bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytoreductive radical nephrectomy (cRN) and level II-IV infereior vena cava (IVC) thrombectomy for metastatic renal cell carcinoma (mRCC).
Authors: Klink Joseph C. , Westesson Karin E. , Rini Brian I. , Rabets John C. , Campbell Steven C. , Ghoneim Islam , Stephenson Andrew J. , Krishnamurthi Venkatesh 
Published: February 2017

382 Background: cRN for mRCC is associated with a modest improvement in survival when combined with cytokine therapy in patients with good performance status. A level II-IV IVC thrombus renders cRN technically challenging with increased risks of perioperative morbidity and mortality. The outcome of these patients relative to the overall cRN population is poorly defined. Methods: Clinical information and follow-up data were obtained from an institutional retrospective data base for patients who underwent cRN and IVC thrombectomy between 1990–2011.The operative outcomes, complications, and cancer outcomes were compared. Results: cRN was performed on 56 patients with mRCC and level II (N =19), III (N =25) or IV (N =12) IVC thrombus. Age ranged from 23 to 84 years old and 36 (64%) were male. Predominant sites of metastases were: lung, 22 (39%); liver 3 (5%); mediastinum 3 (5%); multiple sites 17 (30%). Local clinical stage was T3a in 2 (3.6%), T3b in 38 (68%), T3c in 12 (21%), and T4 in 4 (7%). Twenty (36%) patients were clinical N1. Median tumor size was 10.2 cm (range, 1.4–21). Histologic classification was clear cell in 40 (71%), papillary in 4 (7%), and unclassified in 12 (21%). Intraoperatively, 2 patients had embolization of thrombus. Postoperatively, Clavien grade 3–5 complications occurred in 3 (5%) patients, including two (3.6%) mortalities. Follow-up information was available for 49 patients and the median follow-up was 13 months (IQR: 6–33). Of these patients, 31 (63%) received postoperative systemic therapy with cytokines (14), targeted agents (16), or both (1). The overall median survival was 13 months (95% CI: 10–16), and was similar before (median 12 months) and after (median 13 months) the introduction of targeted therapy. Conclusions: Among patients with mRCC with level II–IV IVC thrombus managed at a high-volume kidney center, cRN and IVC thrombectomy is associated with acceptable perioperative morbidity and mortality. The median survival of patients in our cohort is similar to the overall population of patients managed with cRN and cytokine therapy though less than those managed with cRN and targeted therapy based on data from published randomized trials.
Nodal disease in the setting of metastatic renal cell carcionoma: Can a lymph node dissection alter outcomes?
Authors: Chapin Brian Francis , Delacroix Scott Edward , Kenney Patrick Aloysius , Nogueras Gonzalez Graciela M , Tamboli Pheroze , Jonasch Eric , Tannir Nizar M. , Wood Christopher G. 
Published: February 2017

386 Background: The impact of lymph node dissection (LND) in patients with metastatic renal cell carcinoma (mRCC) undergoing cytoreductive nephrectomy (CN) is unclear. The aims of this study were to determine the predictive ability of LN status for overall survival (OS) in patients treated with CN in the targeted therapy era and if LND increases the morbidity of CN. Methods: We performed a retrospective review of all patients with mRCC treated with CN at a single institution between 2004–2010. Patients participating in open or unpublished trials were excluded, leaving 173 patients for analysis. LNs >1cm by long axis diameter were considered clinically positive (cN+). OS was calculated using COX proportional hazard regression. Complications were classified using the modified Clavien system. Results: Sixty-five (37.6%) patients were clinically node positive (cN+). Median OS was significantly worse for the cN+ patients compared to cN0 patients [17.5 vs 29.1 mos;HR 1.8;(1.3-2.6)]. Clinical node status remained an independent predictor of OS on multivarible analysis (MV) [HR 1.7;CI 1.1-2.7]. LND was performed in 61/65 (93.4%) cN+ patients and in 56/108 (52%) of cN0 patients. Pathologic node positive disease (pN+) was more common in cN+ compared to cN0 patients (75% vs. 23%,p <0.001). pN+ patients had worse median OS than pN0 patients [16.0 v 35.5 mos;HR 2.3(1.5-3.6)]. Among pN+ patients (n=54), complete resection of all identifiable nodal disease was associated with an improved OS compared to patients with unresectable nodal disease (n=4) [16.0 v 5.6 mos;HR 2.9(1.0-8.3)]. On univariate analysis LND patients were more likely to have a post-operative complication (64% vs 43%,p=0.008) and more specifically chylous ascites (12 v 0,p=0.01). Despite this association, LND did not reach statistical significance when MV analysis was performed [OR 1.9;(0.9-3.8)]. Conclusions: Among patients undergoing CN, those with cN+ disease had worse OS. Likewise, pN+ patients have worse OS than pN0 patients. LND is associated with higher morbidity than CN alone. Further efforts are needed to determine removal of pathologic nodes alters the natural history of the disease, and if the benefit offsets the increased morbidity.
A population-based overview of sequences of targeted therapy in metastatic renal cell carcinoma (mRCC).
Authors: Heng Daniel Yick Chin , Lee Jae-Lyun , Harshman Lauren Christine , Bjarnason Georg A. , Razak Albiruni R , MacKenzie Mary J. , Wood Lori , Vaishampayan Ulka N. , Tan Min-Han , Rha Sun Young , Donskov Frede , Agarwal Neeraj , Kollmannsberger Christian K. , North Scott A. , Rini Brian I. , Choueiri Toni K. ,   International mRCC Database Consortium
Published: February 2017

387 Background: There are several types of targeted therapy (TT) available to treat mRCC and data on outcomes and different sequences of therapies are required. Methods: Consecutive series of patients with mRCC treated with TT were examined. Multivariable analysis was performed when significant differences on univariable analysis were seen. Results: 2106 patients were included with a median follow-up of 36 months. 907 (43%) and 318 (15%) patients received subsequent second-line and third-line TT, respectively. Baseline characteristics of the groups below were not different except there were more patients with non-clear cell histology in the VEGF to mTOR group compared to the VEGF to VEGF group. When adjusting for the Heng et al poor risk criteria and non-clear cell histology, the hazard ratio of death for the VEGF to mTOR group vs the VEGF to VEGF group was 0.833 (95%CI 0.669-1.037, p=0.1016). When adjusting for poor risk criteria, the hazard ratio of death for the sunitinib to everolimus vs sunitinib to temsirolimus sequences was 0.774 (0.52-1.153, p=0.2086). Conclusions: The sequence of TT may not have a substantial effect on outcome but results of prospective randomized studies are awaited. [Table: see text]
Analgesic use and the risk of renal cell carcinoma (RCC): Results from a large up-to-date meta-analysis.
Authors: Cho Eunyoung , Je Youjin , Choueiri Toni K. 
Published: February 2017

395 Background: Analgesics have been linked to an increased risk of developing renal cell carcinoma (RCC), but the evidence is mixed. Using a meta-analysis design of all available studies, we investigated the association between analgesic use and RCC risk. Methods: We searched the MEDLINE database to identify eligible case-control or cohort studies published in English from 1966 to July 1, 2011 for 3 categories of analgesics: acetaminophen, aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs). Study-specific effect estimates were pooled to compute an overall relative risk (RR) and its 95% confidence interval (CI), using a random effects model, for each category of the analgesics. Analyses were conducted according to regular/any use and high dose or long-duration of use, separately. Results: We identified 18 studies (12 for acetaminophen, 12 for aspirin, and 5 for other NSAIDs) that were performed in 6 countries. Regular/any use of acetaminophen and other NSAIDs were each associated with an increased risk of RCC: pooled RR, 1.33 (95% CI 1.18-1.49) for acetaminophen and 1.26 (95% CI, 1.09-1.44) for other NSAIDs, respectively. For use of aspirin, we found no significant increased risk (pooled RR, 1.14 [95% CI, 0.98-1.33]). Similar risk trends were seen with high dose of analgesics intake. No significant difference in associations was found by study design (case-control vs. cohort), type of controls in case-control study (population based vs. hospital based), outcome (RCC vs. kidney cancer), and gender (male vs. female). There was no indication of publication bias for the 3 analgesics. Conclusions: In this meta-analysis of analgesics use and RCC risk, we found that use of acetaminophen and non-aspirin NSAIDs was associated with a significant increased risk of developing RCC.
Tumor burden as an independent prognostic factor in metastatic renal cell carcinoma (mRCC).
Authors: Escudier Bernard J. , Iacovelli Roberto , Lanoy Emilie , Albiges Laurence , Fizazi Karim 
Published: February 2017

397 Background: During the last ten years, several classifications have been used to assess the prognosis in mRCC. In none of them, tumor burden (TB) has been considered. This study investigates the prognostic role of baseline TB in terms of progression free survival (PFS) and overall survival (OS), in patients with mRCC. Methods: All patients with clear cell mRCC enrolled in our center, in 2 second-line trials, post cytokine, with sunitinib and sorafenib or placebo (Escudier JCO 2009, Escudier NEJM 2007), were selected for this analysis. TB was defined as the sum of the longest unidimensional diameter of each target lesions assessed using RECIST criteria. PFS and OS were estimated using Kaplan-Meier method and compared using the log-rank test. Association between TB and PFS or OS was evaluated using the Cox proportional hazards model. Multivariable analyses were adjusted for modified MSKCC risk class and treatment. Non-parametric Spearman rank test (rs) was used to assess the correlations between TB and MSKCC risk groups or ECOG Performance Status (PS). Results: Final population included 124 patients: 66% received sorafenib or sunitinib and 34% received placebo; median follow up was 80.1 months (IQR: 68.8 – 88.0). Baseline TB was divided into 3 tertiles (1.3 - 9.4 cm; 9.5 - 19.0 cm; 19.1 - 47.3 cm). TB was related to PFS and OS and, when adjusting for modified MSKCC risk class and treatment, these associations remained significant: each 1 cm increase in TB increased the progression risk by 5% (HR: 1.05; 95%CI, 1.02 – 1.07; p < 0.0001) and the death risk by 5% (HR: 1.05; 95%CI, 1.03 – 1.08; p < 0.0001). OS decreased with TB: the median tertiles OS values were: 42.1 months (95%CI: 24.0 – 60.2), 20.1 months (95%CI: 14.5 – 25.7), and 11.2 months (95%CI: 4.8 – 17.6), respectively (p < 0.0001, figure 2). The TB was positively related to ECOG PS (rs = 0.357; p < 0.0001) and to MSKCC risk score (rs = 0.478; p < 0.0001). Patients with higher TB had shorter PFS, shorter OS, poorer MSKCC score and increased ECOG PS. Conclusions: TB is easy to calculate with standard CT and significantly relates to OS and PFS in patients with mRCC. We report for the first time the independent prognostic role of baseline TB in mRCC.
Use of meta-analysis of clear cell renal cell carcinoma gene expression to define a variant subgroup and identify gender influences on tumor biology.
Authors: Haake Scott Mattox , Brannon A. Rose , Hacker Kate , Pruthi Raj , Wallen Eric , Nielsen Matthew Edward , Rathmell Kimryn 
Published: February 2017

412 Background: Clear cell renal cell carcinoma (ccRCC) displays molecular and histological heterogeneity. Previously described subsets of this disease, ccA and ccB, were defined based on multi-gene expression profiles, but it is unclear if these subgroupings reflect the full spectrum of disease or how these molecular subtypes relate to histological descriptions or gender. We sought to determine whether additional subtypes of ccRCC exist, and whether these subtypes are related to VHL inactivation, HIF1/HIF2 expression, tumor histology, or gender. Methods: Six large publically available ccRCC gene expression databases were identified that cumulatively provided data for 480 tumors for meta-analysis via meta-array compilation. Unsupervised consensus clustering was performed on the meta-arrays. Tumors were examined for the relationship of multigene-defined consensus subtypes and expression signatures of VHL mutation and HIF status, tumor histology, and gender. Results: Two dominant subsets of ccRCC were observed. However, a minor third cluster was revealed which correlated strongly with a wild type VHL expression profile and indications of variant histologies. When variant histologies were removed, ccA tumors naturally divided by gender. This technique is limited by potential for persistent batch effect, tumor sampling bias, and restrictions of annotated information. Conclusions: ccA and ccB subsets of ccRCC are robust in meta-analysis among histologically conventional ccRCC tumors. A third group of tumors was identified, which may represent a new variant of ccRCC. Within definitively clear cell tumors, gender may delineate tumors in such a way that could have implications regarding current treatments and future drug development.
Efficacy and safety of pazopanib as a subsequent treatment after failure of other targeted agents in patients with metastatic renal cell carcinoma (mRCC).
Authors: Tan Jiahuai , Heilbrun Lance K. , Fontana Joseph A. , Smith Daryn , Heath Elisabeth I. , Baranowski Karen , Vaishampayan Ulka N. 
Published: February 2017

415 Background: Pazopanib is an oral tyrosine kinase inhibitor and is currently approved for treatment of patients with advanced or mRCC in the first-line, or second-line setting, after progression on cytokine therapy. No reports of efficacy and safety are available post targeted therapy. We conducted a retrospective analysis of cases receiving pazopanib after failure of other targeted agents. Methods: The study was reviewed and approved by our Institutional Review Board. Review of medical records of advanced renal cancer patients, treated with second-line pazopanib from April 2010 to August 2011 at Karmanos Cancer Center was performed. The Common Terminology Criteria for Adverse Events version 4.0 was used to grade the severity of definitely treatment-related adverse events (AEs). Results: 14 patients are included to date in this ongoing data collection and analysis study. Median age was 58 years, 8 were Caucasian, 4 African American, and 2 other races. By the MSKCC criteria, 1 patient was favorable, 6 were intermediate and 7 poor risk. Pazopanib was utilized as second line in 4 patients, third line in 5, and even later in 5. Prior line targeted therapies included sunitinib (8), temsirolimus (9), everolimus (4), sorafenib (1), bevacizumab (1) and axitinib (1). Nine of 14 patients to date were treated with pazopanib for at least 2 months and were assessed for response by imaging studies. One achieved partial remission; 5 had stable disease, and 3 had progression. The median time to progression after starting pazopanib was 4.0 months. The predominant AEs were grade 1 or 2, which included fatigue (4), liver enzyme elevation (3), diarrhea (2), hypertension (2), skin rash (1), depression (1) and hyponatremia (1). No grade 3 or 4 AEs, or definitely treatment-related deaths were observed. Conclusions: Pazopanib appears to maintain efficacy and tolerability in mRCC even after failure of other targeted therapies. Further investigations of larger patient cohorts in this setting are recommended.
Incidence and oncologic outcome of renal cell carcinoma in hemodialysis patients detected by annual computed tomography (CT) screening.
Authors: Hatakeyama Shingo , Yamamoto Hayato , Yoneyama Takahiro , Hashimoto Yasuhiro , Koie Takuya , Kamimura Noritaka , Ohyama Chikara 
Published: February 2017

426 Background: Patients with maintenance hemodialysis (HD) have been recognized as a high risk group for cancer. The aim of this study was to verify the incidence and oncological outcomes of patients on maintenance hemodialysis with renal cell carcinoma (RCC) compared with RCC patients without renal dysfunction. Methods: We have been carried out annual screening for renal mass for the hemodialysis patients.The oncological outcome of pT1N0M0 RCC detected by annual screening of CT imaging were retrospectively reviewed in 1217 patients with HD between January 2002 and December 2010 at Oyokyo kidney Research Institute and Hirosaki University Hospital, Hirosaki, Japan. Overall and cancer specific survival was compared with age matched 106 of pT1N0M0 RCC patients without renal dysfunction who performed radical nephrectomy at the same periods. Results: Among the hemodialysis patients, 14 RCCs were incidentally detected by screening CT examinations and RCC detection rate in HD patients was 0.27% per year. Total 119 pT1N0M0 RCC patients (13 with HD group, 106 normal kidney function group) were incidentally detected by regular abdominal CT imaging without symptoms. There were no significant differences on age and gender between HD and normal kidney function group. Cancer specific survival after tumor diagnosis was not different, but overall survivals were significantly superior in patients without renal dysfunction compared to those with chronic renal failure (P < 0.0001). Cancer specific and Overall 5-year survival was 95% and 96% in patients without renal dysfunction, 92% and 54% in those with chronic renal failure. Conclusions: There was no significant difference in cancer specific survival of pT1 RCC between the two groups. However, overall survival was significantly worse in HD patients. Oncological effectiveness of annual CT screening for the HD patients was not evident in the present retrospective study.
Signaling pathway-based stratification of clear cell renal cell carcinoma.
Authors: Bongarzone Italia , Cremona Mattia , Espina Virginia A. , Miccichè Francesca , Veneroni Silvia , Colecchia Maurizio , Pierobon Mariaelena , Deng Jianghong , Mueller Claudius , Procopio Giuseppe , Lanzi Cinzia , Petricoin Emanuel , Liotta Lance A. 
Published: February 2017

434 Background: There are marked differences in responses to therapy among patients with clear cell renal cell carcinoma (ccRCC), which makes the outcome difficult to predict. This study is aimed to define a new classification system that would elucidate distinctions between carcinomas in order to facilitate selection of the appropriate treatment. We mapped cell signaling pathways in individual renal cell carcinomas and identified different classes based on commonly shared phosphorylation-driven signaling networks. Methods: Laser capture microdissection and reverse-phase protein arrays were used to profile 75 key nodes in 16 primary clear cell renal cancers. These nodes represent many signaling pathways known to be important in tumorigenesis and progression. Results: Statistical analysis revealed significant differences (p <0.05) in signaling levels between two groups of samples, group A (4 samples) and group B (12 samples), for 27 of the 75 endpoints tested. In group A, high activation levels of EGFR, RET, and RASGFR1 converged to activate AKT/mTOR. Group B, showed high phosphorylation levels of ERK1/2 and STAT transcription factors and samples significantly partitioned in two clusters of 7 and 5 cases designated C and D. Group C showed elevated expression of a regulator of autophagy, LC3B; group D showed activation of Src and STAT transcription factors, suggesting the presence of cytokine-mediated cell survival pathways. A DNA copy number analysis was performed on the same samples and the results showed that group B represents some paradigmatic cases of ccRCC, with VHL loss-of-function mutations. Conclusions: The proteins identified appeared to be linked to pathways that are targeted by drugs typically used to treat clear cell renal cell carcinoma. Thus, this type of analysis could be useful for stratifying patients and selecting the best therapeutic approaches.
Vascular endothelial growth factor (VEGF) therapy in metastatic renal cell carcinoma (mRCC): Differences between Asian and non-Asian patients.
Authors: Wang Ying , Choueiri Toni K. , Lee Jae-Lyun , Tan Min-Han , Rha Sun Young , North Scott A. , Kollmannsberger Christian K. , Heng Daniel Yick Chin 
Published: February 2017

451 Background: Several reports have indicated that VEGF targeted therapy in metastatic renal cell carcinoma (mRCC) may be more toxic in the Asian versus Caucasian populations. Comparative efficacy of these agents with respect to ethnicity is not well characterized. Methods: Eight centers participating in the International mRCC Database Consortium with available dose reduction data on patients with mRCC treated with VEGF targeted therapy were included in this analysis. Asian patients were derived from centers in Korea and Singapore. Results: 1024 patients with a median follow-up of 29.4 months were included in this analysis. Baseline characteristics are below. The percentage of dose modifications/reductions between non-Asians and Asians was similar (55% vs 61% p=0.1197) but more patients completely discontinued treatment due to toxicity in the non-Asian vs the Asian group (28% vs 21% p=0.0197). When adjusted for the Heng et al poor prognostic criteria, there was no difference in overall survival (HR 0.887, 95%CI 0.729-1.08, p=0.2322) or progression-free survival (HR 1.069, 95%CI 0.910-1.256, p=0.4184) between non-Asians and Asians. Interestingly, when patients were dose reduced due to toxicity, they had a longer treatment duration and overall survival than those that did not require a dose reduction in both the non-Asian (10.6 vs 5.0 months p<0.0001 and 22.6 vs 16.1 months p=0.0016, respectively) and in the Asian populations (8.9 vs 5.4 months p=0.0028 and 28.0 vs 18.7 months p=0.0069). Conclusions: After adjusting for risk groups, there appears to be no difference in outcome between Asians vs. non-Asian patients with mRCC treated withVEGF-targeted therapy. Judicious dose reductions may allow for better outcomes in both populations possibly due to longer treatment durations, but direct comparisons are needed. [Table: see text]