bluuebunny/crossref_metadata_2025_split huggingface dataset:
PLUTO: A randomised phase II study of pazopanib versus paclitaxel in relapsed urothelial tumours.
Authors: Powles Thomas , Hussain Syed A. , Protheroe Andrew , Birtle Alison , Chakraborti Prabir R , Huddart Robert , Jagdev Satinder , Bahl Amit , Stockdale Andrew , Sundar Santhanam , Crabb Simon J. , Dixon-Hughes Judith , Alexander Laura , Bray Caroline A , Stobo Jamie , Wimalasingham Akhila Ganeshi , Ackerman Charlotte , Paul James , Jones Rob 
Published: February 2017

430 Background: Two previous single arm trials have drawn conflicting conclusions regarding pazopanib in urothelial bladder cancers (UBC) after failure of platinum-based chemotherapy. PLUTO is a randomized phase II trial to compare the efficacy of pazopanib with paclitaxel in this setting. Methods: It was planned for 140 patients with progressive, advanced UBC (with at least a component of transitional cell carcinoma) who had previously received a single prior platinum containing chemotherapy regimen for advanced UBC to be randomised(1:1). Patients in arm A received weekly paclitaxel 80mg/m2 and those in arm B received pazopanib (800mg once daily) until progression. The primary endpoint was overall survival analysis of which would occur after 110 events. The efficacy was assessed by an independent data monitoring committee during the trial. Results: Between Aug 2012- Oct 2014, 131 patients were randomised. 74.0% of patients had visceral metastases. The study was terminated early by the IDMC due to futility of pazopanib. Final analysis after 110 deaths occurred in July 2015. The median number of cycles of paclitaxel received was 4 (12 weeks). The median time on pazopanib was 11 weeks. Median overall survival was 8.0 months for paclitaxel [80% confidence interval (CI) 6.9 to 9.7 months] and 4.7 months for pazopanib [80% CI 4.2 to 6.4 months]. The hazard ratio (HR) adjusted for baseline stratification factors was 1.25 [80% CI 0.96 to 1.63; 1-sided p = 0.86] in favour of paclitaxel. Median progression free survival was 3.2 months for paclitaxel [80% CI 2.9 to 5.0 months] and 3.1 months for pazopanib [80% CI 2.7 to 3.8 months]. The adjusted HR for PFS was 1.06 [80% CI 0.83 to 1.36; 1-sided p = 0.62] (in favour of paclitaxel). Discontinuations for toxicity occurred in 6.3% and 20.0% for paclitaxel and pazopanib respectively. VHL, HIF1alpha, VEGFR2 and PD-L1 expression were measured from archived tissue and correlated with outcome. Conclusions: Pazopanib does not have greater efficacy than paclitaxel in the second line treatment of UBC. There is a trend towards superior OS with paclitaxel. Clinical trial information: NCT00949455.
Sarcopenia as a marker for prediction of long-term survival following radical cystectomy.
Authors: Kramer Mario , Hensen Bennet , Jansen Max Clemens , Hennig Martin JP , Hupe Marie C , Tezval Hossein , Wacker Frank , Kuczyk Markus A. , Merseburger Axel S. 
Published: February 2017

435 Background: Patients undergoing radical cystectomy (RC) face a relevant risk of tumor relapse and mortality based on variable factors. Risk stratification may be enhanced by objective measures such as sarcopenia (loss of skeletal muscle mass) which has been described as a potential biomarker associated with survival after radical cystectomy. However, data on this highly interesting biomarker in conjunction with urothelial carcinoma of the bladder are sparse. Methods: A retrospective study including patients that were treated with RC at Hannover Medical School between 2005 and 2011 were included. The lumbar skeletal muscle index (SMI) was measured on preoperative computed tomography (CT) which was performed within 60 days prior to surgery. MeVisLab 2.7 was used to perform calculations. The fat mass index (FMI) was calculated based on the same CT slides. The body mass index (BMI) was used as a comparative value. Cut off points were developed for men and women separately. Results: Indices were measured on 103 patients (79 men, 24 women, mean age: 67.5 yrs). 72 (70%) pts. had muscle-invasive disease, 21 (20%) pts. were lymph node positive and 6 (6%) pts. had synchronous metastasis. Median follow-up time was 39 months. SMI (cm2/m2), FMI (kg/m2) and BMI (kg/m2) for men were calculated with mean scores of 51.2, 9.6 and 27.0, respectively. The corresponding calculated means for women were 38.7, 10.0 and 25.3. None of the stratification markers correlated with overall survival (OS) using Kaplan-Meier plots. However when applied on patients that survived at least 12 months, the sarcopenia index (SMI) became statistically significant (p < 0.05). Conclusions: The presence of sarcopenia may be predictor of poor overall survival later than 12 months after radical cystectomy. BMI and FMI may not be used in risk stratification models. Further research is needed to validate the current findings.
TOUCAN: A randomised phase II trial of carboplatin and gemcitabine +/- vandetanib in first line treatment of advanced urothelial cell cancer in patients who are not suitable to receive cisplatin.
Authors: Jones Robert J. , Crabb Simon J. , Chester John D. , Elliott Tony , Huddart Robert Anthony , Birtle Alison J. , Evans Linda , Lester Jason Francis , Huang Chao , Casbard Angela Claire , Madden Tracie-Ann , Griffiths Gareth 
Published: February 2017

448 Background: Whilst cisplatin combination therapy remains the standard of care for patients with advanced urothelial cancers, many patients are unsuitable for cisplatin and go on to receive carboplatin combination therapy. Although responses are frequent, overall outcomes remain poor, and there is a high unmet need for more effective first line treatment. Vandetanib is a well-tolerated, oral inhibitor of vascular and epidermal growth factor receptor tyrosine kinases, both of which are implicated in the pathogenesis of urothelial cancers. Methods: Patients with metastatic or inoperable urothelial cancer who had no prior chemotherapy and were unsuitable for cisplatin were randomly allocated to receive carboplatin (AUC 4.5, day 1) plus gemcitabine (1000mg/m2, days 1 and 8) plus either vandetanib (100mg od, days 1-21) (GCV) or matching placebo (GCP) in 21-day cycles up to a total of 6 cycles. Treatment allocation was double-blind. There was a planned safety review after the first 40 patients had received at least one cycle. The primary endpoint was progression free survival (PFS). Sample size (n=82) was calculated using a one-sided alpha of 0.2 and power 80% to detect a HR of 0.65 for PFS. We present the final efficacy results. The trial was coordinated by the Wales Cancer Trials Unit at Cardiff University and funded by Cancer Research UK (CRUK/09/024) and AstraZeneca. Results: Of 82 patients, 40 received GCV. 62 (76%) had a bladder primary, and 56 (68%) had poor renal function. The arms were well balanced except for age > 75 (13 (16%) GCV, 23 (28%) GCP). Median PFS was 8.5 months (m) (95% CI 6.0, 9.7) and 8.8 m (5.8, 9.0) for GCV and GCP respectively (adjusted hazard ratio (HR) 0.93 (0.50, 1.71), P=0.89). Overall survival was 10.8 m (8.0, 13.0) and 13.8 m (11.1, 16.6) for GCV and GCP respectively (adjusted HR 1.38 (0.77, 2.46), P=0.24). Response rates were 50% (n=20) and 55% (n=23) for GCV and GCP. All-grade adverse events were similar but there were significantly more grade 3+ events in the GCV arm. Conclusion: Vandetanib did not improve efficacy of chemotherapy but increased toxicity in advanced urothelial cancer not suitable for cisplatin. Clinical trial information: 68146831.
The relationship between travel distance to cystectomy and likelihood of readmission.
Authors: Sukhu Troy , Lomboy Jason , Macey Matthew , Meyer Anne-Marie , Meng Ke , Nielsen Matthew Edward , Pruthi Raj , Wallen Eric , Woods Michael , Smith Angela 
Published: February 2017

462 Background: Population-based estimates of readmissions following cystectomy range from 25-43%. Recent studies have investigated the relationship between complications and other patient- and hospital-level factors; however, the relationship between distance traveled for surgery and risk of readmission remains unclear. We hypothesized that larger distances would increase the risk of readmission following surgery. Methods: Using a linked data resource combining NC Central Cancer Registry with administrative claims data from Medicare, Medicaid, and private insurance plans, we included adult patients undergoing radical cystectomy for bladder cancer from 2003-2008. Complications were carefully coded and grouped based on previously published standards: genitourinary, gastrointestinal, wound, infection, venous thromboembolism, and others. Travel distances were calculated by using straight-line distances between zip codes of the patient and cystectomy provider. Bivariable analyses were performed, and multivariable logistic regression was used to evaluate the association of travel distance to cystectomy with likelihood of readmission within 30 and 31-90 days. Results: Of 735 patients who underwent cystectomy, 171 (23%) were readmitted within 30 days, and n = 156 (21%) were readmitted between 31-90 days. Mean age was higher among those readmitted, but was statistically non-significant. No significant differences were noted based on race, stage, comorbidity status, or complication type. However, on bivariable analysis, distance to the cystectomy provider > 30 miles was associated with a higher likelihood of readmission (p = 0.0009). On multivariable analysis, the only predictor of 30-day readmission was a longer travel distance to the cystectomy provider (OR 1.27, 95% CI: 1.05, 1.54). Results were also analyzed for 31-90 day readmissions, but no significant predictors were identified. Conclusions: Longer travel distance to a cystectomy provider is associated with higher 30-day readmission rates, suggesting that complications occurring during this time period may benefit from closer follow-up.
Molecular tumor grading of non muscle invasive bladder cancer based on whole transcriptome analysis.
Authors: Shen Jess , Noon Aidan , LIU Yu , Kuk Cynthia , Ilczynski C , Ni R , Sukhu B , Chan K , Gunaratne Adrian , Erlich Annette , Cremer Chris , Morris Quaid , Barbosa-Morais Nuno L , Fleshner Neil Eric , Kulkarni Girish S. , Blencowe Ben , Azad Azar , van der Kwast Theodorus , Zlotta Alexandre , Wrana Jeff L 
Published: February 2017

467 Background: There is an unmet need for a comprehensive genomic characterization of non muscle invasive bladder cancer (NMIBC). NMIBC comprise over 70% of all bladder cancers at presentation. They have highly variable clinical behavior that is not always adequately predicted on the basis of their histological grade (2004 World Health Organization low and high grade, LG-HG). The discrepancy between phenotype and genotype is compounded further by interobserver variability in pathological grading. We have previously established methods for whole transcriptome RNAseq from formalin fixed paraffin embedded tissues (FFPE). Methods: Whole transcriptomic analysis of 110 NMI FFPE BC both LG and HG was performed incorporating messenger RNA expression, splice variants, gene fusion, and pathway perturbation. We used a discovery (n = 40) and a validation cohort (n = 70). These data were integrated and tested for correlation with both pathological grading and clinical outcomes. Grade Risk Index (GRI) score quantifying how closely a patient's transcriptome is related to a reference set of LG NMIBC samples was established. Conventional pathological grading was reviewed by 3 different expert uro-pathologists and interobserver variability calculated. Results: Unsupervised clustering of data from RNA sequencing uncovered classification of three robust - - nonoverlapping, prognostically significant subtypes of NMIBC with distinct GRIs and signatures. When applied by expert pathologists, interobserver variability in histological grading was observed in 17.5%. In the intermediate group (GRI 0.13 to 0.19), pathologists disagreed in 37.5% whether BC was LG or HG. HG NMIBC clustered with MIBC. LG NMIBC in the intermediate GRI group included either very bulky tumors or extremely rare metastatic LG BC (n = 4). HG disease was associated with a shift in BMP signaling and a germ stem cell-like phenotype. Multiple components of the centromere complex and APOBEC3B were upregulated in HG BC. FGFR3::TACC3 fusion events were observed in LG NMIBC only (11.5%). Conclusions: Whole transcriptomic sequencing data delineated three molecular classes of NMIBC.
Baseline neutrophil to lymphocyte ratio as a prognostic marker for patients with muscle-invasive bladder cancer being treated with neoadjuvant chemotherapy.
Authors: Kaiser Jeenan , Li Haocheng , Seah Jo-An , Leibowitz-Amit Raya , North Scott A. , Sridhar Srikala S. , Heng Daniel Yick Chin , Alimohamed Nimira S. 
Published: February 2017

468 Background: The neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, has been associated with a poor prognosis in several solid malignancies. In muscle-invasive bladder cancer (MIBC), an elevated pre-cystectomy NLR has been shown to predict for poor survival; however, its role in prognostication for patients being treated with neoadjuvant chemotherapy (NAC) is unknown. We evaluated the baseline NLR as an independent prognostic factor in patients with MIBC treated with NAC. Methods: Patients with MIBC treated with NAC in Alberta from 2005 to 2015, and at the Princess Margaret Hospital in Ontario from 2005 to 2013 were evaluated. All 290 patients treated with NAC were included; 272 were evaluable for NLR and outcomes. Patient, disease, and treatment-related factors were evaluated. NLR was examined prior to initiation of preoperative chemotherapy. The prognostic role of NLR on overall survival (OS) and progression-free survival (PFS) was determined using Cox proportional hazard regression analysis. Results: The median age of patients was 66 years (range 36-87). The majority of patients (77%) were male. Median baseline NLR at diagnosis was 2.9. NLR > 3.0 at baseline was independently associated with PFS and OS after adjustment for age, gender and stage (Table). Patients with an NLR > 3 had a median PFS of 14.1 months compared to 25.1 months in those patients with a baseline NLR ≤ 3 (HR 0.63, p = 0.01). Similarly, OS was 19.4 months in patients with a baseline NLR > 3 compared to 33.4 months in those with a baseline NLR ≤ 3 (HR 0.65, p = 0.04). Conclusions: NLR is an independent prognostic factor for patients with MIBC undergoing NAC. [Table: see text]
Optimization of an imaging protocol for stage I seminoma surveillance based on variations in relapse location over time.
Authors: McPartlin Andrew , Hosni Ali , Bedard Philippe L. , Hansen Aaron Richard , Jewett Michael A.S. , Hamilton Robert James , O'Malley Martin , Sweet Joan , Warde Padraig Richard , Chung Peter W. M. 
Published: February 2017

475 Background: Surveillance is recommended for patients with stage I seminoma post orchidectomy but CT imaging involves ionising radiation, with risk of associated secondary malignancies. We assessed site of disease relapse during surveillance to guide development of a risk adapted imaging protocol. Methods: Data was obtained from a prospectively maintained database of patients with stage I seminoma on surveillance after orchidectomy from 1981-2011. Relapse was determined by clinical and/or radiographic finding with or without pathological confirmation or tumour marker elevation. Results: 753 patients were identified. The median age at orchidectomy was 33.7 years. With a median follow up of 10.5 years, range 1.1-30.1, 115 (15.3%) patients relapsed. Relapse was detected radiologically in 114 (99.1%), with 9 (7.8%) having simultaneously elevated tumour markers. A clinical diagnosis of relapse was made in 1 case (inguinal node – 0.9%). The location and time to relapse are shown in table. Conclusions: In stage I seminoma surveillance, pelvic nodal relapse was restricted to the early period of follow up. Excluding the pelvis during CT imaging after the third year of surveillance may optimise the detection of relapse whilst minimising total radiation exposure. This has now been adopted at our centre since 2011 without any subsequent late pelvic relapses. [Table: see text]
Prognostic factors of adjuvant chemotherapy with taxane, cisplatin, and 5FU combination (TPF) in patients (pts) with nodal metastases of penile squamous cell carcinoma (PSCC).
Authors: Necchi Andrea , Lo Vullo Salvatore , Nicolai Nicola , Raggi Daniele , Giannatempo Patrizia , Colecchia Maurizio , Catanzaro Mario , Torelli Tullio , Piva Luigi , Biasoni Davide , Stagni Silvia , Mariani Luigi , Salvioni Roberto 
Published: February 2017

479 Background: Little is known about the outcomes and prognostic factors of adjuvant chemotherapy for locally advanced PSCC after regional lymphadenectomy (LAD). Perioperative TPF combination regimen showed activity in PSCC in our series (Nicolai N et al, Clin Genitourin Cancer 2015). Methods: We retrospectively reviewed the clinical and histological data of 21 pts who had received 3-4 cycles TPF (q3wks) in the adjuvant setting at our center. Univariable and multivariable Cox regression analyses were done evaluating potential prognostic factors of disease-free (DFS) and overall survival (OS) of TPF: number of prior LAD, time from diagnosis of nodal disease to start TPF, time from LAD to start TPF, pN3, pelvic, and bilateral nodal disease, and p53 immunohistochemical (IHC) expression in nodal metastases. Results: Pts had received TPF from 07/04 to 07/12, after inguinal (n = 6) or inguinal + pelvic LAD (n = 15) and the median follow up was 52 months. LAD was radical in all cases and none had received radiotherapy. After surgery, 13 (61.9%) had pelvic and 5 (23.8%) bilateral inguinal nodal metastases. Median time from LAD to TPF was 5.4 wks (IQR: 4.1-7.3) and median time from diagnosis of N disease to TPF was 8.3 wks (IQR: 4.1-15.4). 11 of 19 available pts (57.9%) had p53+ve IHC. Univariably, only p53+ve IHC trended to poorer DFS (HR: 4.14, 95%CI: 0.87-19.68, p = 0.074) and OS (HR: 4.54, 95%CI: 0.95-21.56, p = 0.056). The same results were obtained multivariably for DFS (HR: 3.76, 95%CI: 0.78-17.96, p = 0.096) and OS (HR: 4.29, 95%CI: 0.89-20.57, p = 0.067). The bias-corrected c-indexes of the models were 0.64 and 0.62, respectively. Median DFS was 8.9 months (IQR: 5.9-22.7) for p53+ve pts vs not estimable (NE) for p53-ve pts (p = 0.051) and median OS was 17.2 months (IQR: 12.8-22.7) and NE, respectively (p = 0.037). Conclusions: In pts who had received adjuvant TPF for node-positive PSCC, p53 IHC positivity seemed to be associated with poorer outcome, and further study is warranted in larger datasets to confirm these findings. This information might be useful to select the optimal candidates to multimodal therapy for advanced PSCC.
Pazopanib in patients (pts) with advanced germ cell tumors (GCT): Results from an open-label, single-group, phase 2 trial (Pazotest-01).
Authors: Necchi Andrea , Raggi Daniele , Giannatempo Patrizia , Calareso Giuseppina , Togliardi Elena , Nicolai Nicola , Crippa Flavio , Mariani Luigi , Salvioni Roberto 
Published: February 2017

481 Background: Therapeutic options for pts with chemoresistant GCT are limited and prognosis is poor. Pazopanib (PZP) is a potent and selective tyrosine kinase inhibitor (TKI) with distinct antiangiogenic activity. Methods: Pazotest-01 enrolled pts who were given PZP 800 mg/day orally until disease progression (PD) or unacceptable toxicity. Eligibility included failure of ≥ 2 platinum-based regimens, including high-dose chemotherapy (HDCT). Baseline serum tumor markers (STM), a computed tomography and a FDG-PET were repeated after 4 wks of PZP and q8 weeks thereafter. The primary endpoint was PFS (H0: 3-month PFS ≤ 10%, H1: ≥ 25%, α = 5%/β = 20%). PD was defined as rising STM, an increase in tumour size, or the appearance of new lesions. An enrolment of 43 pts was planned from a single center (NCT01743482). Results: From 05/2013 to 07/2015, 32 pts were enrolled (27 [84.4%] with nonseminoma, including 5 [15.6%] with malignant transformation, and 5 seminomas). 5 (15.6%) had primary mediastinal nonseminoma (PMNSGCT). 3 had failed two prior regimens, 15 (46.9%) three, and 14 (43.7%) > 3 regimens, including HDCT in 15 (46.9%). 20 (62.5%) had liver, bone, or brain metastases. 29 pts had elevated STM: 18 of them (62.1%) had a STM decline (mean: -53.5%). 1 PR, 19 SD (64.5% clinical benefit) and 12 PD were obtained according to RECIST v1.1. 8 pts (25%) had a densitometric and 10 (29%) a metabolic partial response. The kinetics of response was predictable in all pts: best response was seen within 4wks of starting PZP, neither PR nor STM decline occurred > 4wks. Median follow up was 15.7 months. Median PFS was 2.73 months, 3-month PFS was 28% (95%CI: 13.3-44.8). 4 pts (12.5%) were progression-free at > 5 months FUP (including 1 PMNSGCT). Median OS was 4.9 months. 4 cases (12.5%) of G3 AST/ALT increase, and 1 case of G3 diarrhea and vomiting each have been observed. 7 pts (21.9%) had G2 asthenia. Conclusions: PZP is endowed with potent anti-tumor activity in extensively pretreated patients with GCT. PZP was well tolerated, and the combination with paclitaxel is a rational next step to improve the response duration. The primary endpoint is pending confirmation in the full sample-size, and mature results will be presented. Clinical trial information: NCT01743482.
An update on penile cancer: Evaluating management trends and clinical outcomes using the National Cancer Data Base.
Authors: Mossanen Matthew , Holt Sarah , Gore John L. , Lin Daniel W. , Wright Jonathan L. 
Published: February 2017

492 Background: Penile cancer remains a rare disease in the United States and may be associated with substantial morbidity and even mortality. Though the understanding of penile cancer is limited by the uncommon nature of the disease, the use of large volume datasets may help reveal recent management trends and clinical factors associated with treatment. We sought to describe penis cancer management over the past several years using the National Cancer Data Base. Methods: We performed a retrospective review of data obtained from the National Cancer Data Base from 1998-2012. We analyzed patient characteristics, demographic information, and therapeutic approaches within two clinical scenarios: 1) use of partial penectomy for early stage (clinical Ta-T2 disease); and 2) use of chemotherapy for metastatic disease. We performed multivariate logistic analysis to determine factors associated with these treatments. Results: A total of 2,677 patients presented with cTa-T2 penile carcinoma. Of these, the proportion receiving partial penectomy increased from 73.9% in 1998-2000, to 80.4% in 2010-2012 (p < 0.001). Compared to those aged 50-59, partial penectomy was more common in the old (age > 80, OR 1.52, 95% CI 1.05 – 2.20) and young (age < 50, OR 1.47, 95% CI 1.04 – 2.07). Treatment at academic centers and those without insurance were less likely to receive partial penectomy (both p < 0.01), as were patients with cT2 and node positive disease (both p < 0.001). Of those presenting with metastatic disease (n = 817), use of chemotherapy increased over the time period from 39% receiving chemotherapy in 1998-2000, to 49% in 2010-2012 (p <0.03). Patients least likely to receive chemotherapy were older and with higher Charlson Comorbidity score (both p < 0.05), African American (OR 0.46, 95% CI 0.29 – 0.70), and those living > 50 miles from the nearest treatment hospital (OR 0.37, 95% CI 0.25 – 0.55). Conclusions: Penile sparing surgery and use of chemotherapy are becoming more commonly utilized over the last several years. Multiple factors appear to be associated with these trends, and further work is needed to define both clinical and non-clinical factors associated with treatment.