bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparision of histologic distribution of RCC in young and older patients: Results from the SEER database.
Authors: Daugherty Michael R. , Blakely Stephen , Shapiro Oleg , Bratslavsky Gennady 
Published: February 2017

419 Background: Renal cell cancer (RCC) incidence is relatively low in younger patients, encompassing 3-5% of all RCC tumors. These tumors tend to be due to hereditary syndromes and genetic mutations that predispose to cancer development. Patients with hereditary renal cancer (HRC) are at a higher risk of multiple tumors and bilateral disease. We hypothesize that there is a difference in histologic distribution in the younger patients and that the younger distribution contains more aggressive histologic subtypes. Methods: SEER 18-registries database was queried for all patients ≥20 years old that were surgically treated for renal cell carcinoma between the years 2001 and 2008. Patients with unknown race, grade, stage, or histology were excluded from the study. Histologies selected were clear cell, papillary, chromophobe, sarcomatoid, and collecting duct. Three cohorts were created with the ages 20-44, 45-64, and ≥65 year olds that contained 3,926, 19,661, and 16,323 patients respectively. Chi-square analysis was used to compare the histologic distributions between the cohorts. Results: There was no difference in the incidence of clear cell RCC between the three cohorts (p = 0.63). The histology distribution was not different in the 45-64 year olds compared to those ≥65 (p = 0.47). The non-clear cell histologies were different between the 3 age groups (p < 0.001). There were a larger percentage of patients in the younger patients that had chromophobe tumors compared to all non-clear cell histologies (p< 0.001). Conclusions: The difference in the non-clear cell histologic distribution between the groups is most likely due to genetic mutations predisposing these patients to chromophobe RCC. There has been limited data on HRCs, due in large part to its low incidence. Although the HRCs are known to have a most common histology, it is likely that this information is incomplete, as younger patients have undiagnosed genetic mutations that led to development of chromophobe tumors. [Table: see text]
Tumor shrinkage during VEGF inhibitor therapy as an independent predictor of PFS and OS in renal cell carcinoma (RCC).
Authors: Gruenwald Viktor , Busch Jonas , Weikert Steffen , Seidel Christoph 
Published: February 2017

423 Background: Response to VEGF targeted therapies has been recently shown to be an important prognostic and predictive marker in metastatic RCC. However, whether the extent of tumor shrinkage (TS) correlates with distinct clinical outcome remains unknown. We investigated the role of early TS fractions on median progression free survival (PFS) and median overall survival (OS). Methods: Tumor evaluations according to RECIST 1.1 were performed within 3 months (mo) of targeted therapy with a VEGF inhibitor in 108 patients (pts). Pts were then categorized in fractions of TS: a) -100% to -60%; b) -60 % to -30% and c) -30% to 0% or gain in tumour size: d) 0% to +20% and e) > +20%. Kaplan-Meier and log-rank analyses were performed to estimate PFS and OS with a landmark set to 6 mo. Multivariate Cox proportional hazard model was utilized for evaluation of prognostic factors. Results: First-line VEGF inhibition achieved a PFS of 10.6 mo (95% CI 8.7 – 12.5) and an OS of 29.8 mo (95% CI 23.9 – 35.6) in all pts. 5 pts achieved a complete remission (4.6%), 28 pts a partial remission (25.9%), 52 pts. stable disease (48.2%), and 23 pts. had progressive disease (21.3%) as best response. In univariate analyses histology (clear cell differentiation vs. others) and TS were associated with PFS (p = 0.026; p <0.0001) and OS (p = 0.017; p = 0.009). Multivariate analyses confirmed the relevance of TS as a prognostic variable for OS (p = 0.021; HR 1.49) and PFS (p = <0.001; HR 1.91). Conclusions: TS is an independent predictive and prognostic marker in first-line treatment with VEGF inhibitors in mRCC. [Table: see text]
A pharmacodynamic trial of sequential sunitinib (Su) with bevacizumab (Bev) in patients (Pts) with renal cell carcinoma and other advanced solid malignancies.
Authors: Bruce Justine Yang , Hammers Hans , Kolesar Jill , Stein Mark N. , Eickhoff Jens C. , Carmichael Lakeesha , Johnston Susan , Perlman Scott , Jeraj Robert , Liu Glenn 
Published: February 2017

434 Background: Su treatment results in a compensatory increase in plasma VEGF levels. Acute withdrawal of Su results in a proliferative withdrawal flare, primarily due to elevated VEGF levels. Higher flare corresponded to shorter PFS. Concurrent Su plus Bev is poorly tolerated with high (37%) incidence of microangiopathic hemolytic anemia (MAHA). Based on biological rationale and to improve the toxicity profile, we evaluated a sequential design administering Bev during the Su treatment break. We planned to evaluate the ability of Bev to suppress the Su withdrawal flare using FLT PET/CT. Methods: Pts with no prior VEGF treatment were enrolled in this multi-institutional study. All pts had target lesions amenable to serial FLT PET/CT imaging. Su was given at 37.5 mg on day 1-28 every 6 weeks with Bev 5 mg/kg on day 29. If safe and tolerable, Su would increase to 50 mg. Once the Su dose was established, FLT PET/CT scans would be obtained at baseline (D1), week 4, and week 6 to evaluate pharmacodynamics of the sequential combination. Su pharmacokinetics and total, free, and bound VEGF levels were obtained on each cycle at D1, pre-Bev (D29), 4 hours post Bev (D29H4) and day 42 (D42). Results: Six pts enrolled in the safety cohort of Su 37.5 mg plus Bev. One pt experienced gr 1 MAHA and after discussion with CTEP, the trial was closed to further accrual. No imaging scans were obtained due to early closure. Data assessing VEGF dynamics appears in the table. Conclusions: Subclinical MAHA was seen despite using sequential Su with low dose Bev and this combination was not feasible for further development. As predicted, VEGF levels increased during Su exposure followed by a rapid decline after Bev. Due to the long half-life of Bev, we expected VEGF ligand suppression through D42, but instead observed a complete rebound in total/free VEGF levels by D42. VEGF ligand production may be increased as a result of Bev, implying a robust host compensatory mechanism to VEGF signaling pathway inhibition. A greater understanding of the compensatory mechanism would aid future sequencing strategies of new agents. Clinical trial information: NCT01243359. [Table: see text]
Dynamic molecular changes with VEGF targeted therapy in metastatic clear cell renal cancer.
Authors: Powles Thomas , Sharpe Kevin , Berney Dan , Kayani Irfan , Doshi Rukma , Stewart Grant Duncan , Reynolds Andrew , Bex Axel , Sarwar Naveed , Chowdhury Simon 
Published: February 2017

437 Background: The purpose of this study was to investigate for specific molecular changes associated with VEGF targeted in metastatic clear cell renal cancer (mRCC). This was achieved by taking tissue before and after VEGF TKI therapy. Methods: The study combined the data from 3 similar phase II prospective studies, investigating the role of VEGF therapy (pazopanib or sunitinib) prior to planned nephrectomy in untreated mRCC. A structured treatment break occurred during the planned nephrectomy (4 weeks). Paired tumour samples before and after 12-16 weeks of pazopanib or sunitinib were collected from these studies. Histopathology assessment (Furman grade, Ki-67, vascular density [CD31]), growth factor expression [FGF-2, c-MET, S-6-protein kinase] and immune parameters (CD3, 4, 8, PDL-1, FOXP3) before and after therapy were compared. Sequential functional imaging [FDG-PET] was performed to address the relationship between the primary tumour and metastatic sites. Results: Overall 62 patients had sequential tissue taken from these 3 prospective trials. Adequate quantities of sequential tissue were available from 48 patients. Pathological examination of the matched pairs before and after VEGF TKI showed a significant increase in tumour grade, Ki-67, lymphocyte infiltrate, and necrosis (p>0.05), there was also a significant decrease in CD31 (p<0.05). Significant changes to FGF-2, c-MET and FOXP3 expression was seen in the treated samples (p<0.05). FDG-PET results from 23 patients showed a significant correlation in the response seen in the primary renal tumour and metastatic sites with sunitinib (r=0.46 p<0.001). During the structured treatment break for nephrectomy (4 weeks) 37% of patients had disease progression (RECIST v1.1) underlining the aggressive nature of the disease after VEGF TKI therapy. This was associated with an increased risk of death on multivariate analysis (HR: 3.17; 95% CI, 1.46-6.86, p<0.03). Conclusions: These results suggest VEGF targeted therapy is associated with a more aggressive tumor phenotype. Changes to immune parameters and up regulation of growth factors potentially implicated in resistance to VEGF targeted therapy occurred.
Partial nephrectomy in the setting of metastatic renal cell carcinoma.
Authors: Babaian Kara , Matin Surena F. , Tamboli Pheroze , Tannir Nizar M. , Jonasch Eric , Wood Christopher G. , Karam Jose A. 
Published: February 2017

440 Background: Up to one-third of patients with renal cell carcinoma present with metastatic disease (mRCC). Cytoreductive nephrectomy remains the standard of care for appropriately selected patients. However, cytoreductive nephrectomy is not always practical. We sought to identify the indications and outcomes for partial nephrectomy (PN) in our cohort of patients with mRCC, with particular attention to different PN subgroups. Methods: Using our institutional database, 30 patients with mRCC who underwent PN between 1996 and 2011 were identified. Demographic, clinical, and pathologic variables were collected. Non-parametric statistics and log-rank tests were used. Cancer specific survival (CSS) was estimated using Kaplan-Meier method according to presentation, tumor size, and presence of metastatic disease, from the time of PN to last follow-up or death. Results: The median age at PN was 57 years (range 32-84). 8 patients presented with bilateral synchronous renal masses; 17 presented with a metachronous contralateral renal mass; and 5 presented with a unilateral renal mass (including 3 in a solitary kidney). Median follow-up after PN was 32 months (range 1-184). Overall, 23 patients (77%) died of disease at a median of 27 months (range 7-86) after PN. Patients who underwent PN for a metachronous contralateral renal mass had a median CSS of 61 months compared to those with bilateral synchronous or unilateral renal masses (CSS 26.5 months, HR 2.98, p =.012 and CSS 31, HR 2.12, p =.069, respectively). Patients who underwent PN for a renal mass ≤4cm and >4cm had a median CSS of 42 and 26.5 months, respectively (HR 2.49, p =.037). Median CSS for patients with and without metastatic disease at original diagnosis was 27 and 61 months, respectively (HR 2.85, p =.013). In this study, patients who became M0 after metastasectomy did not have improved CSS compared to patients who did not (42 and 32 months, p =0.152). Conclusions: Our findings suggest that the burden of disease at initial diagnosis, timing of presentation of the PN index lesion, and the size of the renal mass at PN play an important role in survival. These factors should be taken into consideration when determining which patients would benefit from PN in the setting of mRCC.
Preoperative C-reactive protein combined with SSIGN score as an independent predictor of cancer-specific survival in patients with clear cell renal cell carcinoma.
Authors: Herrel Lindsey Allison , Tai Caroline Gar-Ling , Westby Ruth , Ogan Ken , Canter Daniel , Pattaras John , Nieh Peter , Master Viraj A. 
Published: February 2017

451 Background: Renal cell carcinoma (RCC) demonstrates heterogeneous behavior. Approximately 30% to 40% of patients with clinically localized RCC will later metastasize. Current tools are imperfect for predicting who will have distant spread of disease. C-reactive protein (CRP) levels and the Mayo Clinic SSIGN scores are widely use to predict outcomes of clear cell RCC. We investigated the predictive value of the combined use of pre-operative CRP and SSIGN score for cancer specific survival. Methods: Patients undergoing nephrectomy for clinically localized RCC from 2005 to 2010 were studied. Inclusion criteria required clear cell histology, no nodal or metastatic disease at the time of surgery, two years follow-up time, and a recorded preoperative CRP level. SSIGN score was based on postoperative data and was categorized into scores 0-2, 3-5, and ≥ 6. A cut-point of 20 mg/l was used to classify elevated preoperative CRP. Univariate analysis identified variables associated with cancer specific survival (CSS). Variables significant in univariate analysis at p < 0.05 were entered into a multivariate Cox regression model using forward stepwise regression to identify significant predictors of CSS. Results: Study criteria identified 284 patients. Of these patients, 62% were men and 13% had preoperative CRP values ≥ 20 mg/L. No patients had T4 disease, while 22% had T3, 7% had T2, and 70% had T1 disease. SSIGN scores of 0-2, 3-5, and ≥ 6 were assigned to 57%, 30%, and 13% of patients, respectively. On univariate analysis CRP ≥ 20 mg/L was a statistically significant predictor of CSS (p < 0.0004, HR 7.07, CI 95% 2.42, 20.68). Multivariate Cox Regression found preoperative CRP (p = 0.033, HR 3.65, CI 95% 1.11, 11.97) to be an independent predictor of CSS despite controlling for age at surgery (p < 0.05) and SSIGN score (p < 0.05), which were also independent predictors of CSS. Conclusions: In patients with clear cell RCC, pre-operative CRP levels in combination with SSIGN score provides additional information for predicting CSS.
Body mass index and survival of patients with metastastic renal cell carcinoma: Data from the German prospective RCC registry.
Authors: Mueller Lothar , Goebell Peter J. , Von Verschuer Ulla , Hurtz Hans-Juergen , Franzem Melanie , Vogt Michele , Marschner Norbert 
Published: February 2017

454 Background: Being overweight is a known risk factor for developing renal cell carcinoma (RCC). On the other hand, overweight patients may harbor a less aggressive type of disease. A recent meta-analysis was able to demonstrate that a high preoperative BMI was an independent prognostic indicator for better overall survival in patients with RCC. We present data on the prognostic impact of the postoperative BMI, at the start of systemic treatment in patients with advanced or metastatic RCC (mRCC). Methods: The German RCC registry is a prospective, longitudinal, multicenter study conducted by a network of 133 office-based medical oncologists in Germany to document treatment of unselected patients with mRCC. Based on the inclusion criteria for this analyses we identified 475 prospectively documented patients who received 1st-line systemic treatment. Patients were grouped by their BMI and overall survival was estimated by Kaplan-Meier analysis. A multivariate cox proportional hazards model was used to determine the impact of potentially prognostic variables at the start of systemic treatment (sex, age, BMI, comorbidity, Motzer’s score, tumor stage [TNMRG], and number of metastatic sites) on overall survival. Results: The mean age of patients at the start of systemic treatment was 68 years and the median follow-up was 23.8 months. 118 (25%) presented with a BMI < 24, 195 (41%) with a BMI 24 - 28 and 162 (34%) with a BMI > 28. Patient characteristics did not differ between groups, except more patients in the low BMI group had a higher prognostic risk according to Motzer-score (11% vs. 5 % vs. 6 %). Median overall survival was 10.0 month, 16.7 month and 23.4 month in the low, medium and high BMI group, respectively. In a multivariate analysis, BMI (HR 0.94, 95% CI 0.91-0.98, p < .001) and Motzer-Score (HR 1.83, 95% CI 1.59-2.12, p < .001) had a significant impact on overall survival. Conclusions: In addition to Motzer’s prognostic score, the BMI at the start of palliative treatment may be used to discriminate mRCC patients with good and poor prognosis. Patients with a higher BMI tend to live longer than patients with low or normal BMI supporting evidence from previous meta-analyses on preoperative BMI and outcome.
Are there geographic differences in the outcome of patients (pts) with metastatic renal cell carcinoma (mRCC) treated with sunitinib (su)?
Authors: Keizman Daniel , Ish-Shalom Maya , Maimon Natalie , Gottfried Maya , Pili Roberto , Hammers Hans J. , Eisenberger Mario A. , Sinibaldi Victoria J. , Boursi Ben , Weitzen Rony , Hayat Henry , Peer Avivit , Neumann Avivit , Kovel Svetlana , Sella Avishay , Mermershtain Wilmosh , Roubinov Keren , Berger Raanan , Carducci Michael Anthony 
Published: February 2017

458 Background: Geographic differences in the outcome of pts have been described in various cancers. The VEGFR inhibitor su is a standard treatment (tx) for mRCC. The effect of geographic differences on the outcome of su tx in mRCC is poorly defined. We aimed to study the effect of geographic differences on outcome of su tx in mRCC. Methods: We performed an international multicenter retrospective study of unselected cohort of 275 mRCC pts, who were treated with su from 2004 to 2012 in 7 centers across the United States and Middle East (ME; Israel). Clinicopathologic and prognostic factors, and tx outcome were compared between United States (n=133) and ME (n=142) pts. Chi-square and Fisher's exact tests were used to compare categorical variables, and two-sample t-test was used to compare continuous endpoints. Progression free survival (PFS) and overall survival (OS) were determined by Cox regression. Results: Median age was 61 (United States) vs. 65 (ME, p = 0.01). The groups were balanced regarding gender, Heng risk, past nephrectomy, RCC histology, presence of ≥ 2 metastatic sites, lung/liver/bone metastasis, use of angiotensin system inhibitors (ASI), prior cytokines/ targeted txt, su induced HTN, and su dose reduction/tx interruption secondary to side effects. The incidence of active smokers (28% vs. 15%, p =0.01), bisphosphonates users (23% vs. 13%, p = 0.03) and pts with pre-tx neutrophil to lymphocyte ratio (NLR) ≤ 3 (63% vs. 49%, p = 0.04) was higher among ME pts. In United States vs. ME pts, objective response was partial response/stable disease 77% (n=102) vs. 79% (n=112), and progressive disease at first imaging evaluation within the first 3 months (mos) 23% (n=31) vs. 21% (n=30) (p = 0.77, OR 1.1). Median PFS was 8 vs. 12 mos (HR=1.8, p < 0.0001), and median OS 21 vs. 22 mos (HR=0.94, p = 0.9) in United States vs ME pts. Factors associated with PFS in multivariate analysis of the entire cohort (n=275) were geographic location (United States vs. ME), Heng risk, RCC histology, su induced HTN, ASI use, pre-tx NLR, and smoking status. Conclusions: Geographic differences in clinicopathologic factors and PFS of pts with mRCC treated with su may exist. This should be further investigated, and if validated, applied in clinical practice and clinical trials.
Difference in adverse-event profiles between mTOR inhibitors, temsirolimus, and everolimus for advanced renal cell carcinoma.
Authors: Nozawa Masahiro , Kikuchi Takashi , Nishimoto Mitsutoshi , Kobayashi Yasuyuki , Uemura Hirotsugu 
Published: February 2017

461 Background: Everolimus and temsirolimus have proven their efficacy and are used for patients with metastatic renal cell carcinoma (mRCC). They both are rapamycin derivatives and are categorized as mTOR inhibitors. There have been few reports that examined the difference between these two agents regarding adverse events. Our objective was to investigate the difference in the safety of both agents on the basis of our clinical experience. Methods: We identified patients with mRCC who had been treated with everolimus or temsirolimus at our hospital. Treatment duration, relative dose intensity, laboratory data, and adverse events during treatment with each agent were evaluated. Results: A total of 55 patients were evaluable. 43 of those had been treated with everolimus, 22 with temsirolimus, and 10 with both agents. There was no significant difference in age and gender between the two treatment groups. Median treatment durations of the everolimus and temsirolimus groups were 2.4 months and 1.8 months, respectively. Relative dose intensities of the everolimus and temsirolimus groups were 71.6 % and 75.4 %, respectively. Anemia, hyperglycemia, stomatitis, and interstitial lung disease (ILD) were detected with higher frequency in the everolimus group. In the everolimus group, 31 % of patients developed any grade of ILD including 15 % of grade 3, whereas ILD was reported in only one patient treated with temsirolimus with no grade 3 or higher. Frequencies of adverse events of grade 3 or higher were 49 % in the everolimus group and 26 % in the temsirolimus group. Conclusions: Adverse-event profiles of everolimus and temsirolimus may differ from each other. Respiratory disorders may occur more frequently and severely in patients treated with everolimus than temsirolimus. These findings suggest the difference in the pharmacodynamics, pharmacokinetics, and treatment regimen of these two agents may result in different adverse events even though they target the same molecule.
PSA-detected prostate cancer in the United States: A population-based study of 70,345 men with AJCC stage T1cN0M0 disease.
Authors: Zhang Hong , Travis Lois B. , Messing Edward M. , Hyrien Ollivier , Chen Rui , Milano Michael T. , Brasacchio Ralph Anthony , Chen Yuhchyau 
Published: February 2017

50 Background: The U.S. Preventive Services Task Force (USPSTF) recently recommended against prostate-specific antigen (PSA)-based screening for prostate cancer. This recommendation has heightened the debate about risks and benefits of prostate cancer screening, and underscored our limited understanding of PSA-detected prostate cancer. The purpose of this study was to determine the frequency of various risks of prostate cancer based on patient characteristics and PSA levels. Methods: This population-based study used the Surveillance, Epidemiology, and End Results (SEER) program to identify men with AJCC stage T1cN0M0 disease diagnosed between 1/2004 and 12/2008. Multivariate logistic regression was conducted to model the probability of developing low (PSA <10 mg/L and Gleason score ≤6), intermediate (PSA between 10 mg/L to 20 mg/L and/or Gleason score 7), and high risk diseases (PSA ≥20 mg/L, and/or Gleason score ≥8). Results: A total of 70,345 men with PSA-detected T1cN0M0 prostate cancer were evaluated. Among them, 47.6%, 35.9% and16.5% had low, intermediate, or high risk disease, respectively. Odds ratios (OR) of having intermediate or high risk disease in patients ≥75 years old were 4.47 (95% confidence interval (CI) 3.81 to 5.26, p<0.01) and 9.39 (95% CI 7.25 to 12.16, p<0.01), respectively, when compared with patients aged <50. Also, black men had increased ORs for intermediate and high risk disease compared with white men (OR 1.50, 95% CI 1.42 to 1.58, p<0.01 for intermediate risk disease; OR 1.84, 95% CI 1.72 to 19.97, p<0.01 for high risk disease). While men aged >75 accounted for 11.8% of the population at risk, they accounted for 24.3% of intermediate and 26.1% of high risk disease. Conclusions: A substantial number of PSA-detected prostate cancer patients have either intermediate or high risk disease at diagnosis. Men age >75 or of black race have the highest risk of presenting with intermediate or high risk disease.