bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of chromosomal copy number variation on outcome in metastatic clear cell renal cell carcinoma patients treated with antiangiogenic agents.
Authors: Jonasch Eric , Thakur Suresh , Sircar Kanishka , Tamboli Pheroze , Tannir Nizar M. , Monzon Federico A. 
Published: February 2017

393 Background: Antiangiogenic agents (AA) are used to treat metastatic clear cell renal cell carcinoma (ccRCC). Currently there are no biomarkers of therapeutic efficacy with these agents. We have previously shown that chromosome copy number variation (CNV) is associated with poor (14q loss) or more favorable outcomes (5q31-ter gain) in nonmetastatic patients. The purpose of the current study was the impact of CNV on response, progression free survival (PFS) and on overall survival (OS) after AA in patients with metastatic ccRCC. Methods: We obtained archival FFPE or frozen tumor specimens from patients with mRCC treated with sorafenib (after tumor removal), bevacizumab or sunitinib (neoadjuvant treatment). DNA was analyzed with Affymetrix 250K Nsp SNP microarrays. We identified the presence of genomic imbalances and loss of heterozygosity (LOH) to obtain “virtual karyotypes”. We then compared CNV to outcome using Wilcoxon-Gehan statistical analysis. Results: A total of 83 patients were used to analyze CNV after treatment with AA: 22 sorafenib, 29 sunitinib, 31 bevacizumab. Gain of 8q (p = 0.036) and loss of 16q (p = 0.0031), 20p (p = 0.038) or 20q (p = 0.022) were associated with a shorter OS, whereas gain of 1q (p = 0.037) and 5q (p = 0.019) were associated with longer OS in this patient cohort. When 14q loss was combined with 8q gain, median OS was further decreased (p 0.01). Surprisingly, when assessed as a group, no specific CNV was associated with PFS. However, when compared separately, 5q gain was predictive for better PFS in sorafenib or bevacizumab treated patients (p = 0.006), but no such effect was seen in the sunitinib treated cohort. Conclusions: Our results show that chromosomal imbalances are associated with divergent clinical outcome in metastatic ccRCC patients treated with AA, and are predominantly prognostic. Dissecting out driver tumor suppressor or tumor activating genes within these chromosomal regions will guide our understanding of what defines a particularly lethal phenotype. The possibility exists that specific CNV profiles predict for response to therapy, but a larger sample size is required to validate this possibility.
Real-life patterns of use and effectiveness of sunitinib in patients with metastatic renal cell carcinoma: The SANTORIN study.
Authors: Ravaud Alain , Culine Stephane , Grelaud Angela , Chevreau Christine , Lamarque Stephanie , Balestra Aurelie , Bernard Marie-Agnes , Moore Nicholas , Noize Pernelle , Bay Jacques-Olivier , Fourrier-Réglat Annie 
Published: February 2017

400 Background: Until 2006, treatment options for metastatic renal cell carcinoma (mRCC) were limited to cytokine therapy and surgery. Sunitinib, an oral antiangiogenic agent, received European marketing authorisation in Jan 2007 for first-line treatment in advanced and/or mRCC. The SANTORIN study was designed to describe patterns of use and estimate survival outcomes in mRCC patients treated with sunitinib in a real-life setting. Methods: SANTORIN was an observational cohort conducted in 36 French centres including patients initiating first-line treatment with sunitinib from Jan 2008-Apr 2010, followed 2 years after treatment onset. Treatment characteristics, response (evaluated by investigator based on RECIST criteria) and survival outcomes were collected from medical files. Overall and progression-free survival (OS and PFS) results were estimated using Kaplan-Meier method. Results: Characteristics of the 302 included patients were: mean age 64.3 years; male 73.2%; clear-cell histological component 83.1%; ECOG ≥2 9.9%, prior nephrectomy 85.4%. Baseline sunitinib dose was 50 mg/day for 83.4% of patients. The median duration of first-line treatment was 10.7 months (median number of cycles: 6). Dose reduction occurred in 65.2% of patients. Reasons for discontinuation of first-line treatment were progressive disease (61.1%), death (31.2%), adverse events (6.8%), and other reasons (1.0%). OS was 70.8% at 1 year (95%CI [65.3;75.5]) and 49.5% at 2 years [43.7;55.0]. Median OS was 23.6 months [19.9;27.4] (not reached in patients with clear-cell component). PFS was 38.2% at 1 year [32.7;43.7] and 16.4% at 2 years [12.5;20.9]. Median PFS was 8.4 months [7.6;9.9] (9.5 months [8.1;11.0] in patients with clear-cell component). Overall best response was 31.1% (2.3% complete, 28.8% partial), 40.1% had stable and 18.5% progressive disease. Conclusions: Despite certain differences regarding severity of cancer, these results demonstrated that effectiveness of sunitinib in mRCC is close to efficacy reported in the pivotal clinical trial (median OS: 26.4 months [95% CI 23.0 ; 32.9], median PFS: 11.0 months [11.0 ; 13.0]), especially in patients with clear-cell component.
Tumor thrombus transection in renal cell carcinoma.
Authors: Klink Joseph C. , Westesson Karin E. , Gao Tianming , Stephenson Andrew J. , Krishnamurthi Venkatesh 
Published: February 2017

409 Background: Inferior vena cava (IVC) tumor thrombectomy with radical nephrectomy (RN) for renal cell carcinoma (RCC) is difficult when a large renal mass is present, but completing the RN by transecting the renal vein with tumor thrombus inside can facilitate dissection of the IVC for thrombectomy. We compared the outcomes of patients in whom the thrombus was purposely transected to those in whom the IVC thrombus was removed en bloc with the kidney. Methods: At our institution between 2000-2011, 152 patients with RCC and level II (N =53), III (N =52) or IV (N =47) IVC thrombus underwent RN and IVC thrombectomy. In 92 patients the kidney was removed prior to initiating the IVC thrombectomy. In 60 patients, the tumor thrombus and kidney were removed en bloc. Clinical information was obtained from an institutional database. Since thrombus level greatly affects surgical technique and complications, outcomes were analyzed within each level. Results: Thrombus level and clinical stage were higher in the transected group, but other baseline characteristics did not differ significantly. The primary endpoint, the overall rate of complications including intra-op and post-op events, was not statistically significantly different (all p >0.2) between the en bloc and transected groups for level 2 (8/37 vs. 6/16), level 3 (7/17 vs. 15/35), and level 4 (2/6 vs. 25/41). Operative times were similar within level 2 (300 vs. 300 minutes, p=0.2), level 3 (312 vs. 360, p=0.1), and level 4 (325 vs. 402, p=0.7). Units of blood products transfused were also similar within level 2 (3 vs 5, p=0.3), level 3 (5 vs. 9, p=0.06), and level 4 (6 vs. 14, p=0.4). Due to the low event numbers within each subgroup, multivariable analysis could not be reliably run on these outcomes. Three patients, all in the transected group, experienced intraoperative tumor thrombus embolization to the pulmonary artery requiring surgical embolectomy, but all 3 survived to discharge without any serious sequelae. Conclusions: Complications, operative time, and transfusion rates were similar between the en bloc and transected techniques when stratified by tumor thrombus level. Because of the rarity of this disease, statistical power of these comparisons is low, but our study suggests no evidence of advantage to either technique.
B7H1 expression and association with clinical response to sunitinib therapy in patients with metastatic renal cell carcinoma (mRCC).
Authors: Kim Jenny J. , Xu Haiying , Haddad Housam , Anders Robert , Arslankoz Sehbal , Wang Hang , Zhang Zhe , Rapp Sarah , Wood Laura S. , Netto George J. , Drake Charles G. , Rosner Gary L. , Rini Brian I. 
Published: February 2017

416 Background: Preliminary data support that B7H1 expression is associated with objective response (OR) to anti-PD-1 antibody treatment in multiple solid tumors. The aim of this study was to retrospectively evaluate a possible association between B7H1 expression and clinical response to sunitinib therapy in mRCC patients. Methods: mRCC patients receiving sunitinib therapy (50mg 4/2) were identified and data regarding patient characteristics and clinical outcome to sunitinib were recorded. Immunohistochemistry (IHC) staining of B7H1 was done on pretreatment formalin fixed paraffin embedded (FFPE) tissue sections according to available protocol at Hopkins. IHC scorings were done by 2 independent pathologists who were blinded to outcomes and a 3rd pathologist was used if there was a discrepancy between the first 2. Association of B7H1 expression with OR was assessed using Fisher’s exact test. Progression free survivals (PFS) were estimated using the Kaplan-Meier method and compared using log-rank test. Multivariate analyses were performed using logistic regression and Cox regression. Results: 20 cases were identified of which 18 had available FFPE for IHC analysis. 78% were male; median age was 55 (range 35-79); 72% ECOG PS of 0; 94% had prior nephrectomy; 89% were therapy naïve. 50% were intermediate risk category according to Heng criteria and the rest were poor risk. 55.6% (10/18) were positive for B7H1 expression (>5% positive cell membranous staining). 30% of B7H1 positive patients had OR whereas 50% of B7H1 negative patients had OR (p = 0.63). Median PFS were 19.3 and 6.2 mos for B7H1 negative and positive groups, respectively (p = 0.56). In multivariate models, B7H1 expression was neither associated with OR (odds ratio = 0.54, 95% CI = 0.07-4.23, p = 0.56) nor PFS (hazard ratio =1.06, 95% CI = 0.34-3.34, p = 0.92) after adjusting for Heng risk classification. Conclusions: In this study, B7H1 expression was not associated with clinical outcome to sunitinib therapy in metastatic RCC patients.
Survival trends among patients with advanced renal cell carcinoma (RCC) in the United States.
Authors: Shah Binay Kumar , Ghimire Krishna Bilas 
Published: February 2017

422 Background: Since approval of sorafenib in December 2005, several targeted therapeutic agents have been approved by the FDA for the treatment of advanced renal cell carcinoma. This study was conducted to find out whether the improvements in survival of advanced RCC patients with targeted agents have translated into survival benefit in population-based cohort. Methods: We analyzed the Surveillance, Epidemiology, and End Results (SEER) 18 registry database to compare 1- and 3-year relative survival rates among advanced RCC patients during 2001-2009, 2001-2004, and 2006-2009. We also evaluated the survival rates by age (<65 and ≥65 years) and sex. We used SEER*Stat software to analyze the data. Results: The total number of advanced RCC patients during 2001-2009, 2001-2004, and 2006-2009 were 7,055, 3,355 and 2,985 respectively. During 2001-2009, the 1- and 3-year relative survival rates were 26.7± 0.6% and 10.0±0.4% respectively. The 1-year relative survival rates during 2001-2004 and 2006-2009 were 27.0±0.8% and 27.1±0.9%, (p value=1.3) respectively. Similarly, the 3-year survival rates during 2001-2004 and 2006-2009 were 10.1±0.6% and 9.6±0.8%, (p value=1.42), respectively. There was no significant difference in survival rates during 2001-2004 and 2006-2009 periods by age and sex. Conclusions: This population based study showed that there was no significant improvement in relative survival rates among advanced RCC patients in the era of targeted agents. As with other database analyses, limitations of this large study may be incomplete reporting practices and lack of data on treatment.
Outcomes of second-targeted therapy for mRCC: A retrospective chart review of community practices in the United States.
Authors: Jonasch Eric , Signorovitch James E. , Lin Peggy L. , Liu Zhimei , Culver Kenneth W. , Pal Sumanta Kumar , Scott Jeffrey A. , Vogelzang Nicholas J. 
Published: February 2017

424 Background: Sequential use of targeted therapies has become standard practice for the treatment of metastatic renal cell carcinoma (mRCC). This study describes treatment outcomes of the 2nd-targeted therapy among patients with mRCC treated in the community setting. Methods: A retrospective chart review and survey was conducted during May through June 2012 among community-based oncologists or hematologists. Charts were reviewed for adult mRCC patients initiated on 2nd -targeted therapy on or after January 1, 2010. Abstracted data included patient demographics, disease characteristics, treatment duration, dose adjustment, progression, mortality, and imaging test patterns. Kaplan-Meier analysis was used to estimate treatment duration, overall survival (OS) and progression-free survival (PFS) during 2nd-targeted therapy. Patients were censored at the most recent contact. Results: Charts were reviewed for 433 mRCC patients. Mean age was 63 years at initial mRCC diagnosis and 64% were male. The most commonly used 2nd targeted therapies were everolimus (36% of patients), temsirolimus (17%), pazopanib (15%), and sunitinib (14%). The median duration of 2nd -targeted therapy was 10.5 months (95% CI: 8.8-11.5). The majority of patients (73%) had no dose adjustment on 2nd-targeted therapy; the most common reason for adjustment was drug toxicity (70%). Among the 44% of patients who discontinued 2nd-targeted therapy, disease progression was the most common reason for discontinuation. The proportion of patients who received imaging test within 3, 6, and 12 months after 2nd-line treatment initiation was 57%, 92%, and 99%, respectively. Routine monitoring (83%) was the most common reason for imaging tests. Median durations of OS and PFS after initiation of the 2nd-targeted therapy were 30.4 months (95% CI: 23.5-not reached) and 10.7 months (95% CI: 8.4-12.2), respectively. Conclusions: In this large, retrospective chart review study, median treatment duration of 2nd -targeted therapy was 10.5 months, median OS was 30.4 months, and median PFS was 10.7 months. Median treatment duration in community practice was longer than in clinical trials for targeted therapies in mRCC.
Hypertension and myelosuppression as biomarkers of sunitinib efficacy in Chinese patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: Qin Shukui , Jin Jie , Guo Jun , Wang Jin-Wan , Zhou Fang-Jian , Huang Yi-Ran , Ren Xiu-Bao , Ye Ding-Wei , Pan Sharon , Sajben Peter , Wang Qiao 
Published: February 2017

426 Background: In an open-label, phase IV study of sunitinib as 1st-line treatment (Tx) in Chinese pts with mRCC, median progression-free survival (PFS) and overall survival (OS) were 61.7 and 133.4 wk, respectively; objective response rate (ORR) was 31.1% (Ann Oncol 2012;23:851P). We retrospectively investigated correlations between on-Tx hypertension (HTN), neutropenia (N), and thrombocytopenia (T) and efficacy endpoints in pts from this trial. Methods: HTN was defined by either maximum systolic blood pressure ≥140 mm Hg (S-HTN) or maximum diastolic blood pressure ≥90 mm Hg (D-HTN). Using CTCAE assessment, N grade ≥2 and T grade >1 were used as cut-points for the analyses. Median PFS and OS were estimated by Kaplan−Meier method. The log-rank test was used to compare PFS and OS between groups with and without HTN, N grade ≥2, or T grade >1. Fisher’s exact test was used for ORR. Results: 102 pts were included in the HTN analyses, 60% with S-HTN versus 40% without S-HTN. Pts with S-HTN had greater ORR and longer PFS and OS than pts without S-HTN (Table). (Results were similar with D-HTN; see Table.) 103 pts were included in the N and T analyses, 67% with N grade ≥2 versus 33% with N grade <2, and 56% with T grade >1 versus 44% with T grade ≤1. Pts with N grade ≥2 had significantly greater ORR and significantly longer PFS and OS than pts with N grade <2 (Table). Pts with T grade >1 had greater ORR and significantly longer PFS and OS than pts with T grade ≤1 (Table). Conclusions: The developments of N grade ≥2 and T grade >1 during Tx with sunitinib were significantly associated with better outcome. Median PFS was more than twice as long for pts with S-HTN as for those without S-HTN, but the association did not reach statistical significance. [Table: see text]
First-line mTOR inhibition in metastatic renal cell carcinoma (mRCC): An analysis from the International mRCC Database Consortium.
Authors: Harshman Lauren Christine , Wood Lori , Srinivas Sandy , Heng Daniel Yick Chin , Choueiri Toni K. 
Published: February 2017

430 Background: mTOR inhibitors (mTORi) are an important class of targeted therapies for mRCC that may act through regulation of mTOR as well as hypoxia-inducible factor and its resultant downstream angiogenesis pathways. FDA approval was based on efficacy in poor risk patients in the first-line setting for temsirolimus (T) and in sunitinib- and sorafenib-refractory patients for everolimus (E). Little is known about T’s effectiveness in good and intermediate risk patients and E’s outcomes in the first-line setting. Methods: We evaluated our international mRCC database to evaluate the outcomes of patients who received mTORi as their first-line targeted therapy. Results: Of the 2,370 patients in the database, 49 received a first-line mTORi (7 E, 42 T). Median age was 61 years and median KPS was 80%. 63% had clear cell and 37% had non-clear cell histology. 65% had prior nephrectomy. Of the 38 patients with available Heng prognostic risk criteria, 21%, 21%, and 58% were good, intermediate, and poor risk respectively. Median PFS and OS are detailed below. Objective responses and disease stabilization were achieved in 5% and 58%. Second-line therapy was administered in 21 patients of which 17 received VEGF inhibitors. Conclusions: Outcomes for good and intermediate risk patients treated with first-line mTORi were lower than historically expected for patients treated with VEGF targeted therapies. These results may be due to inclusion of non-clear cell histologies, treatment biases, small sample size, or other undefined confounders that need further exploration. Greater data capture of this important cohort of patients to confirm these results is planned and will be presented. [Table: see text]
Outcomes of RCC patients with venous thrombus presenting with pulmonary embolism: A multicenter analysis of 782 consecutive patients.
Authors: Abel Edwin Jason , Wood Christopher G. , Kenney Patrick , Eickstaedt Nathan , Bagrodia Aditya , Ramirez Daniel , Gayed Bishoy A. , Youssef Ramy F. , Odom Christopher , Margulis Vitaly 
Published: February 2017

433 Background: Renal cell carcinoma (RCC) patients who present with pulmonary embolism (PE) and venous thrombus may not be offered surgery because of concerns with anti-coagulation and presumed poor post-surgical outcomes. The objective of this study was to evaluate post-surgical recurrence and disease specific survival (DSS) in RCC patients with venous thrombus who had PE diagnosed at initial presentation. Methods: After IRB approval, we reviewed the records from 2000-2011 at 3 tertiary hospitals (UW, UTMDACC, UTSW) for all consecutive RCC patients who had nephrectomy with thrombectomy. Clinical and pathologic predictive factors for recurrence and survival were collected for each patient. Univariate and multivariate analysis was used to evaluate whether PE at presentation was associated with RCC recurrence or DSS after nephrectomy with thrombectomy. Results: Preoperative PE was diagnosed in 35/782 (0.5%) RCC patients undergoing nephrectomy with thrombectomy with a median follow-up time of 22 months. Patients with PE at initial diagnosis were more likely to have higher level thrombus (p<0.01) but no differences were found between groups for age, gender, race, tumor diameter, Fuhrman grade, sarcomatoid de-differentiation, peri-nephric fat invasion or histologic subtype. In N0M0 patients, there was no difference (p=0.36) in the rate of RCC recurrence for 395/782(50%) or 7/17(41%) patients without PE or with PE respectively. On multivariate analysis, peri-nephric fat invasion, Fuhrman grade, and thrombus height, but not preoperative PE status, were predictive of recurrence risk. Similarly, there was no difference in the rates of lung metastases for 67/123 (53%) N0M0 patients without PE or 3/7 (43%) patients with PE (p=0.71). Preoperative PE diagnosis was not predictive of death from RCC (p=0.58). On multivariate analysis, peri-nephric fat invasion, sarcomatoid de-differentiation, Fuhrman grade, and thrombus height, were independently predictive of risk of death from RCC. Conclusions: PE at initial diagnosis is not associated with worse post-surgical recurrence or survival in RCC patients with tumor thrombus.
Prospective assessment of circulating endothelial cells (CECs) as early markers of clear cell renal cell carcinoma (CCRCC) progression in first-line setting: The Circles study (SOGUG 2011-01).
Authors: Oyarvides Victor , Castellano Daniel , Leon Mateos Luis , Esteban Emilio , Basterretxea Laura , Gonzalez del Alba Aranzazu , Arranz Arija Jose Angel , Mendez Maria Jose , Garcia Del Muro Francisco Javier , Climent Miguel Angel , Virizuela Juan Antonio , POLO Susana Hernando , Garcia-Donas Jesus ,   Spanish Oncology Genitourianry Group
Published: February 2017

436 Background: Angiogenesis inhibitors have become a cornerstone in the management of clear cell renal cell carcinoma (CCRCC). Since circulating endothelial cells (CECs) counts have been proposed as surrogate biomarkers of angiogenesis, they could potentially be used to assess the activity of such drugs. Methods: An observational prospective study is being performed in 11 institutions members of the SOGUG group. Patients with confirmed CCRCC on first-line treatment who have not progressed after 3 months of therapy are considered eligible. CECs (CD 105+,CD 45-, DAPI + cells assessed by the Cell Search system), are determined every 6 weeks for 15 months or radiological tumor progression. Results: Up to 64 of the 75 scheduled patients have already been recruited. Mean age was 64 years, 73% were men and 27% women. Distribution upon MSKCC risk cathegories was: good 30%, intermediate 58%, poor 3% and not available (N/A) 9%. 57 (90%) patients received sunitinib, 3 (5%) pazopanib, 1 (2%) temsirolimus and was N/A in 3 (5%). The CECs counts were determined in 60 patients. At baseline median was 47 cells/4 ml (range 4-480). When comparing patients who experienced tumor progression while on study (11 cases) with patients who did not (28 CECs/4 ml vs. 73 CECs/4ml respectively), a significant difference was found (p = 0.002, t-student). Several exploratory analysis regarding concomitant conditions and patients and tumor characteristics showed that cases with heavily treated hypertension (8 in 60 patients) had lower baseline CECs counts, though without statistical significance (p = 0.068, t-student). Conclusions: Our data point to a different behaviour of CECs counts among CCRCC patients tretated with anitangiogenic drugs that could lead to identify specific subpopulations. Mature results will be presented at the meeting.