bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilization of neoadjuvant chemotherapy in stages II and III urothelial carcinoma of the bladder.
Authors: Huang B. , Tucker T. , Bylund J. R. , Rinehart J. J. , Rowland R. G. , Strup S. E. , Crispen P. L. 
Published: February 2017

292 Background: Level 1 evidence supports the use of neoadjuvant chemotherapy (NC) prior to cystectomy in patients with stage II and III urothelial carcinoma of the bladder. However, the utilization of NC in appropriate patients prior to cystectomy is unknown. Here we examine the use of and potential predictors for the use of NC prior to cystectomy. Methods: The Kentucky Cancer Registry was reviewed from the years 2000 to 2007 for patients undergoing cystectomy for stage II and III (T2-4aN0M0) bladder cancer. Histologic subtypes of bladder cancer other than urothelial carcinoma were excluded. Multiple logistic regression was utilized to examine factors associated with the use of neoadjuvant chemotherapy prior to cystectomy. Results: A total of 223 patients undergoing cystectomy during the study period were identified. Median age was 66 years and 74% of patients were male. The majority of patients, 66%, had AJCC stage II disease. 6.3% (14/223) of patients received NC prior to cystectomy. Bivariate analysis did not reveal significant differences in age, gender, stage, geographic location, or insurance status when comparing patients receiving and not receiving NC prior to cystectomy. Year of treatment was significantly associated with the use of NC with 2.8% and 9.6% of patients receiving NC between the years 2000–2003 and 2004–2007, respectively (p = 0.034). Year of diagnosis remained significantly associated with the use of NC on multiple logistic regression (OR 4.23, CI 1.12–15.9). Conclusions: Although a significant increase in the number of patients receiving NC prior to cystectomy has been observed since 2003, the overall utilization of NC remains low despite the proven survival benefit noted in randomized trials. Further investigation of the low utilization of NC in this population is warranted. No significant financial relationships to disclose.
Cessation of VEGF-targeted therapy in patients with metastatic renal cell carcinoma (mRCC): Feasibility and clinical outcome.
Authors: Sadeghi S. , Albiges L. , Wood L. S. , Black S. L. , Gilligan T. D. , Dreicer R. , Garcia J. A. , Escudier B. J. , Rini B. I. 
Published: February 2017

307 Background: Standard practice in the treatment (tx) of mRCC with VEGF targeted agents is continuous tx until progression of disease (PD) or unacceptable toxicity. Chronic mild to moderate toxicity and risk of long-term toxicity ensue for a subset of pts. It is hypothesized that a subset of pts with an initial response to tx can maintain disease control off all tx for a period of time. Methods: A retrospective study of mRCC pts who initiated VEGF-targeted tx between January 2004 and November 2009 was conducted. Pts had achieved disease control on tx, then were taken off all tx. Pt, disease and tx characteristics were recorded. Progression free survival (PFS) was measured as the time from discontinuation of tx to RECIST PD. Results: A total of 30 pts were identified. All pts had prior nephrectomy and had clear cell histology, and 9 patients had prior immunotherapy. At the time tx was stopped 16 pts were receiving sunitinib, 7 pts were receiving sorafenib (2 in combination with AMG 386), and 7 pts were receiving bevacizumab (6 in combination with temsirolimus, 1 with IFN-alpha). Six pts had achieved CR, 19 PR and 5 SD by RECIST. Using Heng's prognostic risk group criteria, 14 pts had favorable, 14 had intermediate, and 2 had poor risk disease prior to initiation of VEGF-targeted tx. Therapy was held for severe adverse events (5pts; 2 MIs, 3 CVAs), toxicity (16 pts; 4 diarrhea, 3 skin, 3 proteinuria, 2 cardiac, 1 fatigue, 1 stomatitis, 1 pneumonitis, 1 nausea), cost (1 pt; high co-pay), pt choice (6 pts) and interventions (2 pts; 1 angioplasty and 1 kidney stone). Median follow up is 29 months (range 11– 82). Median duration of tx prior to discontinuation was 14.6 months (range 3–79). Thirteen pts (43%) had PD off tx (lymph nodes (6), lungs (8; 3 with new lesions), bones (1), brain (2; 1 with new lesions)) with a median PFS of 10 months (range 3–27). After PD, 4 pts were offered sunitinib, 1 pazopanib, 1 everolimus, 1 local RF tx, and 6 continued expectant management. After a median follow-up to date of 7.5 months (2–28), 17 pts (57%) still did not have RECIST PD. Conclusions: Select mRCC pts with disease control on VEGF-targeted tx can be safely observed off all tx. Further prospective investigation is needed to define the risks and benefits of this approach. [Table: see text]
The effect of low serum sodium on treatment outcome to vascular endothelial growth factor (VEGF)-targeted therapy in metastatic renal cell carcinoma: Results from a large international collaboration.
Authors: Schutz F. A. , Xie W. , Heng D. Y. , Donskov F. , Wood L. , Vaishampayan U. N. , Tan M. , MacKenzie M. J. , Kollmannsberger C. K. , Choueiri T. K. 
Published: February 2017

322 Background: Hyponatremia has been associated with poor survival in many solid tumors and more recently found to be of prognostic and predictive value in metastatic renal cell cancer (mRCC) patients (pts) treated with immunotherapy (Jeppesen et al, Br J Cancer. 2010). We sought to investigate the influence of baseline hyponatremia in mRCC pts treated with contemporary vascular endothelial growth factor (VEGF)- targeted therapy in a larger international and multi-institutional database. Methods: Baseline characteristics and outcomes on 855 pts treated with first-line anti-VEGF therapy for mRCC were available from 8 Cancer Centers to study the impact of hyponatremia (defined as serum Na<135 mmol/L) on clinical outcome as measured by overall survival (OS), time to treatment failure (TTF), best response (CR, PR, SD and PD). Results: Median OS after treatment initiation was 16.8 months (mos) (95% CI: 14.9, 18.5 mos), with 334 (39%) of patients remaining alive. Median follow-up in pts alive was 18.8 mos. Median baseline serum sodium was 138 mmol/L (range: 122–159), and hyponatremia was found in 16.7% of pts. On univariate analysis, hyponatremia was associated with shorter OS (6.5 vs. 18.8 mos; HR 2.32 [95% CI: 1.86–2.89], p<0.0001), shorter TTF (2.8 vs. 6.9 mos.; HR 2.20 [95% CI: 1.81–2.68], p<0.0001), and lower disease control rate (DCR) as defined by CR+PR+SD (51.2% vs. 74.6%, OR 0.36 [95% CI: 0.2–0.57], p<0.0001). In multivariate analysis adjusted for MSKCC or Heng's risk criteria (JCO 2009), these effects remain significant with p<0.001 for OS and TTF and p=0.01 for DCR. The results were similar (p<0.001) if sodium was analyzed as a continuous variable. Conclusions: This is the first large multi-institutional report to show that low serum sodium is independently associated with a worse outcome in mRCC pts treated with VEGF-targeted agents. No significant financial relationships to disclose.
Activity of tivozanib (AV-951) in patients (Pts) with different histologic subtypes of renal cell carcinoma (RCC).
Authors: Bhargava P. , Esteves B. , Al-Adhami M. , Nosov D. , Lipatov O. N. , Lyulko A. A. , Anischenko A. A. , Chacko R. T. , Doval D. , Slichenmyer W. 
Published: February 2017

327 Background: This phase 2 randomized discontinuation trial evaluated tivozanib, a potent and selective vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3 kinase inhibitor. Median progression-free survival (PFS) in all pts was 11.8 mo, and the objective response rate (ORR) was 27%. Methods: Pts received 1.5 mg/d tivozanib (3 wk on, 1 wk off = 1 cycle). A retrospective analysis evaluated efficacy and safety by histologic subtype. Response was evaluated by independent radiology review using standard RECIST criteria. Results: 272 pts were enrolled: 70% were male; median age was 56 y (range, 26–79). 226 (83%) pts had clear cell (CC) RCC; 46 had non–clear cell (NCC) RCC, including 11 with papillary RCC. Of pts with CC RCC, 176 (78%) had undergone nephrectomy; of pts with NCC RCC, 23 (50%) had undergone nephrectomy. Median treatment duration was 8.5 mo (range, 0.03– 23.8) as of the data cutoff. Median PFS was 12.5 mo (range, 9.9–17.7) for pts with CC RCC, not yet reached for pts with papillary RCC, and 5.4 mo (range, 3.7–12.0) for pts with other NCC subtypes. ORR and disease control rate (DCR; ORR + stable disease), respectively, were 29% and 85% for pts with CC RCC, 18% and 100% for pts with papillary RCC, and 17% and 74% for pts with other NCC subtypes. For pts with CC RCC, median PFS, ORR, and DCR, respectively, were 14.8 mo, 32%, and 88% for those who had undergone nephrectomy and 8.9 mo, 18%, and 76% for those who had not. Among pts with NCC RCC, median PFS was 6.6 mo for pts who had undergone nephrectomy and 7.2 mo for pts without nephrectomy; ORR was 17% for both NCC subgroups, with a DCR of 78% for pts who had undergone nephrectomy and 83% for pts who had not. Common drug- related adverse events (AEs) for pts with CC and NCC RCC, respectively, included hypertension (49% and 48%), dysphonia (22% and 22%), asthenia (12% and 13%), and diarrhea (13% and 9%). The most common grade ≥3 drug-related AE was hypertension (CC, 8%; NCC, 4%). Conclusions: Disease control was observed for pts with all RCC histologic subtypes. The rate of AEs was similar among patients with CC and NCC RCC and consistent with that of a selective VEGFR inhibitor with minimal off-target toxicities. Tivozanib is currently being tested in a phase 3 trial in pts with CC RCC. [Table: see text]
Fatigue, quality of life, and cognitive functions in metastatic kidney cancer patients with antiangiogenic treatment.
Authors: Noal S. , Lange M. , Escudier B. J. , Sevin E. , Dauchy S. , Clarisse B. , Daireaux A. , Leger I. , Rieux C. , Joly F. 
Published: February 2017

328 Background: Fatigue is commonly reported by patients under anti-angiogenic therapies, with sometimes cognitive complains. However, few studies have explored these problems. A longitudinal multicentric prospective study is ongoing in France on fatigue, cognitive functions, quality of life (QoL), anxiety and depression among metastatic kidney cancer patients receiving anti-angiogenic therapies. Objectives: The main objective is to assess fatigue. Secondary objectives are to assess cognitive functions, QoL, anxiety, and depression. Methods: Assessments are made at baseline, at 3 and 6 months. Evaluations were made by: autoquestionnaire MFI-20 to assess fatigue, FACT-G and FKSI to assess QoL, Spielberger's and Beck's questionnaires to assess respectively anxiety and depression. Cognitive functions were assessed by a neuropsychologist with the Working Memory Index (WAIS-III), Grober and Buschke test, Rey Complexe Figure test, verbal fluency and Trail Making test, exploring respectively working memory, episodic memory and executive functions. Preliminary results are presented. Results: 35 patients were enrolled, and 20 of them had the second assessment at 3 months. Most of patients received sunitinib (51%), others received bevacizumab and interferon, or sorafenib. At baseline, 45% of patients expressed general fatigue and 50% at 3 months (p=0.04). Other domains of fatigue (physical, mental, reduced activity and motivation) did not change over time. At baseline, few patients had cognitive disorders (working memory 6%; executive functions 0%; episodic memory 11%), with no decline at 3 months. However, there was an impairment of QoL in FKSI score (p=0.01) and of FACT-G physical well-being (p=0.01). No differences were found in social, emotional or functional well-being. There was no difference on depression nor on anxiety over time. Conclusions: Fatigue significantly increased during the first 3 months of anti-angiogenic treatment, with no impact on cognitive functions but a decline of QoL. These preliminary findings need to be confirmed by further follow-up and more patients. Final results will be provided with 120 patients. No significant financial relationships to disclose.
Everolimus-associated pneumonitis (EAP) in metastatic renal cell cancer patients (mRCC): A single-center experience.
Authors: Cauley D. H. , Atkinson B. J. , Corn P. G. , Jonasch E. , Tannir N. M. 
Published: February 2017

332 Background: Pneumonitis is a known adverse effect (AE) of mammalian target of rapamycin-inhibitors, with a literature reported incidence for everolimus ranging from 4 to 45%. The goal of this review was to characterize the incidence, timing, management, and outcomes related to everolimus-associated pneumonitis (EAP). Methods: Retrospective review of 86 mRCC patients (pts) with complete, evaluable records, given everolimus (E) between 4/2009 and 3/2010. We assessed baseline patient (pt) characteristics, previous therapies, time on E therapy, pt symptoms, physician management of AE, NCI-CTC pneumonitis grading, and survival outcomes. Radiologic CT indicated ground glass, inflammatory, and/or parenchymal opacities. Results: (See table.) EAP occurred in 28% of pts on E therapy, confirmed radiologically. 8% of EAP patients reported no symptoms. In EAP pts, 58% reported cough, 75% dyspnea and/or SOB, 17% fever, 71% fatigue. The median number of symptoms/patient was 3. 46% of pts received steroids (median 21 days (3-120)), 38% received antibiotics, 25% received pulmonary consultation, and 8% required oxygen. In pts who developed EAP, providers discontinued E in 75%, held and dose reduced E in 8%, and continued E in 17%. The median NCI-CTC pneumonitis grade was 2 (1-3); there were no treatment-related deaths. The median time to EAP onset was 67 days (8-442). There was no statistically significant difference in outcomes between EAP pts and non-EAP pts. Conclusions: EAP occurs often in mRCC pts treated with E. It is an important AE that can negatively affect pt symptoms, but did not adversely impact pt outcomes in our single-center experience. [Table: see text] [Table: see text]
Use of CDK1 and CDK2 activity to predict renal cell cancer recurrence.
Authors: Hongo F. , Takaha N. , Kimura Y. , Nakamura T. , Mikami K. , Nakayama S. , Matsushima T. , Ishihara H. , Sakai T. , Miki T. 
Published: February 2017

341 Background: We established original methods enabling simultaneous analysis of protein expressions and kinase activities of the CDK (cyclin-dependent kinase) molecules in lysate of tumor tissue in a clinical setting (C2P technology, Ishihara et al: Biochim Biophys Acta. 1741; 226-233, 2005). The clinical utility of the technology was first evaluated in breast cancer, and combination analysis of CDK1 and CDK2 activity was shown to be a significant prognostic indicator for relapse (Kim et al. Ann Oncol. 19;68-72,2009). The objective of our study is to evaluate the efficacy of CDK1 and CDK2 activity as a prognostic marker in human renal cell carcinoma (RCC). Methods: Surgical specimens were obtained from 115 patients with RCC without metastasis. These patients were selected randomly for this study. Protein expression and kinase activity of CDKs and cyclins were analyzed using a newly developed assay system. The system to measure the CDK specific activity (SA) is named C2Ps (Sysmex, Kobe, Japan). We then examined the specific activities of CDK1 and CDK2 and calculated CDK2/CDK1 ratio in RCC. Also, risk score (RS) was examined as described in previous study (JGH van Nes et al: Br J Cancer. 100; 494-500, 2009). Cut off value was calculated by ROC analysis. Results: 115 cases were tested, though 32 cases were excluded of low sample quality (30 cases) and of assay failure (2 cases). 83 cases were analyzed. They included 63 male and 20 female patients, ranging in age from 19 to 83 years. At a median follow up of 33 months (1-109M), tumor with low CDK2/CDK1 ratio showed significantly better 5-year progression-free survival (PFS) than those with high CDK2/CDK1 ratio (91.2% vs. 51.6%, p=0.0016). Also, RS enabled the classification of RCCs into high-risk and low-risk groups, patients with tumors classified as low RS showed better PFS than patients with tumors with high RS (88.9% vs. 63.9%, p=0.0488). Conclusions: CDK1 specific activity of tumors and the CDK2 specific activity are both associated with recurrence and prognosis. Analysis of cyclin-dependent kinase activity in the clinical setting could be a powerful approach for predicting cancer recurrence and prognosis in RCC after surgery and has potential for use as a routine laboratory test. No significant financial relationships to disclose.
Relationship between plasma pazopanib concentration and incidence of adverse events in renal cell carcinoma.
Authors: Lin Y. , Ball H. A. , Suttle B. , Mehmud F. , Amado R. G. , Hutson T. E. , Pandite L. N. 
Published: February 2017

345 Background: Pazopanib (P), an oral angiogenesis inhibitor targeting VEGFR, PDGFR, and c-Kit, is approved by the US FDA for the treatment of advanced renal cell cancer (mRCC). Exploratory analyses of data from a Ph II mRCC study (Hutson T, J Clin Oncol. 27, 2009:1) indicated that 70% of patients (pt) receiving 800mg once daily had a week (wk) 4 plasma P trough (Cmin) >20.6μ g/mL that is associated with improved efficacy (Suttle B, J Clin Oncol. 28, 2010:S3048). In this further analysis of the dataset, we investigated the relation between plasma P concentrations at wk 4 and clinically important adverse events (AE) reported within the first 12 wks of treatment. Methods: The % of patients with hypertension (defined as ≥ 15mmHg - baseline on 3 occasions)- a recognized PD marker for this class of agents- or other AEs (CTC grades), occurring during the first 12 wks of treatment were calculated by wk4 Cmin quartiles (Q1-Q4: median and range). Results: P concentrations at 4 wks and AE data were available for 205 out of 225 pts. The incidence of hypertension was 58% in Q1, increasing with concentration to 78% at Q4. The incidence of diarrhea, hair color change, ALT increase, HFS (marked increase), and stomatitis were concentration-dependent, with ≥ 2 fold increase from Q1 to Q4. The incidence of nausea, fatigue, vomiting, dysgeusia, and rash were variable or displayed a flat relationship with Cmin. Conclusions: The incidence of some AEs, such as diarrhea, ALT, HFS (marked relation), and stomatitis increased with plasma Cmin while others did not. We suggest that concentration-dependent AEs are more likely to respond to P dose reduction and as such, provides support for development of a dose optimization strategy. [Table: see text] [Table: see text]
Functional and oncologic outcomes of nephron-sparing surgery (NSS) for patients with renal cell carcinoma (RCC) greater than 4 cm in diameter.
Authors: Piper C. , Richter S. , Brehmer B. , Pfister D. J. , Epplen R. , Heidenreich A. 
Published: February 2017

347 Background: Organ preserving surgery represents the guideline recommended surgical treatment of choice for patients with small renal tumors ≤ 4cm in diameter. There are only few data in the literature with regard to the oncological and functional outcome of elective NSS in RCC larger than 4cm. Methods: We retrospectively reviewed the charts of all patients who underwent elective NSS for RCC at our institution during 2004-2009. We identified 288 patients of whom 196 (68.1%) patients and 92(31.9%) patients underwent NSS for a tumor < 4cm (group 1) and a tumour ≥ 4cm (group 2), respectively. We analyzed tumor size, TNM-classification, OR time, surgical margins, complications, mortality, recurrences and metastases in both groups. Results: We identified significant differences between group 1 and 2 for the following variables: mean tumor size (2.9 vs. 8.6cm, p = 0.03), necessity for warm ischemia (15.1% vs. 51%, p = 0.001), mean ischemia time (3.5 vs. 10.2 min, p = 0.002), need for endoluminal stenting due to involvement of the renal pelvis (0.5% vs. 24.2%, p = 0.001). Significantly less pT2 (12.7% vs. 29.7%, p = 0.03) and pT3 tumors (8.7% vs. 12%, p = 0.05) were identified in group 1 when compared to group 2. There were no significant differences with regard to mean OR time (61 vs. 74 min), positive surgical margins (1/192 vs. 1/92), hospital stay, and perioperative complications. There were no significant differences with regard to stage specific overall survival, cancer-specific survival and progression-free survival. There was no significant survival difference between NSS and radical nephrectomy. Conclusions: NSS can be safely performed in RCC > 4 cm without increasing the frequency of treatment-associated complications or decreasing cancer-specific survival. NSS should represent the treatment of choice in all patients with RCC of 4-7cm in diameter if technically feasible. No significant financial relationships to disclose.
Metastatic renal cell carcinoma treated with pazopanib after progression on other targeted agents: A single-institution experience.
Authors: Matrana M. R. , Atkinson B. J. , Corn P. G. , Jonasch E. , Tannir N. M. 
Published: February 2017

351 Background: Pazopanib, a multityrosine kinase inhibitor (TKI), prolongs PFS compared to placebo in treatment-naive and cytokine refractory metastatic renal cell carcinoma (mRCC). No data has been reported about pazopanib salvage therapy after treatment with other targeted agents. Methods: We retrospectively reviewed the records of 88 consecutive patients (pts) with mRCC (median age 62.7, M:F 63/25, 84% clear cell) who received salvage pazopanib between 11/09-8/10. All pts failed previous treatment with one or more targeted agents (median number of prior targeted agents was 2, range 1-5; median time on previous treatments was 632 days). 78% of pts had progressed on sunitinib, 40% on sorafenib, 20% on temsirolimus, 51% on everolimus, and 26% on bevacizumab. 26% received previous chemotherapy and 16% received previous cytokines in addition to targeted therapies. 58% failed both TKI/VEGF inhibitors and mTOR inhibitors. 57% had intermediate-risk disease and 43% had poor-risk disease by MSKCC criteria. All pts had follow-up at least every 3 months after initiating pazopanib. Results: Median time to last follow-up was 114 days (range 30-278 days). 42% continued pazopanib at last follow- up. 25% had partial response (PR) by treating physician assessment. 50% failing 1-2 previous targeted therapies remained on pazopanib at last follow-up, compared to 27% of those failing more than 2 targeted therapies (p=0.04). 56% of pts with intermediate-risk disease by MSKCC criteria continued pazopanib at follow-up compared to 27% with poor-risk disease (p=0.002). 42% of those failing 1 prior targeted therapy achieved PR compared to 18% failing >1 prior targeted therapy (p=0.02). 35% discontinued pazopanib due to progressive disease (PD) (median time to PD 71 days, range 36-198 days), 10% discontinued due to adverse drug events, and 10% died of PD on treatment. There were no treatment related deaths. Conclusions: In this retrospective study, pazopanib demonstrated clinically relevant activity in mRCC following PD with other targeted therapies. Mature survival data will be provided with final presentation. No significant financial relationships to disclose.