bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prerandomization factors and utilization of neoadjuvant chemotherapy in a clinical trial of extended versus standard pelvic lymphadenectomy at the time of radical cystectomy for bladder cancer.
Authors: Lerner Seth P. , Li Hongli , Svatek Robert Scott , Koppie Theresa M. , Alva Ajjai Shivaram , La Rosa Francisco G. , Bangs Rick , Pal Sumanta Kumar , Daneshmand Siamak , Kibel Adam S. , Canter Daniel J. , Tangen Catherine M. , Thompson Ian Murchie 
Published: February 2017

295 Background: Despite level I evidence supporting the use of cisplatin-based NAC, this practice has not been widely adopted. We assessed contemporary utilization of NAC within the context of an ongoing prospective clinical trial (SWOG S-1011; NCT01224665) in order to identify clinical and/or demographic factors that are associated with receipt of NAC. Methods: S1011 tests the hypothesis that an extended pelvic lymphadenectomy (PLND) is associated with a 10-12% improvement in recurrence-free survival compared to a standard PLND among patients with clinical stage T2-4aN0-2M0 urothelial cell carcinoma of the bladder. Patients are registered prior to RC and are randomized intra-operatively to extended vs. standard PLND. Receipt of NAC, including type and duration are is a stratification factor and prospectively recorded at registration. We evaluated the association of pre-randomization factors, including age, gender, clinical stage, performance status, and institution with the receipt of NAC. Results: 243 patients have been registered as of 9/18/2013 and 229 randomized. Among randomized patients, 119 (52%) received NAC, including 97 (82%) treated with cisplatin-based NAC. The most common NAC regimens, Gem-Cis (gemcitabine-cisplatin) and MVAC (methotrexate, vinblastine, adriamycin, and cisplatin), were administered to 58 and 35 patients, respectively. 63% (40/64) of patients with cT3-4a disease received NAC vs. 48% (79/165) with cT2. There was no association of age, gender, race, ethnicity or PS with receipt of NAC. Among 8 institutions with at least 10 patients registered, the range of utilization of neoadjuvant chemotherapy received was 7% to 83%. Reason for not giving NAC is recorded at time of registration and a detailed analysis will be presented. Conclusions: Interim analysis of S1011, a prospective surgical trial, reveals the highest rate of integration of NAC with RC to date and reflects a considerable change in evidence based practice patterns. The institutional variation in utilization of NAC warrants further exploration of factors influencing delivery of care. Clinical trial information: NCT01224665.
Molecular profiling of infiltrating urothelial carcinoma of the bladder.
Authors: Millis Sherri Z. , Bryant David , Basu Gargi Dan , Bender Ryan , Vranic Semir , Gatalica Zoran , Vogelzang Nicholas J. 
Published: February 2017

311 Background: Infiltrating urothelial carcinoma (UC) is the most common variant of urinary bladder cancer. The prognosis for muscle infiltrating or metastatic UC of the bladder is poor with no major advances made in the last 20 years. We investigated a large cohort of such patients for specific genetic/biomarker alterations and compared them to other, less common urothelial malignancies. Methods: We reviewed 602 cases; 518 cases (86%) were locally advanced or metastatic UCs of the bladder and the remaining 84 cases (14%) were non-bladder UCs. Multiple methodologies for optimal assessment of biomarker expression (Caris Molecular Intelligence, Caris Life Sciences, Phoenix, AZ) were employed: Mutation analysis (Next-generation sequencing, Sanger, pyrosequencing, qPCR, RFLP), in-situ hybridization (fluorescent and chromogenic), immunohistochemistry, and RNA fragment analysis. Results: Bladder UC showed slightly higher rates of HER2/neu gene amplification (12% in bladder vs. 6% non-bladder, p=0.32) and EGFR gene amplification (22% vs. 12%, p=0.25). HER2/neu and EGFR protein expressions were more common in the bladder than in non-bladder sites (10% vs. 1%, p=0.03, and 77% vs. 60%, p=0.5, respectively). Pathogenic mutations in HER2/neu and EGFR were rare. Although c-Kit and c-Met receptor kinases were more frequently overexpressed in bladder than in non-bladder cancers (10% vs. 6% and 25% vs. 8%, respectively), activating mutations were also rare. PIK3CA and/or PTEN mutations were more frequently observed in non-bladder (27%) than in bladder UCs (21%). Non-bladder UC harbored high FGFR3 gene mutation (33%), which was not observed in any of the UC of the bladder (p=0.02). TP53 gene mutations were frequently identified in both bladder and in non-bladder cancers (49% vs. 27%, respectively, p=0.15), while KRAS was frequently mutated in the bladder adenocarcinomas (56%, p<0.001). Other therapeutically targetable biomarkers over-expressed in bladder UC compared to non-bladder UC included androgen receptor (16% vs. 8%, p=0.07) and MGMT (63% vs. 47%). Conclusions: Comprehensive molecular profiling of urothelial carcinoma identifies a number of potentially actionable targets, which can be managed by the novel treatment modalities.
Cancer-specific survival in patients with urothelial carcinoma of the bladder with recurrence after radical cystectomy: External validation of the prognostic risk stratification model.
Authors: Nakagawa Tohru , Kume Haruki , Kanatani Atsushi , Ikeda Masaomi , Matsumoto Akihiko , Taguchi Satoru , Hiramatsu Kanae , Komemushi Yoshimitsu , Kawai Taketo , Enomoto Yutaka , Kondo Yasushi , Suzuki Motofumi , Fujimura Tetsuya , Fukuhara Hiroshi , Okaneya Toshikazu , Hirano Yoshikazu , Tomita Kyoichi , Tanaka Yoshinori , Nishimatsu Hiroaki , Homma Yukio 
Published: February 2017

325 Background: Prognosis of the patients with urothelial carcinoma of the bladder (UCB) who developed recurrence after radical cystectomy (RC) is generally poor, but can be variable. We previously showed that shorter time to recurrence (TTR) after RC, presence of symptoms on recurrence, more than one metastatic sites (organs), high serum C-reactive protein (CRP) level were associated with decreased survival in those patients, and proposed a model to stratify patients into 3 separate risk groups (Nakagawa et al. J Urol. 2013; 189:1275). The aim of this study was to evaluate the prognostic value of this model in a multi-institutional cohort of patients. Methods: We identified 267 patients who experienced disease recurrence after RC for UCB from 9 academic and community hospitals. Patients were categorized into three groups based on the presence of four risk factors, TTR of <1 year, presence of symptoms on recurrence, more than one metastatic sites (organs), and CRP level of ≥0.5 mg/dl: the favourable risk group included patients with none or one of these risk factors; the intermediate risk group with 2 risk factors; and those with 3 or 4 risk factors were assigned to the poor risk group. Results: Overall, median survival time (MST) of the entire cohort was 8.3 months (95%CI, 6.4-9.1). Two hundred and nineteen patients died of their disease with a median survival of 5.9 months. In a multivariate analysis, all of the 4 risk factors were statistically significant for the cancer-specific survival. Sixty-five (27.4%), 84 (35.4%), and 88 (37.1%) patients were in the favorable, intermediate and poor risk group, respectively. Thirty patients were excluded because CRP value was not obtained. MSTs of the patients in the favorable, intermediate and poor risk group were 22.2 (95% CI 16.1-28.3), 7.6 (95% CI 6.3-9.5), and 3.6 (95% CI 2.6-4.4) months, respectively, and the difference was statistically significant (p<0.001, log-rank test). Conclusions: We confirmed the prognostic value of our previous criteria based on the four variables in patients with recurrence after RC for UCB. This criteria would help in patient counseling and clinical trial design.
Association of time delays to radical cystectomy by use of neoadjuvant chemotherapy with higher rates of progression.
Authors: Parker William P. , Nehra Avinash , Griffin Joshua , Lopez-Corona Ernesto , Holzbeierlein Jeffrey M. 
Published: February 2017

345 Background: Neoadjuvant chemotherapy (NC) is utilized to improve survival for patients with muscle invasive bladder cancer. However, this results in a protracted treatment course of 3−4 chemotherapy cycles given over several months. Previous series have suggested that delays in radical cystectomy (RC) from initial diagnosis are associated with inferior survival rates. We investigated if similar trends are seen in a population of patients treated with neoadjuvant chemotherapy. Methods: A retrospective review of our RC database was performed to identify patients treated with NC over the last five years. Time interval was calculated from date of initial diagnosis of muscle invasive disease to date of surgery. Kaplan Meier and multivariate analysis methods were used to assess recurrence free and cancer specific survival based on pathologic stage, nodal status, margin status, and time to RC with estimation of hazard ratios for those variables. Results: 72 patients from 2006−2012 were identified. Mean age was 64 years and 80% were male. 79% of the cohort had 3 or more cycles of NC, with gemcitabine−cisplatin as the most common regimen (75%). Mean time from diagnosis to RC was 173 days. Pathologic stage distribution was T2−20.8%, T3−20.8%, T4− 18.1% and T0 status was obtained in 27.8%. 95% was of pure urothelial carcinoma histology. Node positive disease was found in 30%. At most recent follow up 33% of the cohort had died and 13% had recurrent disease. Higher tumor stage and positive nodal status were associated with lower recurrence free and cancer specific survival. When stratifying the cohort by time to RC (1−4 months, 5months, 6 months) there was no statistical difference in recurrence free or cancer specific survival. However, on multivariate analysis patients who had RC less than 5 months from diagnosis had lower rates of progression (OR 0.14; 95% CI .02−.08, p 0.038) compared to those with RC after 5 months (OR 4.86 95% CI 0.9−26, p 0.06). Conclusions: Time delays associated with use of NC of greater than five months correlated with lower recurrence free survival in our cohort but there did not appear to be any effect on cancer specific survival. This should be further validated with a larger multicenter analysis.
Forward and inverse-planned intensity-modulated radiotherapy (IMRT) in the CHHiP trial: A comparison of dosimetry and normal tissue toxicity.
Authors: Naismith Olivia Frances , Griffin Clare , Syndikus Isabel , Mayles Helen , Hall Emma , Dearnaley David Paul ,   CHHiP Trial Management Group
Published: February 2017

37 Background: CHHiP (CRUK/06/016) is a multicentre randomised controlled trial investigating the use of hypofractionated radiotherapy dose schedules for treatment of localised prostate cancer. RT treatment employs a complex target volume treated with either a multi-segment “forward” plan or inverse-planned intensity-modulated radiotherapy (IMRT). This study compares dose-volume histogram (DVH) and toxicity data for rectum and bladder for the two planning techniques. Methods: Three hundred thirty seven patients (230 forward-planned [F]; 107 inverse-planned [I]) with prospectively collected 2 year toxicity and DVH data for rectum and bladder dose constraints were included. Patients were paired for comparison by matching on (1) rectum and prostate + seminal vesicle PTV volumes for the rectal dose comparison (53 matched pairs available); and (2) bladder and prostate-alone PTV volumes for bladder dose comparison (61 matched pairs). For the toxicity comparison patients were additionally matched on randomised dose schedule. Results: Forward-planned patients had significantly larger volumes of rectum irradiated to 50 to 70Gy and bladder at 50 to 60Gy. In contrast, inverse-planned patients had significantly larger volumes of bladder irradiated to 74 Gy. Acute bowel toxicity (G2+ toxicity within 18 weeks of start of RT) was significantly worse in forward-planned patients (27/53 [52%] F vs 11/53 [21%] I; Mann-Whitney p=0.0002). There were no significant differences in acute urinary symptoms. Late toxicity was rare in both planning groups with only two patients (0 F; 2 I) reporting RTOG G2+ bowel/bladder effects at 24 months. Considering LENTSOM data, there was a suggestion of less late bowel toxicity in the inverse group (G1+ at 18 months: 16/53 (30%) F vs. 6/53 (11%) I; p=0.008). Patient reported outcomes of bowel habits showed no consistent differences between planning methods, although there was a tendency for worse urinary function scores in the inverse group at 12 months. Conclusions: Both planning techniques were associated with low late toxicity. Significant differences were found between DVHs from forward and inverse plans. There were some associations between DVH differences and normal tissue effects; these resolved by 2 years. Clinical trial information: CRUK/06/016.
Postoperative complications of radical nephrectomy with atrial thrombectomy: A contemporary population-based analysis.
Authors: Borza Tudor , Chung Benjamin I. , Chang Steven L. 
Published: February 2017

423 Background: The mainstay treatment for patients with stage T3c renal cell carcinoma is radical nephrectomy with atrial thrombectomy (RN−AT). Although this procedure is widely recognized to have substantial morbidity and mortality, little data exist on the actual rates of postoperative complications. Using a contemporary population−based cohort, we sought to determine the postoperative complication rates among patients undergoing RN−AT. Methods: We queried the Premier Perspective Database (Premier, Inc, Charlotte, NC) to identify patients that underwent nephrectomy (ICD9 55.51) between January 1, 2003 and December 31, 2010. We limited our analysis to patients who concurrently underwent cardiopulmonary bypass, determined through billing codes, as these patients were assumed to have undergone RN−AT. We captured patient and hospital data as well as determined 90−day postoperative complications defined by the Clavien System through review of ICD9 codes and disposition data. Results: Our study cohort included a weighted sample size of 1417 patients; the majority were men (63.7%) and Caucasian (61.9%) with a mean age of 58 years. One−third of patients had metastatic disease while one−quarter had significant comorbidities (i.e., Charlson Comorbidity Score (CCS) ≥2). Ninety−day major complication (Clavien grade 3−5) was present in 38% of patients with half (19%) suffering mortality (Clavien grade 5). The predictors of a major complication included age <50 years (vs >70 years, Odds Ratio [OR] 3.1, p=0.01), CCS ≥3 (vs CCS 0, OR 5.7, p<0.0001), and surgery in an urban hospital (vs rural, OR 8.5, p=0.047). Increased complication rate was not associated with gender, race, metastatic disease, teaching institution, or hospital size. Conclusions: We confirm that RN−AT is associated with significant morbidity and mortality. The mortality rate for this procedure exceeds those reported for other complex surgeries. The higher complication rate seen in younger patients is likely secondary to selection bias. This information is important for preoperative counseling for patients considering RN−AT. Future studies are needed to compare the outcomes of RN−AT versus systemic therapy.
Everolimus as second-line therapy for metastatic renal cell carcinoma (mRCC) after one previous VEGF-targeted therapy: Final results of the noninterventional change study.
Authors: Goebell Peter J. , Kube Ulrich , Staehler Michael , Doehn Christian , Steiner Thomas , Kindler Manfred , Herrmann Edwin , Janssen Jan , Weikert Steffen , Scheffler Michael Thomas , Schmitz Joerg , Overkamp Friedrich , Guderian Gernot , Albrecht Michael , Bergmann Lothar 
Published: February 2017

469 Background: The mTOR inhibitor everolimus is approved for the treatment of mRCC following failure of VEGF-targeted therapy. To evaluate the effectiveness and tolerability of everolimus following the first VEGF-targeted therapy in routine clinical practice, we conducted the prospective, noninterventional CHANGE study in Germany. Methods: Patients (pts) with mRCC (any histology) were registered at the time of everolimus initiation, or within 90 days thereof, following treatment with either VEGFR-TKI or bevacizumab. Other previous systemic therapies (e.g., cytokines) were permitted. Pts received everolimus 10 mg/d according to the summary product characteristics until disease progression or intolerable toxicity. Study objectives included assessing treatment duration, time to progression (TTP), progression-free survival (PFS), Karnofsky performance status (KPS), and safety. Results: 334 pts were documented at 116 German sites between August 2009 and January 2012 (median age, 68 years; 75% male; median KPS, 80%; 88% clear cell histology). At the start of first-line therapy, MSKCC risk status was favorable in 35%, intermediate in 56%, and poor in 9%. Effectiveness results are shown in the table. In the safety population (n=318), median time to ≥10% deterioration in KPS was 8.4 months (95% CI, 6.1-10.1 months); the most common AEs (any grade) were dyspnea (17%), anemia (14%), and fatigue (12%). Treatment adherence was high, with <2% of patients per visit showing <50% intake of the expected doses. Conclusions: The CHANGE study demonstrates favorable effectiveness and tolerability for everolimus when given in routine clinical practice to pts with mRCC. Our data confirm the use of everolimus as a standard second-line therapy following VEGF-targeted treatment. [Table: see text]
MRC SORCE trial: Analysis of patients' presenting characteristics, tumor staging, and surgical approach.
Authors: Ritchie Alastair W. S. , Meade Angela M. , Choo Louise , Smith Ben , Welland Andrew , Gregory Adam , Kaplan Richard S. , Eisen Tim ,   SORCE Trial Management Group
Published: February 2017

496 Background: SORCE is a randomised double blind trial of sorafenib, given for one or three years, versus placebo for patients at moderate or high risk of disease recurrence after surgical excision of primary renal cell carcinoma (RCC). Methods: Between July 2007 and April 2013, 1,711 patients were recruited from the UK (78%), Australia, France, Belgium, Denmark, The Netherlands and Spain. We describe the presenting characteristics, staging and surgical details of the randomised population. The surgical approach was at the surgeon’s discretion. Results: Baseline information is available for 1,681 patients (98%). Median age was 59 years (range 19 to 86): 1,195 (71%) were male. Histology was conventional/clear cell in 86%. T category was pT1a (<1%), pT1b (11%), pT2 (23%), pT3a-4 (65%). 47% were at high risk of recurrence with Leibovich scores of ≥6. Surgical data are available for 1,528 patients (89%). Total (radical) nephrectomy was performed for 97% of patients with 44% having laparoscopic surgery, of which 60% had a transperitoneal approach and 10% required conversion to open surgery. Some form of lymph node dissection was performed in 25% of patients (33% of open procedures and 15% of lap. procedures). The ipsi-lateral adrenal was removed in 47% and 11% had simultaneous resection of other structures/organs. Excision of venous extension was required in 19%. Laparoscopic procedures were performed for 58% of patients with maximum tumour diameter (MTD) <10cm and 17% of those with MTD ≥ 10 cm. Intra-operative complications were reported in 6% and post-operative complications reported in 12%. Hospital stay was median (IQR) 4 days (3-5) for patients having laparoscopic procedures and 7 days (5-8) for open surgery. Hospital stay was median (IQR) 8 days (6-11) for those having post-operative complications compared to 5 days (4-7) for uncomplicated recovery. Conclusions: These data reveal the varied surgical approaches to excision of primary RCC and will inform future adjuvant trials. The use of lymph node dissection appears arbitrary and evidence of benefit from randomised controlled trials is required. Analysis of the effect of sorafenib on disease free survival is likely to be performed in 2016. Clinical trial information: ISRCTN38934710.
Renal nephrometry score and predictors of complications in partial nephrectomies.
Authors: Pruthi Deepak K. , Drachenberg Darrel E , McGregor Thomas B 
Published: February 2017

512 Background: Feasibility of partial nephrectomy for small renal masses extends beyond standard clinical tumor size. We analyze patient characteristics and anatomic tumor factors to determine variables associated with surgical complications after partial nephrectomy. Methods: Retrospective review of all patients who underwent partial nephrectomy at our institution between January 1, 2012 and Aug 31, 2013. Follow-up extended to 8 week post-operative outpatient clinic visit. The R.E.N.AL. Nephrometry score is a tumor descriptive (the maximum radius, exophytic/endophytic, nearness to collecting system/sinus, anterior/posterior position, location relative to polar line) that was applied to each pre-operative scan. Standardized grading systems and statistical analysis were applied. Results: Of the 83 patients who underwent partial nephrectomy 72 had a laparoscopic approach. Seventeen (20%) patients had complications and seven were Clavien-Dindo grade 3 to 4. Two patients had laparoscopic partial nephrectomies converted intra-operatively to radical nephrectomies; two other laparoscopic partial nephrectomies were converted to open partial nephrectomies. Forty-three (52%) of operated patients were either obese, morbidly obese, or super obese. Fifteen (18%) of patients had pathologic oncocytomas or angiomyelipomas. In univariate analysis Charlson comorbidity score (>6 p=0.0027), diabetes (42% p=0.0195), age (>70 p=0.02034), and total R.E.N.A.L. Nephrometry score (10-12, 67%, p=0.0254) were associated with complications. Nephrometry score also correlated with warm ischemic time (WIT) in laparoscopic cases (low 26 min [SD +/- 11.71], intermediate 31 min [SD +/- 7], high 34 min [SD +/- 14]). Conclusions: Categorizing renal masses according to the R.E.N.A.L. Nephrometry score may help us council patients towards expected WITs, complication rates, and predicted renal function outcomes. This is increasingly important as the majority of our patients are either obese, elderly, or have significant comorbidities; all of which have been shown to be associated with increased complication rates.