porten Sima P. , Efstathiou Jason A. , Eapen Libni , Christodouleas John Paul 
Published: February 2017

409 Background: Several organizations are developing clinical trials to evaluate adjuvant radiotherapy (RT) for bladder cancer patients at elevated risk of locoregional failure (LF). However, the clinical target volumes (CTVs) & organs at risk (OARs) for this treatment have not been defined in detail. Our purpose was to define multi-institutional consensus CTVs & OARs for male & female bladder cancer patients undergoing adjuvant RT in clinical trials. Methods: We convened a multi-disciplinary group of bladder cancer specialists from 9 centers in 3 countries. 5 radiation oncologists (ROs) & 7 urologists participated in the development of the proposed contours. The group proposed initial language for the CTVs & OARs and contoured them on CT scans of a male & female cystectomy patient with input from ≥ 1 urologist at each center. Using the binomial maximum-likelihood estimates method, we generated 95% level initial contours. We evaluated the contours for level of agreement using the Landis & Koch interpretation of the K statistic. Based on the initial contouring, the group updated its descriptions of the CTVs & OARs. To determine if the revised language produced consistent contours, the cystectomy bed (CB) contour was redrawn on the CT sets by an additional 5 ROs. Results: The group proposed that patients at elevated risk for LF with R0 resections should be treated to the pelvic nodes alone (internal/external iliac, distal common iliac & presacral) whereas patients with ≥ R1 resections should be treated to the pelvic nodes & CB. The group proposed the rectum, bowel space, bone marrow & urinary diversion as OARs. The level of agreement for the initial CTVs & OARs from the group varied substantially (Table). Consensus language to describe CTV & OAR structures where the initial contours varied was successfully developed. Contours & feedback from the validation group are being analyzed. Conclusions: Initial descriptions of CTVs & OARs have been successfully developed. External validation & feedback are pending. The results will be applicable to clinical trials of adjuvant RT in bladder cancer. [Table: see text]
Safety and efficacy of combination therapy with low-dose gemcitabine, paclitaxel, and sorafenib in patients with cisplatin-resistant urothelial cancer.
Authors: Miyata Yasuyoshi , Ohba Kojiro , Matsuo Tomohiro , Sakai Hideki 
Published: February 2017

418 Background: Various chemotherapeutic regimens have been examined. However, there is no effective regimen, and some studies have been stopped because of severe adverse events. Therefore, maintenance of quality of life is also important. This study examine the anti-cancer effects, changes in the quality of life (QoL), and safety of combined therapy of low dose gemcitabine, paclitaxel, and sorafenib in these patients. Methods: Twenty patients were treated with gemcitabine (700 mg/m2 on day 1), paclitaxel (70 mg/m2 on day 1), and sorafenib (400 mg/day on days 8–22). QoL and pain relief were evaluated using the short-form survey (SF)-36 and the visual analogue scale (VAS). Data on QoL and pain were collected on the day before the first cycle was started and 8 weeks after starting the therapy. A total of 124 cycles were administered and the median (IQR) number of treatment cycles per patient was 5 (3–8) cycles. Results: Among 20 patients, 12 and 8 patients were received as 2nd- and 3rd-line therapy, respectively. In 2nd-line therapy, median / interquartile range of VAS scores after therapy (2 / 2–3) significantly decreased (p = 0.012) compared to their pretreatment levels (3 / 2–5). Likewise, a significant decrease was also found in 3rd-line therapy (5/ 4–6 to 3/ 2–3, p = 0.028). Similar findings were confirmed by the bodily pain score from the SF-36 survey. A decrease in analgesic consumption was seen in three patients (17.6%), and 2 patients (11.8%) was improved the pain without increasing the dose. Complete responses, partial responses, and stable disease were found in 0 (0.0%), 1 (5.0%), and 13 patients (65%), respectively. The period of overall survival after starting of this therapy was 7 (5–11) months. Three patients (15.0%) stopped therapy because of grade 3 fatigue and hand-foot reactions. Conclusions: Combined therapy of low dose gemcitabine, paclitaxel, and sorafenib was well tolerated. QoL was maintained and improvements in their pain levels were found after treatment. We suggest that this treatment regimen is worthy of consideration as 2nd- and 3rd-line therapy for patients with CDDP-resistant UC. Clinical trial information: 000010957.
Treatment of urinary bladder cancers by growth hormone-releasing hormone antagonists: A preclinical report.
Authors: Rick Ferenc G. , Popovics Petra , Block Norman L. , He Jinlin , Zhang Xian Yang , Vidaurre Irving , Szepeshazi Karoly , Schally Andrew V. 
Published: February 2017

433 Background: Urinary bladder cancer is the fifth most frequent cancer diagnosed and among the most expensive cancers to treat in the United States. The management of muscle-invasive tumors presents a clinical challenge because of the toxicity and limitations in efficacy and durability of current therapeutic modalities. Novel therapeutic strategies for this disease are of paramount importance. Growth hormone-releasing hormone (GHRH) receptors and its splice variant were detected in a series of urothelial malignancies and GHRH has been shown to influence the growth of these tumors. Herein we evaluated the effect of GHRH antagonists on the growth of various experimental human urinary bladder cancers in vitro and in vivo in nude mice. Methods: We investigated the effects of several GHRH antagonists MIA 602, MIA 606 and MIA 690 on growth of urothelial HT-1376, J82, and RT-4 tumors xenografted into nude mice. The presence of GHRH receptors was validated by Western blotting. Results: The receptors for GHRH and their main splice variant, SV1, were detected in tumor samples of all 3 human bladder cancer models. In the HT-1376 tumors, the GHRH antagonists caused a 30-60% reduction in volume and 52-70% decrease in tumor weights (p < 0.05). All three antagonists strongly inhibited growth of J82 cancers as shown by a 62-75% reduction in tumor volume and 54-66% decrease in tumor weights (p < 0.05). Treatment with MIA-602 and MIA-606 resulted in a similar marked inhibition of growth of RT-4 cancers; tumor volume and weights were reduced by about 51-71% in the treated groups (p < 0.05). The mice tolerated this therapy well; body and organ weights were not significantly changed by the treatments. No toxicity from the GHRH antagonists was noted. Conclusions: We demonstrated the efficacy of potent GHRH antagonists and their lack of toxicity in inhibiting the growth of experimental models of bladder cancer in vivo. The expression of GHRH receptors was detected in all 3 models of human primary urothelial bladder carcinomas. Our findings warrant further development of GHRH antagonists for clinical therapy of bladder cancer alone or in combination with current chemotherapeutic agents and Exploration of their mechanism of action.
The clinical impact of routine bladder biopsy after BCG treatment of high grade non muscle invasive bladder cancer.
Authors: De Jong Igle J. , Jonker Leonie Theresa , Weerink Maud Anne Sien , Cornel Erik Bastiaan , Luijendijk Daphne , Leliveld Anna Maria 
Published: February 2017

438 Background: The need for invasive and costly routine bladder biopsies after an induction course of intravesical Bacillus Calmette-Guérin (BCG) in patients with high-grade non-muscle invasive bladder cancer is being questioned. Previous studies focused on differences in tumor detection between cystoscopic, cytologic and histologic results, whereas the clinical impact was disregarded. The aim of this study is to determine the impact of routine bladder biopsies on treatment. Methods: This retrospective multicenter trial included 348 patients from four hospitals in the Netherlands, who had had their BCG therapy evaluated by routine bladder biopsies between 2005 and 2014. The results of urethrocystoscopy (UCS) and/or cytology were compared to pathology outcomes. The influence of malignancies missed by UCS and/or cytology on further treatment was analyzed in 348 patients and in subgroups of patients with and without carcinoma in situ (CIS). A number needed to test was calculated. Secondary outcomes were costs and complications. Results: In patients with a normal UCS, malignancies were detected in 27/228 (11,8%), 19/136 (14%) and 8/92 (8,7%) in respectively all patients, patients with CIS and patients without CIS. This resulted in a radical cystectomy in only six (2,6%) patients, of which five (3,7%) with and one (1,1%) without CIS. Thirty-eight patients with a normal UCS have to undergo routine biopsies to effect therapeutic treatment in one (Number needed to test, NNT = 38). Estimated costs of one change of treatment are $81.300 USD(€72.818). Twenty-three of 348 (6,6%) transurethral biopsies were complicated. Conclusions: Considering the small clinical impact and high costs, routine bladder biopsies to evaluate BCG-induction are not recommended. The decision to perform bladder biopsies should be based on cystoscopic and cytologic results.
Characterization of urothelial carcinoma with seminal vesicle involvement in locally advanced bladder cancer.
Authors: Salami Simpa Samuel , Udager Aaron , Miller Brady Garland , Palapattu Ganesh S. , Tomlins Scott , Chinnaiyan Arul M. , Spratt Daniel Eidelberg , Feng Felix Yi-Chung , Kunju Lakshmi Priya , Wu Angela J. , Morgan Todd Matthew , Weizer Alon Z. , Montgomery Jeffrey Scott , Lee Cheryl T. , Mehra Rohit 
Published: February 2017

440 Background: Muscle-invasive bladder cancer is associated with poor clinical outcomes, especially in locally advanced (pT4) disease. There is a paucity of data, however, regarding the clinical impact of seminal vesicle (SV) involvement. Therefore, we sought to characterize clinicopathologic features of patients with urothelial carcinoma involving seminal vesicles, and evaluate clinical outcomes in patients with locally advanced (pT4) bladder cancer with or without SV involvement. Methods: After institutional review board (IRB) approval, we retrospectively identified all men with pT4 (per the 7th edition of the AJCC Cancer Staging Manual) bladder cancer who underwent radical cystectomy between 2002 and 2013 at a single large academic institution. Clinicopathologic and follow-up data for all patients were obtained from the electronic medical record. The presence or absence of divergent differentiation, including aggressive forms (plasmacytoid, nested, micropapillary, and sarcomatoid), was recorded. Estimates of overall survival (OS) were compared by plotting Kaplan-Meier curves and using log-rank test. Results: A total of 62 patients were eligible for analysis. The median age and follow-up duration were 72 (range: 46 – 87) years and 12 (range: 0 – 141) months respectively. SV involvement was present in 17.7% (11/62) of patients. The frequency of divergent differentiation (including aggressive forms), angiolymphatic invasion, nodal disease (pN1-3), and positive soft tissue margins was relatively higher among those with SV involvement (not significant, all p >0.05). The 1 and 2-year OS for patients with SV involvement were 32.7% and 0% respectively, compared with 51.0 % and 24.9% respectively for patients without SV involvement. There was no statistically significant difference between the median OS of men with and without SV involvement (9 vs. 13 months, respectively; p = 0.19). Conclusions: In this relatively limited sample size cohort, we did not observe any difference in the overall survival of locally advanced bladder cancer patients with and without SV involvement.
The expression and clinical significance of PD-L1 in patients with upper tract urothelial carcinoma.
Authors: Sheng Xinan , He Zhisong , Kong Yan , Chi Zhihong , Si Lu , Cui Chuanliang , Tang Bixia , Mao Li Li , Wang Xuan , Lian Bin , Yan Xieqiao , Li Si Ming , Dai Jie , Guo Jun 
Published: February 2017

444 Background: Primary upper tract urothelial carcinoma (UTUC) is rare. In China UTUCs are more common than in Western populations and account for 20–30% of all TCCs.An antibody that targets programmed death ligand-1 (PD-L1) pathway has been shown to be active towards various types of cancer including bladder urothelial carcinoma. In this study, we investigated the PD-L1 expression and prognostic significance in UTUC. Methods: Formalin-fixed paraffin-embedded tumor samples from 78 patients with upper tract urothelial carcinoma from Peking University Cancer Hospital and Peking Universiy First Hospital were retrieved. PD-L1 expression was evaluated by immunohistochemistry using rabbit monoclonal anti-PD-L1 antibody. PD-L1 positivity on tumor cell membrane was defined as ≥ 1% of tumor cell membrane staining.The clinical data of patients were retrospective collected. The multivariate analysis was used to assess the association of PD-L1 expressionwith tumor staging, pathological N classification, whether firstly diagnosed with metastasis, disease free survival(DFS) and overall survival (OS) in patients. Results: The positive rates of PD-L1 expression were 42.3% (33/78) for upper tract urothelial carcinoma. Sex,location, pathological tumor staging, pathological N classification, whether firstly diagnosed with metastasis did not correlate with PD-L1 expression. In patients with upper tract UC, PD-L1 expression was not associated with DFS and OS on univariate analyses. Conclusions: To our knowledge, this is first study about PD-L1 expression in UTUC patients. In this study, We found the PD-L1 expression in UTUC was higher than in the bladder urothelial carcinoma. It means anti-PD-L1 treatment may be better for advanced UTUC. There was no correlation between PD-L1 expression and outcome.