bluuebunny/crossref_metadata_2025_split huggingface dataset:
ABO blood group and risk of renal cell cancer.
Authors: Cho Eunyoung , Joh Hee-Kyung , Choueiri Toni K. 
Published: February 2017

371 Background: The genetic determinants of sporadic renal cell cancer (RCC) are largely unknown. Previous studies have suggested associations between the ABO blood group and risk of various cancers, however, its relationship to RCC remains unclear. Methods: We prospectively evaluated the association between the ABO blood group and risk of RCC in two large independent cohorts of women (the Nurses’ Health Study) and men (the Health Professionals Follow-up Study) from 1996 to 2008. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models with adjustment for other risk factors for RCC including obesity, smoking, and hypertension. All statistical tests were two-sided. Results: During 12 years of follow-up of 77 242 women and 29 548 men, 163 cases of incident RCC were documented in women and 84 cases in men. After multivariate adjustment, non-O blood group (combined group of A, AB, and B) was associated with a 1.5-fold elevated risk of RCC (95% CI 1.09–2.09) than O blood group in women. In contrast, no significant associations were observed between the ABO blood group and risk of RCC in men. The associations between the ABO blood group and RCC were consistent across strata of known risk factors including obesity, smoking status, and history of hypertension (Pinteraction≥ 0.58) in both cohorts. Conclusions: We show for the first time that non-O blood group is significantly associated with a higher risk of RCC compared with blood group O in women. Further studies that elucidate the biological mechanisms underlying this association are warranted.
Tumor suppressor effects for miR-215 identified through use of miRNA profiling in metastatic renal cell carcinoma.
Authors: Bjarnason Georg A. , White Nicole MA , Khella Heba WZ , Grigull Joerg , Adzovic Sonja , Youssef Youssef M. , Honey R. John , Stewart Robert , Pace Kenneth T , Jewett Michael A , Evans Andrew , Gabril Manal , Yousef George M. 
Published: February 2017

392 Background: Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney. Metastatic RCC is difficult to treat. The five-year survival rate for metastatic RCC is <10%. Recently, microRNAs (miRNAs) have been shown to have a role in cancer metastasis and potential as prognostic biomarkers in cancer. Methods: We preformed a miRNA microarray to identify a miRNA signature characteristic of metastatic compared to primary RCC. Results were validated by quantitative real time PCR. Target prediction analysis and gene expression profiling identified many of the dysregulated miRNAs could target genes involved in tumor metastasis. The effect of miR-215 on cellular migration and invasion was shown in a RCC cell line model. Results: We identified 65 miRNAs that were significantly altered in metastatic when compared to primary RCC. Nine (14%) miRNAs had increased expression while 56 (86%) miRNAs showed decreased expression. miR-10b, miR-196a, and miR-27b were the most downregulated while miR-638, miR-1915, and miR-149* were the most upregulated. A non-supervised 2D-cluster analysis showed that a sub-group of the primary tumors clustered under the metastatic arm with a group of miRNAs that follow the same pattern of expression suggesting they have an inherited aggressive signature. We validated our results by examining the expressions of miR-10b, miR-126, miR-196a, miR-204, and miR-215, in two independent cohorts of patients. We also showed that overexpression of miR-215 decreased cellular migration and invasion in a RCC cell line model. In addition, through gene expression profiling, we identified direct and indirect targets of miR-215 that can contribute to tumor metastasis. Conclusions: Our analysis showed that miRNAs are altered in metastatic RCC and can contribute to kidney cancer metastasis through different biological processes. Dysregulated miRNAs represent potential prognostic biomarkers and may have therapeutic applications in kidney cancer.
Long-term toxicity and associated cost of initial treatment and subsequent toxicity-related intervention for patients treated with prostatectomy, external beam radiotherapy, or brachytherapy: A SEER/Medicare database study.
Authors: Ciezki Jay P. , Reddy Chandana A. , Angermeier Kenneth , Ulchaker James , Stephans Kevin L. , Tendulkar Rahul D. , Altman Andrew , Chehade Nabil , Klein Eric A. 
Published: February 2017

4 Background: Treatment-related toxicity for prostate cancer (CaP) is rarely reported more than 5 years after therapy. We examined the SEER-Medicare linked database with the potential of having 16 years of follow-up data on toxicity requiring procedural intervention. Methods: The SEER-Medicare database was queried for CaP patients treated with prostatectomy (RP), external beam radiotherapy (EBRT), or brachytherapy (PI) between 1991-2007. We identified procedural billing codes associated with toxicity-related treatments. We obtained information on the Medicare reimbursement rates for the initial treatment and any toxicity-related interventions. We then computed the cost per patient-year within each treatment modality over time. Results: A total of 137,427 patients who were 65 years or older at the time of CaP diagnosis and who had CaP as their only cancer diagnosis were retrieved from the SEER/Medicare database: 59,559 (43.3%) treated with RP, 60,806 (44.2%) treated with EBRT, and 17,062 (12.4%) treated with PI. No patient received combined therapy. The median follow-up is 71 months. Overall, 10,585 (7.3%) patients experienced a toxicity requiring intervention. Within treatment modalities, the percentages receiving toxicity-related intervention were: RP 6.9%, EBRT 8.8%, and PI 3.7%. The gastrointestinal (GI) and genitourinary (GU) toxicity comparisons are listed in the table. Dilation of a urethral stricture was the most common GU toxicity (3.6% of all patients) while cauterization of rectal bleeding was the most common GI toxicity (0.8% of all patients). Conclusions: The long-term toxicity and cost per patient-year of the major prostate cancer treatment modalities differ. EBRT is the most toxic and most costly. [Table: see text]
Reassessment of a proposed molecular classification system for clear cell renal cell cancer (ccRCC): Results from a randomized phase II trial of pazopanib.
Authors: Mims Martha P. , Gagnon Robert C. , Liu Yuan , Heath Elisabeth I. , Lara Primo 
Published: February 2017

404 Background: Understanding the molecular basis of ccRCC heterogeneity could optimize the use of targeted therapies. Using consensus clustering and logical analysis of data (LAD) of gene expression data (Agilent), Brannon et al (Genes Cancer 2010) identified two distinct subtypes of ccRCC [ccA & ccB] defined by a predictive gene set. Patients (pts) with ccA tumors had better disease-specific survival vs. ccB (8.6 vs 2.0 years, P = 0.002). We evaluated these results in an independent dataset. Methods: Gene expression analysis of archival FFPE samples obtained from pts in a randomized phase II trial of pazopanib in ccRCC (Hutson, JCO 2009) were done using Affy U133 plus chips. Corresponding probe sets from the Agilent and Affy platform were identified using Unigene ID’s (DAVID alignment tool). LAD was applied; pts were stratified into ccA/ccB. Kaplan-Meier analysis was used to compare progression-free survival (PFS) for pts stratified by ccA/ccB. Results: RNA was available for 46 pts. Of 110 genes, 108 were mapped to the Affy platform (probe closest to 3` was used). The 108 Affy genes were assessed for signal (present/absent calls) across the 46 samples. 74/108 genes were present in at least 20% (9/46) of pts, 96/108 genes were present in at least 1/46, and 12/108 were not present (0/46). No obvious patterns of expression were evident from heat maps of the 74 or 96 genes. LAD scoring was problematic due to loss of information imposed by using genes present. Of the total LAD patterns in the Brannon paper, 59% or 78% were available using 74 or 96 genes present. PFS based on ccA/ccB were not statistically distinct using either set of present genes. Conclusions: FFPE samples are routinely available from pts with ccRCC and could be used for gene expression studies which could inform clinical practice. Using the Affy platform and FFPE-RNA samples, stratification of ccRCC pts into ccA/ccB subtypes did not reveal PFS differences. While the analysis was confounded by differences in cross-study platform performance, results suggest that further investigation will be necessary to identify a robust set of genes that separates ccRCC into prognostic categories.
Epigenetic inactivation of HOXA5 and MSH2 gene in clear cell renal cell carcinoma.
Authors: Choi Seung-Kwon , Lee Joong Geun , Yoo Koo Han 
Published: February 2017

424 Background: The high-throughput method using microarray is easy and fast way to analyze the methylation status of hundreds of preselected genes and to screen them for signatures in methylation. The aim of our study is to detect hypermethylated genes and to analyze the association between methylation status and clinicopathological parameters of clear cell renal cell carcinoma. Methods: The genetic substrate included 62 cancer tissues and 62 matched adjacent normal kidney tissues. We adapted the GoldenGate genotyping assay to determine the methylation state of 1505 specific CpG sites in 807 genes. Results: We identified two genes (HOXA5 and MSH2) with β-value differences of more than 0.3 between cancer and normal tissues. High methylation group in HOXA5 had high Fuhrman’s nuclear grade (P=0.041). Other data in HOXA5 and MSH2 were not significant with methylation status (P>0.05). Survival curve of high methylation group in HOXA5 was slightly lower than that of low methylation group. However, the statistical significances of overall survival in HOXA5 and MSH2 were low (P>0.05). Conclusions: We report the hypermethylation of two genes in clear cell renal cell carcinoma. The data we obtained could provide the basis for a diagnostic test pathological assessment, or prognosis in clear cell renal cell carcinoma.
Therapies and outcomes of non-renal cell carcinoma (non-RCC) neoplasms of the kidney: A single-institution experience.
Authors: Matrana Marc Ryan , Rao Priya , Atkinson Bradley J. , Guo Charles , Tannir Nizar M. 
Published: February 2017

431 Background: Non-RCC neoplasms of the kidney include neuroendocrine tumors (small cell carcinoma and carcinoid) and Primitive Neuroectodermal Tumors (PNET). Small cell carcinoma and renal carcinoids are small blue cell tumors that rarely occur as primary renal neoplasms. PNET, known as extraskeletal Ewing sarcoma, is characterized by t(11;22), the gold standard for diagnosis. It is a small round cell tumor derived from the neural crest and treated with chemotherapy; the role of nephrectomy is unclear. Methods: We reviewed records of patients seen at MDACC between 01/01/2001 and 01/01/2011 for PNET, small cell carcinomas, and carcinoid tumors of the kidney. Overall survival (OS) was determined from diagnosis to death. Results: 21 pts met inclusion criteria. Disease-specific data is shown in the table. Common treatments included: carboplatin/etoposide for small cell carcinomas; vincristine/doxorubicin/ifosfamide, vincristine/doxorubicin/cyclophosphamide, and doxorubicin/ifosfamide alternating with cisplatin/etoposide for PNET. Irinotecan was a common salvage agent in PNET. Most carcinoid tumors were treated with surgery alone. Two patients with small cell received whole brain radiation for brain metastases. Conclusions: Carcinoid tumors of the kidney had better outcomes compared to renal small cell carcinomas or PNET. Local carcinoid tumors of the kidney were generally managed with surgery alone. Renal small cell carcinomas and PNET were treated with systemic therapies. [Table: see text]
Impact of pretreatment C-reactive protein on overall survival for patients with metastatic renal cell carcinoma treated with sunitinib.
Authors: Yasuda Yosuke , Saito Kazutaka , Sukegawa Gen , Tanaka Hajime , Ito Masaya , Kitsukawa Shinichi , Yuasa Takeshi , Urakami Shinji , Yamamoto Shinya , Takahashi Shunji , Fukui Iwao , Yonese Junji 
Published: February 2017

436 Background: C-reactive protein (CRP) has been shown to be a significant prognostic factor for metastatic renal cell carcinoma (mRCC) in cytokine era. We further evaluated the prognostic impact of CRP for mRCC treated with sunitinib. Methods: Consecutive 37 patients were treated with sunitinib for mRCC from April 2008 to January 2011 at our institution. Seven patients were excluded because they received prior other tyrosine kinase inhibitors, sorafenib. Among eligible 30 patients, 9 patients (30%) had prior immunotherapy and 16 patients (55.5%) had prior nephrectomy. All clinical charts of the patients were reviewed for variables. Overall survival were estimated using the Kaplan-Meier method. Variables including hemoglobin, albumin, calcium, lactate dehydrogenase (LDH), thrombocytosis, number of the metastatic sites, ECOG performance status (PS), prior immunotherapy, prior nephrectomy, and pretreatment CRP concentration were evaluated. The cut-off point of pretreatment CRP concentration was set at 8mg/l. Multivariate analysis was carried out by Cox proportional hazard model. For all analysis the difference was considered significant when p < 0.05. Results: Median follow up period was 9 months (range; 1 to 25 months). The 1-year overall and progression free survival rates for the entire cohort were 68.9% and 45.8%. During follow up, 6 patients (20 %) died of disease. In univariate analysis, pretreatment CRP was a significant factor for overall survival as well as thrombocytosis. Multivariate analysis showed pretreatment CRP was solely an independent prognostic factor for overall survival. The elevations of pretreatment CRP concentrations were found in 14 patients (46.7%). The median overall survival length of patients with nonelevated CRP concentrationswas not reached compared with that of patients with elevated CRP concentration of 9.9 months. The 1-year overall survival rates of the patients with preoperative CRP elevation (35.7%) were significantly worse than those of patients without CRP elevation (91.7%) (p = 0.012). Conclusions: CRP had also prognostic impact on overall survival for patients with mRCC treated with sunitinib.
Phase I trial of the HDAC inhibitor LBH589 in combination with sorafenib in patients with renal cell carcinoma, non-small cell lung cancer and soft tissue sarcomas.
Authors: Butler Charles Mackie , Laboccetta Lydia T. , Brisendine Alan , Keane Thomas E. , Sherman Carol Arthur , Drabkin Harry A. 
Published: February 2017

440 Background: LBH589 is a novel histone deacetylase inhibitor (HDACi) that induces apoptosis of tumor cells. In renal cell carcinoma (RCC) and non-small-cell lung cancer (NSCLC) cell lines, the combination of sorafenib and HDACi was found to have synergistic inhibition, which correlated with the induction of an ER stress response. In this phase I study, we evaluated the combination of LBH589 and sorafenib in previously treated patients with RCC (9pts), soft tissue sarcomas (1pt), and NSCLC (6pts). The trial was designed to determine the safety profile and maximum tolerated dose of LBH589 and sorafenib when administered concurrently. Methods: Patients were dosed with either i.v. or oral LBH 589 (three times per week, continuously) every twenty eight days in combination with standard daily dose sorafenib (400 mg bid). The dose escalation was based on a “3+3” algorithmic design. LBH was initially administered at an i.v. dose of 5 mg/m2 with escalation to 10 mg/m2. Due to the manufacturer’s phase-out of the i.v. formulation, this was then changed to an oral formulation administered three times a week (doses 15 mg, 20 mg, and 25 mg). Results: Sixteen patients, median age 57 years, have been treated. Dose limiting toxicities were observed with grade 4 thrombocytopenia in two patients at the oral dose of 25 mg. There were no other grade 4 events. Grade 3 events included fatigue (2 pts), hypophosphatemia (2 pts), hypertension (1 pts), anemia (1 pt), rash (1 pt) and hand-foot erythroderma (1 pt). Common toxicities for the combination were fatigue (81%), weight loss (62%), loss of appetite (56%), diarrhea (56%), rash (50%), thrombocytopenia (31%), and hand-foot erythroderma (25%). No patients had significant QT prolongation. There was 1 partial response in a patient with lung cancer (31 weeks). Stable disease was noted in seven patients with RCC (78+, 48, 47, 31, 21, 17, and 10+ weeks). Seven patients had progressive disease Conclusions: The administration of oral LBH589 at a dose of 20 mg was found to be well tolerated and will be used in the expansion phase of the trial. Prolonged stable disease was observed in patients previously treated with sorafenib alone, sunitinib and axitinib.
What is the benfit of mTOR inhibitors (mTORi) rechallenge in metastatic renal clear cell carcinoma (mRCC) patients (pts) initially treated with TKI?
Authors: Maj-HES Agnes , Elaidi Reza-Thierry , Medioni Jacques , Scotte Florian , Kramer Gero , Hoeltl Wolfgang , Gachet Julie , Teghom Corine , Gornadha Yohan , Oudard Stephane 
Published: February 2017

442 Background: question regarding the benefit of a mTORi re-challenge for pts treated with a previous line of TKI and 1 line of mTORi remains unanswered in mRCC. Methods: this study retrospectively investigated Treatment Duration (TD), best overall response (OR) in pts treated with TKI and mTORi in a sequence temsirolimus-everolimus (T-E) or everolimus-temsirolimus (E-T). Eligibility criteria: TKIs prior to either sequence of mTORi. Pts characteristics and prognostic factors (Heng’s score) were considered prior to TKI and 1st mTORi. Response was defined with respect to TD and best OR: E: Non Responders (NR): < 4.9 months (m) + progressive disease (PD), Responders (R): >4.9m + SD/PR; T: Non Responders (NR): < 3.6 months (m) + PD; Responders (R): >3.6 m + SD/PR. Results: 12 pts were eligible. 5 and 7 pts received 1 and 2 TKIs prior to 1st mTOR, respectively. 9 and 3 pts were in the intermediate and poor risk group respectively prior 1st mTORi (Heng’s score). 7 pts received E and 5 pts received T as first mTORi. Whatever the sequence, 7 pts out of 12 were responders to E and 2 out of 12 were responders to T (3 pts did not respond to any mTORi). In the E-T sequence, 5 pts were responders to E with no response to T, 1 pt no responder to E but responder to T (1 pt didn’t respond to both mTORi). In the T-E sequence, 2 pts were responders to E, 1 pt was responder to T and 2 pts didn’t response to both mTORi. Median TD for E-T and T-E sequences was 10.3m (95%CI: 8.8-19.2) and 5.8m (95%CI: 2.9-19.3), respectively. Response was not related to pt’s prognosis group. Conclusions: despite the small effective of this study, results suggest that responders to everolimus as 1st mTORi could not benefit from a re-challenge with temsirolimus. Pts who were not responders to temsirolimus could still be responders to everolimus. This observation should be confirmed with larger databases and prospective studies. [Table: see text]
A hypothesis-generating exploratory analysis of efficacy and safety of abiraterone acetate (AA) in African American (Af Am) patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Efstathiou Eleni , Assikis Vasily J. , North Scott A. , Showel John , Hutson Thomas E. , Riggs Stephen Boyd , Waxman Jonathan , Park Youn Choi , Kheoh Thian San , Haqq Christopher M. , Logothetis Christopher , Molina Arturo 
Published: February 2017

55 Background: The reported increased prostate cancer lethality in Af Ams has been attributed by some to altered androgen receptor (AR) signaling. We compared toxicity, PSA response, time-to-PSA progression (TTPP), and radiographic progression-free survival (rPFS) in Af Am vs non Af Am pts with CRPC treated with AA + prednisone (P) vs placebo + P. We hypothesized that differences in response to AA may be observed if differences in AR signaling exist in Af Ams. Methods: COU-AA-301 is a randomized double blind study of AA (1000 mg + P 5 mg po BID) vs placebo + P post-docetaxel. Results: TTPP, rPFS, and PSA response rate were higher with AA vs placebo. In Af Am pts, treatment emergent AEs (TEAEs) for AA vs placebo occurred in 96.4% vs 100.0% of pts (50.0% and 66.7%, respectively, grade 3/4); serious TEAEs occurred in 42.9% and 33.3% of pts (28.6% and 26.7%, respectively, grade 3/4). The safety profile of AA appears comparable between the Af Am and overall study populations. Conclusions: Although the small number of Af Am pts in this study precludes formal conclusions regarding efficacy and safety of AA in this pt population, the overall trend suggests these pts experienced clinical benefit from AA with a safety profile comparable to the overall study population. These findings do not appear to support the hypothesis that AR signaling accounts for the increased lethality of prostate cancer seen in Af Ams. Further studies of AA in Af Am pts are planned to understand the potential benefit in this population. Additional efforts are needed to increase participation of Af Am pts in clinical trials. [Table: see text]
Impact of marital status on prostate cancer-specific mortality and overall mortality after radical prostatectomy.
Authors: Nepple Kenneth Gerard , Kibel Adam Stuart , Sandhu Gurdarshan S , Kallogjeri Dorina , Strope Seth A. , Grubb Robert L. , Wolin Kathleen Y. , Sutcliffe Siobhan 
Published: February 2017

73 Background: Analysis from population-based cancer registry data has suggested that being married is associated with improved survival in men with prostate cancer. However, a limitation of such analysis is the inability to control for PSA or medical comorbidity which may differ by marital status. We investigated the association between marital status and both prostate cancer specific mortality (PCSM) and overall mortality (OM) in men treated with radical prostatectomy. Methods: The study population included 3596 men treated with radical prostatectomy at a single institution between 1994 and 2004 and followed for a median of 72 months. Disease specific factors (PSA, clinical stage, and biopsy Gleason grade), comorbidity (validated ACE-27 comorbidity index), ethnicity, age, and marital status at time of treatment were retrieved from an institutional cancer registry. Differences between marital status groups were evaluated by Chi square or ANOVA. Multivariable Cox proportional hazard regression models were used to estimate the hazard ratio (HR) of PCSM and OM by marital status. Results: 86.9% of men were married, 5.3% divorced, 2.4% widowed, and 5.5% never married. Marital status was associated with differences in PSA (p<0.01), comorbidity (p=0.04), and age (p<0.01). Married men had the lowest mean PSA at diagnosis and never married men were younger and the most likely to have no known medical comorbidity. A total of 386(11%) men were dead at the end of follow up, but only 55 of them died of prostate cancer. In multivariable analyses (Table), never married men had a significantly increased risk of PCSM and OM compared to married men, whereas no additional risk was observed for divorced or widowed men. Conclusions: Never married men had an increased risk of PCSM and OM. Factors associated with social isolation or unhealthy behaviors may have a detrimental effect on survival after prostatectomy. [Table: see text]