bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity of single-agent bevacizumab (B) in patients with metastatic renal cell carcinoma (RCC) previously treated with VEGF- and mTOR-based therapies.
Authors: Armstrong Andrew J. , Turnbull James D. , Cobert Julien , Jaffe Tracy , Harrison Michael Roger , George Daniel J. 
Published: February 2017

435 Background: Given a lack of clinical information on therapeutic efficacy of agents following progression after vascular endothelial growth factor (VEGF) tyrosine kinase inhibition (TKI) and mammalian target of rapamycin (mTOR) inhibition in metastatic renal cell carcinoma (mRCC), we investigated the activity of single agent bevacizumab (B) in this setting. Methods: We conducted a retrospective analysis of single agent B-treated patients with mRCC in the second/third line setting, and identified 21 subjects who met inclusion criteria. The primary endpoint was progression-free survival (PFS). Baseline characteristics, survival, response efficacy outcomes, and toxicities were assessed and summarized. Results: 21 patients (15 women/6 men) were treated with B at a dose of 5 mg/kg/week, dosed q2-3 weeks. Median age was 63, 80% were white, 14% black; 80% had clear cell histology. Median time from diagnosis to B therapy was 3 years (range 1-18); 100% had prior VEGF TKI therapy; 43% had prior mTOR inhibitor; 43% had prior IFN and 19% prior IL-2; median number of prior therapies was 3 (range 1-7); 100% were considered Motzer intermediate risk. Median PFS on B for all subjects was 4.4 mo (95% CI 2.8-9.6) and median OS was 19.4 mo (95% CI 9.9-NR) from start of B therapy. ORR was 2 CR/PR (9.5%), 11 SD (52%), 5 PD, 3 NE. For subjects treated with prior VEGF and mTOR inhibitors, median PFS and OS were 4.4/13.2 mo. Toxicities were as expected and severe adverse events included grade 3-4 fatigue (6), grade 3-4 dehydration (5), and grade 4 failure to thrive (2), grade 4 constipation (2), and grade 3 muscle weakness (2). Conclusions: Single agent B therapy has acceptable toxicity and moderate disease stabilizing activity in selected patients with mRCC who have failed prior VEGF TKI and mTOR inhibitor therapy, and suggests a benefit to continued ongoing VEGF inhibition. Further prospective study of B alone, in combination with mTOR inhibition, or with alternative targeted agents is warranted.
Influence of risk factors for renal cell carcinoma (RCC) on outcome of patients (pts) with metastatic disease treated with sunitinib.
Authors: Keizman Daniel , Ish-Shalom Maya , Taksey Jason David , Pili Roberto , Hammers Hans J. , Eisenberger Mario A. , Boursi Ben , Berger Raanan , Maimon Natalie , Gottfried Maya , Hayat Henry , Peer Avivit , Kovel Svetlana , Sella Avishay , Carducci Michael Anthony 
Published: February 2017

437 Background: Obesity, smoking, hypertension (HTN) and diabetes (DM) are risk factors for RCC development. Their presence has been associated with a worse outcome of therapy (tx) in various metastatic cancers. We sought to determine their influence on the progression free survival (PFS) and overall survival (OS) of Su tx in mRCC. Methods: We performed a multicentre retrospective study of pts with mRCC, who were treated with Su. We analyzed the pre-tx status of smoking (active vs past vs never), BMI (obese=BMI≥30 vs overweight=BMI 25-29.9 vs normal weight=BMI <25), HTN, DM, and known prognostic factors including past nephrectomy, clear cell/non clear cell histology, time from initial diagnosis to Su tx, > 2 metastasis (mets) sites, lung/liver/bone mets, ECOG performance status, anemia, calcium level > 10 mg/dL, elevated alkaline phosphatase (AP), platelets count, pre-tx neutrophil to lymphocyte ratio (NLR) >3, Su induced HTN, use of angiotensin system inhibitors (ASIs), past cytokines/targeted tx, and mean Su dose/cycle. PFS and OS were determined by the Kaplan-Meier method. Multivariate analyses using Cox Regression model were performed to determine their independent effect. Results: Between 2004-2011, 209 pts with mRCC were treated with Su. 40 pts were active smoker, 51 obese, 55 diabetic, and 122 had pre-tx HTN. In the entire pt cohort, median PFS was 8 months (mos) and OS 15 mos. Factors associated with PFS were active smoking (HR 2.5, p= 0.005, median PFS 4 vs 10 mos in past smokers vs 10 mos in never smokers), non clear cell histology (HR 1.8, p=0.023), pre-tx NLR >3 (HR 0.2, p<0.0001) and the use of ASIs (HR 1.66, p=0.028). Factors associated with OS were were active smoking (HR 2.1, p= 0.03, median OS 8.5 vs 18 mos in past smokers vs 18 mos in never smokers), AP (HR 1.76, p=0.049), pre-tx NLR >3 (HR 0.294, p<0.0001), and liver mets (HR 0.553, p=0.04). BMI, DM, and pre-tx HTN were not associated with PFS or OS. Conclusions: Active smoking may decrease the PFS and OS of pts with mRCC that are treated with Su. BMI, DM, and pre-tx HTN were not found to be associated with outcome. These results should be investigated prospectively, and if validated applied in clinical practice and clinical trials.
Clinical prognostic factors associated with outcome in patients with metastatic clear-cell renal cell cancer treated with everolimus.
Authors: Amato Robert J. , Flaherty Amber , Saxena Somyata , Stepankiw Mika 
Published: February 2017

443 Background: Everolimus, an oral mammalian target of rapamycin (mTOR) inhibitor, has demonstrated efficacy affects tumor growth by blocking growth factor stimulation, arresting cell cycle progression, and inhibiting angiogenesis. mTOR inhibitors and agents with primarily antiangiogenic activity have been shown to have efficacy in renal cell cancer (RCC). This study expanded the original everolimus study of 41 patients with metastatic clear cell renal cell cancer to 66 patients to examine outcome and clinical prognostic factors associated with outcome Methods: Patients had confirmed predominantly clear cell RCC. Everolimus was given at a dose of 10 mg daily orally without interruption (28-day cycle), with dose modifications for toxicity (graded according to National Cancer Institute Common Toxicity Criteria, version 3.0). Patients were evaluated every 2 cycles (8 weeks) using Response Evaluation Criteria in Solid Tumors (RECIST). Results: Of 66 evaluable and treated patients, 73% were male, and 45% were >60. Forty-five percent had right kidney involvement, 49% left kidney involvement, and 6% had dual kidney involvement. Eighty-six percent had prior systemic therapy, and 76% of patients had at least two metastatic sites including lung (72%), liver (26%), bone (48%), lymph nodes (50%), adrenal (21%), and other (39%). Twenty-four (36%) of patients had a progression-free survival (PFS) of ≥12 months, and 40 patients (61%) had an overall survival (OS) ≥12 months. Factors most likely to have an influence on OS benefit was high LDH, alkaline phosphatase, and calcium; low hemoglobin; and prior treatment with tyrokinase inhibitors. Conclusions: Everolimus was found to have clinical benefit in patients with clear cell RCC. Clinical prognostic factors may help determine patients most likely to receive benefit from everolimus. Information regarding curves and correlation between prognostic factors and OS and PFS will be presented.
Does obesity affect the outcome of renal cell carcinoma?
Authors: Mozayen Mohammad , Tesfaye Anteneh , Katato Khalil 
Published: February 2017

444 Background: Obesity has been associated with increased risk of renal cell carcinoma (RCC). However the prognostic significance of obesity in the survival of patients with RCC is still undefined. Our study examined prognostic significance of obesity on the overall survival of patients (pts) with RCC in community hospital settings. Methods: A retrospective review of pts diagnosed with RCC between 1995 and 2008 in a community hospital setting was done. Pts with additional malignancies, lymphoma of the kidneys and no follow up data were excluded from the study. Demographics, body mass index(BMI) at diagnoses, pathology, disease stage, operative note, and subsequent follow up data were reviewed. The WHO BMI classification was used to group pts into Underweight (UW) < 18.5; Normal (NL): 18.5-24.99; Pre-obese (PO): 25-29.99; Obese I (Ob I): 30-34.99; Obese II (Ob II): 35-39.99; Obese III (Ob III): ≥40. The primary outcome was 3 years overall survival. Results: A total Of 205 pts reviewed, 127 (62.3%) were males, 176 (85.9%) were Caucasians. The median age of the study population was 65 (22-91). The prevalence of obesity was 42.3% in the study population; 46.2% in females and 39% in males (p=0.19). The median BMI was 28.8 (16-54.6). Pts were categorized based on their BMI as: UW (1.5%), NL (21.4%), PO (34.7%), Ob I (26%), Ob II (8.2%), and Ob III (8.2%). Clear Cell was the commonest histology (79%). Stage I was seen in 53.9%, II in 23.5%, III in 13.7% and IV in 8.8% of the study population. The 3 year overall survival for the study population was 67.3% (95% CI: 60.4-73.7). The 3-year overall survival of obese and non obese pts with RCC were 66.4% and 69.5% respectively (p=0.34). There was no difference in the 3-year overall survival of patient in the BMI groupings: (UW: 66.7%, NW: 59%, Pre-Ob: 70.6%, Obese I: 70%, II: 75%, III: 62.5%; p=0.8). Conclusions: Our study didn’t find any association between BMI and 3 year overall survival in pts with RCC. Larger randomized trials are warranted before excluding the negative impact of obesity in the overall survival of pts with renal cell carcinoma.
Venous thromboembolism in patients with renal cell carcinoma: Incidence, risk factors, and prognostic implication.
Authors: Lee Ha-young , Park Eunhee , Lee Soohyeon , Hong Soojung , Park Hyun Jung , Shin Sang Joon , Kim Hyo Song , Rha Sun Young 
Published: February 2017

446 Background: Renal cell ca (RCC) is one of solid tumor with relatively highest incidence of venous thromboembolism (VTE). But, there have been to no large-scale studies that focused on VTE in RCC. The aim of this study was to investigate the incidence, time course of VTE, risk factors, and prognosis associated with VTE in RCC patients in Korea. Methods: The medical records of RCC patients (n=1248) histologically diagnosed at Severance Hospital, Yonsei University College of Medicine, Seoul, Korea from Jan 2005 to Mar 2011 were retrospectively reviewed. Results: Among 1248 RCC patients, 69.6% were men, median age was 56years (range: 4∼89), and stage distribution was stage I 65.1%, stage II 9.2%, stage III 10.4%, stage IV 12.5%. The 2-year cumulative incidences of tumor induced VTE (tVTE) was detected in 78 patients (6.3%), while 1-month, 6-months and 1-year cumulative incidence of tVTE were 5.3%, 5.7% and 6.0%, retrospectively. Two-year cumulative incidence of tVTE seemed to increase with stage (0.6%, 3.5%, 22.3% and 24.3% in stages I, II, III and IV, retrospectively). Almost tVTE events developed in the first few months after diagnosis. Stage and metastatic disease were independent risk factors for developing tVTE. In multivariate analysis, the development of tVTE was a significant predictor of survival (P=0.004) and stage, age, ECOG PS was also independent predictor of survival. Conclusions: This is the first study that specially focused on tVTE in RCC. The 2-year cumulative incidence of tVTE in Korean patients with RCC was 6.3%, which is similar to other ethnic group. As tVTE related to poorer survival, RCC patients with advanced stage and metastasis with higher risk of tVTE, close follow-up is recommended and proactive prophylaxis of VTE might be needed.
U.K. experience of sunitinib malate in the treatment of metastatic renal cell carcinoma: Predictors of response from clinical practice.
Authors: Goranova Rebecca Allison , Goranov Bojidar Bojidarov , Pedley Ian David , Azzabi Ashraf , Humphreys Alison , McMenemin Rhona , Frew John A. 
Published: February 2017

455 Background: Sunitinib gained NICE approval in March 2009 as first line treatment for metastatic renal cell carcinoma (mRCC) and UK experience of use of Sunitinib is growing. The North of England Cancer Network (NECN) was the first cancer network in the UK to approve the use of Sunitinib in July 2007 and has the longest UK experience with this drug. The clinical outcomes of the NECN patients are presented. Methods: Data was collected and analysed regarding all patients started on Sunitinib from 01/07/2007 to 30/09/2010. Follow up extended to 28/02/2011. Previously published predictors of response were compared to the NECN data to check applicability in this population. Results: 129 patients were identified with a median age of 63 years (range 21-87), 67% were male and WHO performance status was 0, 1 or 2 (33%, 51%, 16%). 80% of patients had nephrectomy (60% radical) and 22% had prior systemic treatment. Median PFS was 10 months (range 0.25-27). Median OS (from Sunitinib initiation) was 17 months (range 0.25 - 47). Performance status was significantly associated with PFS and OS. The median number of treatment cycles was 5 (range 0.25-27). 64% of patients were dose reduced and 9% had a schedule modification to minimise toxicity. 21% of patients had a delay of 4 weeks or more which was not detrimental to median PFS. Dose reduction at treatment initiation was associated with a significant decrease in OS. 11.6% of patients required treatment for hypothyroidism which was associated with a significant improvement in PFS and OS. 15.5% of patients required treatment for hypertension, which was associated with an improvement in OS, but not PFS. Conclusions: PFS in the NECN population is similar to trial data. Strategies to deal with side effects, including dose reduction (after treatment initiation), treatment delay and schedule changes, did not adversely affect PFS. Performance status 0, the development of new hypertension or new hypothyroidism can be regarded as markers of good prognosis in this population. Initial dose reduction should be avoided as this adversely affects prognosis.
Percutaneous and laparoscopic-assisted cryoablation of small renal cell carcinomas.
Authors: Nielsen Tommy Kjaergaard , Ostraat Oyvind , Borre Michael , Johansen Truls E Bjerklund 
Published: February 2017

462 Background: To evaluate the complication rate and short term oncological outcome of small renal cell carcinomas treated with cryoablation. Methods: 91 biopsy verified renal cell carcinomas were cryoablated between 2006-11. Patients treated had primarily T1a tumors, but exceptions were made. Patients with tumors not directly accessible percutaneously were selected for laparoscopy. To ensure complete coverage of the tumor, cryoneedle placement and freezing procedure was peroperatively monitored by ultrasound in both modalities. Presice machine with Ice-Seet and Ice-Rod needles from Galil Medical was used. Treatment was considered successful when tumors gradually shrunk and showed no sign of contrast enhancement, assessed by CT or MRI. Results: Mean patient age and tumor size was 65 yr [17 - 83] and 26 mm [10 - 62], respectively [min-max]. Treatment modalities consisted of percutaneous route; n=34 (47%) and laparoscopic guided; n=39 (53%). The mean follow-up time was 19 months [1 - 56]. 18 patients were excluded from follow-up analysis (8 pt. with short observation time, 5 pt. treated despite severe co-morbidity with no planned follow-up, 3 pt. lost to follow-up, 1 pt. emigrated, 1 pt. died as a result of bleeding from perforation of iliac artery by troicar). Residual tumor was diagnosed by imaging in 10 patients (perc n=6 and lap n=4, p>0,05) after a mean follow-up time of 13 months [1 - 31]. Diagnosis was confirmed by biopsy in all but one case, in which the diagnosis was necrosis. Of the 10 patients with residual tumor, 8 patients were reablated and 2 patients were referred to oncological treatment. Cancer specific survival was 100%. Overall survival was 91%. Complications: 8 pt. had minor bleeding in relation to cryoneedle removal, requiring Tachosil. 1 pt. had subcutaneous bleeding, 2 pt. was readmitted due to pain and discharged the following day. No patients required blood transfusion. Conclusions: Although percutaneous and laparoscopic guided cryoablation are minimally invasive procedures and the overall complication rate is low, serious complications may occur. Close follow-up and continuous evaluation of criteria for patient selection and relapse is necessary. An international database is recommended.
Detection of prostate cancer with histoscanning: A retrospective analysis in 85 patients.
Authors: Epplen Robin , van Essen Julius , van Erps Thomas , Porres Daniel , Pfister David J. K. P. , Heidenreich Axel 
Published: February 2017

53 Background: HistoScanning is a tissue differentiation and visualization tool which identifies changes to solid organ tissues. It uses a specific three dimensional transrectal ultrasound device to acquire and transmit data to a software program. Data is processed and suspicious areas in the prostate are projected in 3D. Our objective was to compare HistoScanning with histopathology of radical prostatectomy specimens and to determine sensitivity regarding the detection of cancer volume and localization. Methods: We analyzed the preoperative results of histoscanning in 85 men underwent radical prostatectomy. All prostatectomy specimens were processed according to the Stanford protocol by an experienced uro-pathologist.Results were correlated with final pathology according to localisation and volume. A match was defined as a HistoScan positive lesion in a correspondent histopathologically positive area.Results were analyzed according to pT-stadium, GS, PSA, cancerous tissue volume and volume of HistoScanning-lesions. Results: Mean patients’ age was 62,8 yrs, PSA 11.83ng/ml, prostate volume was 47,5 ml and mean tumor volume was 4,80ml. 44 patients had a pT2 tumor, 38 had a pT3 carcinoma (3 pts pT4). 8 pts had salvage prostatectomy. 9 patients had GS of 6,50 and 18 pts had GS 7 and GS ≥8 respectively. HistoScanning had 74% overall sensitivity.Sensitivity was higher for pT3 tumors (92%) than for pT2 carcinoma (61,36%). HistoScanning detected (5/9=55%) of GS 6, (37/50= 74%) of GS 7 and 15/18=83% of GS ≥8 carcinoma. Preoperative PSA had no statistical significance. HistoScanning detected small tumors (<1 ml) in 50%, intermediate (1-5ml) in 57,5% and large(>5ml) in 86% respectively. Identical results are seen regarding the volume of suspicious lesions. For small (≤0,5 ml), intermediate (0,5-2ml) and large (>2ml) lesions, it correctly predicted prostate cancer localisatio 33%, 78,5% and 64,7%, respectively. Conclusions: HistoScanning seems to have a great potential in the detection of significant prostate cancer. In particular, extracapsular, poor differentiated and large prostate cancers show a high detection rate. However, larger prospective studies are needed to verify these preliminary results.
Evaluation of circulating tumor cells (CTCs) enumeration and 18F-Choline positron emission tomography/computed tomography (FCH PET/CT) as early efficacy response biomarkers in metastatic castration-resistant prostate cancer (CRPC) patients (pts) treated with abiraterone acetate.
Authors: Le Moulec Sylvestre , Massard Christophe , Gontier Eric , Farace Françoise , Chargari Cyrus , Vielh Philippe , Aupee Olivier , Vedrine Lionel , Foehrenbach Herve , Fizazi Karim 
Published: February 2017

63 Background: Circulating tumor cells (CTCs) and FCH PET/CT are both promising tools for treatment monitoring in CRPC pts. In this study, we assessed prostate specific antigen (PSA), CTC and FCH PET/CT for monitoring treatment response in metastatic CRPC pts receiving recently approved abiraterone acetate therapy after chemotherapy. Methods: Twenty nine metastatic CRPC pts progressing after docetaxel chemotherapy received abiraterone acetate 1,000 mg daily with prednisone 5 mg twice daily in continuous 28-day cycles. Pts were evaluated monthly for efficacy and safety. CTCs counts (using the CellSearch assay) and FCH PET/CT were performed at baseline and at 4 weeks (PERCIST criteria and SUV Peak). Results: After one month of treatment, 12 pts (41%) had a PSA rise and 17 pts (59%) had a PSA decline. At baseline, 18 pts had detectable CTCs (at least 5 CTCs), and 6 of them (33%) had a decline from at least 5 to less than 5 CTCs after 4 weeks of treatment. 10 of 29 pts (34%) had a > or = 30% decline in CTCs. Amongst 22 pts who were evaluable by FCH PET/CT, response assessment was as follows: response (n=8), stable disease (n=12), progression (n=1). PSA decline and CTCs levels correlated in 16 of 29 pts (55%), and were discordant in 13 of 29 pts (45%). In all 12/29 pts (41%) with a 50% or more decline in PSA both a CTCs response and a FCH PET/CT response was observed. In patients with a PSA rise while on abiraterone acetate, 8 pts did not have a CTCs increase or a CTC conversion from unfavourable to favorable, and 7 of 8 pts had a PSA decline at 3 months or a FCH PET/CT response. No flare phenomenon on FCH PET/CT was observed. Conclusions: Monitoring pts with CRPC who receive abiraterone using both CTCs and metabolic imaging indicate discrepancy in 45% with response assessment using PSA. Association between CTC drop, early FCH PET/CT response and clinical benefit is currently under study.
The influence of growth hormone/insulin-like growth factor deficiency on prostatic dysplasia in pbARR2-cre PTEN knockout mice.
Authors: Ibuki Naokazu , Takahara Kiyoshi , Gaffari Mazyar , Tearle Howard , Ong Christopher J. , Pollak Michael N. , Gleave Martin E. , Cox MIchael E. 
Published: February 2017

66 Background: Signaling through GH/IGF-I axis has been linked to PCa risk. The GH/IGF-I axis is an important regulator of growth, survival, and metastatic potential in a variety of malignancies and is strongly implicated in PCa etiology. A range of therapeutic approaches including reducing ligand availability by GH antagonist, IGF-I antibodies, and recombinant IGFBPs, reducing IGF-1R expression by antisense and RNA interference, or inhibiting of IGF-1R signaling by IGF-1R antibodies and small molecule tyrosine kinase inhibitors are under investigation in PCa. Methods: To investigate the role of GH/IGF-I axis on in vivo prostate carcinogenesis and neoplastic progression, we crossed pbARR2-Cre, PTEN(fl/fl) mice (PTEN-/-) with IGF-I deficient lit mice, and produced lit/lit and lit/+ PTEN-/- mice. To complement the in vivo experiments, in vitro growth and growth factor signaling of murine PTEN-/- cells derived from the prostate (MPPK) using serum from lit/lit or lit/+ mice was examined. Results: No obvious differences in prostatic dysplasia were observed in lit/lit mice at 15 and 20 weeks of age when compared to lit/+ littermates measured as normalized prostatic wet weight or for expression of the murine prostatic differentiation markers, probasin and PSP94. However the rate of decreased expression of E-cadherin and increased expression of N-cadherin was slightly delayed in PTEN-/- prostates from lit/lit mice as compare to lit/+ mice. In vitro, growth of MPPK cells was decreased when cultured in serum from lit/lit mice as compared with serum from lit/+ mice. Suppressed growth of MPPK cells in lit/lit serum could be restored by addition of IGF-I, and to a lesser extent, GH. Addition of GH or IGF-I to lit/lit serum increased steady-state activation of AKT without affecting ERK1/2 activation. Conclusions: Our data suggest that initiation of prostate carcinogenesis by loss of PTEN is not influenced by germ line variation of genes encoding signaling molecules in the GH/IGF-I axis, but suggests that such factors may affect the progression of dysplasic phenotype.