bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment and overall survival (OS) in metastatic renal cell carcinoma (mRCC): A Swedish population-based study (2000–2008).
Authors: Harmenberg Ulrika , Lundstam Sven , Wahlgren Thomas , Kowalski Jan , Jakobsson Maria , Sandin Rickard , Ljungberg Börje , Sandström Per 
Published: February 2017

389 Background: This retrospective register study assessed OS in all mRCC patients in Sweden diagnosed before (2000–2005) and after (2006–2008) the introduction of targeted therapies, plus factors and treatment options influencing OS. Methods: Three Swedish national health registers were used: the Swedish Cancer register (diagnosis and death), the National Patient Register (in-/out-patient data), and the Swedish Prescribed Drug Register. From 2000-2008, 3,243 patients were identified with mRCC; 602 were recorded as receiving 1st-line treatment. Cox proportional hazards regression analysis, including estimation of adjusted OS, was used in three models with the covariates: diagnosis period, age, gender, institution size, nephrectomy status, geographic region (all models); mRCC treatments, defined as any tyrosine kinase inhibitor (TKI; Model 1; n=417); sunitinib (SU), sorafenib (SO), and interferon-alfa (IFN-α) in the 1st-line setting (Model 2; n=602 [SU=244, SO=110, IFN-α=248]); and variations of these drugs as 1st- and 2nd-line treatment sequences (Model 3; n=602). Results: Amongst mRCC patients diagnosed from 2006–2008 compared with 2000–2005, median adjusted OS was 16.1 vs. 10.9 months, respectively (HR=0.76, 95% CI: 0.69, 0.83; P<0.001). In all three models, factors independently associated with significantly improved OS included female gender, large institution, and prior nephrectomy. Prescription of any TKI (Model 1: HR=0.82, 95% CI: 0.73, 0.93; P=0.002) and 1st-line SU treatment (Model 2: HR=0.79, 95% CI: 0.67, 0.94; P=0.007) were associated with significantly improved OS compared with other or no treatments. A similar significant improvement in OS was also confirmed for patients treated with SU only in Model 3; however, due to a low number of observations, the model had insufficient statistical power to be appropriate for all sequences. Conclusions: An improved OS for mRCC patients was demonstrated for the period 2006-2008 compared with 2000-2005. Although the observed survival advantage is multifactorial in origin, contribution of targeted therapies is highly probable. Of the drugs studied, given design limitations, only SU was associated with improved OS.
New safety and efficacy data of the ongoing phase I/II study (ASET Study) with an allogeneic tumor vaccine and adjuvant in patients with metastatic renal cell carcinoma.
Authors: Grünwald Viktor , Weikert Steffen , Schmidt-Wolf Ingo GH , Hauser Stefan , Tschaika Marina , Weith Ekaterina , Schroff Matthias , Schmidt Manuel , Wittig Burghardt 
Published: February 2017

398 Background: The purpose of this first-in-man phase 1-2 study is to assess safety and efficacy of treatment with investigational drug MGN1601 in patients with advanced renal cell carcinoma. MGN1601 consists of two active 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, acting as adjuvant. Methods: The ASET study is conducted as multicenter, open, single-arm phase 1-2 study. The study therapy consists of 8 MGN1601 treatments administered as follows: the first 3 treatments are administered weekly, and the consecutive 5 treatments bi-weekly. Patients who achieve disease control are proposed to continue the therapy in an extension phase. Such patients receive 5 further applications up to week 120. In this study, safety and efficacy of the study treatment will be evaluated based on extensive clinical and laboratory assessments, monitoring of patients’ quality of life, immunological tests, and radiological investigations. Results: Eighteen patients have been included into the study so far and received up to 9 treatments with MGN1601. Eight patients completed the 12 week treatment per protocol (TPP). Two of these patients (25% of TPP) achieved disease control (one PR and one SD) after 12 weeks and currently continue the treatment in the extension phase. 48 adverse events were reported during the treatment phase. Of them, 10% were judged as possibly related, 23% unlikely and 67% as not drug-related by the investigators. Possible adverse events include mild fever, edema of the ankle, exanthema crook of the arm, pruritus crook of the arm and arthralgia intermittent. The therapy is well tolerated – no treatment-limiting toxicities or grade 2–4 toxicities occurred in these patients. Conclusions: The results of the clinical study in late stage RCC patients show promising efficacy and a favourable safety profile of the cell-based tumor vaccine consisting of genetically modified allogeneic transfected RCC cells and the immunomodulator.
Use of R.E.N.A.L. nephrometry scoring system to predict the functional efficacy of nephron-sparing surgery in the solitary kidney.
Authors: Buethe David D. , Moussly Sammy , Lin Hui-Yi , Zhao Xiuhua , Spiess Philippe E. , Sexton Wade Jeffers 
Published: February 2017

399 Background: Recently, the R.E.N.A.L. nephrometry scoring system was introduced to objectively describe renal masses with respect to size, the degree to which they are exo/endophytic, the nearness to the collecting system, whether they are anterior or posterior and the location relative to polar lines. It is our aim to evaluate the R.E.N.A.L. nephrometry scoring system’s ability to predict functional renal loss attributed to nephron-sparing surgery (NSS). Methods: We evaluated 42 patients presenting with either an anatomic (32) or functionally solitary (10) kidneys undergoing partial nephrectomy (PN). Each renal unit was assigned a R.E.N.A.L. nephrometry score utilizing pre-operative cross-sectional imaging. The CKD−EPI equation was applied to serum creatinine levels to generate corresponding estimated glomerular filtration rates (eGFR). The difference between the eGFR at baseline and at post-operative time points served as a measurement of renal function loss attributed to PN. Results: Forty-two patients underwent PN with mean pre-operative eGFR of 61.5 mL/min/1.73m2. The median total nephrometry score was 8, ranging from 4–10. Twenty-eight (66.7%) of the renal lesions were ≤ 4 cm, 13 (31%) were between 4 and 7 cm, and 1 (2.4%) was >7 cm in diameter. The majority (54.8%) of the patients had tumors with more than 50% of tumor burden lying outside the expected renal border whereas 3 patients (7.1%) had tumors considered to be completely endophytic. Twenty-seven (64.3%) were within 4 mm of the collecting system. Tumor locations defined as: completely polar, interpolar, and completely central were assigned to 11, 15, and 16 lesions respectively. By post-operative month 6, the overall average eGFR of 53.9 mL/min/1.73m2 was significantly less (p = 0.0293) than the pre-operative value. However, we were unable to correlate change in post-operative eGFR with pre-operative total or individual R.E.N.A.L. scoring parameters. Conclusions: Neither the individual components of the R.E.N.A.L. nephrometry scoring system nor the total nephrometry score correlated with realized functional loss as assessed by eGFR in patients with a solitary kidney undergoing NSS.
Prognosis of patients with renal cell carcinoma with disease recurrence following nephrectomy for localized disease.
Authors: Shinohara Nobuo , Abe Takashige , Maruyama Satoru , Sazawa Ataru , Nonomura Katsuya 
Published: February 2017

400 Background: We investigated the prognosis of Japanese patients with recurrent renal cell carcinoma (RCC) following nephrectomy, and analyzed the prognostic impact of metastasectomy and Memorial Sloan-Kettering Cancer Center (MSKCC) risk classification in these patients. Methods: Between 1995 and 2005, 214 patients with recurrent RCC were the subjects of this retrospective analysis. At recurrence, MSKCC risk classification was used to classify patients as being at favorable, intermediate, and poor risk. The endpoint of the present study was overall survival (OS) from time of recurrence. Relationships between overall survival and potential prognostic factors were assessed using the Cox proportional hazard model. Results: Median time to recurrence following nephrectomy was 25 months. At recurrence, 148 (69%) patients had metastasis in one organ and lung was the most common site of recurrence (123 pts, 57%). The median survival from the time of recurrence was 40 months; the estimated 2-year survival rate was 66% (95% CI 60-73). When the MSKCC risk classification was applied to the patients, the median overall survival was not reached, 29 months, and 11 months in the patients classified as favorable (59 pts), intermediate (101 pts), and poor risk (24 pts), respectively. Metastasectomy was performed in 76 (36%) patients. The median survival from the time of recurrence in these patients was 122 months, which was significantly longer than the median survival (27 months) of patients who did not undergo metastasectomy (p<0.001). Multivariate analysis demonstrated that a better risk category of MSKCC risk classification and metastasectomy were associated with more favorable survival (p<0.001). Conclusions: In patients with recurrent RCC following nephrectomy for localized disease, patients classified as favorable risk according to MSKCC risk classification have a good opportunity for long-term survival, especially those who undergo metastasectomy.
Cytogenetic changes in renal cell carcinoma: Basis for sensitivity and resistance to everolimus.
Authors: Caldwell Imogen Rose , Oei Paul , Ng Daniel , Fong Peter C.C. , Broom Reuben James 
Published: February 2017

403 Background: The mTOR inhibitors have improved outcomes for pts with metastatic renal cell carcinoma (mRCC) but the duration of benefit is variable. Currently there are no predictive biomarkers for pre-selecting pts who are likely to respond to these agents. We undertook an exploratory translational study evaluating cytogenetic changes in the context of response to everolimus therapy. Methods: 10 pts with mRCC treated with everolimus therapy were enrolled. Pre-treatment paraffin-embedded tissue specimens were analysed for cytogenetic changes using fluorescence in situ hybridisation (FISH) and clinical data including PFS (RECIST 1.1) were obtained. The gene probes chosen for this analysis were; VHL, FHIT, FGFR1/3, PDGFb, PDGFRb, EGFR, MYC and IGH@. Results: Results are displayed in the table below. The median PFS was 8.25mo (months). Eight pts were treated 1st-line (on clinical trial), one 2nd-line and one 3rd-line. The longest responder (PFS 25.5mo, 3rd-line) had a normal VHL status but loss of FHIT. Two pts with the longest PFS and one with a PFS of 5.5mo had gain of both PDGFb and PDGFRb. Gain of FGFR1 and FGFR3 was seen in two and three pts respectively. Two specimens were unsuitable for full analysis. Conclusions: Loss of FHIT but a normal VHL status was seen in one pt with mRCC who had an enduring response to everolimus. Concomitant gain of PDGFband PDGFRb was observed in three pts with a good response. FGFR1/3 may be of relevance in the setting of alternative targeted therapies. Further research evaluating the utility of these potential biomarkers is required. [Table: see text]
Association of high cytoplasmic expression of p27 Kip1 on cancer-specific survival in clear cell renal cell carcinoma.
Authors: Bedke Jens , Amend Bastian , Scharpf Marcus , Sievert Karl-Dietrich , Stenzl Arnulf , Kruck Stephan 
Published: February 2017

418 Background: p27Kip1 is considered to contribute to the progression of ccRCC and is targeted by next generation dual-therapies. Cytoplasmic and nuclear differences of p27 Kip1 expression and localization in benign and clear cell renal cell carcinoma (ccRCC) were analyzed with regard to overall survival (OS) and cancer-specific survival (CSS). Methods: In 140 patients, ccRCC and corresponding benign kidney tissue were analyzed for nuclear and cytoplasmic staining of p27Kip1 by immunohistochemistry using a tissue microarray technique. Staining intensity and percentage of positive stained cells are given as expression scores. p27Kip1 expression was categorized as high if ccRCC tissue stained stronger than the respective level of the corresponding benign tissue and categorized as low if ccRCC tissue stained less than or equal to the corresponding benign tissue. Differences in OS and CSS were analyzed by log-rank analysis and expression levels were correlated with tumour and patient characteristics using Fisher’s exact test. Results: Cytoplasmatic (mean [SD]: 13.8% [1.2%] vs 10.7% [1.7%]; P = 0.04) and nuclear (mean [SD]: 75.6% [2.7%] vs 13.6% [2.1%]; P < 0.001) staining of p27Kip1 were significantly stronger in ccRCC tissues compared to benign tissue. High cytoplasmic p27Kip1 expression was significantly associated with a higher T and N stage, Fuhrman grade and the presence of metastatic disease (P < 0.001). The median follow-up time was 38.2 months. There was no difference in OS between the low and high expression groups, although CSS was significantly lower in patients with high cytoplasmic p27Kip1 (P < 0.001) and CSS heavily tended to be lower in the nuclear low expression group (P = 0.069). Conclusions: High cytoplasmic p27Kip1 levels in renal cancer tissues are associated with advanced disease and reduced cancer specific survival, whereas low nuclear expression levels appear to be beneficial. The present study corroborates the consideration of cytoplasmic p27Kip1 for future diagnostic and targeted therapeutic approaches in RCC establishing a potential protective shift of p27Kip1 from the cytoplasm to the nucleus.
Discrepancy between reported progressive disease per radiology report and treating oncologist tumor measurements in patients with metastatic renal cell carcinoma (mRCC) receiving sunitinib.
Authors: Ali Khaled B. , Shah Shetal N. , Wood Laura S. , Garcia Jorge A. , Dreicer Robert , Gilligan Timothy D. , Rini Brian I. 
Published: February 2017

420 Background: The determination of progressive disease (PD) on sunitinib in mRCC by conventional tumor size criteria is often complex. Frequently, radiology reports cite disease progression that does not meet RECIST criteria or does not adequately describe index lesions. Characterization of the frequency and magnitude of this phenomenon has not been previously reported. Methods: The medical records of a subset of mRCC patients treated at The Cleveland Clinic who had received sunitinib for > 12 months were retrospectively reviewed. All Radiology reports from post-baseline scans were reviewed for the presence of text in the body or conclusion of the report consistent with disease progression (specifically the terms ‘progressive’, ‘new’ and/or ‘interval enlargement/worsening’). The date of the report first containing one or more of these terms was recorded, as was the date of RECIST-defined PD determined by the treating Oncologist. Results: Twenty patients were identified in an initial review. Patient characteristics included: 85% male, 100% clear cell histology, 90% prior nephrectomy and 80% with prior systemic therapy. Thirteen patients (65%) had a radiology report citing a progressive disease term prior to treating physician-determined RECIST-defined PD. The median time from first radiology report citing a progressive disease term until RECIST PD per Oncologist measurements was 2.9 months (range, 0 to 12.8 months). Conclusions: There is significant discrepancy between the first mention of disease progression by a Radiology report and when a treating Oncologist measures disease progression per RECIST criteria. This discrepancy could impact patient care by influencing drug discontinuation. These data emphasize the importance of multidisciplinary scan review and tumor measurements by both radiologists and treating physicians. Analysis is ongoing in additional patients.
Upper pole kidney tumors: Open or laparoscopic partial nephrectomy?
Authors: Narayanan Ramkishen , O'Malley Rebecca Leigh , Mehedint Diana , Schwaab Thomas 
Published: February 2017

429 Background: Partial nephrectomy in upper pole kidney tumors represents a distinct surgical challenge. Data on minimally invasive nephron sparing surgery in this context are scarce. We set out to investigate the role of laparoscopic and open approaches to partial nephrectomy in these tumors. Methods: The Roswell Park Cancer Institute prospective, IRB-approved kidney surgery database was reviewed containing 690 patients. Only patients completing a radical or partial nephrectomy for unilateral, localized, non-metastatic tumors < 7cm were included. The resulting cohort contained 400 patients. Average patient age at surgery was 59.9 ± 13.2 years (range: 22-88). Tumor stages included benign (13.5%), T1a (53.0%), T1b (25.0%), T2 (1.5%), T3a (7.0%). Upper pole tumors (n=128; 27%) and lower pole/ mid-pole tumors (n=270; 67.5%) were recorded. Intraoperative complications were recorded; postoperative complications were tabulated as low or high grade per Clavien-Dindo classification. SPSS (version 19.0) software was used to analyze the dataset. Results: Total intraoperative complication rate was 11.3% (45/400 cases). After stratification by tumor location and partial vs. radical nephrectomy, intraoperative complication rates were higher for laparoscopic/robotic partial nephrectomies involving upper pole tumors (72.7% of all intraoperative complications) compared to lower pole tumors (27.3%, p=0.04), in Chi-Square test. In the delayed postoperative period, total low-grade Clavien complication rate was 97.8% (391/400 cases); high-grade complication rate was 2.3% (9/400). After controlling for tumor location and nephrectomy extent, the high-grade delayed complications were present only in the open nephrectomies involving upper-pole tumors. However, laparoscopic/robotic partial nephrectomies involving upper-pole tumors had significantly more delayed low-grade complications (92.4% of all delayed complications) compared to lower-pole tumors (7.6%, p<0.01), in Chi-Square. Conclusions: Upper pole kidney tumors represent a challenging surgical situation. We here demonstrate that minimally invasive partial nephrectomy in this context requires significant surgical expertise and an open approach could be considered.
Novel prognostic model of overall survival in patients undergoing cytoreductive nephrectomy: Importance of pretreatment clinical and serological parameters.
Authors: Buethe David D. , Verma Nilesh , Lin Hui-Yi , Pow-Sang Julio , Sexton Wade Jeffers , Zhao Xiuhua , Fishman Mayer N. , Spiess Philippe E. 
Published: February 2017

430 Background: Over the past decade, there has been an increasing interest in combining surgical and systemic therapy to combat metastatic renal cell carcinoma (mRCC) with upfront cytoreductive nephrectomy (CN) favored in well selected patients. This study presents a novel risk stratification model to identify those who may benefit from upfront CN within the current targeted therapy era. Methods: Eighty-two patients with mRCC who underwent CN within our tertiary care referral center were identified. Potential pre-operative clinical and serologic predictors of overall survival (OS) were evaluated using both univariate and multivariable Cox-Regression analyses. A Recursive Partitioning and Regression Tree (RPART) model was subsequently developed allowing for stratification of patients into risk groups on the basis of OS. Results: The derived RPART tree, was able to stratify patients into 4 risk groups ranging from “low risk” to “very high risk” with respect to their expected OS utilizing the number of metastatic sites at diagnosis, serum hemoglobin (Hgb), and serum white blood cell count (WBC) count as partitioning parameters. Within the 4 groups, the median OS ranged from 4.3 months to 72 months. Conclusions: Our proposed simple quantitative risk-stratification model based on the pre-operative metastatic burden, Hgb, and WBC count is useful to predict OS when contemplating upfront CN prior to systemic therapy. Furthermore, a pre-operative serum WBC count ≥ 7.15 K/uL appears to be indicative of a poor prognosis.
Nephrotoxicity induced by VEGF-target agents in patients with metastatic renal cell cancer.
Authors: Kato Tomoyuki , Nakayama Shoko , Narisawa Takafumi , Yamagishi Atsushi , Sakurai Toshihiko , Naito Sei , Kawazoe Hisashi , Ichiyanagi Osamu , Bilim Vradimir , Nagaoka Akira , Tomita Yoshihiko 
Published: February 2017

432 Background: A study was undertaken to investigate the association between treatment with vascular endothelial growth factor (VEGF)-targeted therapy for metastatic renal cell cancer (mRCC) and nephrotoxicity. Methods: Retrospective data were collected for mRCC patients received VEGF-targeted therapy between January 2005 and December 2010. We investigated renal adverse events and clinically significant increased serum creatinine level in patients who received VEGF target therapy. GFR was estimated with the Modification of Diet in Renal Disease (MDRD) formula. Results: Ninety one patients with mRCC who received sunitinib (n=46), sorafenib (n=38), axitnib (n=9) were included in this analysis. As for renal adverse events, acute renal failure occurred in 1 (2.2%) of 46 sunitinib recipients. Facial edema occurred 17 (37.0%) in sunitinib recipients, 2 (5.3%) of sorafenib recipients, 2 (22.2%) of axitinib recipients. In sunitinib recipients, all of these adverse events observed in ‘off’ period. During administration, gradual and significant increase of serum creatinine was observed in sunitinib recipients compared for sorafenib or axitinib recipients (p= 0.04). Significant decrease of GFR compared for baseline correlated with increase of serum creatinine level developed in ‘on’ period of 6 sunitinib administration cycle (p=0.013), but returned to baseline level after 2weeks cessation. No significant change was observed in serum creatinine level and GFR in patients received other VEGF-target agents. Conclusions: Our data suggest that nephrotoxicity developed in a high percentage of patients on sunitinib compared for sorafenib and axitinib in mRCC patients. Clinicians should observe renal function of sunitinib recipients more carefully in ‘off’ period as well as ‘on’ period.