bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thromboembolic events (TE) in men treated with bleomycine-etoposide-cisplatin (BEP): A monocentric review over one year.
Authors: Boyle Helen Jane , Lavergne Emilie , Bonnin Nathalie , Rosay Herve , Flechon Aude 
Published: February 2017

375 Background: BEP chemotherapy (CT) is the standard regimen for patients (pts) with metastatic germ cell tumours (MGCT). Over the past years, it seemed that more pts developed TE. Methods: Files of all male pts treated with BEP CT for a MGCT, at the Centre Léon Bérard in 2012, were reviewed. The incidence of thrombosis was assessed and then, the study population was described by comparing affected pts with the others using the non parametric Wilcoxon test for the quantitative data and Fisher exact test for the qualitative one. Results: Finally, 45 men received BEP for MGCT at our institution in 2012. Median age at CT initiation was 33.6 years (range: 16.9-43.6). All pts but 1 had a testicular primary, 1 had a mediastinal primary. Ten had seminomas (22%) and 35 a non-seminomatous tumour (78%). According to the IGCCCG classification, 28 pts were classified as good prognosis (62%), 12 as intermediate prognosis (27%) and 5 as poor prognosis (11%). Seven pts received CT on a port-a-cath (16%), 13 pts on a brachial PICC line (29%) and 25 on a central venous cathether (CVC) inserted in the jugular (55%). Fifteen pts (33%) developed venous thrombosis: 4 of them had a pulmonary embolism. The TE was symptomatic for 9 pts and was discovered on a routine CT-scan for the other 6 pts. TE was related to tumoral compression for 4 pts (27%, 3 TE diagnosed before CT) and to the venous catheter for 8 pts (53%). For the 3 other pts no “obvious” cause was found. Median time from catheter insertion to thrombosis was 35 days (range: -32-80 days). TE occurred in 29% of pts with a porthacath, 31% of pts with a PICC line and 36% of pts with a CVC. No significant relationship was observed between thrombosis occurrence and age, IGCCCG prognostic group, type of venous catheter, presence of metastasis and lymph nodes status. Among the 27 pts (60%) who underwent post-CT surgery, 41% were on curative anticoagulant therapy (low molecular weight heparin). Conclusions: Incidence of TE is higher in this small study than those reported in other series. The reason for this is unclear and needs more investigations. Prospective evaluation of prophylactic use of anticoagulants and/or of new practices concerning catheters, as removing it on day 6, to avoid TE may be explored.
Relationship between abiraterone exposure, prostate-specific antigen (PSA) kinetics, and overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) .
Authors: Xu Steven , Ryan Charles J. , Stuyckens Kim , Smith Matthew R. , Saad Fred , Griffin Thomas W. , Park Youn Choi , Yu Margaret K. , Vermeulen An , Poggesi Italo , Nandy Partha 
Published: February 2017

39 Background: Abiraterone, the active metabolite of abiraterone acetate (AA), is an effective androgen biosynthesis inhibitor for patients with metastatic castration-resistant prostate cancer (mCRPC). We conducted a sequential exposure-biomarker-survival modeling analysis to explore the relationship between prostate-specific antigen (PSA) kinetics and overall survival (OS) and to establish the exposure response for PSA kinetics and OS in chemotherapy-naïve and -pretreated patients with mCRPC following AA administration. Methods: The exposure-PSA-survival modeling framework was based on two phase III studies, COU-AA-301 (chemotherapy-pretreated, N = 1184) and COU-AA-302 (chemotherapy-naïve, N = 1081), and included a mixed-effects tumor growth inhibition (TGI) model to describe PSA dynamics in response to AA and a Cox proportional hazards survival model to evaluate the relationship between relative risk of death and PSA dynamic end points. Results: The TGI model best described the longitudinal PSA dynamics following AA treatment. Abiraterone exposure significantly increased PSA decay rate (maximum effect of 2.72, p < 0.0001). The estimated concentration for 50% of the maximum effect (EC50) was 4.75 ng/mL. The abiraterone effect on PSA kinetics was similar in chemotherapy-naïve and -pretreated subjects, and approximately 90% of subjects had a steady-state concentration greater than the EC50. All model-predicted PSA metrics were strongly associated with OS in both populations; model-based post-treatment PSA doubling time showed the strongest association (hazard ratios approximately 0.9 in both populations). Simulations showed that the modeling framework could accurately predict the survival outcome for both studies. Conclusions: The analysis revealed a similar effect of abiraterone on PSA kinetics and association between PSA kinetics and OS in chemotherapy-naïve and -pretreated subjects, providing additional evidence for surrogacy of PSA kinetics and the use of PSA end points to indicate clinical benefit of abiraterone in subjects with mCRPC regardless of prior chemotherapy. Furthermore, the study confirmed that the recommended 1,000 mg/d dose of AA leads to adequate clinical exposure above the effective level. Clinical trial information: NCT00638690, NCT00887198.
Lymphopenia as an independent predictor of worse survival in papillary renal cell carcinoma.
Authors: Mehrazin Reza , Uzzo Robert G. , Kutikov Alexander , Tomaszewski Jeffrey J. , Ginzburg Serge , Ruth Karen J. , Al-Saleem Essel , Chen David Y. T. , Viterbo Rosalia , Greenberg Richard E. , Smaldone Marc C. , Al-Saleem Tahseen I. 
Published: February 2017

397 Background: Lymphopenia signifies inflammatory response and is an index of poor systemic immunity which can be associated with poor survival outcomes. The aim of this study was to evaluate the prognostic relevance of preoperative absolute lymphocyte count (ALC) in patients with papillary renal cell carcinoma (RCC). Methods: We retrospectively analyzed our institutional, prospectively maintained, renal cancer database and identified patients with pathologic diagnosis of papillary RCC after partial or radical nephrectomy. Patients with preoperative ALC value within 3 months prior to surgery were eligible for the study. ALC of 1,300 cells/µl was used as the cutoff value (our lowest laboratory reference value). We evaluated the correlation between ALC and age, gender, Charlson comorbidity index (CCI), pathologic T stage, nuclear grade, and overall TNM stage. Differences in overall survival (OS) by ALC status were assessed using the log−rank test. Cox proportional hazards modeling was used for multivariable analyses. Results: We identified 314 out of 2,732 patients with a pathologic diagnosis of papillary RCC after partial or radical nephrectomy from 1997 to 2013. Those undergoing multiple surgical procedures (multifocal or bilateral disease) or missing preoperative ALC were excluded from the study. A total 205 patients met inclusion criteria with a median follow up of 37.3 months. As a continuous variable, low absolute lymphocyte count was associated with higher pT stage (p=0.038), TNM stage (p=0.029) and older age (p=0.022). Lymphopenia below 1,300 cells/µl was also associated with pT stage (p=0.008) and TNM stage (p=0.018). On multivariable analysis, independent of stage, older age,and CCI, lymphopenia was associated with inferior overall survival (HR 2.1 [CI 1.1−4.03], p=0.037). Conclusions: In our series of patients with papillary renal cell carcinoma, lymphopenia was associated with lower overall survival independent of stage, age,and charlson comorbidity index. ALC significantly increases the accuracy of already established prognostic factors and can be helpful for patient counseling and design of clinical trials.
Cardiovascular events associated with androgen deprivation therapy in patients with prostate cancer: A systematic review and meta-analysis.
Authors: Carneiro Arie , Sasse Andre Deeke , Wagner Andrew , Toneto Bruno , Serpa Neto Ary , Chang Peter , Lima-Pompeo Antonio Carlos , Machado Marcos Tobias 
Published: February 2017

40 Background: A recently published meta-analysis of randomized clinical trials (RCT) showed that androgen deprivation therapy (ADT) did not significantly increase cardiovascular mortality in prostate cancer patients. However, cardiovascular morbidity, which can impact quality of life, was not evaluated. Objectives: To evaluate the risk of cardiovascular morbidity and mortality associated with long-term ADT in patients with prostate cancer. Methods: We conducted a literaturesearch from 1960 and June 2012. We selected RCT and large cohort studies that evaluated first-line endocrine therapy, ADT greater than 6 months, and follow up greater than 1 year. Results: Thirteen studies (137,658 patients) were included. Of four cohort studies, 126,898 patients were included and 10,760 patients were part of nine RCTs. Analysis of the RCTs showed no differences in development of acute myocardial infarction (AMI) (OR 1.23; 95% CI: 0.92 – 1.64; I2: 0%) or stroke (OR 1.02; 95% CI: 0.71 – 1.46; I2: 0%) among patients receiving ADT or not. The analysis of three randomized studies that reported other nonfatal cardiovascular events demonstrated a significant increase in such events in the group receiving ADT (OR 1.55; 95% CI: 1.09 – 2.20; I2: 0%). When large cohort studies were included in the analysis, an increased risk of AMI among men who had ADT was found ( OR 2.01, 95% CI:1.90 – 2.13; I2: 91.3%). Conclusions: ADT in prostate cancer patients for at least 6 months is not associated with cardiovascular mortality, acute myocardial infarct and stroke. However, patients receiving ADT had a significant increase in nonfatal cardiovascular events.
Professional practice gaps and barriers to optimal care of renal cell carcinoma (RCC) among oncologists in the United States.
Authors: Rini Brian I. , Bowser Andrew , Lazure Patrice , Goldin Luba , Peloquin Sophie , Hayes Sean , Mortimer Jim A. , Peterson Eric D , Hutson Thomas E. 
Published: February 2017

404 Background: New therapies for advanced RCC have improved patient outcomes while increasing the complexity of care. We sought to quantify practice gaps and barriers to optimal care among oncologists treating patients with RCC at academic and/or community centers in the United States. Methods: In total, 248 oncologists were recruited for a 2-phase (qualitative/quantitative) study. Eligible participants who had fully completed either one of the 2 phases were included in the analyses (n = 169). In the first phase, participants (n = 27) completed a brief online case-based survey and a 45-minute telephone interview on the attitudinal, contextual, and behavioral factors that influenced diagnosis and treatment. Selected interviews were transcribed and analyzed through thematic analysis. In the second phase, participants (n = 142) completed an online survey including case vignettes. Respondents’ answers were compared with optimal answers based on National Comprehensive Cancer Network kidney cancer guidelines (version 1.2013) and evidence-based opinions of 2 RCC experts. Results: Forty-six percent of participants correctly identified all predictors of short survival/poor risk in RCC. Regarding treatment options for a poor-risk patient, 37.5% chose temsirolimus and 11% sunitinib, both felt to be reasonable options. In a scenario focused on dose and treatment modification in a patient with treatment-related hypertension, 34% selected a nonoptimal management option. In a scenario focused on the importance of recognizing clinical symptoms as a component of treatment decision making, 40% of respondents were in agreement with expert- and evidence-supported treatment approach. Detailed results of this analysis will be presented. Conclusions: This study revealed clinically relevant practice performance gaps that affect delivery of care and patient health outcomes. Not recognizing predictors of poor risk or the importance of evaluating clinical symptoms can result in missed opportunities to change treatment strategy, leading to suboptimal outcomes. These results will support design of educational programs and performance improvement interventions.
c-Met abnormatities in patients with genitourinary (GU) malignancies and outcomes with c-MET inhibitors.
Authors: Fontes Jardim Denis Leonardo , Gagliato Debora De Melo , Falchook Gerald Steven , Wheler Jennifer J. , Zinner Ralph , Janku Filip , Subbiah Vivek , Piha-Paul Sarina Anne , Fu Siqing , Tannir Nizar M. , Corn Paul Gettys , Tang Chad , Hess Kenneth R. , Roy-Chowdhuri Sinchita , Kurzrock Razelle , Meric-Bernstam Funda , Hong David S. 
Published: February 2017

407 Background: c-MET is a tyrosine kinase receptor involved in cancer growth, migration, development of metastasis and angiogenesis. Deregulation of this gene has been associated with poor prognosis and resistance to treatment in prostate, bladder and renal cell cancer (RCC). Methods: Patients with GU malignancies referred to the phase I clinic were evaluated for the presence of c-MET mutation and amplification. Their outcomes on protocols containing c-METinhibitors were also analyzed. Results: c-MET amplification was detected in 7 out of 97 (7.2%) patients (4/27 renal, 1/18 urothelial and 2/12 adrenocortical carcinoma), while c-MET mutation/variant in 3 out of 53 (5.7%) patients (2/20 renal and 1/15 prostate cancer). No demographic characteristics were associated with either c-MET abnormalities, but patients tested positive for either mutation or amplification had a higher number of metastatic sites (median number of sites of 4 versus 3 for wild type patients). Median overall survival from phase I consult was 4.4 and 10.6 months for patients with and without a c-MET alteration, respectively. Twenty-nine (25%) patients were treated under a protocol containing a c-MET inhibitor. Overall 6 (21%) patients had a partial response (all prostate and RCC) and 10 (34%) had stable disease as best response. Median time to tumor progression was 2.3 months (0.4-19.7) for all treated patients. No responses were detected in patients with a c-MET genetic abnormality or treated with a specific c-MET inhibitor as a single agent. Conclusions: c-MET mutation and amplification are present in different GU malignancies conferring a worse prognosis for patients referred to the phase I program. We observed activity of c-MET inhibitors for patients without c-MET genetic abnormalities and when c-MET inhibition was combined with other targets/drugs.
Open-label, phase II raptor study of everolimus (EVE) for papillary mRCC: Efficacy in type 1 and type 2 histology.
Authors: Escudier Bernard J. , Bracarda Sergio , Maroto Rey José Pablo , Szczylik Cezary , Nathan Paul D. , Negrier Sylvie , Cattaneo Agnese , Weiss Claudia , Porta Camillo , Gruenwald Viktor 
Published: February 2017

410 Background: Prospectively collected data evaluating therapy for papillary mRCC are limited. RAPTOR (NCT00688753) evaluated the efficacy and safety of EVE as first-line therapy for papillary mRCC. Methods: Eligible pts had histologically confirmed type 1 or 2 papillary mRCC, ECOG PS ≤1, and no previous systemic therapy for mRCC. Central histology review was mandatory. EVE 10 mg/d was given until disease progression or intolerable toxicity. The primary end point was the PFS rate at 6 months assessed per RECIST 1.0 (central review) in the first 44 pts of the per-protocol population (PPFF; lack of centrally confirmed papillary histology was a protocol violation). Secondary end points included PFS, OS, and safety. Sensitivity (per protocol [PP] and ITT populations), supportive (local review), and subgroup (type 1 and 2 histology) analyses were performed. Results: 92 pts enrolled (median age, 60 y; 78% men). Among pts with papillary RCC per local review (99%), 58% had type 2 and 16% had type 1 (25% missing). Central review confirmed papillary histology in 76% of pts, 59% with type 2 and 33% with type 1 (9% missing). Reasons for discrepancies will be presented. Efficacy results are shown (Table). In the safety population (n=92), the most common grade ≥3 AEs were asthenia (11%), anemia (5%), and fatigue (5%). Conclusions: The RAPTOR study showed that EVE was well tolerated by and provided clinical benefit to pts with both type 1 and type 2 papillary mRCC, although both PFS and OS were longer in type 1. These results support further evaluation of EVE for pts with papillary mRCC. Clinical trial information: NCT00688753. [Table: see text]
Safety and efficacy of addition of VEGFR and EGFR-family small-molecule tyrosine kinase inhibitors to cytotoxic chemotherapy in solid cancers: A meta-analysis.
Authors: Funakoshi Tomohiro , Latif Asma , Galsky Matt D. 
Published: February 2017

415 Background: The approach of combining cytotoxic chemotherapy with small molecule tyrosine kinase inhibitors (TKIs) has been explored in a large number of randomized trials, in a diverse range of tumor. We performed a systematic review and meta-analysis to evaluate the safety and efficacy of this therapeutic approach. Methods: PubMed and the ASCO databases were searched up to March 2013. Eligible studies included randomized trials in which the FDA approved TKI in combination with chemotherapy was compared with chemotherapy alone in patients with any type of solid cancer. The endpoints included safety [fatal adverse events (FAEs), treatment discontinuation, any severe (grade 3 or 4) adverse events (AEs), and individual severe AEs] and efficacy [progression-free survival (PFS), and overall survival (OS)]. The pooled relative risk (RR) or hazard ratio (HR), with corresponding 95% confidence intervals (CI) were calculated. Results: A total of 16,011 patients from 43 trials were included. Among the 43 trials, ten met their primary efficacy endpoints. Among the 21 phase III trials, two led to Food and Drug Administration approval for the combination. Compared with chemotherapy alone, the addition of a TKI significantly increased the risk of FAEs (RR, 1.63; 95% CI, 1.32-2.01), treatment discontinuation (RR, 1.80; 95% CI, 1.58-2.06), and any severe AE (RR, 1.25; 95% CI, 1.16-1.36). Compared with chemotherapy alone, the addition of a TKI was associated with a significant improvement in PFS (HR, 0.82; 95% CI, 0.76-0.89), but not OS (HR, 0.99; 95% CI, 0.95-1.03). Chemotherapy plus TKI was also associated with a significant higher risk of seven of the 11 evaluated individual AEs: neutropenia (RR, 1.18; P =.004), thrombocytopenia (RR, 1.70; P <.001), febrile neutropenia (RR, 1.48; P <.001), hypertension (RR, 3.01; P <.001), skin toxicities (RR, 6.38; P <.001), diarrhea (RR, 2.57; P =.002) and fatigue (RR, 1.35; P <.001). Conclusions: The addition of a VEGFR or EGFR-family TKI to chemotherapy in solid cancers increases the risk of severe toxicities and treatment discontinuations. These findings might explain the general lack of a survival benefit with these regimens.
PD-L1 expression in non-clear cell renal cell carcinoma.
Authors: Fay André P , Callea Marcella , Gray Kathryn P. , Ho Thai Huu , Song Jiaxi , Carvo Ingrid , Lampron Megan E. , Stanton Melissa L. , McDermott David F. , Atkins Michael B. , Freeman Gordon J , Hirsch Michelle S. , Signoretti Sabina , Choueiri Toni K. 
Published: February 2017

424 Background: Programmed death-1 (PD-1) receptor negatively regulates T cell-mediated responses.PD-1 ligand (PD-L1) is aberrantly expressed in clear cell renal cell carcinoma (ccRCC) and is associated with worse prognosis. Levels of PD-L1 expressions in non-ccRCC and its association with clinicopathological features and survival are unknown. Methods: Formalin-fixed paraffin-embedded (FFPE) specimens were obtained from 97 patients with chromophobe (CHR), papillary (PAP), translocation Xp11.2 (TrL) RCC and oncoytoma (ONC) and were included in the analysis. PD-L1 expression was evaluated by immunohistochemistry using a mouse monoclonal anti-PD-L1 antibody (405.9A11). The assay was validated using FFPE cell line controls known to be positive or negative for PD-L1 expression by flow cytometry. PD-L1 tumor positivity (PD-L1+) was defined as ≥5% tumor cell membrane staining. For PD-L1 expression in immune cells, a combined score based on the intensity of infiltrate and percentage of positive cells was used. Baseline characteristics including stage/grade, and survival data were collected. Comparisons between PD-L1 expression and clinicopathological features were evaluated using chisq or wilcoxon rank sum tests. Cox model tests for association of PD-L1 expression with OS in univariate and multivariable analysis. Results: Among 97 patients, 12 (12.4%) were considered PD-L1+ in tumor cells: 2/36 (5%) of CHR RCC, 5/50 (10%) of PAP RCC, 3/7 (43%) of TrL RCC, and 2/4 (50%) of ONC. PD-L1 positivity in tumor cells was significantly associated with higher stage (p=0.026) and grade (p=0.046), as well as lower OS on univariate (p=0.02) but not multivariate analysis (p=0.29). On the other hand, PD-L1 positivity by immune cells was observed in 50 (51.5%) patients: 13/36 (36%) of CHR RCC, 30/50 (60%) of PAP RCC, 6/7 (86%) of TrL RCC, and 1/4 (25%) of ONC. PD-L1 positivity in immune cells did not correlate with stage (p=0.7), grade (p=0.1) or OS (p=0.8). Conclusions: PD-L1 expression is variable in non-ccRCC and depends on histology and tumor vs. immune cells scoring. Only PD-L1 positivity in tumors cells was associated with aggressive features. Patients with non-ccRCC should not be automatically excluded from trials of agents that target the PD-1/PD-L1 pathway.
Impact of angiotensin system inhibitors (ASI) on outcomes in patients (pts) with metastatic renal cell carcinoma (mRCC): Results from a pooled clinical trials database.
Authors: McKay Rana R. , Rodriguez Gustavo Enrique , Lin Xun , Simantov Ronit , Choueiri Toni K. 
Published: February 2017

437 Background: Increasing evidence suggests that angiotensin II modulates angiogenesis and tumorigenesis. In this study, we utilized a clinical trials database to evaluate the role of ASIs (angiotensin-converting enzyme inhibitors and angiotension-receptor blockers) on survival outcomes in pts with mRCC. Methods: We conducted an analysis of pts with mRCC treated from 2003-2013 on phase III (NCT00083889, NCT00065468, NCT00678392, NCT00474786, NCT00631371, NCT00920816) and II clinical trials (NCT00054886, NCT00077974, NCT00267748, NCT00338884, NCT00137423, NCT00835978). We evaluated pts treated with ASIs at baseline or within the first 30 days of study. Statistical analyses were performed using Cox regression and the Kaplan-Meier method. Results: We identified 4,736 pts treated with sunitinib (n=1,059), sorafenib (n=772), axitinib (n=896), temsirolimus (TEM) (n=457), TEM + interferon-alfa (IFN-α) (n=208), bevacizumab (BEV) + TEM (n=393), BEV + IFN-α (n=391), or IFN-α (n=560). Most pts were < 65 years of age (69%), male (71%), with clear-cell histology (89%) and prior nephrectomy (70%). With regard to International mRCC Database Consortium risk groups, 14%, 42%, and 24% had favorable, intermediate, and poor-risk disease, respectively. 1383 (29%) pts received treatment with an ASI. Baseline hypertension was present in 84% of ASI users and 33% of ASI non-users. ASI use was associated with improved progression-free survival (PFS) and overall survival (OS) when compared to pts who did not receive an ASI (Table). This association was retained in multivariable analysis adjusted for age, gender, presence of bone metastases, and risk groups. Conclusions: This is the largest retrospective study to date evaluating the role of ASIs on outcomes in cancer pts. In this analysis, we demonstrate that concomitant use of ASIs may improve survival outcomes in pts with mRCC treated in the era of targeted therapy. [Table: see text]