bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokine and angiogenic factor (CAF) profiling for identification of markers associated with response to cediranib in metastatic renal cell carcinoma (mRCC).
Authors: Zurita A. J. , Khajavi M. , Mulders P. , Yan S. , McKee K. S. , Tran H. T. , Pike L. , Mookerjee B. , Jurgensmeier J. , Heymach J. 
Published: February 2017

362 Background: Cediranib is a highly potent and selective signaling inhibitor of vascular endothelial growth factor (VEGF) receptors−1, −2, −3 and c-Kit. In a phase II trial, patients (pts) with mRCC were randomized 3:1 to treatment with cediranib or placebo to primarily assess the difference in change in tumor size at 12 weeks. Cediranib resulted in a significant reduction in tumor size vs. placebo (Mulders et al. ESMO. 2009). Here we investigated soluble biomarkers in serum and concentration changes during treatment. Methods: Pts received cediranib 45 mg/day PO or placebo for the first 12 weeks on treatment. At that time (or upon progression if earlier), treatment was unblinded and pts on placebo were given the option of receiving cediranib. Serum was collected from 61 pts at baseline (BL; cediranib 46, placebo 15), from 50 pts on day (D) 28, and from 45 pts on D84. Multiplex bead suspension arrays and ELISA were used to measure CAF concentrations including VEGF, placental growth factor (PlGF), sVEGFR-2, PDGFbb, HGF, MMP-9, multiple chemokines and interleukins (IL). The objectives of this exploratory analysis were to assess whether baseline CAFs were associated with changes in tumor size after 12 weeks of treatment and whether CAF levels changed while on treatment. Results: Of 39 CAFs available at BL, lower than median (‘low') concentrations of IL-10, VEGF, PlGF, stem cell factor (SCF), and monokine-induced by interferon-gamma (MIG) were associated with larger decreases in tumor size than high concentrations (independent of treatment arm), whereas the opposite trend was observed for IL-5 and TRAIL. Consistent with inhibition of VEGF signaling, cediranib treatment resulted in changes over time in VEGF (increase), sVEGFR-2 (decrease) and PlGF (increase) concentrations. In addition, SCF, a c-Kit ligand and M-CSF decreased, while VCAM-1 and TRAIL increased during cediranib treatment. Conclusions: Candidate CAFs associated with response to cediranib in mRCC such as IL-10 and VEGF were identified. Patients treated with cediranib showed distinct CAF changes compared with placebo. These results require independent validation in a larger trial. [Table: see text]
Extracellular proteases in renal cell carcinoma.
Authors: Lipe B. , Ernstoff M. S. , Gui J. , Seigne J. D. , Schned A. , Petrella B. 
Published: February 2017

363 Background: Tumor growth and metastasis relies on extracellular matrix remodeling, which is primarily mediated by the matrix metalloproteinase (MMP) family of enzymes. Extracellular matrix metalloprotease inducer (EMMPRIN, E) is a glycoprotein also implicated in tumor progression and has been shown to function in concert with MMPs. MMPs and E are highly expressed on the surface of many malignant tumors, including renal cell carcinoma (RCC). We investigated whether MMPs and E represent molecular prognostic factors in RCC. Methods: Protein expression was evaluated in 77 patients with immunohistochemical analysis of a tissue microarray (TMA) consisting of two tumor samples and an adjacent normal renal sample from each patient. Tumors represented on the TMA were clear cell (57), chromophobe (9), papillary (4), oncocytomas (3), clear cell with sarcomatoid differentiation (2), and metastatic (2). Protein expression scores were correlated with clinical outcomes to determine prognostic significance by univariate and multivariate analyses. Results: Using univariate analysis of all RCC tumors, membranous E correlated with overall survival (OS), metastasis-free survival (MFS), size, stage and overall 5-yr survival. Cytoplasmic E correlated with OS, MFS, size, grade, stage and 5-yr survival. Membranous MT1-MMP correlated with MFS, and endothelial MMP-2 correlated with grade. In multivariate analysis, membranous E was an independent indicator of stage, whereas cytoplasmic E was an independent indicator for size, stage, grade and MFS. In the clear cell population, membranous MT1-MMP correlated with OS and MFS, and endothelial MMP-2 correlated with grade in univariate analysis. In multivariate analysis, membranous MT1-MMP was an independent indicator for MFS. Conclusions: We identified EMMPRIN as an independent prognostic indicator for size, grade, stage, and MFS in RCC. While MT1-MMP and MMP-2 both significantly correlated with disease outcome in the clear cell RCC population, only MT1-MMP was an independent prognostic factor for MFS. We conclude that MMPs and E mediate important steps in RCC progression. Further investigation is warranted using larger datasets and a prospective study to determine the strength of the prognostic significance of these findings. No significant financial relationships to disclose.
Utilization of partial nephrectomy at a cancer center in the modern era.
Authors: O'Malley R. L. , Kowalik T. , Hayn M. H. , Collins T. B. , Underwood W. , Kim H. L. , Schwaab T. 
Published: February 2017

370 Background: Analyses of population-based databases have demonstrated a striking under-utilization of partial nephrectomy (PN) despite its superiority in functional outcomes. Disparities in treatment patterns exist in the community and at some tertiary centers, based on age, gender and some comorbidities. The goal of the current study was to determine predictors of PN utilization at a cancer center in the modern era. Methods: An institutional renal tumor database was used to identify patients who were potential candidates for elective PN (solitary tumors ≤ 7cm, baseline creatinine ≤ 1.5 mg/dL and a normal contralateral kidney). We estimated the effects of hypothesized predictors on the likelihood of undergoing radical nephrectomy (RN) versus PN by univariable (UV) and multivariable (MV) logistic regression. Variables included were: age, gender, race, smoking status, Charlson comorbidity index, body mass index (BMI), preoperative creatinine, year of surgery (YOS), radiographic tumor size, and whether diagnostic biopsy was performed. Results: Of the 244 patients identified, 64% underwent PN and 37% underwent RN between August 2004 and June 2010. The cohort was composed of 11% non-Caucasians, 59% males and 22% current smokers with a mean age, BMI and tumor size of 61 years, 31 kg/m2 and 3.5cm, respectively. Of the cohort, 17% underwent biopsy. On UV analysis advanced age, larger tumor size, earlier YOS and Caucasian race all predicted RN (OR 1.03 CI 1.02-1.06, OR 2.09 CI 1.70-2.58, OR 0.56 CI 0.46-0.70, OR 0.36 CI 0.13-0.99, respectively). On MV analysis using all variables, tumor size and YOS remained independent predictors (OR 2.89 CI 2.11-3.95, OR 0.44 CI 0.33-0.59, respectively). Renal cell carcinoma (RCC) on biopsy was also independently predictive on MV analysis (OR 0.37 CI 0.14- 0.97). Conclusions: Predictors of PN utilization at a cancer center differ from previous analyses and include decreasing tumor size, more recent YOS and RCC on biopsy. Appropriately, age and gender (when comorbidity is included) are not predictors of type of surgery. The significance of RCC on biopsy as a predictor of PN is unclear but may represent co-varying selection bias for lesions that are both accessible to biopsy and more appropriate candidates for PN. No significant financial relationships to disclose.
Incidence of benign pathologic lesions at nephrectomy for renal masses presumed to be stage I renal cell carcinoma in Japanese patients: Impact of sex, age, and tumor size.
Authors: Fujii Y. , Saito K. , Iimura Y. , Yasuda Y. , Koga F. , Masuda H. , Yonese J. , Ishikawa Y. , Fukui I. , Kihara K. 
Published: February 2017

374 Background: The widespread use of modern imaging techniques has resulted in the increased detection of small, asymptomatic renal tumors. Some recent studies from Western countries have reported that the incidence of benign lesions is approximately 15% in patients undergoing definitive surgery for renal masses presumed to be clinical stage I renal cell carcinoma (RCC). The high level of noncancerous lesions is, to some extent, due to the fact that no imaging feature can accurately distinguish either oncocytoma or lipid-poor angiomyolipma (AML) from RCC. This study attempts to determine the incidence of benign pathologic findings for such renal masses in Asian patients. Methods: Between 1991 and 2009, 711 consecutive patients (218 women and 493 men) underwent partial (n=206) or radical (n=505) nephrectomy for renal masses presumed to be stage T1N0M0 (T1a/T1b= 503/208) sporadic RCC on preoperative imaging in two Japanese centers. The mean size of the lesions was 3.3 cm (range 0.3-7.0). The pathologic features were reviewed by an experienced pathologist. Results: Of the 711 masses, 53 (7.5%) revealed benign pathologic findings. Twenty-two (3.1%) were AMLs, 13 (1.8%) were oncocytomas, 8 (1.1%) were complicated cysts, and 10 were others. Twenty-eight (12.8%) of the 218 females and 25 (5.1%) of the 493 males had benign lesions (p=0.0005). Of the 357 patients aged 60 years or younger, 37 (10.4%) had benign lesions while only 16 (4.5%) of the 354 patients over 60 years did (p=0.024). Forty six (9.2%) of the 503 T1a and 7 (3.4%) of the 203 T1b masses were benign (p=0.0071). A multivariate logistic regression model showed that sex, age and tumor size were all independently predictive of benign histology, particularly of AML. Conclusions: The present incidence (7.5%) of benign lesions in presumed clinical stage T1N0M0 RCC masses at nephrectomy was lower than the incidence of approximately 15% previously reported from Western countries, probably because of the low incidence of oncocytomas in Japanese patients. Female gender, young age and small tumor size are all independently predictive of benign lesions, particularly of AML in Japanese patients. No significant financial relationships to disclose.
Percutaneous radiofrequency ablation therapy as a first choice for renal tumor in patients with von Hippel-Lindau disease.
Authors: Uematsu K. , Saika T. , Kanbara D. , Kobayashi Y. , Gobara H. , Hiraki T. , Mimura H. , Kanazawa S. , Nasu Y. , Kumon H. 
Published: February 2017

375 Background: Forty percent of patients with von Hippel-Lindau (VHL) disease have multifocal, bilateral renal cell carcinoma (RCC). The advent of ablative therapy has allowed many of these tumors to be approached percutaneously. Probe-based radiofrequency ablation (RFA) have recently been shown to be feasible nephron-sparing therapies for RCC, and have been proposed as first-line treatments for patients with VHL. We evaluated the feasibility, safety and therapeutic effects of RFA for VHL patients. Methods: We reviewed the outcomes of VHL patients with RCC treated by RFA from 2003 to 2010. Follow-up consisted of serum creatinine measurement, physical examination and serial contrast enhanced computerized tomography or magnetic resonance imaging. Results: The 42 tumors of 15 patients (23-70 years old, median 40) received a total of 43 RFA treatments to a 7 to 28 mm renal tumor (median 16). Seven of the patients had bilateral renal tumors. Tumor enhancement was eliminated and the renal function was preserved after the treatment in all tumors. There were no major complications related to the procedures though eight of small subcapsular hematomas, one of hematuria, one of small urine overflow, and one of nausea were seen after RFA. There was no recurrence after RFA during a mean follow-up period of 28.9 months (range 4.0-89.0, median 20.0 months). The overall recurrence-free survival rate was 100%. There was also a 100% metastasis-free and disease specific survival rate in the cohort. Conclusions: The result of the present study showed percutaneous RFA was a feasible, safe, and promising therapy for the treatment of VHL patients with RCC. No significant financial relationships to disclose.
Second primary cancers and their prognostic significance in patients with renal cell carcinoma.
Authors: Hauke R. J. , Tarantolo S. R. , Batra S. , Chakraborty S. 
Published: February 2017

377 Background: To study the overall and site specific risk and prognostic significance of second primary cancers (SPC) in patients diagnosed with renal cell carcinoma (RCC). Methods: The Surveillance Epidemiology and End Results (SEER) database was queried for all patients with RCC as the first cancer and one or more SPC (1973-2006). SPC diagnosed within 1 month of diagnosis of RCC or at autopsy/death were excluded. Deidentified information was obtained to analyze the effect of SPC on overall survival (OS) of RCC patients. Results: A total of 3,795 patients with RCC and ≥ 1 SPC were identified. The ratio of observed/expected cases (O/E ratio) of RCC and ≥ 1 SPCs was 1.18 (95% C.I. 1.15-1.22), significantly greater than the general population (p<0.05). The overall age-adjusted rate of SPC was 0.6 per 100,000 and rate of SPCs was higher in males and in blacks. The O/E ratio of SPCs was significantly higher in younger patients (6.6 vs. 1.3 and 1.13 for those aged <30, 30-59 and ≥60 yrs respectively), in blacks (1.38 vs. 1.15 in whites), for larger tumors (1.3, 1.2 and 1.05 for tumors <5cm, 5-<10cm and ≥10cm in diameter), and those who did not receive radiation. The risk was similar for both genders. There was variation in the site-specific risk of SPC depending on age at time of RCC diagnosis, gender, race, size of the tumor and presence or lack of radiation therapy. Patients with SPC had longer OS than those with RCC as the only primary tumor on univariate but not multivariate analysis. Older age (≥60yrs), radiation therapy, and a short interval (<12 mo) between the diagnosis of RCC and a SPC were associated with significantly shorter OS in RCC patients with SPC on multivariate analysis. Conclusions: Our comprehensive analysis of SPCs in patients with RCC as the first primary malignancy using SEER data suggests that about 10% of RCC patients develop SPC and that several patient, tumor and treatment-related factors affect the risk of SPC at specific sites. Further, SPC can adversely influence the prognosis of patients with RCC, especially those >60 years old, receiving radiation or diagnosed with a SPC within 1 year after RCC diagnosis. These results may have significance in planning surveillance strategies to improve the survival of patients with RCC. No significant financial relationships to disclose.
Correlation of hypothyroidism with survival in metastatic renal cancer patients treated with sorafenib or sunitinib.
Authors: Riesenbeck L. , Bierer S. , Hoffmeister I. , Koepke T. , Hertle L. , Thielen B. , Herrmann E. 
Published: February 2017

379 Background: To investigate prognostic markers in patients with metastatic renal cell carcinoma (mRCC) undergoing treatment with the tyrosine kinase inhibitors (TKIs) sorafenib (So) or sunitinib (Su). Methods: Eighty-three patients with mRCC, who were treated at our institution between 2006 and 2009, were evaluated prospectively. Clinical and laboratory parameters were investigated, as well as, treatment-related adverse events. Subclinical hypothyroidism was characterized by serum TSH above the upper limit of normal and both total triiodtyronine (T3) and thyroxine (T4) within normal limits. Clinical hypothyroidism was defined as low serum T3 and T4 together with elevated TSH. Results: Thirty-one (37.3%) patients received So, and 52 (62.7%) were treated with Su. In univariate analyses, a poor ECOG status was associated with an unfavorable progression-free survival (PFS) (p<0.0001); similarly high risk MSKCC criteria correlated with a worse PFS (p=0.003). Furthermore, response to therapy was a surrogate parameter (p<0.0001). Twenty-one of 66 (31.8%) patients developed hypothyroidism during treatment, which was associated with a positive prognosis (p=0.032). In multivariate analyses, only the ECOG status (ECOG 0/1 vs. ECOG 2, p=0.018) and hypothyroidism (p=0.01) were independent prognostic parameters. Conclusions: The development of hypothyroidism during treatment might be useful as a clinical predictor of PFS for mRCC patients undergoing treatment with targeted agents. No significant financial relationships to disclose.
Recurrence and survival following preoperative sorafenib for advanced renal cell carcinoma.
Authors: Rathmell K. , Cowey C. L. , Grigson G. , Watkins C. , Wallen E. , Nielsen M. E. , Pruthi R. , Godley P. A. , Whang Y. E. , Kim W. Y. 
Published: February 2017

384 Background: The impact of neoadjuvant or preoperative therapy in the setting of advanced renal cell carcinoma on recurrence-free or survival outcomes is not known. Methods: 28 patients with renal cell carcinoma were treated with preoperative sorafenib in a prospective pilot study (LCCC 0603). Patient files were reviewed a median of 885 days (2.42 years) following nephrectomy. Records were evaluated for 13 patients with nonmetastatic disease for development of recurrence, and for 15 patients with stage IV disease for survival. Results: For the nonmetastatic patients, only 2 patients had developed recurrent disease, one underwent metastectomy and remains in surveillance and the other is on second line systemic targeted therapy. A median recurrence-free survival has not been met after a median 2.5 years. For stage IV disease patients at a median follow up of 2.3 years, a median survival has also not been reached. Four patients are deceased, one patient is lost to follow up, and 10 remain alive. Treatments for metastatic disease included continued sorafenib, high dose interleukin-2, sunitinib, pazopanib, temsirolimus, and everolimus. Some stage IV patients have also enjoyed prolonged treatment-free intervals ranging from six months to over two years, with biopsy confirmed, but indolent disease. Conclusions: Although these data are descriptive, these observations are suggestive that preoperative therapy with sorafenib is unlikely to accelerate the growth of grossly metastatic or micrometastatic disease. Further studies are needed to determine whether preoperative therapy is valuable in improving recurrence-free or overall survival endpoints. [Table: see text]
Use of C-reactive protein to predict perinephric or renal sinus fat invasion in patients with clinical T1N0M0 renal cell carcinoma.
Authors: Iimura Y. , Saito K. , Fujii Y. , Ishioka J. , Iwai A. , Numao N. , Okada Y. , Koga F. , Masuda H. , Kihara K. 
Published: February 2017

385 Background: Indication of nephron sparing surgery (NSS) for renal cell carcinoma (RCC) has been extending, as NSS can be considered for not only cT1a but also cT1b tumors. However, some cT1 diseases have pathological perinephric or renal sinus fat invasion. It is useful to know the probability of the presence of fat invasion before surgery, but diagnostic ability of imaging studies such as CT for predicting pT3a disease is limited. Therefore, estimation of the risk for pT3a disease in cT1 RCC patients could be helpful. C-reactive protein (CRP) has been shown to be a strong prognostic factor in RCC patients, reflecting tumor aggressiveness. We evaluated the predictive ability of preoperative CRP for pT3a disease in cT1N0M0 RCC patients. Methods: Of consecutive 386 patients treated with radical nephrectomy for cT1a-bN0M0 RCC, 82 were excluded due to hemodialysis, inflammatory disease, bilateral synchronous renal tumors, synchronous other malignant disease or loss of each data. The remaining 304 patients constituted the current study cohort. Cut off point of CRP was 3 mg/L. Associations were analyzed between pT3a and preoperative factors including age, sex, BMI, laterality, tumor size, CRP, hemoglobin, platelet, LDH, ALP, calcium and albumin. We developed a multivariate model for predicting pT3a disease in cT1 RCC. Results: Of the 304 patients, 28 (9%) had pT3a disease. Of 43 patients with elevated CRP level, 10 (23%) had pT3a disease. In contrast, of the remaining 261 patients with non-elevated CRP level, 18 (7%) had (p=0.002). Univariate and then multivariate analyses identified age (p=0.021), tumor size (p=0.007), and CRP (p=0.024) as independent and significant predictors for pT3a disease. Incorporating these three factors, we developed a predictive model for pT3a disease with predictive accuracy of area under the ROC curve of 0.772. Conclusions: Preoperative CRP is an independent predictor for pT3a disease in cT1 RCC along with age and tumor size. The model could be useful to estimate the risk of the probability of fat invasion before surgery, especially NSS. No significant financial relationships to disclose.
Renal cancer treatment in Spain: An online survey.
Authors: Duran I. , Sanchez Maurino P. , Garcia-Donas J. , Berthold D. R. 
Published: February 2017

397 Background: Renal cancer incidence has increased in the last decades. Many treatment options have also been developed in this period. Knowledge about oncologists' attitudes in the management of this disease could help to implement better treatment protocols. Methods: An online survey about therapeutic options for renal cancer was developed by an expert committee. Oncologists with expertise on the treatment of genitourinary malignancies that fulfilled all inclusion criteria in Spain were listed (n=200) and 80 were randomly selected to complete the survey. Survey items considered renal carcinoma management in the daily clinical practice. The questionnaire posed multiple tests, protocols, or therapeutic options. Results: From the 80 selected oncologists, 53 responded to the online survey (66% response rate). The mean number of newly diagnosed cases per year was 201 (SD: 12) patients of whom 15 corresponded to renal carcinoma. Seventy nine per cent of participants reported to apply a protocol for treatment decisions, being the NCCN recommendations the most frequently followed (54.7%). Surprisingly, local or European recommendations were scarcely used. When asked about management of metastatic disease, most physicians (83%) reported that they would use sunitinib as the preferred first line treatment for good or intermediate prognosis patients. If further treatment would be required, 69.8% (n=37) and 79.2% (n=42) of oncologists would recommend a change in the mechanism of action by switching to an mTOR inhibitor (everolimus) for first and further relapses, respectively. Regarding the management of first line non-clear cell histologies, almost half of the physicians would utilize a TKI, while 38% would prefer an mTOR inhibitor. Conclusions: NCCN are the most frequently followed recommendations. There is agreement among oncologists about which treatment should be used for renal carcinoma after first line treatment failure by switching the mechanism of action of the selected treatment. The management of non-clear cell patients remains a matter of debate with no consensus among the participants. No significant financial relationships to disclose.