bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicenter prospective phase II study of sunitinib in non-clear cell type renal cell carcinoma.
Authors: Lee J. , Ahn J. , Lim H. , Lee S. , Kim T. , Lee D. , Cho Y. M. , Hong J. , Kim C. , Ahn H. 
Published: February 2017

325 Background: Sunitinib has been shown to produce a high response rate (RR), and improved progression-free survival (PFS) in patients (pts) with clear cell RCC. Retrospective data suggest sunitinib may be effective in papillary and chromophobe RCC. We conducted a multicenter phase II trial of sunitinib in non-clear cell RCC (nccRCC). Methods: Eligibility criteria included PS 0-1, measurable disease, and adequate organ function. Pts with brain metastases were not excluded if controlled without steroid dependence. Response assessment was performed every 6 weeks. Primary endpoint was RR. Secondary endpoints were TTP, safety and OS. Results: Between 6/2008 and 7/2010, 29 pts with nccRCC were enrolled (total accrual 35: P0=5%, P1=20%, alpha=0.05, beta=0.2, drop-out rate 15%). Median age was 52 (18–76). Twenty-four pts (84%) had prior nephrectomy. Seven pts (24%) had poor risk and 13 (45%) had intermediate risk disease by MSKCC criteria. Twenty-one pts had papillary RCC (type II in 11 and type not- specified in 10), and 4 patients had chromophobe RCC. Two pts discontinued protocol treatment due to toxicity prior to completion of cycle 1 (one pt had cardiogenic shock 27 days after start of therapy and the other refused further treatment 5 days after therapy). Eleven pts out of 29 had partial response with a RR of 38% (95% CI, 20.2%–55.6%) and additional 15 patients (52%) had SD with a disease control rate of 90%. Response rates were not significantly different according to the histologic type (43% in papillary type and 25% in chromophobe type). Median duration of response was 12.7 months (95% CI, 2.3∼23.1) and median TTP was 6.4 months (95% CI, 4.5∼8.3). With a median FU duration of 16 months (95% CI, 8.6∼23.4), 10 pts have been dead resulting in an estimated median OS of 17.9 months. Toxicity profiles were commensurate with prior reports on Korean patients (Yoo, et al. Jpn J Clin Oncol 2010). However, there was one treatment-related death caused by acute heart failure in patient without relevant risk factors for heart disease. Conclusions: Although our study is ongoing, the primary endpoint has been met and these data suggest that suntinib has promising activity in patients with nccRCC. No significant financial relationships to disclose.
C-reactive protein kinetics superior to radiographic response as a surrogate endpoint for survival in patients with advanced renal cell carcinoma.
Authors: Tatokoro M. , Saito K. , Fujii Y. , Komai Y. , Koga F. , Masuda H. , Kawakami S. , Kihara K. 
Published: February 2017

333 Background: As cytokines and targeted agents against advanced renal cell carcinoma (aRCC) are considered to achieve high stable disease (SD) rate rather than objective response (OR) by radiographic measurement, we often face the therapeutic dilemma in deciding whether to continue the ongoing treatment and when to change it. Therefore, other valid surrogate endpoints have been desired. We have previously demonstrated C-reactive protein (CRP) kinetics could predict prognosis of pts with aRCC (Eur Urol. 2009:1145-53). Methods: This study was performed on 56 pts with aRCC (metastatic: 54, unresectable: 2) enrolled in a phase II trial of interferon-alpha, cimetidine, COX-2 inhibitor and renin-angiotensin-system inhibitor (I-CCA; Cancer Sci. in press). CRP levels were measured at pretreatment, thereafter almost every visit. Pts were divided into 3 groups according to CRP kinetics. Pts whose pretreatment CRP levels were < 5 mg/l were assigned to nonelevated group. Pts whose pretreatment CRP levels were > 5 mg/l but normalized (< 5 mg/l) at least one time during I-CCA were assigned to normalized group. Pts whose CRP level never decreased to normal level were assigned to non-normalized group. Radiographic response was assessed by WHO criteria; survivals were estimated by Kaplan–Meier method and prognostic factors were assessed by Cox's proportional hazard model. Results: Median follow-up was 26 mo. An OR and clinical benefit rate to I-CCA were 20 and 64%, respectively. The median progression-free and overall survival (OS) was 12 and 45 mo, respectively. The median OS was 74, 83 and 13 mo in in non-elevated (n=26), normalized (n=16) and non-normalized (n=14) group, respectively (p<0.0001). Of the 25 pts achieving SD, CRP kinetics was independent prognostic factor for OS (p<0.0001). Of the pts whose pretreatment CRP was elevated, all pts achieving OR had CRP normalization and multivariate analysis revealed CRP normalization was independent prognostic factor for OS (p=0.0008), whereas achieving OR was not (p=0.19). Conclusions: CRP kinetics compares favorably with objective response to systemic therapy as a valid surrogate endpoint for survival. No significant financial relationships to disclose.
Tyrosine kinase inhibitors and development of brain metastasis in metastatic renal cell carcinoma: A retrospective review.
Authors: Verma J. , Jonasch E. , Allen P. , Tannir N. M. , Mahajan A. 
Published: February 2017

340 Background: Tyrosine kinase inhibitors (TKIs) have been shown to improve overall survival (OS) in metastatic renal cell carcinoma (mRCC) but their effect on brain metastasis (BM) development is unclear. The purpose of our study is to evaluate the impact of TKIs on incidence of BM and OS in patients with mRCC. Methods: Searched the M. D. Anderson Cancer Center (MDACC) tumor registry for patients who presented with mRCC in 2002-2003 and 2006-2007 with no BM at initial staging. The following items were retrospectively collected: age, sex, Fuhrman grade, sites of disease, nephrectomy, systemic therapy including TKIs (sorafenib or sunitinib), MSKCC risk category, BM treatment, and vital status. Interaction between OS and incidence of BM and these variables was estimated using the Cox proportional hazards model. OS and incidence of BM were estimated using the Kaplan-Meier (K-M) method. Results: 338 patients were identified; 154 (46%) were treated with a TKI prior to BM, and 184 (54%) were not. There were no significant differences in age, histology, involved sites of disease other than lung, nephrectomy, or MSKCC risk category between the groups. A higher proportion of the nonTKI group received other systemic agents and had lung metastasis at initial staging (p=0.03). Median OS was longer in the TKI-treated group (25 months versus 12.1 months, p<0.0001). In Cox multivariate analysis, TKI treatment (HR=0.53, 95% CI 0.38-0.74, p<0.001) was associated with improved OS and lung/mediastinal involvement and ECOG performance status > 2 (HR 1.87, 95% CI 1.28-2.71, p=0.001) were associated with poor OS. Median OS after BM was not significantly different between TKI treated and untreated groups. 44 patients (13%) developed a BM, including 29 (15.8%) of the nonTKI group and 15 (9.7%) of the TKI group. In K-M analysis, the 5-year incidence of BM was 40% versus 17% respectively (logrank p<0.001). In Cox multivariate analysis, TKI treatment was associated with lower incidence of BM (HR=0.39, 95% CI 0.21-0.73, p=0.003). Lung metastasis increased the risk of BM (HR=9.61, 95% CI 2.97-31.1, p<0.001). Conclusions: Treatment with TKI agents reduces the incidence of BM in mRCC. Lung metastasis is a risk factor for BM development. No significant financial relationships to disclose.
Impact of pathologic tumor characteristics in patients with sarcomatoid renal cell carcinoma.
Authors: Shuch B. , Bratslavsky G. , Shih J. H. , Finley D. , Castor B. , Linehan W. , Pantuck A. J. , Said J. , Belldegrun A. S. 
Published: February 2017

343 Background: Patients with sarcomatoid renal cell carcinoma (sRCC) are known to have a poor prognosis and response to therapy. We sought to determine the influence of pathologic tumor characteristics on outcome in order to aid clinical management. Methods: A single center database was reviewed from 1989-2009 to identify all patients with sRCC. Clinical and staging variables were collected and pathologic information including histology, necrosis, percentage of sarcomatoid features (PSF), and microvascular invasion (MVI) was recorded. Influence of clinicopathologic variables on outcome was assessed. Results: A total of 104 patients had confirmed sRCC. The median size of tumors was 9.5 cm (range 2.5-30), 65% of patients had areas of clear cell RCC, and 69.2% had metastatic disease at presentation. The PSF did not influence tumor size, stage, necrosis, MVI, nodes, or metastasis. A total of 85 patients (81.7%) died during the follow-up period with a median survival of 5.9 months. In the overall cohort poor performance status, metastatic disease, and MVI were independent predictors of poor survival. Increased PSF was associated with worse outcome, but it failed to reach significance on multivariate analysis. In a subset analysis of those with non-metastatic disease, MVI and non-clear histology influenced prognosis, but only PSF was the only predictor of outcome. Conclusions: The PSF has limited influence on pathologic characteristics. However, increased PSF amounts may impact survival, especially in those with non-metastatic disease. The presence of MVI is an independent predictor of poor outcome while carcinoma grade and subtype have limited impact on survival. When counseling patients or designing clinical trials for these patients, PSF and MVI, not carcinoma grade or subtype should be considered. No significant financial relationships to disclose.
Use of preoperative erythrocyte sedimentation rate (ESR) to predict overall survival in localized renal cell carcinoma following radical nephrectomy.
Authors: Master V. A. , Kucuk O. , Harris W. , Cross B. , Abbasi A. , Michigan A. , DeRosa A. , Johnson T. V. , Marshall F. F. 
Published: February 2017

361 Background: Systemic inflammation has been associated with increased tumor grade and disease progression in renal cell carcinoma (RCC). Erythrocyte sedimentation rate (ESR) reflects systemic inflammation in other disease states. However, the relationship between ESR and survival remains unclear in localized RCC following potentially curative nephrectomy. We hypothesized that preoperative ESR would be a prognostic indicator of overall survival in localized RCC following radical nephrectomy. Methods: 167 patients undergoing nephrectomy for localized RCC had ESR measured preoperatively. Receiver operating characteristics (ROC) curves were constructed and used to determine the area under the curve (AUC) and relative sensitivity and specificity of preoperative ESR in predicting overall survival. From this curve, cut-offs for low risk (0.0-20.0 mm/hr), intermediate risk (20.1-50.0 mm/hr), and high risk (> 50.0 mm/hr) groups were created. Kaplan-Meier analysis was conducted to assess the univariate impact of these ESR-based risk groups on overall survival. Finally, univariate and multivariate Cox regression analysis was conducted to assess the potential of these groups to predict overall survival, adjusting for other patient and tumor characteristics. Results: 55.2%, 27.0% and 17.8% were in the low, intermediate, and high risk groups, respectively. Median (95% CI) survivals for these groups were 44.1 (42.6-45.5), 35.5 (32.3-38.8), and 32.1 (25.5-38.6) months, respectively. After controlling for patient age, race, gender, Charlson Comorbidity Index, T-Stage, Fuhrman Nuclear grade, and tumor size, intermediate risk and high risk groups experienced a 4.5-fold (HR: 4.509, 95% CI: 0.735-27.649) and 18.5-fold (HR: 18.531, 95% CI: 2.117-162.228) increased risk of overall mortality, respectively. Conclusions: Preoperative ESR values represent a robust categorical predictor of overall survival following nephrectomy in localized renal cell carcinoma in this cohort. Clinicians may consider including ESR measurements in counseling patients before nephrectomy, as well as managing patients according to their ESR-based risk category. No significant financial relationships to disclose.
Econimic burden of reoperative renal surgery: Do the means justify the ends?
Authors: Agochukwu N. , Linehan W. , Bratslavsky G. 
Published: February 2017

364 Background: Despite the high morbidity of reoperative renal surgery (RRS) most patients are able to preserve adequate renal function to obviate the need for dialysis. Nevertheless, the economic burden of RRS has not been evaluated so far. We aim to provide cost analysis for patients requiring RRS on a solitary kidney and patients needing completion nephrectomy and dialysis. Methods: We reviewed the charts of patients treated at the NCI requiring RRS from 1989 to 2010. The data extracted included total time in the OR, ICU stay, total hospital stay, need for additional procedures, blood products, laboratory evaluation, and surveillance imaging until the next intervention on the operated unit or most recent follow up. The hospitalization cost was calculated based on current Medicare reimbursement rates based on current procedural terminology (CPT) codes. Those costs were compared to the estimated cost of completion of uncomplicated nephrectomy, AV fistula placement, and hemodialysis. Results: We identified 30 patients treated with RRS on a solitary renal unit. The average procedure lasted 7.76 hours (4.25-11 hours) requiring an average of 7.16 units of blood transfused (0-32 units). The average time of hospitalization was 9.56 days (6-30 days), with the average ICU stay of 4.03 days (range 1-12 days), and an average floor stay of 6.64 (2-18 days). The estimated cost for hospitalization per patient was $52,058, while the estimated cost for uncomplicated nephrectomy, AV fistula placement, and a year of dialysis was $59,572. The financial benefit of RRS is reached at 0.9 years. At our median follow up of 4 years, the average cost saving per patient is estimated to be greater than $100,000 with the numbers likely to increase as these patients continue to avoid dialysis. Conclusions: While associated with high morbidity, the RRS on the solitary unit may provide an opportunity for the majority of patients to retain their native renal remnants, preserve quality of life, and allow for savings for the healthcare system. These benefits are in addition to savings not included in our analysis that are associated with the morbidity and complications associated with dialysis in addition to the costs of care required for patients on dialysis. No significant financial relationships to disclose.
Single-fraction radiosurgery for the treatment of renal tumors in singular renal units.
Authors: Staehler M. D. , Nuhn P. , Karl A. , Bader M. , Stief C. , Wowra B. , Muacevic A. 
Published: February 2017

368 Background: High-dose local radiation treatment (stereotactic radiosurgery [SRS]) was added for selected patients to improve local control and overall survival in metastases. We report on toxicity and local tumor control in patients with renal tumors who were treated with aggressive local irradiation using a single fraction SRS with the Cyberknife in singular renal units to avoid hemodialysis. Methods: n=18 patients with renal tumors and an eastern cooperative oncology group (ECOG) status of 0 or 1 were treated with SRS. Patients with surgically removable renal lesions were not included. Prior to SRS gold markers were planted into the renal parenchyma under ultrasonographic guidance. Results: Nine patients had transitional carcinoma of the renal pelvis, six patients had renal cell carcinoma and three had other tumor entities. No skin toxicity occurred after SRS, and SRS did not induce other side effects. Local tumor control 9 months after SRS was 98% (95% CI: 89-99%). There were no treatment related deaths, and late complications after SRS were not noted so far. Renal function so far remained stable without a change in serum creatinine. Conclusions: SRS for selected patients with renal tumors is safe and effective. Single-fraction delivery as an outpatient procedure allows for convenient integration of SRS into various oncological treatment concepts. Further studies are needed to determine the limits of SRS in this setting. No significant financial relationships to disclose.
A novel web-based tool for risk quantification and objectification of treatment of renal cell carcinoma.
Authors: Canter D. , Kutikov A. , Bland J. , Sterious S. , Rozenfeld B. , Chen D. , Uzzo R. 
Published: February 2017

382 Background: Despite the development of treatment guidelines, the management of renal cell carcinoma (RCC) remains overly subjective. Nomograms and statistical algorithms promise more objective decision making by patients and physicians by quantifying risk. Unfortunately, these tools remain underutilized in daily clinical practice because they are both cumbersome and time-consuming. We sought to create a novel website where all the available and relevant nomograms for RCC could be easily accessible for patients and practitioners, minimizing the subjectivity associated with clinical risk stratification and decision-making. Methods: The existing literature was reviewed to identify published nomograms relevant to RCC. Nomograms were grouped by defining characteristics (preoperative versus postoperative predictive models, predictive models for metastatic disease, etc). Additional operationalized models included staging tools, surveillance models and cancer statistics. Nomograms were selected based on predictive accuracy, applicability, and ability to objectify risk stratification. Only nomograms with an AUC of greater than 0.7 were operationalized. The times required to extract clinical metrics for four hypothetical clinical scenarios were compared between the original paper version and our web-based model. Results: www.cancernomograms.com organizes and operationalizes interactive predictive models for RCC for both physicians and patients. Each model was developed as an independent software program and deployed as an interactive flash object embedded in an HTML page allowing point of care risk calculation. In an initial sample of 15 subjects, the website decreased nomogram metric output from minutes to seconds, proving that utilization of a computer-based platform for these nomograms is faster (p=0.0003). Conclusions: www.cancernomograms.com is a novel website that allows point of care risk quantification and objectified decision making using published statistical models. This web tool may help improve physician and patient communication and clinical care. No significant financial relationships to disclose.
Can contemporary targeted therapies provide clinically meaningful changes in renal cell carcinoma venous tumor thrombi?
Authors: Delacroix S. E. , Chapin B. F. , Cost N. , Karam J. A. , Culp S. H. , Abel E. J. , Gonzalez G. , Margulis V. , Wood C. G. 
Published: February 2017

390 Background: Renal cell carcinoma (RCC) tumor thrombus regression has been reported after treatment with contemporary targeted therapies. We sought to identify clinically meaningful changes in tumor thrombi in a series of patients treated with targeted therapies. Methods: A University of Texas M. D. Anderson institutional database was queried for patients treated with targeted therapy while the primary RCC remained in situ. The subset of patients with a vascular tumor thrombus was assessed for radiographic responses of tumor thrombi. Pathology was obtained from a percutaneous biopsy or the surgical specimen. The modified Clavien system was used to grade complications within 12 months of surgery. Clinically meaningful changes were defined as changes in the anatomic thrombus level or changes altering surgical approach. Results: A total of 178 patients were treated with targeted therapy with the primary tumor in situ. Venous tumor thrombus was present in 27% (n=48) and comprised our study cohort. The primary histology was clear cell in 75% of cases and 47/48 patients presented with metastatic disease. Prior to treatment, the tumor thrombus was within the renal vein (RV) in 60% (29/48-Level 0), the first 2 cm of the inferior vena cava in 10% (5/48-Level 1), > 2 cm above the RV in 21% (10/48-Level 2), at the level of the hepatics but below the diaphragm in 6% (3/48-Level 3), and above the diaphragm in 2% (1/48-Level 4). After a median duration of therapy of 2.75 months, clinically meaningful changes occurred in 25% of patients (12/48). Of these, progression occurred in 58% (7/12) while 42% (5/12) had regression of tumor thrombus. Fourteen patients (30%) received surgery after targeted therapy. Clavien categorized complications ≥ grade 3 occurred in 50% of surgical cases. No patient experienced a pulmonary embolism with treatment or during follow up. Conclusions: To our knowledge,this is the largest reported series of RCC patients with an in-situ venous tumor thrombus treated with targeted therapy. Although no patient experienced a pulmonary embolism, the use of targeted therapy with the primary goal of obtaining clinically meaningful reductions in tumor thrombi does not appear to be a promising therapeutic option. No significant financial relationships to disclose.
Preliminary safety results of an ongoing phase I/II clinical study of MGN1601, a tumor vaccine comprising allogeneic, gene-modified, and irradiated tumor cells in combination with an immunomodulator in patients with metastatic renal cell carcinoma (ASET study).
Authors: Tschaika M. , Weikert S. , Gruenwald V. , Schmidt-Wolf I. , Schroff M. , Wittig B. , Schmidt M. 
Published: February 2017

392 Background: MGN1601 is a cell-based RCC tumor vaccine MGN1601 consisting of two active pharmaceutical ingredients: genetically modified allogeneic (human) cells transfected with four different MIDGE vectors encoding IL-7, GM-CSF, CD80 and CD154 and a synthetic DNA-based immunomodulator dSLIM-30L1, a TLR-9 agonist. The vaccine is being developed for treatment of patients with advanced RCC. Its prophylactic and therapeutic anti-tumor activity has been shown in several in-vivo models. A good safety profile of MGN1601 was shown in a wide program of acute and chronic toxicity studies. Based on these promising data, this phase 1/2 study was started in patients with advanced RCC. Methods: This multicentric open clinical study for the assessment of safety and efficacy of MGN1601 in patients with advanced RCC was initiated in October 2010. A total of 24 patients have to be recruited into the study. The treatment consists of 8 MGN1601 treatments administered as follows: the first 3 treatments are administered on a weekly basis, and the consecutive 5 treatments on a bi-weekly basis. The treatment dose contains 107 transfected tumor cells and 5 mg dSLIM per administration, which has been proven to be safe with a high safety margin in repeated toxicity studies. The efficacy and safety of the study treatment will be evaluated based on extensive immunological tests, radiological assessment, safety laboratory results and assessments of the quality of life. Here, the first safety data are presented. [Table: see text]