bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of everolimus therapy on skeletal muscle wasting in patients with metastatic renal cell carcinoma (mRCC): Results from a placebo-controlled study.
Authors: Albiges L. , Antoun S. , Martin L. , Merad M. , Loriot Y. , Baracos V. , Escudier B. J. 
Published: February 2017

319 Background: We have previously reported that sorafenib induces muscle wasting in mRCC (Antoun, JCO 2010). As everolimus exerts its antineoplastic through inhibition of the mammalian target of rapamycin (mTOR), a key element of intracellular signalling of protein synthesis in skeletal muscle, we hypothesized that muscle wasting would be also an important side effect of everolimus therapy. Methods: All patients with mRCC enrolled in RECORD 1 (everolimus (E) or placebo (P) post TKI failure) in IGR (n=40) were analyzed for this study. Patients were eligible if at least 2 CT scans were available. CT image analysis, which has high precision and specificity for evaluation of specific muscles, was used to define change in total skeletal muscle. The third lumbar vertebra (L3) was chosen as a landmark. Images were analyzed using Slice-O-Matic software V4.3 (Tomovision). Tissue Hounsfield unit thresholds were employed: −29 to +150 for skeletal muscle. Subsequently, tissue cross-sectional areas (cm2) were computed. Results: 35 patients (83% male, median age 60y) were evaluable, 10 on P and 25 on E. In addition, 9 patients initially on P could cross to E (as per protocol) and were analyzed both on P and on E. Median durations of treatment were 79 and 263 days respectively on P and E. Placebo patients had stable body weight, with no significant mean gain or loss of muscle. By contrast, patients on E lost body weight over time: −2.5±3.6 kg by 83 d (p=0.02), −4.9±5.7 (p=0.005) by 167 d and –5.0±7.6 kg (p=0.02) by 286 d. E patients progressively lost skeletal muscle compared .with baseline from −2.5±5.9% at 83d (p=0.06), to −4.0±7.5% at 167d (p=0.03) and −4.8±6.8% at 263d (p=0.01). Interstingly, the 9 patients who had maintained body weight (+2.0 kg) and muscle (+2.7%) whilst on placebo, and crossed to E, promptly lost weight (−4.8 kg, p<0.03) and skeletal muscle (−5.3%) (about 1.5 kg of muscle) when crossed to E. Conclusions: Body weight and muscle wasting are induced by everolimus in mRCC, and are not related to progressive disease. These changes increase over time. Relation between these changes and outcome will be presented at the meeting. [Table: see text]
Use of comparison of cold and warm ischemia during partial nephrectomy in 660 solitary kidneys to investigate the role of nonmodifiable factors in determining ultimate renal function.
Authors: Lane B. R. , Russo P. , Uzzo R. , Hernandez A. V. , Boorjian S. A. , Thompson R. H. , Fergany A. F. , Love T. , Campbell S. 
Published: February 2017

321 Background: Factors that determine renal function after partial nephrectomy (PN) are not well defined, including the impact of cold vs. warm ischemia and the relative importance of modifiable and non-modifiable factors. We studied these determinants in a large cohort of patients with a solitary functioning kidney undergoing PN. Methods: In 1980–2009, 660 PN were performed at 4 centers for tumor in a solitary-functioning kidney under cold (n=300) or warm (n=360) ischemia. Data were collected in IRB-approved registries; follow- up averaged 4.5 years. Pre- and postoperative glomerular filtration rates (GFR) were estimated via CKD-EPI equation. Results: At 3 months after PN, median GFR decreased by equivalent amounts with cold or warm ischemia (21% vs. 22%, respectively, p=0.7) although median cold ischemic times were much longer (45 vs. 22 min. respectively, p<0.001). In multivariable analyses, increasing age, larger tumor size, lower preoperative GFR, and longer ischemia time were associated with decreased postoperative GFR (p<0.05). When percentage of parenchyma spared was incorporated into the analysis, this factor and preoperative GFR proved to be the primary determinants of ultimate renal function, and duration of ischemia lost statistical significance. Conclusions: This non-randomized comparative study suggests that long-term renal function after PN is determined primarily by the quantity and quality of renal parenchyma that can be preserved. Within the relatively strict parameters of conventional practice, i.e. predominantly short ischemic intervals and liberal use of hypothermia, ischemia time was not an independent predictor of ultimate renal function after PN. Nevertheless, type and duration of ischemia remain the most important modifiable factors during PN, and mandate further study. [Table: see text]
Predictors of long-term survival in patients with metastatic renal cell carcinoma in the cytokine era: An analysis of 473 patients treated between 1995 and 2005.
Authors: Shinohara N. , Maruyama S. , Abe T. , Sazawa A. , Nonomura K. ,   Hokkaido Immunotherapy Research Group
Published: February 2017

335 Background: Based on the clinical data in Japanese renal cell carcinoma (RCC) patients who underwent cytokine therapy (Naito et al, Eur Urol 2010), the overall survival (OS) of these patients has been considered to be better than that of Caucasian patients. We identified long-term survivors among a cohort of 473 metastatic RCC patients, and explored clinical predictors of OS in these patients. Methods: Between 1995 and 2005, 473 patients with metastatic RCC were the subjects of this retrospective analysis. Three hundred sixty-one (76%) patients received IFN-α and no patient did molecular-targeted drugs. The patients with survival times of greater than 5 years after the development of metastases were identified as long-term survivors. Multiple logistic regression analysis was performed to evaluate the impact of clinical variables potentially influencing OS. Results: Median OS for all patients was 22.3 months (95%CI 18.7-27.6), the estimated 5-year survival rate was 27.4% (95% CI 22.9-31.9). Sixty-eight patients (14.4%) among 473 patients were identified as long-term survivors. Twenty-six (38%) had metastases at diagnosis of kidney cancer, 3 (4%) and 11 (16%) had liver mets and bone mets, respectively. According to MSKCC risk classification, 19 (28%), 28 (41%), and 6 (9%) were classified as favorable, intermediate, and poor risk, respectively. All patients had undergone prior nephrectomy, and 40 (59%) underwent metastatectomy. Multiple logistic regression analysis from all patients identified metastatectomy (HR 5.0; 95%CI 2.7-9.5) and MSKCC risk group (HR 3.7; 95%CI 1.5-9.1) as adverse prognostic factors for long-term OS. Conclusions: Selected patients with metastatic RCC who can undergo metastatectomy have a good opportunity for long-term survival, especially those with favorable or intermediate risk classified by MSKCC risk classification. No significant financial relationships to disclose.
Hematologic toxicities in renal cell carcinoma and other malignancies treated with bevacizumab: A meta-analysis of clinical trials.
Authors: Fontes Jardim D. L. , Je Y. , Schutz F. A. , Choueiri T. K. 
Published: February 2017

336 Background: Bevacizumab is a humanized monoclonal antibody directed against the VEGF ligand. Clinical trials with this drug mainly included patients with renal cell cancer (in combination with interferon-alpha) and several other solid tumors (in combination with cytotoxic chemotherapy). Although hematologic toxicities are not among the main concerns associated with the addition of bevacizumab, discontinuation of therapy or dose reductions due to these toxicities have been reported. We performed a meta-analysis to determine the incidence and risk of hematologic toxicities associated with bevacizumab use. Methods: The databases of Medline were searched for articles from 1966 to September 2010. Abstracts presented at the American Society of Clinical Oncology meetings were also searched. Eligible studies include randomized trials with bevacizumab, and adequate safety data profile reporting anemia, neutropenia, febrile neutropenia, or thrombocytopenia. Statistical analyses were conducted to calculate the summary incidence, RR, and 95% confidence intervals (CI). Results: A total of 15,239 patients were included in the analysis. The incidence of bevacizumab-associated all-grade anemia, neutropenia and thrombocytopenia were 19.4%, 22.3%, and 14.5%, respectively. The incidences of high-grade events were 3.94%, 18.4% and 3.38%, respectively. Febrile neutropenia was present in 3.75% of patients. Bevacizumab was associated with a decreased risk of high-grade anemia (RR=0.73; 95% CI 0.60-0.89; p=0.002), and increased risks of high-grade neutropenia (RR=1.08; 95% CI 1.02-1.13; p=0.005) and febrile neutropenia (RR=1.31; 95% CI 1.08-1.58; p=0.006), as compared to the non-bevacizumab containing arms. Stratified analysis by the dose of bevacizumab (2.5mg/wk vs. 5mg/wk) demonstrated similar risks. Conclusions: Concurrent use of bevacizumab with chemotherapy or immunotherapy is associated with a lower risk of high-grade anemia and an increased risk of high-grade neutropenia and febrile neutropenia. [Table: see text]
Role of quantitative gene expression using RT-PCR in the prediction of recurrence risk in resected T1 clear cell renal cell carcinoma (ccRCC).
Authors: Campbell S. , Knezevic D. , Maddala T. , Novotny W. F. , Zhou M. , Aydin H. , Elson P. , Parodi L. , Goddard A. D. , Rini B. I. 
Published: February 2017

338 Background: Current pathology and clinical methods do not accurately estimate risk of recurrence in all patients with pT1 ccRCC. Quantitative RT-PCR (qPCR) analysis was performed on resected ccRCC tumors to identify genes associated with recurrence that significantly augment current prognostic tools. Methods: A retrospective observational cohort consisting of 931 patients (434 T1a, 201 T1b, 296 T2/3) with ccRCC was evaluated. All patients underwent nephrectomy between 1985 and 2003 at Cleveland Clinic and had paraffin-embedded tumor blocks. Patients with inherited ccRCC or inadequate follow-up (< 6 months or no recurrence data) were excluded. qPCR analysis of 732 genes was performed on all patients. Cox Proportional Hazards regression models were used to evaluate the association between gene expression and recurrence-free interval (RFI). Results: 448 genes were significantly (unadj. p < 0.05) associated with RFI, from which 72 genes were carried forward for further study (Rini, ASCO 2010, #4501). Angiogenesis is the strongest among the pathways represented, from which 3 genes (AQP1, NOS3, PPAP2B) were selected for this analysis. Incorporating these 3 genes, a subset of higher risk patients among those classified as low risk by Leibovich criteria was identified. By Leibovich criteria, 85% of the patients in the cohort with pT1 tumors (< 7.0 cm) were identified as low risk - 7% recurrence at 5 years (95% CI: 5%, 9%). Incorporating these 3 genes, 9% of these patients were found to be at increased risk for recurrence - 19% at 5 years (95% CI: 7%, 21%). For the subset of T1a patients (< 4.0 cm), 98.6% were low risk according to the Leibovich criteria - 7% recurrence at 5 years (95% CI: 4%, 10%). Incorporating the 3 genes, 11% of these patients were found to be at increased risk - 20% at 5 years (95% CI: 7%, 31%). Conclusions: Addition of 3 angiogenesis-related genes to the Leibovich criteria in patients with pT1 tumors refines stratification of patient risk in a subset of patients. More precise estimation of recurrence risk will help to tailor surveillance and refine inclusion into clinical trials. These genes will be incorporated into an algorithm that requires validation in an external data set. [Table: see text]
NCI 6896: A phase I trial of suberoylanilide hydroxamic acid (SAHA) and 13-cis retinoic acid in the treatment of patients with advanced renal cell carcinoma (RCC).
Authors: Nanus D. M. , Tagawa S. T. , Dutcher J. P. , Akhtar N. H. , Saran A. , Mazumdar M. , Milowsky M. I. , Gudas L. J. 
Published: February 2017

349 Background: Retinoid resistance in RCC inversely correlates with levels of intracellular retinol and retinyl esters suggesting that increasing intracellular levels of all-trans retinoic acid (RA) or enabling RA to become a more potent initiator of transcription will improve RA mediated anti-tumor effects. The combination of all-trans RA and a histone deacetylase (HDAC) inhibitor inhibited renal cancer cell proliferation and tumor growth in a xenograft model more than either drug alone. We performed a phase I clinical trial to evaluate the safety and preliminary efficacy of combining the oral HDAC inhibitor SAHA (vorinostat) plus oral 13-cis RA (isotretinoin) in patients with advanced RCC. Secondary endpoints include analysis of peripheral blood samples to study the effects on retinoid metabolites and retinoid related genes. Methods: Patients (pts) with metastatic RCC (any histology) who have failed at least two lines of prior therapy were eligible. Vorinostat (300 mg bid x 3 consecutive days per week + isotretinoin co-administered at 0.25 mg/kg, 0.375 mg/kg, or 0.5 mg/kg PO bid x 3 days per week in cohorts using standard 3+3 dose escalation. Dose limiting toxicity (DLT) was defined as any grade > 3 toxicity during the first cycle. Results: 14 pts have enrolled on the trial of which 12 are evaluable for toxicity (6 cohort 1; 3 cohort 2; 3 cohort 3) and 11 for tumor response. Common grade 1-2 toxicities included fatigue and GI effects (nausea, diarrhea, anorexia). One pt on dose-level 1 experienced a DLT (grade 3 depression). One patient experienced a partial response and 10 patients had stable disease lasting a median of 4 months (range 2–10 mos). Three patients progressed with brain metastases in the setting of stable systemic disease for at least 6 months. Pharmacokinetic and correlative studies examining expression of retinoid related genes are ongoing. Conclusions: The recommended phase II dose is vorinostat (300 mg bid) + isoretinoin (0.5 mg/kg PO bid) 3 days per week. The combination of vorinostat and isotretinoin was well tolerated, and there was evidence of antitumor activity in this heavily pretreated population of patients with refractory metastatic RCC. [Table: see text]
Use of percent positive biopsy cores to predict prostate cancer–specific death in patients treated with dose-escalated radiotherapy.
Authors: Qian Y. , Feng F. Y. , Halverson S. , Blas K. , Sandler H. M. , Hamstra D. A. 
Published: February 2017

35 Background: The percent of positive biopsy cores (PPC)-considered a surrogate of local disease burden-has been shown to predict biochemical failure (BF) after external beam radiation therapy (EBRT), but most series have used conventional dose RT. Dose-escalated RT has been demonstrated to improve prostate cancer outcomes, but the value of PPC is unclear in the setting of RT doses high enough to decrease local failure. Methods: A retrospective evaluation was performed of 651 patients treated to ≥75 Gy with biopsy core information available. Patients were stratified for PPC by quartile, and differences by quartile in BF, freedom from metastasis (FFM), cause specific survival (CSS), and overall survival (OS) were assessed using the log-rank test. Receiver operated characteristic (ROC) curve analysis was utilized to determine an optimal cut-point for PPC. Cox proportional hazards multivariate regression was utilized to assess the impact of PPC on clinical outcome when adjusting for risk group. Results: With median follow-up of 62 months the median number of cores sampled was 7 (IQR: 6–12) with median PPC in 38% (IQR: 17%-67%). On log-rank test, BF, FFM, and CSS were all associated with PPC (p < 0.005 for all), with worse outcomes only for the highest PPC quartile (>67%). There was no observed difference in OS based upon PPC. ROC curve analysis confirmed a cut-point of 67% as most closely associated with CSS (p<0.001, AUC=0.71). On multivariate analysis after adjusting for NCCN risk group and ADT use, PPC>67% increased the risk for BF (p<0.0001, HR:2.1 [1.4–3.0]), FFM (p<0.05, HR:1.7 [1.1 to 2.9]), and CSS (p<0.06 (HR:2.1 [1.0–4.6]). When analyzed as a continuous variable controlling for risk group and ADT use, increasing PPC increased the risk for BF (p < 0.002), metastasis (p < 0.05), and CSS (p < 0.02), with a 1–2% increase in relative risk of recurrence for each 1% increase in the PPC. Conclusions: For patients treated with dose-escalated RT, the PPC adds prognostic value but at a higher cut-point then previously utilized. Patients with PPC >67% remain at increased risk for failure even with dose-escalated EBRT and may receive benefit from further intensification of therapy. No significant financial relationships to disclose.
Effect of genitourinary cancer mortality calculated using the potential years of life lost (PYLL): Trends from 1972-2006 based on a report from the Surveillance, Epidemiology, and End Results (SEER) database.
Authors: Heshmat S. , Moore P. C. , Kamel M. , Moussa O. , Bissada N. 
Published: February 2017

350 Background: We aim to illustrate the potential years of life lost (PYLL) and the average years of life lost (AYLL); secondary to genitourinary cancer in US during the period from 1972-2006 utilizing the Surveillance, Epidemiology and End Results (SEER) database, and illustrate the trends in the PYLL over this time period. Methods: PYLL were calculated to assess premature mortality trends in US for ureter, urinary bladder, kidney and renal pelvis, penis, testis, and prostate cancers. AYLL is the average of the differences between the actual ages at death and the expected remaining years of life for each person who died of cancer. Calculations were made based on the SEER cancer mortality data. Results: There were a total of 7,733,235 PYLL in both men and women secondary to urogenital cancer in US in the period from 1972-2006. In both males and females, the greatest PYLL were for kidney and renal pelvis cancer related mortality. In both sexes no improvement in PYLL secondary to ureteral and bladder cancer related mortality was observed. In males the greatest reduction in PYLL was in testicular cancer followed by prostate cancer. Conclusions: PYLL and AYLL are two powerful tools that reflect the impact of cancer related mortality on society. There has been an increasing trend in PYLL related to urogenital cancers over the last 35 years for both males and females. Kidney cancer had the highest increase in PYLL among both genders and more efforts are needed to address its progression. No significant financial relationships to disclose.
The economic and clinical costs of chronic kidney disease following radical and partial nephrectomy in the management of small renal masses.
Authors: Chang S. L. , Cipriano L. E. , Harshman L. C. , Chung B. I. 
Published: February 2017

353 Background: Postoperative chronic kidney disease (PCKD), defined as a glomerular filtration rate of < 60mL/min/1.73m2, is a recognized adverse outcome after extirpative therapy for small renal masses (SRM, ≤ 4cm). We quantified the long-term economic and clinical costs of PCKD following radical and partial nephrectomy for the management of SRM. Methods: Using a Markov model, we evaluated open and laparoscopic approaches for radical and partial nephrectomy in the treatment of SRMs. The base case was a 65-year old healthy individual with a unilateral SRM and normal renal function. We used a 3-month cycle length, lifetime horizon, societal perspective, and 3% discount rate. The costs, quality of life adjustments, and transition probabilities were estimated from the literature, Medicare, and expert opinion. Health outcomes were measured in quality-adjusted life-years (QALY) gained and costs in 2008 U.S. dollars. The model was tested with sensitivity analyses. Results: The average discounted lifetime outcomes are listed in the Table. There were minimal differences between the open and laparoscopic approaches. PCKD led to a substantial increase costs and decrease in health outcomes. The impact of PCKD was indirectly associated with age. Conclusions: Partial nephrectomy provides cost-savings and improved health outcomes compared to radical nephrectomy in the management of patients with SRMs. Both procedures incur significant economic and clinical costs due to the development of PCKD. A discussion about the potential for PCKD should be incorporated into the informed consent for surgical treatment of SRMs. [Table: see text] No significant financial relationships to disclose.
Effect of salvage radiofrequency ablation on local control of recurrent renal cell carcinoma.
Authors: Psutka S. P. , Daha A. , Gervais D. , Feldman A. S. 
Published: February 2017

355 Background: Radiofrequency ablation (RFA) has emerged as a safe and efficacious option to manage small renal cell carcinoma (RCC) in patients for whom comorbidities preclude surgical treatment. Salvage surgical excision of disease recurrence after ablative therapy is often complicated by extensive perinephric fibrosis. There are no reports in the literature which assess salvage RFA (sRFA) of recurrent disease (RD). The aim of this study was to assess the overall efficacy, complications, and safety of sRFA. Methods: Between 1998 and 2008, 313 patients underwent RFA for RCC. RD was defined as detectable new enhancing tissue in the prior RFA-cavitation site after a documented complete response. We retrospectively compared patients who developed RD (RD+, n = 15, 5.1%) with patients who remained disease free after a complete response (RD−, n = 296, 95%), assessing tumor characteristics (size, location, biopsy pathology), complications, and disease-free survival. Mean follow-up was 3 years (SD 2.1). Results: RD+ and RD− groups did not differ significantly in age, gender, or tumor type. In tumors < 4cm, 3.3% were RD+. In tumors >= 4cm, 9.6% were RD+ (p<0.0001). RD+ groups were more likely to have central tumors (20% vs. 5.7%, p = 0.04). Mean time to disease recurrence was 1.47 years (SD 0.75, 0.5-3.5 yrs). Of the 15 patients with RD, 7 patients underwent sRFA, 6 patients elected observation due to comorbidities precluding further treatment, one patient received chemotherapy for widespread metastases and one patient underwent salvage partial nephrectomy, which was aborted due to extensive tumor burden and perirenal fibrosis. There were no complications related to sRFA. Of those who underwent sRFA, local recurrences were successfully ablated in 100% of cases with a single salvage RFA treatment. None of these sRFA cases developed locally recurrent disease at an average of 3 years follow-up. Conclusions: RD after RFA remains challenging to treat due to the significant comorbidities of the patients who are candidates for ablative treatment of RCC. RD was more likely to occur in centrally located tumors, > 4cm in size. Salvage RFA successfully can achieve local control in these patients without increased rates of complications. No significant financial relationships to disclose.